 Nitrogen-containing heterocyclic compounds
专利摘要:
The present invention prevents the phosphorylation of PDGF receptors and prevents abnormal proliferation and migration of cells, and thus is effective for the prevention and treatment of cell proliferative diseases such as atherosclerosis, vascular reclosure disease, cancer and glomerulosclerosis. To nitrogen-containing heterocyclic compounds and pharmaceutically acceptable salts thereof: [Formula I] (V is oxygen or sulfur; W is 1,4-piperazindiyl or 1,4-homopiperazindiyl (which may be substituted by a ring unsubstituted alkyl group); X is nitrogen or CR 9 ) , Y is nitrogen or CR 8 , Z is nitrogen or CR 7 , at least one of X, Y and Z is nitrogen; R 1 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl R 2 is substituted alkyl, substituted or unsubstituted cycloalkyl, and the like; R 3 , R 4 , R 5 and R 6 are each hydrogen, halogen, substituted or unsubstituted alkyl, nitro, cyano, -OR 12 , -NR 15 R 16, etc., R 7 is halogen, etc .; R 8 is as defined above in R 7 ; R 9 is hydrogen or -COR 41 ) 公开号:KR19990071843A 申请号:KR1019980704125 申请日:1997-10-01 公开日:1999-09-27 发明作者:겐지 마쓰노；미찌오 이찌무라；유지 노모또；시게끼 후지와라；신이찌 이데；에이지 쓰꾸다；준꼬 이리에；쇼지 오다 申请人:히라타 다다시；교와 핫꼬 고교 가부시끼가이샤； IPC主号:
专利说明:
Nitrogen-containing heterocyclic compounds PDGF is known to act as a factor that exacerbates cell proliferative diseases such as atherosclerosis, coronary angioplasty through the skin and revascularization after angioplasty, cancer, glomerulonephritis, glomerulosclerosis, psoriasis and arthritis rheumatoid Cell, 46,155-169 (1986); Science, 253, 1129-1132 (1991); Nippon Rinsho (Japanese J. of Clinical Medicine), 50, 3038-3045 (1992); Nephrol Dial Transplant, 10, 787-795 (1995); kidney International, 43 (Suppl. 39), 86-89 (1993); Journal of Rheumatology, 21, 1507-1511 (1994); Scandinavian Journal of Immunology, 27, 285-294 (1988), etc.) . For quinazoline derivatives useful as medicaments, N, N-dimethyl-4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboxamide is described in South African Patent No. 67 06512 in bronchodilators. As described. Dimethoxyquinazoline derivatives are described in Japanese Patent Publication Nos. 208911/93 and WO 96/09294 as inhibitors of phosphorylation of epidermal growth factor (EGF) receptors. Quinoline derivatives with benzodiazepine receptor agonist activity are described in Pharmacology Biochemistry and Behavior, 53, 87-97 (1996) and the European Journal of Medicinal Chemistry, 31, 417-425 (1996), parasitic drugs Quinoline derivatives useful as are described in the Indian Journal of Chemistry, 26B, 550-555 (1987). Inhibitors of phosphorylation of the PDGF receptor include bismono-, bicyclic aryl compounds, and heteroaryl compounds (WO 92/20642), quinoxaline derivatives (Cancer Research, 54,6106 (1994)), pyrimidine derivatives ( Japanese Patent Application Laid-Open No. 87834/94) and dimethoxyquinoline derivatives (Abstracts of the 16th Annual Meeting of the Pharmaceutical Society of Japan (Kanazawa) (1996), 2, p. 275, 29 (C2) 15-2 ]) Is known so far. The present invention provides a nitrogen-containing heterocyclic compound having an inhibitory effect on the phosphorylation of platelet-induced growth factor (PDGF) receptors and useful for the treatment of cell proliferative diseases such as atherosclerosis, vascular occlusion, cancer and glomerulosclerosis and their It relates to a pharmaceutically acceptable salt. It is an object of the present invention to inhibit the phosphorylation of PDGF receptors to prevent abnormal cell growth and cell wandering, which is useful for the prevention or treatment of cell proliferative diseases such as atherosclerosis, revascularization, cancer and glomerulosclerosis, In the provision of pharmaceutically acceptable salts thereof. The present invention relates to a nitrogen-containing heterocyclic compound represented by the following general formula (I) and a pharmaceutically acceptable salt thereof: {Wherein V is oxygen or a sulfur atom; W is 1,4-piperazindiyl or 1,4-homopiperazindiyl, in which the carbon of the ring may be substituted with 1-4-alkyl groups which may be the same or different; R 1 is a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted alkenyl group, substituted or unsubstituted Unsubstituted alkynyl group, substituted or unsubstituted aryl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted heteroaryl group, or substituted or unsubstituted heteroarylalkyl group; R 2 is a substituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, substituted or Unsubstituted aryl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted heteroarylalkyl group, -COR 10 (R 10 has the same meaning as R 1 ) Or —SO 2 R 11 (R 11 is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted alkenyl group, substituted Substituted or unsubstituted alkynyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted aralkyl groups, substituted or unsubstituted heteroaryl groups, or Substituted or unsubstituted heteroarylalkyl group); R 3 , R 4 , R 5 and R 6 may be the same or different and each is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a nitro group, a cyano group, -OR 12 [R 12 is equal to R 10 Have the same meaning, or -COR 13 (R 13 has the same meaning as R 10 ) or -SO 2 R 14 (R 14 has the same meaning as R 11 )], -NR 15 R 16 {R 15 is R It has the same meaning as 10, R 16 can have the same meaning as R 10, or or -SO 2 R 17 (R 17 has the same meaning as R 11) or [X 1 is an oxygen atom or a sulfur atom; R 18 has the same meaning as R 10 or -OR 19 (R 19 has the same meaning as R 11 ) or -NR 20 R 21 (R 20 has the same meaning as R 10 and R 21 has R Having the same meaning as 10 , or R 20 and R 21 combine with an adjacent nitrogen atom to represent a substituted or unsubstituted nitrogen-containing alicyclic heterocyclic group); Or R 15 and R 16 combine with an adjacent nitrogen atom to represent a substituted or unsubstituted nitrogen-containing heterocyclic group}, [m represents an integer from 0 to 2; if m is 0 then R 22 has the same meaning as R 10 ; when m is 1 then R 22 has the same meaning as R 11 ; If m is 2 then R 22 has the same meaning as R 11 , or -OR 23 (R 23 has the same meaning as R 10 ) or -NR 24 R 25 (R 24 and R 25 can be the same or different. Each having the same meaning as R 10 , or R 24 and R 25 taken together with an adjacent nitrogen atom to represent a substituted or unsubstituted nitrogen-containing alicyclic heterocyclic group)], or-COR 26 [R 26 is Have the same meaning as R 10 , or -OR 27 (R 27 has the same meaning as R 10 ) or -NR 28 R 29 (R 28 and R 29 can be the same or different, each with R 10 Or R 28 and R 29, in combination with adjacent nitrogen atoms, represent a substituted or unsubstituted nitrogen-containing alicyclic heterocyclic group); Or any two adjacent groups of R 3 , R 4 , R 5 and R 6 combine to represent methylenedioxy or ethylenedioxy; Or any two adjacent groups of R 3 , R 4 , R 5 and R 6 combine with two adjacent carbon atoms to form a substituted or unsubstituted phenyl ring; Or R 3 and R 4 , R 4 and R 5 , or R 5 and R 6 are bonded to two adjacent carbon atoms [A represents an oxygen atom, a sulfur atom or -NR 30- (R 30 has the same meaning as R 10 ); Q 1 has the same meaning as R 10 , or -NR 31 R 32 (R 31 and R 32 can be the same or different and each has the same meaning as R 10 , or R 31 and R 32 are adjacent nitrogen. Combined with an atom to represent a substituted or unsubstituted nitrogen-containing alicyclic heterocyclic group) or -SR 33 (R 33 has the same meaning as R 10 ); or (R 34 and R 35 may be the same or different and each has the same meaning as R 10 ; Q 2 represents an oxygen atom, a sulfur atom or = N-CN), or (R 36 has the same meaning as R 10 ); Z is a nitrogen atom or CR 7 [R 7 R 10 have meanings or have, or halogen atom, -OR 37, such as an (R 37 has the same meaning as R 10), -SR 38 (R 38 is R 10 and Has the same meaning) or -NR 39 R 40 (R 39 has the same meaning as R 10 , R 40 has the same meaning as R 10 , or R 39 and R 40 are bonded to an adjacent nitrogen atom to Or an unsubstituted nitrogen-containing alicyclic heterocyclic group). Y represents a nitrogen atom or CR 8 (R 8 has the same meaning as R 7 ); X represents a nitrogen atom or CR 9 [R 9 represents a hydrogen atom or -COOR 41 (R 41 has the same meaning as R 18 ), and Provided that at least one of X, Y and Z represents a nitrogen atom. Specific examples of the substituents mentioned in the definition for the group of the compound (I) of the present invention are given below. These examples are preferred and are not limited to the present invention. In the definition of groups of formula (I), an alkyl group is a linear or branched alkyl group having 1 to 16 carbon atoms, for example methyl or ethyl, propyl, isopropyl, butyl, having a straight chain or having 1 to 16 carbons, Isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl and hexadecyl. The cycloaliphatic alkyl group has 3 to 12 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohepnyl, cyclooctyl and cyclo dodecyl and pinanyl, 1,7,7-trimethylbicyclo [2.2.1] polycyclic alkyl groups such as heptyl, adamantyl, hexahydro-4,7-methano-1H-indenyl and 4-hexylbicyclo [2.2.2] octyl. Alicyclic heterocyclic groups include tetrahydrofuryl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, piperazinyl, colporinyl, thiomorpholinyl and the like. Alicyclic heterocyclic groups containing nitrogen generated with adjacent nitrogen include pyrrolidinyl, pepperidino, homopiperidino, piperazinyl, homopiperazinyl, morpholinyl, thiomorpholinyl, and the like. Heterocyclic groups containing nitrogen, such as adjacent nitrogen atoms, may be pyrrolidinyl, piperidyl, homopiperidyl, piperazinyl, homopiperazinyl, morpholino, thiomorpholino, pyrrolyl, imidazoryl, Pyrazolyl, triazolyl, tetrazolyl, indolyl, indazolyl, benzimidazolzyl, benzotriazolyl and the like. Alkenyl groups are straight chain or branched alkenyl groups having 2 to 16 carbon atoms, for example vinyl, allyl, 1-propenyl, isopropenyl, methacryl, butenyl, crotyl, pentenyl, hexenyl , Heptenyl, decenyl, dodecenyl and hexadecenyl. Alkynyl groups include, for example, ethynyl, cropatyl, butynyl, pentynyl, hexynyl, heptynyl, decinyl, dodecynyl and hexadecynyl having 2 to 16 carbon atoms. Aryl groups include phenyl, naphthyl, anthyl, pyrenyl and the like. Aralkyl groups include benzyl, phenethyl, phenylpropyl, phenylbutyl, benzhydryl, trityl, naphthylmethyl, naphthylethyl and phenylcyclopropyl having 7 to 15 carbon atoms. Heteroaryl groups are pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolyl, isoquinolinyl, quinazolinyl, phthalazinyl, quinoxalinyl, naphthyridinyl, cynolinyl, thienyl, furyl , Pyrrolyl, imidazolyl, pyrazoryl, triazolyl, tetrazolyl, oxazolyl, triazolyl, thiadiazolyl, benzothienyl, benzofuryl, indoryl, indazoryl, benzimidazolyl, benzotriazolyl, benzotrizo Reel, benzothiazolyl, prinyl and the like. The heteroaryl moiety of the heteroarylalkyl group has the same meaning as the heteroaryl group and the alkyl moiety has the same meaning as the alkyl group. Halogen atoms include fluorine, chlorine, bromine and iodine atoms. Each substituted alkyl group, substituted alkenyl group and substituted alkynyl group have 1 to 3 same or different substituents. Examples of the substituent include nitro group, cyano group, hydroxyl group, oxo group, halogen atom, alicyclic alkyl group, aryl group, alicyclic heterocyclic group, carboxyl group, formyl group, R 42 CO-E 1- (E 1 Represents a single bond or an oxygen atom; R 42 represents an alkyl group, an alicyclic alkyl group, an alicyclic heterocyclic group, an alkenyl group, an alkynyl group, a substituted or unsubstituted aryl group, an aralkyl group, a heteroaryl group, a heteroarylalkyl group, alkoxy Groups, trifluoromethyl groups, trifluoromethoxy groups, alicyclic alkoxy groups, O-alicyclic heterocyclic substituted hydroxyl groups, alkenyloxy groups, alkynyloxy groups, substituted or unsubstituted aryloxy groups, aralkyl Oxy group, heteroaryloxy group, heteroarylalkoxy group, amino group, alkylamino group, alicyclic alkylamino group, N-alicyclic heterocyclic substituted amino group, alkenylamino group, alkynylamino group, substituted or unsubstituted Reel amino group, an aralkyl group, a heteroaryl group or a heteroarylalkyl group), -NR 43 R 44 (R 43 and R 44 are the same or may be different and each represent a hydrogen atom, an alkyl group, an alicyclic alkyl group, an alicyclic heterocyclic group , Alkenyl, malkinyl, substituted or unsubstituted aryl group, aralkyl group, heteroaryl group, heteroarylalkyl group, alkanoyl group, alicyclic alkanoyl group, alicyclic heterocyclic carbonyl group, alkenoyl group, alkinoyl group, Substituted or unsubstituted aroyl group, aralkylcarbonyl group, heteroarylcarbonyl group, heteroarylalkylcarbonyl group, alkoxycarbonyl group, alicyclic alkoxycarbonyl group, O-alicyclic heterocyclic substituted hydroxycarbonyl group, alkenyloxycarbonyl group, alkynyloxy Carbonyl group, substituted or unsubstituted aryloxycarbonyl group, aralkyloxycarbonyl group, heteroaryloxycarbonyl Group, heteroarylalkoxycarbonyl group, alkylsulfonyl group, alicyclic alkylsulfonyl group, alicyclic heterocyclic sulfonyl group, alkenylsulfonyl group, alkynyl sulfonyl group, substituted or unsubstituted arylsulfonyl group, aralkylsulfonyl group, hetero Arylsulfonyl group or heteroarylalkylsulfonyl group), ureido group, thioureido group, alkoxycarbonylamino group, O-alicyclic heterocyclic substituted hydroxycarbonylamino group, alkenyloxycarbonylamino group, alkynyloxycarbonyl Amino group, substituted or unsubstituted aryloxycarbonylamino group, aralkyloxycarbonylamino group, heteroaryloxycarbonylamino group, heteroarylalkoxycarbonylamino group, alkoxy group, alicyclic alkoxy group, O-alicyclic heterocyclic substitution Hydroxy group, alkenyloxy group, alkynyloxy group, substituted or unsubstituted aryloxy group, aralkyloxy group, hete Roaryloxy group, heteroarylalkoxy group, sulfo group, trifluoromethylsulfinyl group, alkylsulfinyl group, alicyclic alkylsulfinyl group, alicyclic heterocyclic sulfinyl group, alkenylsulfinyl group, ilkynylsulfinyl group, substituted or substituted Unsubstituted arylsulfinyl group, aralkylsulfinyl group, heteroarylsulfinyl group, heteroarylalkylsulfinyl group, -SO 2 R 45 (R 45 is a trifluoromethyl group, an alkyl group, an alicyclic alkyl group, an alicyclic heterocyclic group, an alkenyl group. , Alkynyl group, substituted or unsubstituted aryl group, aralkyl group, heteroaryl group, heteroarylalkyl group, alkoxy group, alicyclic alkoxy group, O-alicyclic heterocyclic substituted hydroxy group, alkenyloxy group, alkynyloxy group, Substituted or unsubstituted aryloxy group, aralkyloxy group, heteroaryloxy group, heteroarylalkoxy group, amino group alkylamino group, alicyclic alkylamino group, N-alicyclic heterocyclic substituted sub Mino group, alkenylamino group, alkynylamino group, substituted or unsubstituted arylamino group, aralkylamino group, heteroarylamino group or heteroarylalkylamino group), alkylsulfonyloxy group, alicyclic alkylsulfonyloxy group, alicyclic Group heterocyclic sulfonyloxy group, alkenylsulfonyloxy group, alkynylsulfonyloxy group, substituted or unsubstituted arylsulfonyloxy group, aralkylsulfonyloxy group, heteroarylsulfonyloxy group, heteroarylsulfonyloxy group, mercene Earthenware and -SG 1 -R 46 (G 1 represents a single bond, CO, or SO 2 ; And R 46 represents a trifluoromethyl group, an alkyl group, an alicyclic alkyl group, an alicyclic heterocyclic group, an alkenyl group, an alkynyl group, a substituted or unsubstituted aryl group, an aralkyl group, a heteroaryl group or a heteroarylalkyl group). Substituted alicyclic alkyl group, substituted alicyclic heterocyclic group, alicyclic heterocyclic group including substituted nitrogen, heterocyclic group containing substituted nitrogen, substituted aryl group, substituted aralkyl group each of 1 to 3 Substituted phenyl rings having the same or different substituents. Examples of the substituent include nitro group, cyan group, hydroxyl group, halogen atom, methylenedioxy group,-(OCH 2 CH 2 ) n O- (n is an integer from 1 to 6), triketylene group, trifluoromethyl group , Difluoromethoxy group, trifluoromethoxy group, azido group, thiocyanato group, substituted or unsubstituted alkyl group, substituted or unsubstituted alicyclic alkyl group, alicyclic heterocyclic group, alkenyl group, alkynyl group , Substituted or unsubstituted aryl group, aralkyl group, heteroaryl group, heteroarylalkyl group, carboxyl group, formyl group, R 47 CO-E 2- (E 2 represents a single bond or an oxygen atom; R 47 represents an alkyl group, Trifluoromethyl group, alicyclic alkyl group, alicyclic heterocyclic group, alkenyl group, alkynyl group, substituted or unsubstituted aryl group, aralkyl group, heteroaryl group, heteroarylalkyl group, alkoxy group, alicyclic alkoxy group, O- Alicyclic heterocyclic substituted Hydroxyl, alkenyloxy, alkynyloxy, substituted or unsubstituted aryloxy, aralkyloxy, heteroaryloxy, heteroarylalkoxy, amino, alkylamino, alicyclic alkylamino, substituted or Unsubstituted N-alicyclic heterocyclic substituted amino, alkenylamino, alkynylamino, substituted or unsubstituted arylamino group, aralkylamino group, heteroarylamino group or heteroarylalkylamino group), -NR 48 R 49 ( R 48 and R 49 may be the same or different and each is hydrogen atom, alkyl group, alicyclic alkyl group, alicyclic heterocyclic group, alkenyl group, alkynyl group, substituted or unsubstituted aryl group, aralkyl group, heteroaryl group, hetero Arylalkyl group, alkanoyl group, alicyclic alkanoyl group, alicyclic heterocyclic carbonyl group, alkenoyl group, alkinoyl group, substituted or unsubstituted aroyl group, he Teroarylalkylcarbonyl group, alkyloxycarbonyl group, alicyclic alkoxycarbonyl group, O-alicyclic heterocyclic substituted hydroxycarbonyl group, alkenyloxycarbonyl group, alkynyloxycarbonyl group, substituted or unsubstituted aryloxycarbonyl group, aralkyloxycarbonyl group , Heteroaryloxycarbonyl group, heteroarylalkoxycarbonyl group, alkylsulfonyl group, alicyclic alkylsulfonyl group, alicyclic heterocyclic sulfonyl group, alkenylsulfonyl group, alkynylsulfonyl group, substituted or unsubstituted arylsulfonyl group, aralkyl Sulfonyl group, heteroarylsulfonyl group, or heteroarylalkylsulfonyl group), -CBNR x R y (B is an oxygen atom or a sulfur atom; And R x and R y may be the same or different and each is a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, a substituted or unsubstituted alicyclic heterocyclic group, a substituted Or unsubstituted alkenyl groups, substituted or unsubstituted alkynyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted aralkyl groups, substituted or unsubstituted heteroaryl groups, or substituted or unsubstituted Heteroarylalkyl group), alkoxycarbonylamino group, alicyclic alkoxycarbonylamino group, O-alicyclic heterocyclic substituted hydroxycarbonyl amino group, alkenyloxycarbonylamino group, alkynyloxycarbonylamino group, substituted or substituted Unsubstituted aryloxycarbonylamino group, aralkyloxycarbonylamino group, heteroaryloxycarbonylamino group, hetero Arylalkoxycarbonylamino group, alkoxy group, alicyclic alkoxy group, O-alicyclic heterocyclic substituted hydroxyl group, alkenyloxy group, alkynyloxy group, substituted or unsubstituted aryloxy group, aralkyloxy group, hetero Aryloxy, heteroarylalkoxy, sulfo, trifluoromethylsulfinyl, alkylsulfinyl, alicyclic alkylsulfinyl, alicyclic heterocyclic sulfinyl, alkenylsulfinyl, alkynylsulfinyl, substituted or substituted Unsubstituted arylsulfinyl group, aralkylsulfinyl group, heteroarylsulfinyl group, heteroalkylsulfinyl group, -SO 2 R 50 (R 50 represents a trifluoromethyl group, an alkyl group, an alicyclic alkyl group, an alicyclic heterocyclic group, an alkenyl group, Alkynyl, substituted or unsubstituted aryl group, alkoxy group, alicyclic alkoxy group, O-alicyclic heterocyclic substituted hydroxy group, alkenyloxy group, alkynyloxy group, substituted or unsubstituted aryl jade Group, aralkyloxy group, heteroaryloxy group, heteroarylalkoxy group, amino group, alkylamino group, alicyclic alkylamino group, N-alicyclic heterocyclic substituted amino group, alkenylamino group, ilkynylamino group, substituted or unsubstituted Unsubstituted arylamino group, aralkylamino group, heteroarylamino group or heteroarylalkylamino group), alkylsulfonyloxy group, alicyclic alkylsulfonyloxy group, alicyclic heterocyclic sulfonyloxy group, alkenylsulfonyloxy group, alkynylsulfonyl jade Period, substituted or unsubstituted arylsulfonyloxy group, aralkyl sulfonyloxy group, heteroarylsulfonyloxy group, heteroarylsulfonyloxy group, mersentto group or -SG 2 -R 51 (G 2 is a single bond, CO, Or SO 2 ; R 51 represents a trifluoromethyl group, an alkyl group, an alicyclic alkyl group, an alicyclic heterocyclic group, an alkenyl group, an alkynyl group, a substituted or unsubstituted aryl group, an aralkyl group, a heteroaryl group, or a heteroarylalkyl group) , Substituted or unsubstituted arylazo group, and heteroarylazo group. In the definition of the substituent, an alkyl group, an alkyl group portion of an alkoxy group, an alkylamino group, an alkanoyl group, an alkylsulfonyl group, an alkoxycarbonyl group, an alkylsulfinyl group, and an alkylsulfonyloxy group have the same meaning as the alkyl group. Alicyclic alkyl group moiety of alicyclic alkyl group and alicyclic alkoxy group, alicyclic alkylamino group, alicyclic alkanoyl group, alicyclic alkylsulfonyl group, alicyclic alkoxycarbonyl group, alicyclic alkylsulfinyl group, alicyclic alkylsulfonyloxy group It has the same meaning as an alicyclic alkyl group. Alicyclic heterocyclic moiety of alicyclic heterocyclic group and O-cyclic heterocyclic substituted hydroxyl group, N-alicyclic heterocyclic substituted amino group, alicyclic heterocyclic carbonyl group, alicyclic heterocyclic sulfonyl group, O-alicyclic hetero Ring-substituted hydroxycarbonyl group, alicyclic heterocyclic sulfinyl group and alicyclic heterocyclic sulfonyloxy group have the same meaning as the alicyclic heterocyclic group. The alkenyl moiety of the alkenyl group and alkenyloxy group, alkenylamino group, alkenyl group, alkenylsulfonyl group, alkenyloxycarbonyl group, alkenylsulfinyl group and alkenylsulfonyloxy group have the same meaning as the alkenyl group. The alkynyl moiety, alkynylamino group, alkynyl group, alkynylsulfonyl group, alkynyloxycarbonyl group, alkynylsulfinyl group and alkynylsulfonyloxy group of the alkenyl group and the alkenyloxy group have the same meaning as the alkynyl group. The aryl moiety, arylamino group, aroyl group, arylsulfonyl group, arylcarbonyl group, arylsulfinyl group, arylsulfonyloxy group, and arylazo group of the aryl group and the aryloxy group have the same meaning as the aryl group. The aralkyl moiety, aralkylamino group, aralkyl carbonyl group, aralkylsulfonyl group, aralkyloxycarbonyl group, aralkylsulfinyl group, and aralkylsulfonyloxy group of the aralkyl group and the aralkyloxy group have the same meaning as the aralkyl group. . The heteroaryl moiety, heteroarylamino group, heteroarylcarbonyl group, heteroarylsulfonyl group, heteroaryloxycarbonyl group, heteroarylsulfinyl group, heteroarylsulfonyloxy group, and heteroaryl azo group of the heteroaryl group and heteroaryloxy group are the heteroaryl groups Has the same meaning. Heteroarylalkyl moieties of heteroarylalkyl groups and heteroarylalkyloxy groups, heteroarylalkylamino groups, heteroarylalkylcarboxyl groups, heteroarylalkylsulfonyl groups, heteroarylalkyloxycarbonyl groups, heteroarylalkylsulfinyl groups, and heteroarylalkylsulfonyloxy The group has the same meaning as the heteroarylalkyl group. The halogen atom has the same meaning as the halogen atom. Examples of substituents on a substituted alkyl group and a substituted N-alicyclic heterocyclic substituted amino group include a hydroxy group, an oxo group, and —NR 52 R 53 (R 52 and 53 may be the same or different and each is a hydrogen atom alkyl group). , Alicyclic alkyl group, alicyclic heterocyclic group, alkenyl group, alkynyl group, aryl group, aralkyl group, heteroaryl group, heteroarylalkyl group or alkoxycarbonyl group, or R 52 `and R 53 combined with adjacent nitrogen atoms contain nitrogen And an alicyclic heterocyclic group which is formed together with an alkyl group, an alicyclic alkyl group, an alicyclic heterocyclic group, an alkenyl group, an alkynyl group, an aryl group, an aralkyl group, a heteroaryl group, a heteroarylalkyl group, an alkoxycarbonyl group Alicyclic heterocyclic group containing the same nitrogen has the same meaning as described above). Examples of the substituent of a substituted alicyclic alkyl group include substituted aryl groups, substituted aryloxy groups, substituted arylamino groups, substituted aroyl groups, substituted arylsulfonyl groups, substituted aryloxycarbonyl groups, substituted aryloxycarbonylamino groups , Substituted aryloxy group, substituted arylsulfinyl group, substituted arylsulfonyloxy group, substituted arylazo group and alkyl group, nitro group, cyan group, hydroxy group, halogen atom and -NR 54 R 55 (R 54 and R 55 are Are the same or different and each hydrogen atom, alkyl group alicyclic alkyl group, alicyclic heterocyclic group, alkenyl group, alkynyl group, aryl group, aralkyl group, heteroaryl group, heteroarylalkyl group alkyl group, alicyclic alkyl group, alicyclic hetero ring Group, alkenyl group, alkynyl group, aryl group, aralkyl group, heteroaryl group and heteroarylalkyl group have the same meaning as described above), and the alkyl group and the halogen atom are the same as described above. It has the same meaning. Medically suitable salts of compound (I) include acid addition salts, metal salts, ammonium salts, organic amine addition salts, amino acid addition salts and the like. Medically suitable acid addition salts of compound (I) are inorganic acid addition salts such as hydrochloric acid, sulfates, phosphates, organic acid addition salts such as acetate maleate fumarate, tartarate, citrate and methanesulfonate. Medically suitable metal salts are alkali rapid salts such as sodium salts and potassium salts, alkaline earth metal salts such as magnesium salts, calcium salts, aluminum salts and zinc salts. Pharmaceutically suitable ammonium salts are ammonium salts and tetramethylammonium salts. Pharmaceutically suitable organic amine addition salts are salts comprising morpholine and piperidine. Pharmaceutically suitable amano acid addition salts are salts comprising lysine, glycine, phenylalanine. The method for preparing Compound (I) was as follows. Process 1 Compound (I-a), ie, R 1 is hydrogen and can be prepared according to the following reaction step. (R 2 , R 3 , R 4 , R 5 , R 6 , X, Y, Z, V and W have the same meaning as described above; and W ′ is 1-with or without substituted carbon in the ring. Piperazinyl or 1-homopiperazinyl) Compounds (I-a) are prepared by compound (II) with isocyanates (R 2 NCO) and SR Sandler, et al., Organic Functional Group Preparations, vol. 1, p. 305, Academic Press Inc. New York and London (1968); RB Wagner, et al., Synthetic Organic Chemistry, vol. 3, p. 640, John Wiley (1961), or known methods [SR Sandler, et al., Organic Functional Group Preparations, vol. 1, p. 312, Academic Press Inc. New York and London (1968); RB Wagner et al., Synthetic Organic Chemistry, vol. 3, p. 829, John Wiley, (1961)] isothiocyanates (R 2 NCS) and suitable inert solvents, such as chloroform, halogenated hydrocarbons such as dichloromethane, aromatic hydrocarbons such as benzene, toluene, diethyl ether, tetrahydro Ether solvents such as furan (THF), 1,4-dioxane, lower alcohols such as methanol, ethanol, isopropanol, aprotic solvents such as dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, or their It can be obtained by reacting for 10 minutes to 48 hours at a temperature in the boiling range of the solvent used at 20 ° C. in the same solvent as the mixture. If desired, the reaction can proceed in the presence of an inorganic base such as potassium carbonate, caustic soda, sodium hydride, or a base such as a metal alkoxide such as sodium methoxide or potassium tert-butoxide. Initial compound (II) is described in South African Patent No. 67 06512 (1968) and Ind. J. Chem., 26B, 550-555 (1987)], reference examples of the present application, or the like, or as a next reaction step. (In the scheme, L 1 is a leaving group; R 3 , R 4 , R 5 , R 6 , W, X, Y and Z have the same meaning as above) The leaving group represented by L 1 includes a halogen, a lower alkoxy group, a lower alkylthio group, a lower alkylsulfonyloxy group, an arylsulfonyloxy group and the like. Halogen, lower alkoxy groups, lower alkylthio groups, lower alkylsulfonyloxy groups and arylsulfonyloxy groups have the same meanings as described above. Compound (II) is a mixture of compounds (IV) and WH with lower alcohols such as methanol, ethanol, isopropanol, halogenated hydrocarbons such as chloroform or dichloromethane, aromatic hydrocarbons such as benzene, toluene, diethyl ether, THF, or 1, In an aprotic polar solvent such as ether solvent such as 4-dioxane, dimethylformamide, N-methylpyrrolidone or dimethyl sulfoxide, the reaction is carried out for 10 minutes to 48 hours at a temperature between room temperature and the boiling point of the solvent used. You can get it. If necessary, the reaction is carried out in the presence of an organic base such as triethylamine or pyridine, an inorganic base such as potassium carbide, caustic soda or sodium hydride, or a metal alkoxide such as sodium methoxide or potassium t-butoxide. It can be performed under. In the above reaction, if the defined group is changed under the conditions of the working method or is not suitable to carry out the method, it can be obtained by using protected W-H except the reaction point and releasing the protection. Suitable protect groups are described, for example, in T. W. Greene, Protective Groups in Orgainc Synthesis, John Wiley & Sons Inc. (1981), et al., Ethoxycarbonyl, t-butoxycarbonyl, acetyl and benzyl groups. Protecting groups are described for example in T. W. Greene, Protective Groups in Organic Synthesis, John Wiley & Sons Inc. (1981)] can be introduced and removed according to traditionally used methods. Initial compound (IV) is obtained commercially or described in J. Chem. Soc., 890-899 (1947); J. Chem. Soc., 561-572 (1962); J. Chem. Soc., B, 449-454 (1967); J. Indian Chem. Soc., 36, 787-791 (1959), J. Org. Chem., 17, 1571-1575 (1952); J. Med. Chem., 14, 1060-1066 (1971); French Patent No. 1388756 (1965); J. Am. Chem. Soc., 68, 1204-1208 (1946); Japanese Published Unexamined Patent Application No. 120872/85; J. Med. Chem., 39, 918-928 (1966); South African Patent No. 67 06512 (1968), the method described in the reference examples, etc.). Process 2 Compound (I) can be prepared according to the following reaction step. (In the scheme, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X, Y, Z, V, W and W 'have the same meaning as described above.) Compound (I) is described by Compound (II) and Beilstein, 4, 73 (1992); Beilstein, 4, 75 (1992); Berichte der Deutschen Chemischen Geseschaft, 12, 1163 (1879); And carbamoyl chloride or thiocarbamoyl chloride obtained according to Berichte der Deutschen Chemischen Gesellschaft, 26, 1681 (1893)], halogenated hydrocarbons such as chloroform or dichloromethane, aromatic hydrocarbons such as benzene or toluene, diethyl ether, THF Or ether solvents such as 1,4-dioxane, lower alcohols such as methanol, ethanol or isopropanol, dimethylformamide, aprotic polar solvents such as N-methylpyrrolidone or dimethyl sulfoxide, or mixtures thereof. It can be obtained by reacting from 10 minutes to 48 minutes at a temperature between the boiling point of the solvent used at 20 ° C. in a suitable inert solvent. If necessary, the reaction is carried out in the presence of a base such as an organic base such as triethylamine or pyridine, an inorganic base such as potassium carbide, caustic soda or sodium hydride, a metal alkoxide such as sodium methoxide or potassium t-butoxide can do. Process 3 Compound (I) can also be obtained through the following reaction step. (In the scheme, L 2 is a leaving group; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X, Y, Z, V, W and W ′ have the same meaning as described above. ) The leaving group represented by L 2 includes a lower alkoxy group, lower alkylthio, 4-nitrophenyloxy group and the like. Lower alkoxy groups and lower alcohol thio groups have the same meanings as described above. Compound (I) is a suitable solvent for compounds (II) and (III), ie halogenated hydrocarbons such as chloroform or dichloromethane, aromatic hydrocarbons such as benzene or toluene, ethers such as diethyl ether, THF or 1,4-dioxane Between the boiling point of the solvent used and room temperature in solvents such as solvents, lower alcohols such as methanol, ethanol or isopropanol, aprotic polar solvents such as dimethylformamide, N-methylpyrrolidone or dimethyl sulfoxide, or mixtures thereof It can be obtained by reacting at a temperature of 10 minutes to 48 hours. If necessary, it may be carried out in the presence of an organic base such as triethylamine or pyridine, an inorganic base such as potassium carbide, caustic soda, sodium hydride, or a metal alkoxide such as sodium methoxide or potassium tert-butoxide. Can be. Initial compound (III) is described in S. A. R. Sandler, et al., Organic Functional Group Preparations, vol. 2, p. 223, Academic Press Inc. New York and London (1971), and the like. Process 4 Compound (I) can also be obtained through the following reaction step. (In the scheme, L 1 is a leaving group; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X, Y, Z, V, W and W ′ have the same meaning as described above. ) The leaving group represented by L 1 has the same meaning as described above, and the halogen, lower alkoxy group, lower alkylsulfonyloxy group and lower alkylsulfonyl group have the same meaning as described above. Compound (I) is used to prepare compounds (IV) and (V) in suitable solvents, such as halogenated hydrocarbons such as chloroform or dichloromethane, aromatic hydrocarbons such as benzene or toluene, ethers such as diethyl ether, THF or 1,4-dioxane Between the boiling point of the solvent used and room temperature in solvents such as solvents, lower alcohols such as methanol, ethanol or isopropanol, aprotic polar solvents such as dimethylformamide, N-methylpyrrolidone or dimethyl sulfoxide, or mixtures thereof It can be obtained by reacting at a temperature of 10 minutes to 48 hours. If necessary, it may be carried out in the presence of an organic base such as triethylamine or pyridine, an inorganic base such as potassium carbide, caustic soda or sodium hydride, or a base such as a metal alkoxide such as sodium methoxide or potassium tert-butoxide. Can be. Initial compound (V) can be obtained as described in Japanese Published Unexamined Patent Application No.120872 / 85 and the like. Process 5 (In the scheme, L 3 is a leaving group; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X, Y, Z, V, W and W ′ have the same meaning as described above. ) The leaving group represented by L 3 represents a halogen, a lower alkoxy group, a lower alkylthio, a 4-nitrophenyloxy group, or the like. Halogen, lower alkoxy groups and lower alkylthio groups have the same meanings as described above. Compound (I) is a suitable solvent for compound (VI) and compound (VII), ie halogenated hydrocarbons such as chloroform or dichloromethane, aromatic hydrocarbons such as benzene or toluene, ethers such as diethyl ether, THF or 1,4-dioxane Between the boiling point of the solvent used and room temperature in solvents such as solvents, lower alcohols such as methanol, ethanol or isopropanol, aprotic polar solvents such as dimethylformamide, N-methylpyrrolidone or dimethyl sulfoxide, or mixtures thereof It can be obtained by reacting at a temperature of 10 minutes to 48 hours. If necessary, it may be carried out in the presence of an organic base such as triethylamine or pyridine, an inorganic base such as potassium carbide, caustic soda or sodium hydride, or a base such as a metal alkoxide such as sodium methoxide or potassium tert-butoxide. Can be. Initial compound (VI) is described in South African Patent No. 67 06512 (1968), U. S. Patent No. 3723434 (1973) and the like. In the above process, if the defined groups change under the conditions of the method of operation or are not suitable to carry out the method, the desired compound is conventionally used in organic synthetic chemistry [T. W. Greene, Protective Groups in Orgainc Synthesis, John Wiley & Sons Inc. (1981)] can be obtained by introducing and removing the protecting groups. Conversion of functional groups in substituents is known in addition to the above process [R. C. Larock, Comprehensive Organic Transformations (1989)] and compound (I) can be used as an intermediate of further new synthetic derivative (I). The intermediates and target compounds of the process can be separated and purified by methods conventionally used in organic synthetic chemistry, i.e. neutralization, filtration, extraction, washing, drying, concentration, recrystallization and various chromatographic methods. The intermediate can lead to the next reaction without purification. Some of the compounds (I) may be tautomers and the present invention includes all possible isomers, including tautomers and mixtures thereof. When the salt of the compound (I) is intended and the desired salt is produced, purification can be carried out. When compound (I) is prepared in the free state and a salt thereof is desired, compound (I) is dissolved or suspended in a suitable organic solvent and added with acid or base to form a salt. Medically suitable salts with compound (I) may be present in the form of adducts with water or various solvents, again within the scope of the present invention. Table 1 shows an example of compound (I) obtained by the above preparation method. The pharmaceutical activities of the compounds of the present invention are shown below as test examples. Test Example 1 Phosphorylation Inhibition of PDGF Receptor Dah-Shuhn et al., J. Biol. Chem., 266, 413-418 (1991)] was performed using Chinese hamster ovary cells (CHO) and introducing and expressing human β-PDGF receptor cDNA according to the method described in. Test results were expressed as the concentration of test compound (IC 50 ) that inhibits PDGF receptor phosphorylation by 50%. The results are shown in Table 2. Compound number Phosphorylation inhibitory effect of PDGF receptor IC 50 (μM) 9194554607177787998104105109115121124125135177178180 0.670.110.160.710.050.940.260.580.120.220.340.440.410.360.120.280.050.460.770.411.00 Compound number Phosphorylation inhibitory effect of PDGF receptor IC 50 (μM) 203208228229239240241254255283292297312335339346350357366367394408141426433435 1.390.030.290.310.210.500.400.460.661.400.760.330.260.210.640.280.230.191.470.200.190.210.931.120.380.66 Test Example 2 Growth inhibition on smooth muscle cells Smooth muscle cells in the catheter were explanted from the porcine aorta and used for testing. Cells were placed in 96-well dishes (8000 cells / well) and incubated in Dulbecco's modified Eagle incubator (DMEM; Nissui Pharmaceutiacl Co., Ltd.) containing 10% fetal bovine serum (FBS; Hyclone) for 4 days. It was. It was then incubated for three more days in DMEM containing 0.1% FBS and tuned on the cell growth stationary phase. To each well and test sample was added DMEM containing 0.1% FBS and various concentrations of test sample and cell growth was by PDG-FBB (SIGMA, final concentration: 20 ng / ml). After incubation for 3 days, XTT method [J. Immunol. Methods, 142, 257-265 (1991)] were used to measure cell growth using a cell growth assay instrument (Moehringer Mannheim) and cell growth values were calculated according to the following formula. Cell growth level = 100 × {1- (M-P0) / (P100-P0)} P100: Absorption of XXT reagents when stimulated by PDGF-BB P0: Absorption of XXT reagent when not stimulated by PDGF-BB M: Absorption of XXT reagent after addition of sample when stimulated by PDGF-BB Test results are expressed as concentrations of test compounds that inhibit cell growth by 50% (IC 50 ). The results are shown in Table 3. Smooth muscle cell proliferation inhibitory IC 50 (μM) Compound 19 Compound 45 Compound 60 Compound 77 Compound 78 Compound 79 0.180.080.030.100.740.14 Test Example 3 Inhibitory Effect of Vascular Intima Male SD rats (weight: 375-445 g, Charles River, golden standard) were anesthetized with sodium pentobarbital (50 mg / kg ip), and the neck of each animal was incised by arterial cutting and balloon catheter (2F, Manufacturer Edwards Laboratories) is injected back into the left external carotid artery. Repeat the above procedure seven times, remove the catheter, grab the left external carotid artery, and then suture the wound. In an aqueous solution of Tween 80 at the peritoneal administration, test compounds are suspended at a concentration of 20 mg / ml and a 0.5% methylcellulose 400 solution at a concentration of 6 Mg / ml for oral administration. Suspension is administered once a day for intraperitoneal administration and once or twice a day for oral administration for 15 days from the day before balloon injury. On day 14 after balloon injury, rats were killed and the left carotid artery was removed. The fibers are fixed in formalin and the paraffin is wrapped and cut for Elastica Van Gieson staining. Cleavage of vascular cells (Intima and Media) is examined with an image analyzer (Luzex F, NIREO) and the intima / media area ratio (I / M) is considered to be the degree of abnormal development of vascular intima. The route of administration of each compound and the results are shown in Table 4. For one dose Number of animals used I / M ratio Effective error Solution Group Compound 77 100 mg / kg 99 1.22 ± 0.100.88 ± 0.99 P <0.05 Solution administration group compound 98 30 mg / kg 810 1.00 ± 0.110.69 ± 0.08 P <0.05 Solution administration group compound 208 30 mg / kg 910 0.95 ± 0.070.61 ± 0.07 P <0.005 Solution Group 239 30 mg / kg 910 1.29 ± 0.040.93 ± 0.05 P <0.00005 Route of administration Compound 77 Compound 98 Dihydrochloride Compound 208 Compound 239 Oral administration once a day oral administration once a day oral administration twice a day oral administration twice a day From the above results, it is clear that abnormal development of vascular intima was significantly suppressed due to the administration of the compound of the present invention (P <0.05, Student's t-test). Test Example 4 Evaluation by Rat Adjuvant Arthritis Model Killed cells of Mycobacterium butyricum (Difco Laboratories Inc.) were cleaved in agate mortar, suspended in liquid paraffin to a final concentration of 6.6 mg / ml, and then sterilized by high pressure steam. A 100 ml suspension was then injected into the blood of the right hind limb pad of each herd (6 herds) of 8 week old female Lewis rats (Charles River Japan) and induced adjuvant arthritis. Test compounds were suspended in a 0.5% solution of methylcellulose to a final concentration of 3 mg / ml and the suspension was orally administered 100 ml / 100 g, based on body weight, for 5 days, once a day, just before arthritis was induced. The control group received a 0.5% solution of methylcellulose. The general group did not receive adjuvant treatment or test compound administration. Administration of test compounds continued for 18 days after adjuvant treatment. On day 17, white blood cells in surrounding blood were counted and then dissected. Changes in body weight during this period, color of hind paw species, weight of spleen and thymus, number of leukocytes in surrounding blood, hydroxyproline content in urine, glucose aminoglycan content in urine, SH concentration in serum, serum The concentration of nitrogen monoxide and the concentration of mucoprotein in serum were measured and evaluated. The volume of each hind paw was measured with a rat hind leg edema (TK-101, Unicom). The number of leukocytes in the peripheral blood was counted with an automatic multichannel blood cell counter (Sysmex K-2000, manufactured by Toa Iyo Denshi Co., Ltd.). The hydroxyproline content in urine was measured by the method described in Ikeda, et al., Annual Report of Tokyo Metropolitan Research Laboratories PH, 36, 277 (1985), and the content of glucoseaminoglycans was described in Moriyama, et. al., Hinyo Kiyo, 40, 565 (1994), Klompmakers, et al., Analytical Biochemistry, 153, 80 (1968). The serum SH concentration was measured by the method described in Meissel, et al., Inflammation, 17, 595 (1993) and the concentration of nitrogen monoxide was determined by Tracey, et al., Journal of Pharmacology & Experimental Therapeutics. , 272, 1011 (1995). The concentration of mucoprotein was measured using Aspro GP equipment (manufactured by Otsuka Pharmaceutical Co., Ltd.). The percent inhibition of each application was calculated by the following equation. % Inhibition = {(control group-compound dose) / (control group-normal group)} × 100 The results for compound 115 are shown in Table 5. swarm Volume of left hind limb (ml) Restraining ratio Common flock 1.12 ± 0.03 - Sensitive Flock 1.84 ± 0.18 - Compound dose 1.52 ± 0.16 44 swarm Body weight (g) Restraining ratio Common flock 191 ± 5 - Sensitive Flock 146 ± 4 - Compound dose 159 ± 2 * 29 swarm Weight of spleen (mg / 10g of body weight) Restraining ratio Common flock 21.4 ± 0.3 - Sensitive Flock 53.8 ± 3.8 - Compound dose 40.4 ± 2.5 * 41 swarm NO concentration (μM) Restraining ratio Common flock 11.1 ± 1.0 - Sensitive Flock 56.6 ± 7.0 - Compound dose 37.6 ± 4.0 42 P <0.05 vs Sensitive Group From the above results, it is evident that Compound 115 inhibits the development of adjuvant arthritis. Test Example 5 Activity Model for Proliferative Groleruronpritis in Glomerular Epilepsy Anti-antibody (Anti-rat Thy-1.1 monoclonal antibody OX-7 manufactured by Cedarlane) was injected into the male rat (Wistar-Kyoto, manufactured by Charles River Japan, 160 g, 6 per herd) at 1.0 mg / kg. Administered through. The test compound was suspended in 0.5% methylcellulose solution and the suspension obtained was administered for 7 days twice a day from the day before OX-7 was administered to each rat. On day 7 after OX-7 administration, if the cell growth of the glomerular epilepsy and the development of extracellular matrix were confirmed, the left kidney of each rat was removed, fixed in 20% buffered formalin solution for 6 hours, wrapped with paraffin, and sliced thinly. Paid. The obtained pieces were antigen-immunized fiber stained for proliferating nucleus antigen using antibody PC10 (manufactured by DAKO). After comparative coloring with methyl green coloring solution using diaminobenzidine as the color expression agent, paraffin pieces were enclosed. Half of the glomeruli of the kidney fragments were observed and the number of cells in one glomeruli positive for proliferating nucleus antigens was counted. Tests for valid errors were performed with the Wilcoxon test. The results for compound 208 are shown in Table 6. swarm The number of cells that are positive for the intranuclear antigen of the proliferating cells General Coarse Solvent Administration Coarse Compound Administration 1.8 +/- 0.38.7 +/- 0.46.1 +/- 0.9 From the above results, it is clear that compound 208 exhibits a relaxing effect on proliferative glomerulonephritis of glomerular epilepsy. From the above results, it is evident that Compound 84 exhibits a relaxing effect on proliferative glomerulonephritis of glomerular epilepsy. Pharmaceutically suitable salts with Compound (I) can be administered as above, but are preferably administered in the form of pharmaceutical compositions commonly used in animals and humans. It is desirable to use the route of administration most effective for treatment. For example, it can be administered orally or intranasally, intraorally, subcutaneously or intravenously. Examples of dosage forms include capsules, tablets, granules, powders, syrups, emulsions, suppositories or injections. Liquid compositions such as emulsions or syrups suitable for oral administration include water and sugars such as sucrose, sorbitol, and fructose; It can be prepared using the same preservatives, flavors such as strawberry flavor, peppermint flavor and the like. Capsules, tablets, powders and granules include lactose, glucose, excipients such as sucrose and mannitol, disintegrants such as starch and sodium alginate, lubricants such as magnesium stearate or mica, polyvinyl alcohol, hydroxypropyl cellulose and gelatin and It can be prepared using the same binder, a surfactant such as fatty acid ester, a plasticizer such as glycerin. Synthetic suitable for nasal administration preferably comprises a sterile aqueous preparation containing the active substance isotonic in the recipient's blood. For example, injections are prepared using carriers containing salt solutions, glucose solutions, or mixtures thereof. Composites for topical administration may be prepared by dissolving or suspending the active compound in one or more solvents, such as mineral oil, petroleum and polyhydric alcohols, or using other bases for topical drugs. Composites for enteral administration are prepared using cacao fat, fatty acid hydroxides and fatty acid hydroxides and are provided as suppositories. Compounds for non-oral administration may additionally include one or more of the glycos, oils, spices, preservatives (including antioxidants), excipients, disintegrating reagents, lubricants, binders, surfactants and plasticizers that have been used in the preparation of oral administration compounds. Containing may be formulated. Effective dosages and dosing regimens of Compound (I), or pharmaceutically suitable salts, may vary depending on the route of administration, the age and weight of the patient, and the type or extent of the disease being treated. However, it is usually preferred to administer a dose of 0.01-1000 mg / adult / day, preferably 5-500 mg / adult / day, of the compound (I) and a pharmaceutically suitable salt. All compounds of the present invention can be readily applied as kinase inhibitors to diseases involving mammalian kinases, in particular diseases related to tyrosine kinases. Strictly preferred are compounds having an IC 50 in the range of 10 nM to 10 μM. Certain compounds of the invention may be selected that have the activity of specifically inhibiting one of three types of protein kinases (e.g., kinases that phosphorylate tyrosine, kinases that phosphorylate tyrosine and threonine, kinases that phosphorylate threonine). Tyrosine kinase dependent diseases include hyperproliferative abnormalities caused or maintained by non-ideal tyrosine kinase activity. Examples of these are psoriasis, pulmonary fibrosis, glomerulonephritis, cancer, atherosclerosis and antiangiogenesis (eg tumor proliferation and diabetic retinopathy). The current understanding of the relationship between different kinds of kinases and certain diseases is not sufficient. However, compounds with specific PTK inhibitory activity have useful therapeutic effects. Other kinds of kinases have also been recognized in this way. PTK inhibitors, such as quercetin, genistine, and sterophorin, inhibit many types of protein kinases in addition to tyrosine kinases. However, due to lack of specificity, cytotoxicity is high. Therefore, PTK inhibitors (or inhibitors of different kinases) that are prone to unwanted side effects due to lack of specificity can be identified by routine cytotoxicity measurements. Best Mode for Carrying Out the Invention The invention is illustrated in detail by the following examples. Reference examples and production examples should not be construed as limited to the scope of the invention. Example 1 4- (6,7-dimethoxy-4-quinazolinyl) -N-phenyl-1-piperazincarboamide (Compound 1) 278 mg (0.1 mmol) of 6,7-dimethoxy-4-piperazinylquinazoline obtained by the method disclosed in South African Patent No. 67 06512 (1968) was dissolved in 5 ml of ethanol, and 0.109 ml ( 1.0 mmol) of phenylisocyanate is added. The mixture is heated for 10 minutes, refluxed and cooled to room temperature. Precipitated crystals were collected by filtration and recrystallized in ethanol to give 174.3 mg of colorless target compound. Yield: 44% Melting Point: 121-123 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.40-7.27 (4H, m), 7.11-7.03 (3H, m), 4.03 (3H, s), 3.99 (3H, s ), 3.81-3.69 (8H, m). FAB-Mass: 394 (M + +1) IR (KBr) ν (cm −1 ): 1636, 1507, 1446, 1429, 1240, 1215, 994. In Example 2-99 below, the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used in place of phenylisocyaneart to obtain the desired compound, to obtain the target compound. Example 2 4- (6,7-dimethoxy-4-quinazolinyl) -N-phenyl-1-piperazinthiocarboamide (Compound 2) Yield: 97% Melting point: 230-232 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.38-7.15 (6H, m), 7.09 (1H, s), 4.08-4.05 (4H, m), 4.02 (3H, s ), 3.98 (3H, s), 3.85-3.81 (4H, m). FAB-Mass: 410 (M + +1) IR (KBr) ν (cm −1 ): 1584, 1509, 1481, 1431, 1342, 1209, 994. Example 3 N-benzyl-4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 3) Yield: 87% Melting Point: 167-168 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.39-7.27 (6H, m), 7.10 (1H, s), 4.47 (2H, d, J = 5.4 Hz), 4.03 ( 3H, s), 3.99 (3H, s), 3.71-3.64 (8H, m). FAB-Mass: 408 (M + +1) IR (KBr) ν (cm −1 ): 1629, 1539, 1506, 1430, 1344, 1260, 1210, 988. Example 4 N-benzoyl-4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 4) Yield: 87% Melting point: 122-124 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.78 (1H, s), 8.69 (1H, s), 7.92 (2H, d, J = 7.3 Hz), 7.59 (1H, d, J = 7.6 Hz) , 7.48 (2H, dd, J = 7.6 Hz, 7.3 Hz), 7.28 (1H, s), 7.10 (1H, s), 4.03 (3H, s), 3.99 (3H, s), 3.79 (8H, m) . FAB-Mass: 422 (M + +1) IR (KBr) ν (cm −1 ): 1629, 1539, 1506, 1430, 1344, 1260, 1210, 988. Example 5 N-benzenesulfonyl-4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 5) Yield: 20% Melting point: 98-100 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 8.43 (1H, s), 8.22 (1H, s), 7.72-7.69 (2H, m), 7.32-7.30 (3H, m), 7.12 (1H) , s), 7.04 (1H, s), 3.83 (3H, s), 3.81 (3H, s), 3.51 (4H, m), 3.43 (4H, m). FAB-Mass: 458 (M + +1) IR (KBr) ν (cm −1 ): 1625, 1501, 1440, 1284, 1220, 1131, 1083, 985, 875, 585. Example 6 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-phenylethyl) -1-piperazinthiocarboamide (Compound 6) Yield: 100% Melting point: 76-80 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.36-7.22 (5H, m), 7.27 (1H, s), 7.09 (1H, s), 5.65 (1H, brt, J = 5.0 Hz), 4.02 (3H, s), 4.01-3.94 (6H, m), 3.98 (3H, s), 3.83-3.79 (4H, m), 2.99 (2H, t, J = 6.9 Hz). FAB-Mass: 438 (M + +1) IR (KBr) ν (cm −1 ): 1537, 1504, 1475, 1452, 1429, 1340, 1238, 1209, 993. Example 7 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-phenylbutyl) -1-piperazinthiocarboamide (Compound 7) Yield: 99% Melting point: 112-114 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.31-7.25 (2H, m), 7.24 (1H, s), 7.20-7.17 (3H, m), 7.10 (1H, s ), 5.71 (1H, brt, J = 5.0 Hz), 4.07-4.03 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.86-3.82 (4H, m), 3.72 (2H, m), 2.67 (2H, t, J = 6.9 Hz), 1.71-1.68 (4H, m). FAB-Mass: 466 (M + +1) IR (KBr) ν (cm −1 ): 1576, 1546, 1506, 1480, 1433, 1414, 1344, 1247, 1210, 996, 934, 882, 850, 799, 749, 699. Example 8 4- (6,7-dimethoxy-4-quinazolinyl) -N- (1-naphthyl) -1-piperazinecarboamide (Compound 8) Yield: 73% Melting point: 254-256 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 8.74 (1H, s), 8.60 (1H, s), 7.99-7.90 (2H, m), 7.76-7.74 (1H, m), 7.53-7.43 (3H, m), 7.26-7.23 (2H, m), 3.95 (3H, s), 3.95 (3H, s), 3.78-3.65 (8H, m). FAB-Mass: 444 (M + +1) IR (KBr) ν (cm −1 ): 1633, 1506, 1429, 1391, 1238, 1213, 996. Example 9 4- (6,7-dimethoxy-4-quinazolinyl) -N- (5-indanyl) -1-piperazinthiocarboamide (Compound 9) Yield: 100% Melting point: 207-210 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.74 (1H, brs), 7.23 (1H, s), 7.16 (1H, d, J = 7.9 Hz), 7.08 (1H, s), 7.04 (1H, d, J = 1.7 Hz), 6.93 (1H, dd, J = 7.9 Hz, 1.7 Hz), 4.08-4.04 (4H, m), 4.00 (3H, s), 3.98 (3H, s), 3.82-3.79 (4H, m), 2.90-2.83 (4H, m), 2.09-2.06 (2H, m). FAB-Mass: 450 (M + +1) IR (KBr) ν (cm −1 ): 1575, 1506, 1428, 1338, 1241, 1210, 1136, 993. Example 10 4- (6,7-dimethoxy-4-quinazolinyl) -N- (1-pyrenyl) -1-piperazinthiocarboamide (Compound 10) Yield: 98% Melting point: 140-145 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.59 (1H, s), 8.19 (1H, brs), 8.06-7.90 (8H, m), 7.86 (1H, d, J = 8.3 Hz), 7.17 ( 1H, s), 6.86 (1H, s), 3.95 (4H, m), 3.95 (3H, s), 3.84 (3H, s), 3.61-3.59 (4H, m). FAB-Mass: 534 (M + +1) IR (KBr) ν (cm −1 ): 1505, 1473, 1427, 1331, 1238, 1210, 993, 847. Example 11 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2,2-diphenylethyl) -1-piperazinthiocarboamide (Compound 11) Yield: 96% Melting point: 93-94 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.61 (1H, s), 7.36-7.23 (11H, m), 7.06 (1H, s), 5.59 (1H, brt, J = 5.0 Hz), 4.47 ( 1H, t, J = 7.3 Hz, 4.33 (2H, dd, J = 7.3 Hz, 5.0 Hz), 4.01 (3H, s), 3.97 (3H, s), 3.87 (4H, m), 3.75 (4H, m). FAB-Mass: 514 (M + +1) IR (KBr) ν (cm −1 ): 1576, 1504, 1475, 1450, 1429, 1348, 1240, 1209, 1136, 993, 704. Example 12 (dl) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (trans-2-phenylcyclopropyl) -1-piperazinecarboamide (Compound 12) Yield: 100% Melting Point: 178-182 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.29-7.13 (6H, m), 7.09 (1H, s), 5.23 (1H, brs), 4.02 (3H, s), 3.98 (3H, s), 3.67 (4H, m), 3.62 (4H, m), 2.87 (1H, m), 2.06 (1H, m), 1.21 (2H, m). FAB-Mass: 434 (M + +1) IR (KBr) ν (cm −1 ): 1622, 1504, 1429, 1350, 1257, 1211, 993. Example 13 N-cyclohexyl-4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 13) Yield: 94% Melting Point: 208-210 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.28 (1H, s), 7.11 (1H, s), 4.41 (1H, d, J = 7.4 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.71-3.60 (8H, m), 2.00-1.97 (2H, m), 1.75-1.61 (3H, m), 1.46-1.27 (2H, m), 1.24-1.07 ( 3H, m). FAB-Mass: 400 (M + +1) IR (KBr) ν (cm −1 ): 1615, 1540, 1478, 1429, 1346, 1250, 1210, 992. Example 14 N- (1-adamantyl-4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 14) Yield: 100% Melting Point: 237-238 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.25 (1H, s), 7.11 (1H, s), 4.29 (1H, brs), 4.03 (3H, s), 3.99 ( 3H, s), 3.71-3.67 (4H, m), 3.58-3.54 (4H, m), 2.09 (3H, m), 2.02-2.01 (6H, m), 1.69 (6H, m). FAB-Mass: 452 (M + +1) IR (KBr) ν (cm −1 ): 1324, 1535, 1504, 1430, 1235, 1210, 1134, 993. Example 15 N-allyl-4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 15) Yield: 79% Melting Point: 81-82 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.26 (1H, s), 7.11 (1H, s), 5.97 (1H, ddt, J = 16.8 Hz, 10.2 Hz, 5.9 Hz ), 5.59 (1H, brt, J = 5.3 Hz), 5.31-5.21 (2H, m), 4.38 (2H, dt, J = 5.9 Hz, 5.3 Hz), 4.10 (4H, m), 4.03 (3H, s ), 3.99 (3H, s), 3.87 (4H, m). FAB-Mass: 374 (M + +1) IR (KBr) ν (cm −1 ): 1576, 1506, 1475, 1429, 1350, 1240, 1209, 1136, 991. Example 16 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-propynyl) -1-piperazinthiocarboamide (Compound 16) Yield: 79% Melting Point: 158-160 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.27 (1H, s), 7.08 (1H, s), 5.19 (1H, m), 4.76 (2H, d, J = 5.3 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.71-3.67 (4H, m), 3.65-3.61 (4H, m), 1.77 (1H, s). FAB-Mass: 372 (M + +1) IR (KBr) ν (cm −1 ): 1629, 1612, 1573, 1510, 1448, 1432, 1242, 1216, 1154, 1042, 993, 938, 883, 848, 799. Example 17 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-tolyl) -1-piperazinecarboamide (Compound 17) Yield: 91% Melting Point: 225-228 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.26 (2H, d, J = 8.6 Hz), 7.25 (1H, s), 7.08 (1H, s), 7.04 (2H, d, J = 8.6 Hz), 7.01 (1H, brs), 4.00 (3H, s), 3.98 (3H, s), 3.70 (8H, m), 2.27 (3H, s). FAB-Mass: 407 (M + +1) IR (KBr) ν (cm −1 ): 1643, 1504, 1474, 1240, 1211, 1136, 993. Example 18 N- (4-ethylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 18) Yield: 92% Melting point: 251-252 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.28 (2H, d, J = 7.9 Hz), 7.27 (1H, s), 7.13 (2H, d, J = 7.9 Hz) , 7.11 (1H, s), 6.43 (1H, brs), 4.03 (3H, s), 4.00 (3H, s), 3.74 (8H, m), 2.61 (2H, q, J = 7.6 Hz), 1.21 ( 3H, t, J = 7.6 Hz). FAB-Mass: 422 (M + +1) IR (KBr) ν (cm −1 ): 1641, 1519, 1506, 1417, 1250, 1211, 1134, 993. Example 19 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-isopropylphenyl) -1-piperazinecarboamide (Compound 19) Yield: 70% Melting Point: 252-254 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 8.00 (1H, brs), 7.37 (2H, d, J = 8.2 Hz), 7.25 (1H, s), 7.15 (1H, s), 7.13 (2H, d, J = 8.2 Hz), 4.03 (3H, s), 4.00 (3H, s), 3.77 (4H, m), 3.73 (4H, m), 2.85 (1H, m), 1.23 (6H, doublet, J = 6.9). FAB-Mass: 436 (M + +1) IR (KBr) ν (cm −1 ): 1643, 1531, 1504, 1471, 1419, 1248, 1211, 1134, 993. Example 20 N- (4-butylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 20) Yield: 83% Melting Point: 216-222 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.28 (2H, d, J = 8.3 Hz), 7.25 (1H, s), 7.10 (1H, s), 7.09 (2H, d, J = 8.3 Hz), 6.84 (1H, brs), 4.01 (3H, s), 3.98 (3H, s), 3.72 (8H, m), 2.54 (2H, t, J = 7.3 Hz), 1.56 ( 2H, tt, J = 7.6 Hz, 7.3 Hz), 1.31 (2H, tq, J = 7.6 Hz, 7.3 Hz), 0.90 (3H, t, J = 7.3 Hz). FAB-Mass: 450 (M + +1) IR (KBr) ν (cm −1 ): 1617, 1504, 1417, 1244, 997. Example 21 N- (4-butylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 21) Yield: 80% Melting point: 171-173 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.63 (1H, brs), 7.25 (1H, s), 7.17-7.08 (5H, m), 4.08-4.04 (4H, m ), 4.01 (3H, s), 3.98 (3H, s), 3.84-3.80 (4H, m), 2.58 (2H, t, J = 7.6 Hz), 1.58 (2H, tt, J = 7.6 Hz, 7.6 Hz ), 1.36 (2H, tq, J = 7.6 Hz, 7.3 Hz), 0.92 (3H, t, J = 7.3 Hz). FAB-Mass: 466 (M + +1) IR (KBr) ν (cm −1 ): 1574, 1505, 1472, 1426, 1339, 1244, 1210, 1190, 993, 937, 874. Example 22 N- (4-tert-butylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 22) Yield: 61% Melting point: 221-224 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.53 (1H, brs), 7.36 (2H, d, J = 8.2 Hz), 7.25 (1H, s), 7.13 (2H, d, J = 8.2 Hz), 7.09 (1H, s), 4.08-4.04 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.85-3.82 (4H, m), 1.30 (9H , s). FAB-Mass: 466 (M + +1) IR (KBr) ν (cm −1 ): 1577, 1505, 1479, 1420, 1326, 1243, 1207, 991. Example 23 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (trifluoromethyl) phenyl] -1-piperazinecarboamide (Compound 23) Yield: 95% Melting point: 227-230 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.53 (4H, m), 7.25 (1H, s), 7.19 (1H, brs), 7.10 (1H, s), 4.01 ( 3H, s), 3.99 (3H, s), 3.75 (8H, m). FAB-Mass: 462 (M + +1) IR (KBr) ν (cm −1 ): 1651, 1537, 1504, 1474, 1419, 1327, 1244, 1211, 1115, 1066, 993. Example 24 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-vinylphenyl) -1-piperazinthiocarboamide (Compound 24) Yield: 97% Melting point: 110-111 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.88 (1H, brs), 7.36 (2H, d, J = 8.6 Hz), 7.23 (1H, s), 7.15 (2H, d, J = 8.6 Hz), 7.08 (1H, s), 6.65 (1H, dd, J = 17.5 Hz, 10.9 Hz), 5.68 (1H, d, J = 17.5 Hz), 5.22 (1H, d, J = 10.9 Hz), 4.07-4.04 (4H, m), 4.00 (3H, s), 3.97 (3H, s), 3.83-3.79 (4H, m). FAB-Mass: 436 (M + +1) IR (KBr) ν (cm −1 ): 1576, 1505, 1476, 1427, 1334, 1239, 1209, 992. Example 25 N- (4-decylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 25) Yield: 86% Melting point: 120-121 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.77 (1H, brs), 7.24 (1H, s), 7.14 (2H, d, J = 8.9 Hz), 7.10 (1H, s), 7.10 (2H, d, J = 8.9 Hz), 4.07-4.02 (4H, m), 4.00 (3H, s), 3.98 (3H, s), 3.95-3.79 (4H, m), 2.57 (2H , t, J = 7.3 Hz), 1.56 (2H, tt, J = 7.3 Hz, 6.9 Hz), 1.30-1.23 (14H, m), 0.87 (3H, t, J = 6.7 Hz). FAB-Mass: 550 (M + +1) IR (KBr) ν (cm −1 ): 1576, 1506, 1428, 1336, 1247, 1208, 1135, 1020, 992, 858. Example 26 N- (4-cyclohexylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 26) Yield: 28% Melting Point: 238-241 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.28 (2H, d, J = 8.6 Hz), 7.27 (1H, s), 7.14 (2H, d, J = 8.6 Hz) , 7.11 (1H, s), 6.56 (1H, brs), 4.03 (3H, s), 4.00 (3H, s), 3.73 (8H, m), 2.45 (1H, m), 1.83-1.71 (5H, m ), 1.41-1.34 (5H, m). FAB-Mass: 476 (M + +1) IR (KBr) ν (cm −1 ): 1642, 1505, 1472, 1419, 1352, 1245, 1211, 1134, 994. Example 27 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-biphenyl) -1-piperazinthiocarboamide (Compound 27) Yield: 80% Melting point: 94-95 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.60 (1H, d, J = 7.9 Hz), 7.47-7.25 (9H, m), 7.12 (1H, brs), 7.07 ( 1H, s), 4.02 (3H, s), 3.98 (3H, s), 3.97-3.95 (4H, m), 3.78-3.75 (4H, m). FAB-Mass: 486 (M + +1) IR (KBr) ν (cm −1 ): 1574, 1505, 1478, 1452, 1426, 1336, 1237, 1212, 1018, 990, 740. Example 28 N- (4-biphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 28) Yield: 9% Melting point: 221-224 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.56-7.26 (10H, m), 7.10 (1H, s), 6.84 (1H, brs), 4.02 (3H, s), 3.98 (3H, s), 3.75 (8H, m). FAB-Mass: 470 (M + +1) IR (KBr) ν (cm −1 ): 1640, 1575, 1504, 1238, 1212, 1136, 992. Example 29 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3,5-dimethylphenyl) -1-piperazinecarboamide (Compound 29) Yield: 74% Melting Point: 223-226 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.26 (1H, s), 7.11 (1H, s), 7.02 (2H, s), 6.70 (1H, s), 6.56 ( 1H, s), 4.03 (3H, s), 3.99 (3H, s), 3.73 (8H, m), 2.28 (6H, s). FAB-Mass: 422 (M + +1) IR (KBr) ν (cm −1 ): 1640, 1504, 1476, 1429, 1242, 1212, 996. Example 30 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3,4-dimethylphenyl) -1-piperazinecarboamide (Compound 30) Yield: 84% Melting point: 202-203 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.26 (1H, s), 7.19 (1H, s), 7.10-7.01 (3H, m), 6.74 (1H, brs), 4.02 (3H, s), 3.99 (3H, s), 3.72 (8H, m), 2.21 (3H, s), 2.19 (3H, s). FAB-Mass: 422 (M + +1) IR (KBr) ν (cm −1 ): 1648, 1532, 1505, 1472, 1440, 1414, 1351, 1239, 1214, 1136, 992. Example 31 N- (2,6-diisopropylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 31) Yield: 75% Melting Point: 280-282 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 7.28-7.24 (2H, m), 7.18-7.13 (3H, m), 4.04 (3H, s), 4.01 (3H, s ), 3.71-3.66 (8H, m), 3.21-3.06 (2H, m), 1.22 (12H, d, J = 6.4 Hz). FAB-Mass: 477 (M + +1) IR (KBr) ν (cm −1 ): 1629, 1504, 1428, 1355, 1213, 996. Example 32 N- [3,5-bis (trifluoromethyl) phenyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 32) Yield: 89% Melting point: 251-252 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 7.93 (2H, s), 7.56 (1H, s), 7.26 (1H, s), 7.11 (1H, s), 6.80 ( 1H, brs), 4.04 (3H, s), 4.01 (3H, s), 3.78 (8H, m). FAB-Mass: 529 (M + +1) IR (KBr) ν (cm −1 ): 1647, 1568, 1504, 1473, 1431, 1373, 1279, 1244, 1209, 1176, 1135, 995. Example 33 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-isopropenyl-a, a-dimethylbenzyl) -1-piperazinecarboamide (Compound 33) Yield: 90% Melting point: 190-191 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.48 (1H, s), 7.28 (3H, m), 7.22 (1H, s), 7.06 (1H, s), 5.32 ( 1H, brs), 5.05 (1H, d, J = 1.3 Hz), 4.98 (1H, d, J = 1.3 Hz), 3.99 (3H, s), 3.94 (3H, s), 3.65 (4H, m), 3.58 (4H, m), 2.12 (3H, s), 1.71 (6H, s). FAB-Mass: 476 (M + +1) IR (KBr) ν (cm −1 ): 1632, 1504, 1473, 1429, 1387, 1352, 1254, 1211, 995. Example 34 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-fluorophenyl) -1-piperazinecarboamide (Compound 34) Yield: 100% Melting point: 176-177 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.08 (1H, m), 7.28 (1H, s), 7.14-6.97 (3H, m), 7.12 (1H, s), 6.74 (1H, br), 4.03 (3H, s), 4.01 (3H, s), 3.77 (8H, m). FAB-Mass: 412 (M + +1) IR (KBr) ν (cm −1 ): 1643, 1506, 1479, 1448, 1433, 1242, 1215, 1138, 997, 754. Example 35 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-fluorophenyl) -1-piperazinecarboamide (Compound 35) Yield: 90% Melting point: 214-220 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.33 (1H, s), 7.27 (1H, s), 7.36-7.18 (3H, m), 7.10 (1H, s), 7.05 (1H, m), 6.79-6.71 (2H, m), 4.02 (3H, s), 3.99 (3H, s), 3.74 (8H, m). FAB-Mass: 412 (M + +1) IR (KBr) ν (cm −1 ): 1645, 1539, 1506, 1431, 1242, 1213, 995. Example 36 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-fluorophenyl) -1-piperazinecarboamide (Compound 36) Yield: 100% Melting point: 198-202 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.32 (2H, m), 7.25 (1H, s), 7.10 (1H, s), 6.98 (2H, m), 6.84 ( 1H, brs), 4.02 (3H, s), 3.99 (3H, s), 3.73 (8H, m). FAB-Mass: 412 (M + +1) IR (KBr) ν (cm −1 ): 1633, 1506, 1429, 1236, 1209, 993. Example 37 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-fluorophenyl) -1-piperazinthiocarboamide (Compound 37) Yield: 56% Melting point: 212-217 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.50 (1H, brs), 7.28-7.18 (3H, m), 7.10-7.01 (3H, m), 4.12 (4H, m ), 4.02 (3H, s), 3.99 (3H, s), 3.85 (4H, m). FAB-Mass: 428 (M + +1) IR (KBr) ν (cm −1 ): 1508, 1479, 1456, 1419, 1340, 1207, 990. Example 38 N- (2-chlorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 38) Yield: 100% Melting point: 186-187 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.18 (1H, dd, J = 8.3 Hz, 1.7 Hz), 7.34 (1H, dd, J = 8.3 Hz, 1.3 Hz), 7.25 (1H, ddd, J = 8.3 Hz, 7.6 Hz, 1.3 Hz), 7.26 (1H, s), 7.13 (1H, brs), 7.12 (1H, s), 6.97 (1H, ddd, J = 8.3 Hz, 7.6 Hz, 1.7 Hz), 4.03 (3H, s), 4.01 (3H, s), 3.78 (8H, m). FAB-Mass: 430 (M + +3), 428 (M + +1) IR (KBr) ν (cm −1 ): 1640, 1506, 1477, 1434, 1240, 1213, 995. Example 39 N- (3-chlorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 39) Yield: 86% Melting Point: 223-224 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.48 (1H, dd, J = 2.0 Hz, 2.0 Hz), 7.29-7.15 (3H, m), 7.09-6.98 (3H, m), 4.02 (3H, s), 3.99 (3H, s), 3.73 (8H, m). FAB-Mass: 430 (M + +3), 428 (M + +1) IR (KBr) ν (cm −1 ): 1680, 1645, 1620, 1506, 1481, 1425, 1240, 1215, 990. Example 40 N- (4-chlorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 40) Yield: 100% Melting Point: 217-219 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.58 (1H, s), 8.17 (2H, d, J = 8.9 Hz), 7.76 (2H, d, J = 8.9 Hz), 7.24 (1H, s) , 7.20 (1 H, s), 3.95 (6 H, s), 3.74-3.72 (8 H, m). FAB-Mass: 430 (M + +3), 428 (M + +1) IR (KBr) ν (cm −1 ): 1638, 1533, 1497, 1405, 1346, 1234, 1204, 988. Example 41 N- (4-chlorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 41) Yield: 96% Melting point: 199-204 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.67 (1H, brs), 7.31 (2H, d, J = 8.6 Hz), 7.25 (1H, s), 7.17 (2H, d, J = 8.6 Hz), 7.09 (1H, s), 4.12 (4H, m), 4.02 (3H, s), 3.99 (3H, s), 3.84 (4H, m). FAB-Mass: 446 (M + +3), 444 (M + +1) IR (KBr) ν (cm −1 ): 1574, 1506, 1492, 1479, 1423, 1344, 1327, 1209, 991. Example 42 N- (4-chlorobenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 42) Yield: 77% Melting Point: 218-220 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.29-7.27 (4H, m), 7.22 (1H, s), 7.10 (1H, s), 6.09 (1H, brt, J = 5.0 Hz), 4.89 (2H, d, J = 5.0 Hz), 4.12-4.09 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.87-3.83 (4H, m). FAB-Mass: 460 (M + +3), 458 (M + +1) IR (KBr) ν (cm −1 ): 1575, 1532, 1502, 1475, 1428, 1394, 1322, 1235, 1208, 1135, 991, 938, 864, 799. Example 43 N- (4-chlorobenzenesulfonyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 43) Yield: 67% Melting Point: 228-234 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 8.53 (1H, s), 8.32 (1H, s), 7.80 (2H, d, J = 8.6 Hz), 7.46 (2H, d, J = 8.6 Hz), 7.21 (1H, s), 7.14 (1H, s), 3.93 (3H, s), 3.91 (3H, s), 3.59 (4H, m), 3.53 (4H, m). FAB-Mass: 494 (M + +3), 492 (M + +1) IR (KBr) ν (cm −1 ): 1617, 1549, 1506, 1464, 1428, 1258, 1213, 1131, 1087, 993, 935, 893, 751, 631, 585. Example 44 N- (3-bromophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 44) Yield: 87% Melting Point: 221-222 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.62 (1H, d, J = 1.7 Hz), 7.30 (1H, m), 7.25 (1H, s), 7.17-7.12 ( 2H, m), 7.10 (1H, s), 6.97 (1H, brs), 4.02 (3H, s), 3.99 (3H, s), 3.73 (8H, m). FAB-Mass: 474 (M + +3), 472 (M + +1) IR (KBr) ν (cm −1 ): 1643, 1579, 1506, 1479, 1421, 1238, 1209, 995. Example 45 N- (4-bromophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 45) Yield: 100% Melting Point: 223-228 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.38 (2H, d, J = 8.9 Hz), 7.29 (2H, d, J = 8.9 Hz), 7.25 (1H, s) , 7.09 (1H, s), 6.99 (1H, brs), 4.01 (3H, s), 3.99 (3H, s), 3.72 (8H, m). FAB-Mass: 472 (M + +1) IR (KBr) ν (cm −1 ): 1640, 1531, 1504, 1489, 1410, 1239, 1212, 1135, 994. Example 46 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-iodinephenyl) -1-piperazinecarboamide (Compound 46) Yield: 86% Melting Point: 238-242 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.58 (2H, d, J = 8.3 Hz), 7.26 (1H, s), 7.18 (2H, d, J = 8.3 Hz) , 7.10 (1 H, s), 6.82 (1 H, brs), 4.02 (3 H, s), 4.00 (3 H, s), 3.73 (8 H, m). FAB-Mass: 520 (M + +1) IR (KBr) ν (cm −1 ): 1645, 1584, 1525, 1505, 1487, 1407, 1238, 1212, 1135, 993. Example 47 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-iodinephenyl) -1-piperazinthiocarboamide (Compound 47) Yield: 94% Melting point: 129-132 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.93 (1H, brs), 8.65 (1H, s), 7.63 (2H, d, J = 8.6 Hz), 7.25 (1H, s), 7.13 (2H, d, J = 8.6 Hz), 7.11 (1H, s), 4.03-4.02 (4H, m), 4.00 (3H, s), 3.99 (3H, s), 3.85 (4H, m). FAB-Mass: 536 (M + +1) IR (KBr) ν (cm −1 ): 1581, 1508, 1481, 1429, 1336, 1252, 1207, 1142, 993. Example 48 N- [4-chloro-2- (trifluoromethyl) phenyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 48) Yield: 97% Melting point: 189-190 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.05 (1H, d, J = 8.6 Hz), 7.55 (1H, s), 7.49 (1H, d, J = 8.6 Hz) , 7.26 (1H, s), 7.11 (1H, s), 6.91 (1H, brs), 4.03 (3H, s), 4.01 (3H, s), 3.76 (8H, m). FAB-Mass: 498 (M + +3), 496 (M + +1) IR (KBr) ν (cm −1 ): 1628, 1506, 1479, 1437, 1309, 1263, 1240, 1213, 1124, 995. Example 49 N- [4-chloro-3- (trifluoromethyl) phenyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 49) Yield: 83% Melting Point: 237-238 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.71 (1H, d, J = 2.3 Hz), 7.61 (1H, dd, J = 8.6 Hz, 2.3 Hz), 7.38 (1H) , d, J = 8.6 Hz), 7.29 (1H, brs), 7.25 (1H, s), 7.10 (1H, s), 4.02 (3H, s), 4.00 (3H, s), 3.75 (8H, m) . FAB-Mass: 498 (M + +3), 496 (M + +1) IR (KBr) ν (cm −1 ): 1647, 1539, 1502, 1485, 1471, 1433, 1321, 1244, 1207, 1136, 993. Example 50 N- (2,4-difluorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 50) Yield: 35% Melting point: 174-175 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 8.02-7.97 (1H, m), 7.28 (1H, s), 7.12 (1H, s), 6.91-6.85 (2H, m ), 4.04 (3H, s), 4.00 (3H, s), 3.89-3.71 (8H, m). FAB-Mass: 430 (M + +1) IR (KBr) ν (cm −1 ): 1616, 1500, 1424, 1351, 1238, 1208, 995. Example 51 N- (2,5-difluorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 51) Yield: 89% Melting Point: 187-189 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.95 (1H, m), 7.27 (1H, s), 7.11 (1H, s), 7.00 (1H, m), 6.85 ( 1H, br), 6.66 (1H, m), 4.03 (3H, s), 4.01 (3H, s), 3.77 (8H, m). FAB-Mass: 430 (M + +1) IR (KBr) ν (cm −1 ): 1649, 1508, 1429, 1255, 1242, 1215, 1155, 997. Example 52 N- (2,6-dichlorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 52) Yield: 92% Melting point: 202-207 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.34 (2H, d, J = 7.9 Hz), 7.28 (1H, s), 7.21 (1H, d, J = 7.9 Hz) 7.11 (1 H, s), 6.54 (1 H, brs), 4.03 (3 H, s), 4.00 (3 H, s), 3.78-3.77 (8 H, m). FAB-Mass: 464 (M + +1), 462 (M + +1) IR (KBr) ν (cm −1 ): 1634, 1506, 1428, 1250, 1211, 1135, 997, 933, 853, 799. Example 53 N- (2,4-dichlorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 53) Yield: 100% Melting point: 166-167 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.15 (1H, d, J = 8.9 Hz), 7.36 (1H, d, J = 2.3 Hz), 7.27 (1H, s) , 7.23 (1H, dd, J = 8.9 Hz, 2.3 Hz), 7.12 (1H, s), 7.07 (1H, brs), 4.03 (3H, s), 4.01 (3H, s), 3.78 (8H, m) . FAB-Mass: 464 (M + +3), 462 (M + +1) IR (KBr) ν (cm -1 ): 1676, 1576, 1506, 1474, 1431, 1238, 1207, 1136, 991 Example 54 N- (3,4-dichlorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 54) Yield: 100% Melting Point: 221-222 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.60 (1H, d, J = 2.3 Hz), 7.33 (1H, d, J = 8.6 Hz), 7.26 (1H, s) , 7.23 (1H, dd, J = 8.6 Hz, 2.3 Hz), 7.10 (1H, s), 6.89 (1H, brs), 4.02 (3H, s), 4.00 (3H, s), 3.74 (8H, m) . FAB-Mass: 464 (M + +3), 462 (M + +1) IR (KBr) ν (cm −1 ): 1645, 1587, 1502, 1477, 1431, 1394, 1244, 1207, 1135, 993. Example 55 N- (3,5-dichlorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 55) Yield: 93% Melting Point: 139-140 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.75 (1H, brs), 7.39 (2H, d, J = 2.0 Hz), 7.25 (1H, s), 7.09 (1H, s), 6.97 (1H, d, J = 2.0 Hz), 4.02 (3H, s), 3.99 (3H, s), 3.76-3.70 (8H, m). FAB-Mass: 464 (M + +3), 462 (M + +1) IR (KBr) ν (cm −1 ): 1641, 1585, 1504, 1473, 1416, 1244, 1209, 1136, 993. Example 56 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methoxyphenyl) -1-piperazinecarboamide (Compound 56) Yield: 87% Melting Point: 221-223 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.29-7.24 (3H, m), 7.12 (1H, s), 6.86 (2H, d, J = 8.9 Hz), 4.03 ( 3H, s), 4.00 (3H, s), 3.79 (3H, s), 3.76-3.72 (8H, m). FAB-Mass: 424 (M + +1) IR (KBr) ν (cm −1 ): 1637, 1569, 1507, 1416, 1232, 1208, 989. Example 57 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-ethoxyphenyl) -1-piperazinecarboamide (Compound 57) Yield: 100% Melting point: 165-166 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 8.16 (2H, d, J = 9.6 Hz), 7.29 (1H, s), 7.13 (1H, s), 6.96 (2H, d, J = 9.6 Hz), 6.86 (1H, brs), 4.13 (2H, q, J = 6.9 Hz), 4.04 (3H, s), 4.01 (3H, s), 3.79-3.77 (8H, m), 1.47 (3H, t, J = 6.9 Hz). FAB-Mass: 438 (M + +1) IR (KBr) ν (cm −1 ): 1662, 1538, 1506, 1452, 1425, 1358, 1250, 1211, 991. Example 58 N- (4-butoxyphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 58) Yield: 91% Melting point: 213-214 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.25 (2H, d, J = 8.9 Hz), 7.25 (1H, s), 7.09 (1H, s), 6.82 (2H, d, J = 8.9 Hz, 6.79 (1H, brs), 4.01 (3H, s), 3.98 (3H, s), 3.90 (2H, t, J = 6.6 Hz), 3.70 (8H, m), 1.73 ( 2H, tt, J = 7.3 Hz, 6.6 Hz), 1.46 (2H, tq, J = 7.3 Hz, 7.3 Hz), 0.94 (3H, t, J = 7.3 Hz). FAB-Mass: 466 (M + +1) IR (KBr) ν (cm −1 ): 1637, 1574, 1511, 1419, 1238, 1211, 993. Example 59 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (trifluoromethoxy) phenyl] -1-piperazinecarboamide (Compound 59) Yield: 87% Melting point: 204-205 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.42 (2H, d, J = 8.9 Hz), 7.25 (1H, s), 7.14 (2H, d, J = 8.9 Hz) , 7.10 (1H, s), 4.01 (3H, s), 3.99 (3H, s), 3.74 (8H, m). FAB-Mass: 478 (M + +1) IR (KBr) ν (cm −1 ): 1644, 1500, 1417, 1250, 1205, 1158, 996, 928, 847, 799. Example 60 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 60) Yield: 97% Melting Point: 218-219 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.37-7.26 (5H, m), 7.12 (1H, s), 7.07 (1H, m), 7.00-6.97 (4H, m ), 6.46 (1H, brs), 4.03 (3H, s), 4.00 (3H, s), 3.76 (8H, m). FAB-Mass: 486 (M + +1) IR (KBr) ν (cm −1 ): 1633, 1541, 1506, 1421, 1248, 1234, 993. Example 61 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinthiocarboamide (Compound 61) Yield: 74% Melting Point: 242-243 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.38-7.31 (2H, m), 7.27 (1H, s), 7.26 (1H, brs), 7.21-6.96 (8H, m ), 4.12-4.08 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.88-3.84 (4H, m). FAB-Mass: 502 (M + +1) IR (KBr) ν (cm −1 ): 1576, 1506, 1484, 1432, 1398, 1339, 1241, 1212, 993. Example 62 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (4-nitrophenoxy) phenyl] -1-piperazinthiocarboamide (Compound 62) Yield: 87% Melting point: 204-207 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 8.20 (2H, d, J = 8.9 Hz), 7.56 (1H, brs), 7.34 (2H, d, J = 8.9 Hz) , 7.28 (1H, s), 7.11 (1H, s), 7.09 (2H, d, J = 8.9 Hz), 7.04 (2H, d, J = 8.9 Hz), 4.18-4.14 (4H, m), 4.03 ( 3H, s), 4.00 (3H, s), 3.91-3.87 (4H, m). FAB-Mass: 547 (M + +1) IR (KBr) ν (cm −1 ): 1579, 1505, 1480, 1420, 1337, 1240, 1208, 992, 878, 844. Example 63 N- (4-benzyloxyphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 63) Yield: 83% Melting Point: 103-105 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.63 (1H, brs), 7.43-7.29 (5H, m), 7.24 (1H, s), 7.15 (2H, d, J = 8.9 Hz), 7.09 (1H, s), 6.94 (2H, d, J = 8.9 Hz), 5.03 (2H, s), 4.08 (4H, m), 4.01 (3H, s), 3.97 (3H, s ), 3.82 (4H, m). FAB-Mass: 516 (M + +1) IR (KBr) ν (cm −1 ): 1543, 1508, 1475, 1427, 1336, 1238, 1209, 1016, 991. Example 64 N- (2,4-dimethoxyphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 64) Yield: 100% Melting Point: 187-188 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.98 (1H, d, J = 6.9 Hz), 7.27 (1H, s), 7.13 (1H, s), 6.89 (1H, brs), 6.51-6.48 (2H, m), 4.04 (3H, s), 4.01 (3H, s), 3.87 (3H, s), 3.80 (3H, s), 3.76 (8H, m). FAB-Mass: 454 (M + +1) IR (KBr) ν (cm −1 ): 1640, 1600, 1533, 1502, 1454, 1236, 1207, 990. Example 65 N- (2,5-dimethoxyphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 65) Yield: 93% Melting Point: 215-217 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.92 (1H, d, J = 3.3 Hz), 7.27 (1H, s), 7.24 (1H, brs), 7.13 (1H, s), 6.79 (1H, d, J = 8.9 Hz), 6.52 (1H, dd, J = 8.9 Hz, 3.3 Hz), 4.04 (3H, s), 4.01 (3H, s), 3.86 (3H, s) , 3.79 (3H, s), 3.77 (8H, m). FAB-Mass: 454 (M + +1) IR (KBr) ν (cm −1 ): 1659, 1531, 1502, 1429, 1236, 1209, 1134, 993. Example 66 N- (3,4-dimethoxyphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 66) Yield: 100% Melting Point: 174-176 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.60 (1H, brs), 7.25 (1H, s), 7.10 (1H, s), 6.84-6.73 (3H, m), 4.12-4.08 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.86 (3H.s), 3.86-3.85 (4H, m), 3.85 (3H, s). FAB-Mass: 470 (M + +1) IR (KBr) ν (cm −1 ): 1504, 1479, 1344, 1257, 1240, 1211, 1132, 1025, 991. Example 67 N- (3,5-dimethoxyphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 67) Yield: 83% Melting point: 240-241 ℃ 1 H-NMR (CDCl 3 + DMSO-d 6 ) δ (ppm): 9.17 (1H, brs), 8.60 (1H, s), 7.22 (1H, s), 7.17 (1H, s), 6.54 (2H, d, J = 2.3 Hz), 6.24 (1H, d, J = 2.3 Hz), 4.15 (4H, m), 4.01 (3H, s), 4.00 (3H, s), 3.84 (4H, m), 3.77 ( 3H, s), 3.76 (3H, s). FAB-Mass: 470 (M + +1) IR (KBr) ν (cm −1 ): 1605, 1502, 1477, 1425, 1211, 1182, 993. Example 68 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3,4-methylenedioxyphenyl) -1-piperazinthiocarboamide (Compound 68) Yield: 100% Melting Point: 207-211 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.60 (1H, brs), 7.25 (1H, s), 7.10 (1H, s), 6.79-6.75 (2H, m), 6.63 (1H, dd, J = 8.3 Hz, 2.0 Hz), 5.98 (2H, s), 4.10 (4H, m), 4.02 (3H, s), 3.99 (3H, s), 3.84 (4H, m). FAB-Mass: 454 (M + +1) IR (KBr) ν (cm −1 ): 1541, 1504, 1479, 1431, 1346, 1242, 1209, 1136, 1036, 991, 935, 854. Example 69 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methylthiophenyl) -1-piperazinecarboamide (Compound 69) Yield: 84% Melting Point: 231-233 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.33 (2H, d, J = 8.9 Hz), 7.28 (1H, s), 7.22 (2H, d, J = 8.9 Hz) , 7.10 (1H, s), 6.75 (1H, brs), 4.02 (3H, s), 3.99 (3H, s), 3.73 (8H, m), 2.45 (3H, s). FAB-Mass: 440 (M + +1) IR (KBr) ν (cm −1 ): 1597, 1576, 1506, 1429, 1348, 1292, 1209, 991. Example 70 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (4-nitrophenylthio) phenyl] -1-piperazinthiocarboamide (Compound 70) Yield: 59% Melting point: 144-146 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 8.07 (2H, d, J = 8.9 Hz), 7.67 (1H, brs), 7.52 (2H, d, J = 8.6 Hz) , 7.36 (2H, d, J = 8.6 Hz), 7.27 (1H, s), 7.19 (2H, d, J = 8.9 Hz), 7.11 (1H, s), 4.17-4.15 (4H, m), 4.03 ( 3H, s), 4.00 (3H, s), 3.90-3.86 (4H, m). FAB-Mass: 563 (M + +1) IR (KBr) ν (cm −1 ): 1576, 1507, 1479, 1456, 1416, 1335, 1209, 992, 854. Example 71 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-dimethylaminophenyl) -1-piperazinthiocarboamide (Compound 71) Yield: 73% Melting Point: 226-227 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.28 (1H, s), 7.27 (1H, brs), 7.10 (1H, s), 7.07 (2H, d, J = 8.9 Hz), 6.69 (2H, d, J = 8.9 Hz), 4.09-4.05 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.86-3.82 (4H, m). FAB-Mass: 453 (M + +1) IR (KBr) ν (cm −1 ): 1576, 1506, 1476, 1427, 1338, 1211, 991. Example 72 N- (4-diethylaminophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 72) Yield: 100% Melting Point: 147-148 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.67 (1H, brs), 7.23 (1H, s), 7.09 (1H, s), 7.04 (2H, d, J = 8.9 Hz), 6.60 (2H, d, J = 8.9 Hz), 4.10-4.07 (4H, m), 4.00 (3H, s), 3.97 (3H, s), 3.82-3.81 (4H, m), 3.31 (4H , q, J = 6.9 Hz), 1.13 (6H, t, J = 6.9 Hz). FAB-Mass: 481 (M + +1) IR (KBr) ν (cm −1 ): 1616, 1576, 1520, 1446, 1429, 1396, 1339, 1256, 1210, 1137, 992. Example 73 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (5-dimethylamino-1-naphthalenesulfonylamino) phenyl] -1-piperazinthiocarboamide (Compound 73) Yield: 99% Melting point: 153-156 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 8.47 (1H, d, J = 8.6 Hz), 8.33 (1H, d, J = 8.6 Hz), 8.16 (1H, dd, J = 7.6 Hz, 1.3 Hz), 7.55-7.49 (2H, m), 7.41 (1H, dd, J = 8.6 Hz, 7.6 Hz), 7.27 (1H, s), 7.15 (1H, d, J = 7.6 Hz ), 7.07 (1H, s), 6.99 (2H, d, J = 8.9 Hz), 6.89 (2H, d, J = 8.9 Hz), 4.04-4.02 (4H, m), 4.00 (3H, s), 3.93 (3H, s), 3.78 (4H, m), 2.85 (6H, s). FAB-Mass: 658 (M + +1) IR (KBr) ν (cm −1 ): 1576, 1507, 1475, 1429, 1327, 1210, 1142, 992, 791. Example 74 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (4-dimethylaminophenylazo) phenyl] -1-piperazinthiocarboamide (Compound 74) Yield: 100% Melting Point: 148-149 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.62 (1H, brs), 8.57 (1H, s), 7.78 (2H, d, J = 8.3 Hz), 7.74 (2H, d, J = 8.6 Hz), 7.53 (2H, d, J = 8.6 Hz), 7.26 (1H, s), 7.24 (1H, s), 6.83 (2H, d, J = 8.3 Hz), 4.16 (4H, m), 3.94 ( 3H, s), 3.94 (3H, s), 3.87 (4H, m), 3.06 (6H, s). FAB-Mass: 557 (M + +1) IR (KBr) ν (cm −1 ): 1601, 1506, 1425, 1363, 990. Example 75 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-nitrophenyl) -1- Piperazinecarboamide (Compound 75) Yield: 13% Melting Point: 217-218 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 10.33 (1H, brs), 8.71 (1H, s), 8.66 (1H, dd, J = 8.6 Hz, 1.3 Hz), 8.23 (1H, dd, J = 8.2 Hz, 1.7 Hz), 7.64 (1H, ddd, J = 8.6 Hz, 7.3 Hz, 1.7 Hz), 7.28 (1H, s), 7.12 (1H, s), 7.10 (1H, ddd, J = 8.2 Hz, 7.3 Hz, 1.3 Hz), 4.04 (3H, s), 4.02 (3H, s), 3.86-3.83 (4H, m), 3.81-3.79 (4H, m). FAB-Mass: 439 (M + +1) IR (KBr) ν (cm −1 ): 1660, 1509, 1453, 1430, 1336, 1211, 989, 745. Example 76 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-nitrophenyl) -1-piperazinecarboamide (Compound 76) Yield: 89% Melting point: 123-125 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.23 (1H, dd, J = 2.3 Hz, 2.0 Hz), 7.88-7.83 (2H, m), 7.49 (1H, brs) , 7.42 (1H, dd, J = 8.3 Hz, 8.3 Hz), 7.25 (1H, s), 7.11 (1H, s), 4.02 (3H, s), 4.00 (3H, s), 3.79-3.75 (8H, m). FAB-Mass: 439 (M + +1) IR (KBr) ν (cm −1 ): 1640, 1522, 1503, 1475, 1431, 1336. Example 77 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-nitrophenyl) -1-piperazinecarboamide (Compound 77) Yield: 90% Melting point: 272-274 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.33 (1H, brs), 8.56 (1H, s), 8.15 (2H, d, J = 9.4 Hz), 8.58 (1H, s), 7.75 ( 2H, d, J = 9.4 Hz), 7.23 (1H, s), 7.19 (1H, s), 3.93 (6H, s), 3.72-3.70 (8H, m). FAB-Mass: 439 (M + +1) IR (KBr) ν (cm −1 ): 1664, 1504, 1426, 1324, 1240, 1208, 995. Example 78 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-nitrophenyl) -1-piperazinthiocarboamide (Compound 78) Yield: 100% Melting Point: 177-178 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 10.14 (1H, brs), 8.69 (1H, s), 8.52 (1H, dd, J = 8.6 Hz, 1.0 Hz), 8.16 (1H, dd, J = 8.6 Hz, 1.3 Hz), 7.64 (1H, ddd, J = 8.6 Hz, 8.3 Hz, 1.3 Hz), 7.29 (1H, s), 7.21 (1H, ddd, J = 8.6 Hz, 8.3 Hz, 1.0 Hz), 7.13 (1H, s), 4.29 (4H, m), 4.04 (3H, s), 4.01 (3H, s), 3.94 (4H, m). FAB-Mass: 455 (M + +1) IR (KBr) ν (cm −1 ): 1575, 1504, 1471, 1400, 1338, 1236, 991. Example 79 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-nitrophenyl) -1-piperazinthiocarboamide (Compound 79) Yield: 83% Melting point: 140-143 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.76 (1H, brs), 8.56 (1H, s), 8.32 (1H, d, J = 2.0 Hz), 7.95 (1H, m), 7.87 ( 1H, dd, J = 8.3 Hz, 1.0 Hz), 7.59 (1H, dd, J = 8.3 Hz, 8.3 Hz), 7.26 (1H, s), 7.24 (1H, s), 4.18 (4H, m), 3.94 (3H, s), 3.94 (3H, s), 3.88 (4H, m). FAB-Mass: 455 (M + +1) IR (KBr) ν (cm −1 ): 1529, 1504, 1477, 1429, 1348, 1240, 1209, 993. Example 80 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-nitrophenyl) -1-piperazinthiocarboamide (Compound 80) Yield: 67% Melting point: 221-224 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.22 (2H, d, J = 8.9 Hz), 7.65 (1H, brs), 7.37 (2H, d, J = 8.9 Hz) , 7.27 (1H, s), 7.09 (1H, s), 4.13 (4H, m), 4.03 (3H, s), 4.00 (3H, s), 3.88 (4H, m). FAB-Mass: 455 (M + +1) IR (KBr) ν (cm −1 ): 1576, 1506, 1429, 1348, 1292, 1209, 991. Example 81 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-fluoro-3-nitrophenyl) -1-piperazinecarboamide (Compound 81) Yield: 77% Melting Point: 243-245 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.74 (1H, s), 8.63 (1H, m), 8.28 (1H, dd, J = 6.6 Hz, 2.6 Hz), 7.93 (1H, m), 7.26 (1H, s), 7.19 (1H, brs), 7.14 (1H, s), 4.04 (3H, s), 4.01 (3H, s), 3.98-3.95 (4H, m), 3.78-3.72 (4H, m ). FAB-Mass: 457 (M + +1) IR (KBr) ν (cm −1 ): 1640, 1537, 1504, 1350, 1242, 1207, 990. Example 82 N- (2-chloro-4-nitrophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 82) Yield: 93% Melting point: 194-195 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 8.52 (1H, d, J = 8.9 Hz), 8.30 (1H, d, J = 2.5 Hz), 8.16 (1H, dd, J = 8.9 Hz, 2.5 Hz), 7.43 (1H, brs), 7.28 (1H, s), 7.11 (1H, s), 4.04 (3H, s), 4.01 (3H, s), 3.82 (8H, m) . FAB-Mass: 475 (M + +3), 473 (M + +1) IR (KBr) ν (cm −1 ): 1686, 1506, 1479, 1430, 1340, 1236, 1209, 1135, 991, 742. Example 83 N- (4-chloro-3-nitrophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 83) Yield: 64% Melting point: 253-255 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.04 (1H, d, J = 2.3 Hz), 7.60 (1H, dd, J = 8.9 Hz, 2.3 Hz), 7.46 (1H) , d, J = 8.9 Hz), 7.28 (1H, s), 7.10 (1H, s), 6.62 (1H, brs), 4.04 (3H, s), 4.00 (3H, s), 3.77 (8H, m) . FAB-Mass: 475 (M + +3), 473 (M + +1) IR (KBr) ν (cm −1 ): 1646, 1525, 1500, 1472, 1428, 1338, 1243, 1209, 1135, 992. Example 84 N- (3-cyanophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 84) Yield: 100% Melting point: 240-244 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.76 (1H, s), 7.68 (1H, d, J = 7.9 Hz), 7.44-7.27 (3H, m), 7.24 ( 1H, s), 7.10 (1H, s), 4.01 (3H, s), 3.99 (3H, s), 3.76 (8H, m). FAB-Mass: 419 (M + +1) IR (KBr) ν (cm −1 ): 2208, 1666, 1547, 1504, 1477, 1429, 1242, 1209, 993. Example 85 N- (4-cyanophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 85) Yield: 87% Melting point: 247-252 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.86 (1H, brs), 7.62 (2H, d, J = 8.6 Hz), 7.37 (2H, d, J = 8.6 Hz) , 7.28 (1H, s), 7.10 (1H, s), 4.16-4.08 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.89-3.84 (4H, m). FAB-Mass: 435 (M + +1) IR (KBr) ν (cm −1 ): 2220, 1506, 1483, 1427, 1298, 1215, 991. Example 86 N- (3-acetylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 86) Yield: 77% Melting Point: 241-245 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.26 (1H, m), 8.05 (1H, brs), 7.84 (1H, m), 7.57 (1H, m), 7.37 ( 1H, m), 7.24 (1H, s), 7.13 (1H, s), 4.03 (3H, s), 4.00 (3H, s), 3.98 (4H, m), 3.79-3.73 (4H, m), 2.59 (3H, s). FAB-Mass: 436 (M + +1) IR (KBr) ν (cm −1 ): 1665, 1539, 1505, 1480, 1426, 1383, 1307, 1244, 1205, 1133, 993. Example 87 N- (4-acetylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 87) Yield: 100% Melting point: 220-222 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.91 (2H, d, J = 8.6 Hz), 7.52 (2H, d, J = 8.6 Hz), 7.26 (1H, s) , 7.23 (1H, brs), 7.10 (1H, s), 4.02 (3H, s), 3.99 (3H, s), 3.77 (8H, m), 2.57 (3H, s). FAB-Mass: 436 (M + +1) IR (KBr) ν (cm −1 ): 1662, 1583, 1504, 1473, 1415, 1238, 1211, 993. Example 88 N- (4-benzoylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 88) Yield: 100% Melting Point: 222-223 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.81 (2H, d, J = 8.6 Hz), 7.77 (2H, dd, J = 7.9 Hz, 1.7 Hz), 7.59 (1H) , dd, J = 7.3 Hz, 1.7 Hz), 7.48 (2H, dd, J = 7.9 Hz, 7.3 Hz), 7.30 (2H, d, J = 8 Hz), 7.27 (1H, brs), 7.26 (1H, s), 7.09 (1H, s), 4.12 (4H, m), 4.02 (3H, s), 3.99 (3H, s), 3.86 (4H, m). FAB-Mass: 514 (M + +1) IR (KBr) ν (cm −1 ): 1504, 1425, 1303, 1282, 1209, 990. Example 89 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-ethoxycarbonylphenyl) -1-piperazincaramide (Compound 89) Yield: 96% Melting Point: 242-246 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.98 (2H, d, J = 8.9 Hz), 7.49 (2H, d, J = 8.9 Hz), 7.26 (1H, s) , 7.10 (1H, s), 4.35 (2H, q, J = 7.4 Hz), 4.02 (3H, s), 3.99 (3H, s), 3.73 (8H, m), 1.38 (3H, t, J = 7.4 Hz). FAB-Mass: 466 (M + +1) IR (KBr) ν (cm −1 ): 1700, 1659, 1504, 1417, 1281, 1213, 1174, 991. Example 90 N- (4-butoxycarbonylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarbonamide (Compound 90) Yield: 81% Melting Point: 226-227 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.98 (2H, d, J = 7.9 Hz), 7.48 (2H, d, J = 7.9 Hz), 7.26 (1H, s) , 7.10 (1H, s), 6.96 (1H, brs), 4.29 (2H, t, J = 6.6 Hz), 4.02 (3H, s), 3.99 (3H, s), 3.76 (8H, m), 1.74 ( 2H, tt, J = 7.3 Hz, 6.6 Hz), 1.48 (2H, tq, J = 7.6 Hz, 7.3 Hz), 0.97 (3H, t, J = 7.6 Hz). FAB-Mass: 494 (M + +1) IR (KBr) ν (cm −1 ): 1705, 1654, 1507, 1418, 1283, 1240, 1214, 1177, 994. Example 91 N- [3,5-bis (methoxycarbonyl) phenyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarbonamide (Compound 91) Yield: 93% Melting Point: 252-253 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.37 (1H, d, J = 1.7 Hz), 8.27 (2H, d, J = 1.7 Hz), 7.28 (1H, s) , 7.12 (1H, s), 6.84 (1H, brs), 4.04 (3H, s), 4.01 (3H, s), 3.93 (6H, s), 3.78 (8H, m). FAB-Mass: 510 (M + +1) IR (KBr) ν (cm −1 ): 1727, 1658, 1633, 1549, 1504, 1428, 1336, 1241, 1212, 1129, 994, 755. Example 92 N- [4- (2,3,4,5-tetrahydro-2-oxofuran-3-ylcarbamoyl) phenyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1- Piperazinethiocarboamide (Compound 92) Yield: 71% Melting point: 174-178 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.73 (2H, d, J = 8.6 Hz), 7.67 (1H, brs), 7.25 (1H, s), 7.21 (2H, d, J = 8.6 Hz), 7.09 (1H, s), 6.88 (1H, br), 4.73 (1H, m), 4.56 (1H, m), 4.36 (1H, m), 4.08-4.02 (4H, m ), 4.03 (3H, s), 4.00 (3H, s), 3.89-3.82 (4H, m), 2.90 (1H, m), 2.33 (1H, m). FAB-Mass: 537 (M + +1) IR (KBr) ν (cm −1 ): 1762, 1650, 1578, 1505, 1476, 1424, 1305, 1209, 1020, 991, 853. Example 93 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-sulfamoylphenyl) -1-piperazinthiocarboamide (Compound 93) Yield: 100% Melting point: 172-180 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.63 (1H, brs), 8.54 (1H, s), 7.73 (2H, d, J = 8.4 Hz), 7.51 (2H, d, J = 8.4 Hz), 7.26 (1H, s), 7.24 (2H, s), 7.22 (1H, s), 4.13 (4H, m), 3.93 (3H, s), 3.93 (3H, s), 3.85 (4H, m ). FAB-Mass: 489 (M + +1) IR (KBr) ν (cm −1 ): 1583, 1508, 1479, 1419, 1336, 1205, 1159, 991. Example 94 4- (6,7-dimethoxy-4-quinazolinyl) -N-fufuryl-1-piperazinthiocarboamide (Compound 94) Yield: 99% Melting point: 189-190 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.37 (1H, d, J = 1.6 Hz), 7.24 (1H, s), 7.10 (1H, s), 6.33 (2H, m), 6.13 (1H, brt, J = 4.6 Hz), 4.91 (2H, d, J = 4.6 Hz), 4.12-4.08 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.86-3.82 (4H, m). FAB-Mass: 414 (M + +1) IR (KBr) ν (cm −1 ): 1578, 1505, 1477, 1424, 1353, 1242, 1210, 1138, 990. Example 95 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-furoyl) -1-piperazinthiocarboamide (Compound 95) Yield: 44% Melting Point: 187-189 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 8.68 (1H, brs), 7.58 (1H, d, J = 1.7 Hz), 7.31-7.22 (2H, m), 7.09 ( 1H, s), 6.58 (1H, dd, J = 3.6, 1.7 Hz), 4.04 (3H, s), 4.00 (3H, s), 3.95-3.90 (8H, m). FAB-Mass: 428 (M + +1) IR (KBr) ν (cm −1 ): 1687, 1616, 1585, 1505, 1471, 1451, 1423, 1236, 1207, 1170, 1023, 990, 834. Example 96 4- (6,7-dimethoxy-4-quinazolinyl) -N- [2- (2-thienyl) ethyl] -1-piperazinecarboamide (Compound 96) Yield: 83% Melting point: 184-185 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.26 (1H, s), 7.17 (1H, dd, J = 5.3 Hz, 1.3 Hz), 7.10 (1H, s), 6.97 (1H, dd, J = 5.3 Hz, 3.6 Hz), 6.86 (1H, dd, J = 3.6 Hz, 1.3 Hz), 4.80 (1H, brt, J = 5.6 Hz), 4.03 (3H, s), 3.99 ( 3H, s), 3.70-3.67 (4H, m), 3.61-3.52 (6H, m), 3.08 (2H, t, J = 6.6 Hz). FAB-Mass: 428 (M + +1) IR (KBr) ν (cm −1 ): 1617, 1539, 1505, 1429, 1350, 1212, 1135, 992, 848. Example 97 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-pyridyl) -1-piperazinthiocarboamide (Compound 97) Yield: 100% Melting point: 169-171 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 8.52 (1H, brs), 8.43 (1H, d, J = 2.6 Hz), 8.35 (1H, dd, J = 4.6 Hz, 1.3 Hz), 7.81 (1H, ddd, J = 8.3 Hz, 2.6 Hz, 1.3 Hz), 7.29 (1H, dd, J = 8.3 Hz, 4.6 Hz), 7.23 (1H, s), 7.10 (1H, s) , 4.20-4.16 (4H, m), 4.01 (3H, s), 3.99 (3H, s), 3.88-3.85 (4H, m). FAB-Mass: 411 (M + +1) IR (KBr) ν (cm −1 ): 1575, 1533, 1505, 1474, 1432, 1313, 1241, 1209, 1017, 990, 872, 713. Example 98 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 98) Yield: 100% Melting point: 104-106 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 8.53 (1H, s), 8.52 (1H, m), 7.77 (1H, d, J = 7.9 Hz), 7.29 (1H, dd, J = 7.9 Hz, 4.6 Hz), 7.27 (1H, s), 7.10 (1H, s), 6.20 (1H, brt, J = 5.3 Hz), 4.97 (2H, d, J = 5.3 Hz), 4.14 -4.10 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.88-3.84 (4H, m). FAB-Mass: 425 (M + +1) IR (KBr) ν (cm −1 ): 1582, 1509, 1479, 1450, 1429, 1354, 1340, 1245, 1208, 1140, 1032, 994, 944, 883, 851, 712. Example 99 N- (1,4-dihydroxy-6-phthalazinyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 99) Yield: 93% Melting Point: 153-155 ℃ 1 H-NMR (CDCl 3 + DMSO-d 6 ) δ (ppm): 8.59 (1H, s), 8.07-7.96 (3H, m), 7.23 (1H, s), 7.21 (1H, s), 4.22 ( 4H, m), 4.00 (3H, s), 4.00 (3H, s), 3.88 (4H, m). FAB-Mass: 494 (M + +1) IR (KBr) ν (cm −1 ): 1645, 1581, 1508, 1487, 1434, 1317, 1211, 991. Example 100 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (piperidinomethyl) phenyl] -1-piperazinecarboamide (Compound 100) In a solution in which 593.5 mg (2.16 mmol) of 6,7-dimethoxy-4-piperazinylquinazoline obtained according to the method described in South African Patent No. 67 06512 (1968) was suspended in 10 ml of toluene, 362.6 ml (2.16 mmol) of 4- (chloromethyl) phenyl isocyanate was added, followed by stirring at room temperature for 3 hours. The reaction mixture was filtered and the collected crystals were washed with diisopropyl ether and dried under reduced pressure to give 916.8 mg (2.08 mmol, 96%) of N- [4- (chloromethyl) phenyl] -4- (6,7-dime Toxoxy-4-quinazolinyl) -1-piperazinecarboamide was obtained. 422.9 mg (0.96) of N- [4- (chloromethyl) phenyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide obtained in 10 ml of dimethylformamide mmol) was dissolved, and 0.28 ml (2.83 mmol) of piperazine were added, followed by stirring at room temperature for 7 hours. The reaction mixture is then poured off and purified by silica gel column chromatography to give 430.9 mg (0.88 mmol) of the title compound as colorless crystals. Yield: 92% Melting Point: 122-123 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.33 (2H, d, J = 8.9 Hz), 7.27 (1H, s), 7.25 (2H, d, J = 8.9 Hz) , 7.11 (1H, s), 6.67 (1H, brs), 4.03 (3H, s), 4.00 (3H, s), 3.74 (8H, m), 2.39 (4H, m), 1.60-1.56 (4H, m ), 1.44-1.42 (4H, m). FAB-Mass: 491 (M + +1) IR (KBr) ν (cm −1 ): 1645, 1505, 1471, 1417, 1349, 1238, 1212, 1136, 993. Example 101 N- (4-benzylaminomethylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 101) Except for using benzyl amine instead of piperidine, in fact the same procedure as in Example 100 was repeated to give the desired compound. Yield: 76% 1 H-NMR (CDCl 3 + DMSO-d 6 ) δ (ppm): 9.68 (1H, br), 8.83 (1H, brs), 8.57 (1H, s), 7.68 (1H, s), 7.60-7.56 ( 5H, m), 7.43-7.39 (4H, m), 7.27 (1H, s), 4.22 (4H, m), 4.08 (3H, s), 4.08-4.01 (4H, m), 4.03 (3H, s) , 3.87 (4H, m). FAB-Mass: 513 (M + +1) IR (KBr) ν (cm −1 ): 1625, 1495, 1418, 1313, 1283, 1212, 1134, 989. Example 102 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (4-pyridylmethylaminomethyl) phenyl] -1-piperazinecarboamidetrihydrochloride (Compound 102) Virtually the same procedure as in Example 100 was repeated except that 4-aminomethylpyridine was used instead of piperidine to yield the target compound in free form. While cooling on ice, 208.6 mg of the obtained glassy compound was dissolved in 15 ml of methanol, and a saturated hydrochloric acid solution in 5 ml of ethyl acetate was added and stirred. The solvent was evaporated and the residue was recrystallized in methanol / ethyl acetate to give 102.1 mg of the desired compound. Yield: 21% Melting Point: 182-185 ℃ (HCl) 1 H-NMR (free base, CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.53 (2H, d, J = 5.0 Hz), 7.38-7.24 (7H, m), 7.10 (1H, s) , 6.96 (1H, brs), 4.01 (3H, s), 3.99 (3H, s), 3.80 (2H, s), 3.74-3.70 (10H, m), 1.97 (1H, br). FAB-Mass: 514 (M + +1) IR (HCl, KBr) (cm −1 ): 1626, 1520, 1504, 1421, 1391, 1313, 1284, 1246, 1219, 989. Example 103 N- (4-nitrophenyl) -4- (4-quinazolinyl) -1-piperazinecarboamide (Compound 103) In fact the same as in Example 77, except that instead of 6,7-dimethoxy-4-piperazinylquinazoline, 4-piperazinquinazoline obtained according to the method described in South African Patent No. 67 06512 (1968) was used. The procedure was repeated to yield the target compound. Yield: 88% Melting Point: 155-158 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.74 (1H, s), 8.40 (1H, brs), 8.11 (2H, d, J = 9.2 Hz), 7.92-7.89 (2H, m), 7.77 ( 1H, dd, J = 7.9 Hz, 7.9 Hz), 7.63 (2H, d, J = 9.2 Hz), 7.51 (1H, dd, J = 7.9 Hz, 7.9 Hz), 3.84 (8H, m). FAB-Mass: 379 (M + +1) IR (KBr) ν (cm −1 ): 1670, 1558, 1500, 1476, 1419, 1404, 1346, 1329, 1304, 1261, 1242, 1223, 1109, 939. Example 104 N- (4-phenoxyphenyl) -4- (4-quinazolinyl) -1-piperazinecarboamide (Compound 104) In fact the same as in Example 60, except that instead of 6,7-dimethoxy-4-piperazinylquinazoline, 4-piperazinquinazoline obtained according to the method described in South African Patent No. 67 06512 (1968) was used. The procedure was repeated to yield the target compound. Yield: 42% Melting point: 74-75 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.76 (1H, s), 7.94-7.88 (2H, m), 7.76 (1H, dd, J = 8.6 Hz, 6.9 Hz), 7.49 (1H, dd, J = 8.2 Hz, 6.9 Hz), 7.35-7.27 (4H, m), 7.06 (1H, m), 6.98-6.95 (4H, m), 6.86 (1H, brs), 3.85-3.82 (4H, m), 3.76-3.72 (4H, m). FAB-Mass: 426 (M + +1) IR (KBr) ν (cm −1 ): 1645, 1568, 1538, 1505, 1416, 1350, 1225, 1165, 1014, 993, 937, 869, 836, 770, 750, 688. Example 105 N- (4-nitrophenyl) -4- (6,7-diethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 105) Except for using 6,7-diethoxy-4-piperazinylquinazoline obtained according to the method described in South African Patent No. 67 06512 (1968) instead of 6,7-dimethoxy-4-piperazinylquinazoline In fact, the same procedure as in Example 77 was repeated to give the desired compound. Yield: 22% Melting point: 120-121 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.21 (2H, d, J = 8.9 Hz), 7.58 (2H, d, J = 8.9 Hz), 7.26 (1H, s) , 7.11 (1H, s), 6.87 (1H, brs), 4.26 (2H, q, J = 6.9 Hz), 4.19 (2H, q, J = 6.9 Hz), 1.56 (3H, t, J = 6.9 Hz) , 1.56 (3H, t, J = 6.9). FAB-Mass: 467 (M + +1) IR (KBr) ν (cm −1 ): 1652, 1548, 1502, 1329, 1238, 1205, 1112, 934, 852, 752. Example 106 4- (6,7-diethoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 106) Except for using 6,7-diethoxy-4-piperazinylquinazoline obtained according to the method described in South African Patent No. 67 06512 (1968) instead of 6,7-dimethoxy-4-piperazinylquinazoline In fact, the same procedure as in Example 60 was repeated to give the desired compound. Yield: 21% Melting Point: 187-190 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.37-7.25 (5H, m), 7.13 (1H, s), 7.07 (1H, m), 7.00-6.97 (4H, m ), 6.41 (1H, brs), 4.24 (2H, q, J = 6.9 Hz), 4.18 (2H, q, J = 6.9 Hz), 3.74 (8H, m), 1.56 (3H, t, J = 6.9 Hz ), 1.56 (3H, t, J = 6.9 Hz). FAB-Mass: 514 (M + +1) IR (KBr) ν (cm −1 ): 1632, 1533, 1508, 1489, 1417, 1227, 995, 933, 868, 856, 847, 752. Example 107 N- (4-nitrophenyl) -4- (6,7,8-trimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 107) Instead of 6,7-dimethoxy-4-piperazinylquinazoline 4-piperazinyl-6,7,8-trimethoxyquinazolin obtained according to the method described in South African Patent No. 67 06512 (1968) Except for the use, in fact the same procedure as in Example 77 was repeated to give the desired compound. Yield: 43% Melting point: 197-199 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.72 (1H, s), 8.16 (2H, d, J = 8.6 Hz), 7.62 (1H, brs), 7.61 (2H, d, J = 8.6 Hz) , 6.93 (1H, s), 4.12 (3H, s), 4.07 (3H, s), 3.98 (3H, s), 3.79-3.77 (8H, m). FAB-Mass: 469 (M + +1) IR (KBr) ν (cm −1 ): 1674, 1611, 1545, 1500, 1479, 1417, 1329, 1302, 1124, 992, 851, 752. Example 108 N- (4-phenoxyphenyl) -4- (6,7,8-trimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 108) Instead of 6,7-dimethoxy-4-piperazinylquinazoline 4-piperazinyl-6,7,8-trimethoxyquinazolin obtained according to the method described in South African Patent No. 67 06512 (1968) Except for the use, in fact the same procedure as in Example 60 was repeated to afford the desired compound. Yield: 55% Melting point: 83-84 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.74 (1H, s), 7.34 (2H, d, J = 8.9 Hz), 7.30 (2H, m), 7.06 (1H, m), 6.98 (1H, s), 6.98-6.93 (4H, m), 6.82 (1H, brs), 4.13 (3H, s), 4.07 (3H, s), 3.96 (3H, s), 3.73 (8H, m). FAB-Mass: 516 (M + +1) IR (KBr) ν (cm −1 ): 1645, 1508, 1489, 1416, 1227, 1124, 991. Example 109 4- (7-ethylamino-6-nitro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 109) Except for using 6-7-dimethoxy-4-piperazinylquinazoline instead of 7-ethylamino-6-nitro-4-piperazinylquinazoline obtained according to the method described in WO 95/06648. In fact, the same procedure as in Example 60 was repeated to obtain the target compound. Yield: 67% Melting Point: 242-244 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.88 (1H, s), 8.53 (1H, s), 7.65 (1H, brt, J = 5.0 Hz), 7.35-7.27 (4H, m), 7.08- 6.95 (6H, m), 6.68 (1H, brs), 4.03-3.99 (4H, m), 3.79-3.76 (4H, m), 3.39 (2H, dt, J = 7.3 Hz, 5.0 Hz), 1.41 (3H , t, J = 7.3 Hz). FAB-Mass: 514 (M + +1) IR (KBr) ν (cm −1 ): 1645, 1621, 1545, 1508, 1487, 1419, 1346, 1326, 1222. Example 110 4- (2-phenyl-4-quinazolinyl) -N- (4-nitrophenyl) -1-piperazinecarboamide (Compound 110) Indeed, except that 6,7-dimethoxy-4-piperazinylquinazoline was used instead of 2-phenyl-4-piperazinylquinazoline obtained according to the method described in US Pat. No. 4,306,065 (1981). The same procedure as in Example 77 was repeated to obtain the target compound. Yield: 35% Melting Point: 236-238 ℃ 1 H-NMR (DMSO-d) δ (ppm): 9.37 (1H, brs), 8.54-8.51 (2H, m), 8.18 (2H, d, J = 7.9 Hz), 8.11 (1H, d, J = 8.6 Hz), 7.94-7.83 (2H, m), 7.78 (2H, d, J = 7.9 Hz), 7.59-7.52 (4H, m), 3.95 (4H, m), 3.82 (4H, m). FAB-Mass: 455 (M + +1) IR (KBr) ν (cm −1 ): 1687, 1537, 1500, 1493, 1327, 1225, 1109. Example 111 4- (6,7-dimethoxy-2-phenyl-4-quinazolinyl) -N- (4-nitrophenyl) -1-piperazinecarboamide (Compound 111) Instead of 6,7-dimethoxy-4-piperazinylquinazoline 6,7-dimethoxy-2-phenyl-4-piperazinylquinazoline obtained according to the method described in US Pat. No. 4,306,065 (1981) Except for the use, in fact the same procedure as in Example 77 was repeated to give the desired compound. Yield: 68% Melting Point: 156-157 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.34 (1H, brs), 8.49 (2H, m), 8.18 (2H, d, J = 9.2 Hz), 7.77 (2H, d, J = 9.2 Hz), 7.52-7.49 (3H, m), 7.33 (1H, s), 7.24 (1H, s), 3.98 (3H, s), 3.96 (3H, s), 3.81 (8H, m). FAB-Mass: 515 (M + +1) IR (KBr) ν (cm −1 ): 1676, 1551, 1504, 1419, 1327, 1238, 1111, 997, 852. Example 112 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-nitrophenyl) -1-homopiperazinecarboamide (Compound 112) Except for using 6,7-dimethoxy-4-homopiperazinylquinazoline obtained according to the method described in South African Patent No. 67 06512 (1968) instead of 6,7-dimethoxy-4-piperazinylquinazoline In fact, the same procedure as in Example 77 was repeated to give the desired compound. Yield: 22% Melting Point: 243-244 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.30 (1H, brs), 8.73 (1H, s), 8.06 (2H, d, J = 8.9 Hz), 7.63 (2H, d, J = 8.9 Hz), 7.45 (1H, s), 7.26 (1H, s), 4.32 (2H, m), 4.19 (2H, m), 3.97 (2H, m), 3.97 (3H, s), 3.92 (3H, s ), 3.70 (2H, m), 2.11 (2H, m). FAB-Mass: 453 (M + +1) IR (KBr) ν (cm −1 ): 1666, 1622, 1577, 1549, 1521, 1500, 1331, 1213, 1110, 856, 750. Example 113 4- (6,7-dimethoxy-1-isoquinolyl) -N- (4-nitrophenyl) -1-piperazincarboamide (Compound 113) Except for using 6,7-dimethoxy-1-piperazinylisoquinoline obtained according to the method described in South African Patent No. 67 06512 (1968) instead of 6,7-dimethoxy-4-piperazinylquinazoline In fact, the same procedure as in Example 77 was repeated to give the desired compound. Yield: 73% Melting Point: 247-248 ℃ 1 H-NMR (CDCl 3 + DMSO-d 6 ) δ (ppm): 8.99 (1H, s), 8.13 (2H, d, J = 9.2 Hz), 8.05 (1H, d, J = 5.6 Hz), 7.75 (2H, d, J = 9.2 Hz), 7.39 (1H, s), 7.24 (1H, d, J = 5.6 Hz), 7.11 (1H, s), 4.02 (3H, s), 4.02 (3H, s) , 3.85-3.83 (4H, m), 3.39 (4H, m). FAB-Mass: 438 (M + +1) IR (KBr) ν (cm −1 ): 1670, 1506, 1425, 1336, 1234, 1216, 1111, 991. Example 114 4- (3-Chloro-6,7-dimethoxy-1-isoquinolyl) -N- (4-nitrophenyl) -1-piperazinecarboamide (Compound 114) 3-chloro-6,7-dimethoxy-1-piperazinylisoquinoline obtained according to the method described in South African Patent No. 67 06512 (1968) instead of 6,7-dimethoxy-4-piperazinylquinazoline Except that the target compound was obtained except using, in fact the same procedure as in Example 77 was repeated to obtain the target compound. Yield: 55% Melting point: 227-228 ℃ 1 H-NMR (CDCl 3 + DMSO-d 6 ) δ (ppm): 8.90 (1H, brs), 8.13 (2H, d, J = 9.2 Hz), 7.73 (2H, d, J = 9.2 Hz), 7.30 (1H, s), 7.25 (1H, s), 7.01 (1H, s), 4.02 (3H, s), 4.02 (3H, s), 3.84-3.82 (4H, m), 3.44 (4H, m). FAB-Mass: 474 (M + +3), 472 (M + +1) IR (KBr) ν (cm −1 ): 1650, 1512, 1500, 1424, 1348, 1248, 1215, 1165, 1141, 994, 943, 855, 749. Example 115 4- (7-chloro-4-quinolyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 115) 6,7-dimethoxy-4-piperazinylquinazoline instead of Ind. J. Chem., 26B, 550-555 (1987)], except that 7-chloro-4-piperazinylquinoline obtained according to the method described in the above was practically repeated in the same manner as in Example 60 for the target compound. Obtained. Yield: 100% Melting Point: 159-161 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.75 (1H, d, J = 5.3 Hz), 8.07 (1H, d, J = 2.0 Hz), 7.96 (1H, d, J = 9.2 Hz), 7.46 (1H, dd, J = 9.2 Hz, 2.0 Hz), 7.36-7.27 (4H, m), 7.05 (1H, m), 7.00-6.96 (4H, m), 6.86 (1H, d, J = 5.3 Hz) , 6.68 (1H, brs), 3.81-3.77 (4H, m), 3.26-3.23 (4H, m). FAB-Mass: 461 (M + +3), 459 (M + +1) IR (KBr) ν (cm −1 ): 1639, 1538, 1503, 1488, 1418, 1381, 1243, 1226, 997, 868. Example 116 4- (6,7-dimethoxy-4-quinazolinyl) -N, N-diphenyl-1-piperazincarboamide (Compound 116) 400 mg (1.46 mmol) of 6,7-dimethoxy-4-piperazinylquinazoline obtained according to Bangbab described in South African Patent No. 67 06512 (1968) was dissolved in 10 ml of dimethylformamide and triethylamine Add 1.02 ml. To this mixture is added 406 mg (1.75 mmol) of diphenylcarbamoyl chloride and stirred at room temperature overnight. The reaction mixture is poured into water, the precipitated crystals are collected and purified by silica gel column chromatography to give 680 mg of the target compound in the form of colorless crystals. Yield: 99% Melting point: 196-197 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.36-7.28 (5H, m), 7.24 (1H, s), 7.18-7.08 (5H, m), 7.04 (1H, s ), 4.02 (3H, s), 3.97 (3H, s), 3.61-3.59 (4H, m), 3.56-3.54 (4H, m). FAB-Mass: 470 (M + +1) IR (KBr) ν (cm −1 ): 1662, 1505, 1471, 1418, 1230, 1206, 1133, 996, 748, 697. Example 117 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-morpholinophenyl) -1-piperazinecarboamide (Compound 117) Ice-cooled in a solution of 2.60 g (14.6 mmol) of 4-morpholinoaniline in 20 ml of methylene chloride, 14.07 ml (105 mmol) of triethylamine and 3.53 g (17.5 g) of 4-nitrophenylchloroformate Is added and stirred at room temperature for 7 hours. The solvent is evaporated and water is added to the residue, the precipitated crystals are collected by filtration, washed with water and dried to afford 4-morpholino-N- (4-nitrophenoxycarbonyl) aniline. N- (4-nitrophenyloxycarbonyl) aniline-4-yl morpholine obtained above and 6,7-dimethoxy-4-pi obtained according to the method described in South African Patent No. 67 06512 (1968). 800 mg (2.92 mmol) of ferrazinylquinazoline are heated in 10 ml of N-methylpyrrolidone to 100 ° C. for 12 hours and stirred. The reaction mixture is poured into water, the precipitated crystals are collected by filtration, washed with water and dried and purified by silica gel column chromatography to give 950.0 mg (1.99 mmol) of the title compound in the form of colorless crystals. Yield: 68% Melting point: 254-256 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.28 (2H, d, J = 8.9 Hz), 7.27 (1H, s), 7.12 (1H, s), 6.88 (2H, d, J = 8.9 Hz), 6.34 (1H, brs), 4.03 (3H, s), 4.00 (3H, s), 3.88-3.84 (4H, m), 3.74 (8H, m), 3.13-3.09 (4H , m). FAB-Mass: 479 (M + +1) IR (KBr) ν (cm −1 ): 1635, 1574, 1506, 1472, 1422, 1232, 1212, 1135, 994, 933, 821. Example 118 4- (6,7-dimethoxy-4-quinazolinyl) -N- (5-indoryl) -1-piperazincarboamide (Compound 118) Virtually the same procedure as in Example 117 was repeated except that 5-aminoindole was used instead of 4-morpholinoaniline to afford the desired compound. Yield: 30% Melting Point: 209-210 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 9.01 (1H, brs), 8.67 (1H, s), 7.55 (1H, s), 7.29-7.17 (2H, m), 7.11-7.02 (4H, m ), 6.39 (1H, brs), 3.99 (3H, s), 3.94 (3H, s), 3.65 (8H, m). FAB-Mass: 433 (M + +1) IR (KBr) ν (cm −1 ): 1623, 1547, 1505, 1474, 1451, 1429, 1239, 1211, 996. Example 119 N- [2- (4-chlorophenyl) ethyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 119) 666.8 mg of 4- (6,7-dimethoxy-4-piperazinylquinazolinyl) -1-piperazincarboxylic acid 4-nitrophenylester obtained according to the method described in South African Patent No. 67 06512 (1968) ( 1.52 mmol) and 1.06 ml (7.57 mmol) of 2-4-chlorophenyl) ethylamine were added to 15 ml of dimethylformamide, and the mixture was stirred while heating to 80 DEG C for 3 hours. The reaction mixture is poured into water, extracted with chloroform, the organic layer obtained is washed with water and dried over anhydrous sodium sulfide. The solvent is evaporated and the residue is purified by silica gel column chromatography to give 485.2 mg of the title compound as colorless crystals. Yield: 70% Melting Point: 177-178 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.31 (2H, d, J = 8.6 Hz), 7.24 (1H, s), 7.13 (2H, d, J = 8.6 Hz) , 7.09 (1H, s), 5.02 (1H, brt, J = 5.6 Hz), 4.02 (3H, s), 3.98 (3H, s), 3.67-3.65 (4H, m), 3.60-3.58 (4H, m ), 3.50 (2H, m), 2.83 (2H, t, J = 6.9 Hz). FAB-Mass: 458 (M + +3), 456 (M + +1) IR (KBr) ν (cm −1 ): 1622, 1539, 1506, 1353, 1243, 1212, 1134, 993, 845. Example 120 N- [2- (4-bromophenyl) ethyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 120) Virtually the same procedure as in Example 119 was repeated except that 2- (4-bromophenyl) ethylamine was used instead of 2- (4-chlorophenyl) ethylamine to afford the desired compound. Yield: 72% Melting point: 174-175 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.43 (2H, d, J = 8.3 Hz), 7.25 (1H, s), 7.09 (2H, d, J = 8.3 Hz) , 7.09 (1H, s), 4.67 (1H, brt, J = 5.6 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.69-3.65 (4H, m), 3.58-3.56 (4H, m ), 3.52 (2H, m), 2.81 (2H, t, J = 6.9 Hz). FAB-Mass: 502 (M + +3), 500 (M + +1) IR (KBr) ν (cm −1 ): 1624, 1540, 1506, 1355, 1237, 1212, 993. Example 121 4- (1,3-Dihydro-1,3-dimethyl-2-oxo-2H-imadazo [4,5-g] quinazolin-8-yl) -N- (4-phenoxyphenyl) -1 Piperazinecarboamide (Compound 121) 2,3-dihydro-1,3-dimethyl-2-oxo-8-piperazinyl-2H-imidazo [4] obtained in Reference Example 1 in place of 6,7-dimethoxy-4-piperazinylquinazoline [4] Except for using, 5-g] quinazoline, in fact the same procedure as in Example 60 was repeated to give the desired compound. Yield: 73% (3 steps) Melting point: 250-255 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.73 (1H, s), 7.41 (1H, s), 7.37-7.25 (5H, m), 7.07 (1H, m), 7.01-6.96 (4H, m ), 6.67 (1 H, brs), 3.78 (8 H, m), 3.51 (3H, s), 3.51 (3H, s). FAB-Mass: 510 (M + +1) IR (KBr) ν (cm −1 ): 1735, 1715, 1642, 1543, 1505, 1488, 1224. Example 122 4- (1,3-Diethyl-1,3-dihydro-2-oxo-2H-imidazo [4,5-g] quinazolin-8-yl) -N- (4-phenoxyphenyl)- 1-piperazincarboamide (Compound 122) 1,3-diethyl-2,3-dihydro-2-oxo-8-piperazinyl-2H-imidazo obtained in Reference Example 2 instead of 6,7-dimethoxy-4-piperazinylquinazoline [ Except for using 4,5-g] quinazolin, in fact the same procedure as in Example 60 was repeated to give the desired compound. Yield: 66% Melting Point: 168-169 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 7.45 (1H, s), 7.37-7.26 (5H, m), 7.05 (1H, m), 6.97-6.94 (5H, m ), 4.04-4.00 (4H, m), 3.77 (8H, m), 1.43-1.36 (6H, m). FAB-Mass: 538 (M + +1) IR (KBr) ν (cm −1 ): 1732, 1717, 1645, 1539, 1489, 1416, 1220. Example 123 4- (3-ethyl-1,3-dihydro-2-oxo-2H-imidazo [4,5-g] quinazolin-8-yl) -N- (4-phenoxyphenyl) -1-pipe Ragincarboamide (Compound 123) 197.5 mg (0.38) of N- (4-phenoxyphenyl) -4- (7-ethylamino-6-nitro-4-quinazolinyl) -1-piperazinecarboamide (Compound 109) obtained in Example 109 mmol) is added to a solution of 4 ml of ethanol and 30 mg of 10% palladium-carbon and stirred for 7.5 hours under hydrogen vapor. The catalyst is separated by filtration with Celite and the solvent is evaporated. The obtained residue is taken up in 10 ml of dimethylformamide and 187.2 mg (1.15 mmol) of carbonyldiimidazole are added and stirred at 80 ° C. for 2 hours in an argon atmosphere. After the reaction mixture was poured into water, precipitated crystals were collected by filtration, washed with water, dried and purified by silica gel column chromatography to obtain 65.7 mg (0.13 mmol) of colorless crystals of the title compound. Yield: 34% Melting Point: 248-251 ℃ H-NMR (CDCl 3 ) δ (ppm): 9.23 (1H, brs), 8.73 (1H, s), 7.46 (1H, s), 7.36-7.28 (5H, m), 7.07 (1H, m), 6.99 -6.92 (4H, m), 6.55 (1H, brs), 4.04 (2H, q, J = 7.3 Hz), 3.96 (4H, m), 3.71 (4H, m), 1.42 (3H, t, J = 7.3 Hz). FAB-Mass: 510 (M + +1) IR (KBr) ν (cm −1 ): 1722, 1645, 1506, 1489, 1225. Example 124 4- (3-ethyl-3H-1,2,3-triazolo [4,5-g] quinazolin-8-yl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide ( Compound 124) 394.8 mg (0.77) of N- (4-phenoxyphenyl) -4- (7-ethylamino-6-nitro-4-quinazolinyl) -1-piperazinecarboamide (Compound 109) obtained in Experimental Example 109 mmol) is added to a solution of 8 ml of ethanol, 60 mg of 10% palladium-carbon is added and stirred for 7.5 hours under hydrogen vapor. The catalyst is filtered off with Celite and the solvent is evaporated. The obtained residue is taken up in a mixture of 10 ml of water, 1 ml of concentrated hydrochloric acid, and 10 ml of acetic acid, ice-cooled and 106.2 mg (1.54 mmol) of sodium nitrate are added, followed by stirring at the same temperature for 4 hours. The reaction mixture was poured into concentrated aqueous sodium bicarbonate solution, and the precipitated crystals were collected by filtration, washed with water, dried and purified by silica gel column chromatography to give 119.3 mg (0.24 mmol) of the target compound as colorless crystals. Yield: 31% Melting Point: 167-168 ℃ H-NMR (CDCl 3 ) δ (ppm): 8.73 (1H, s), 8.03 (1H, s), 7.38-7.27 (5H, m), 7.06 (1H, m), 6.99-6.95 (4H, m) , 6.78 (1H, brs), 4.80 (2H, q, J = 7.3 Hz), 4.01-3.97 (4H, m), 3.83-3.80 (4H, m), 1.71 (3H, t, J = 7.3 Hz). FAB-Mass: 495 (M + +1) IR (KBr) ν (cm −1 ): 1641, 1545, 1504, 1487, 1416, 1350, 1223, 1211, 991. In Examples 125 to 136 below, virtually the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used in place of phenylisocyanate to afford the desired compound. Example 125 N-benzyl-4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 125) Yield: 61% Melting Point: 187-189 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.34-7.30 (5H, m), 7.24 (1H, s), 7.10 (1H, s), 5.98 (1H, brt, J = 5.0 Hz), 4.90 (2H, d, J = 5.0 Hz), 4.12-4.07 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.87-3.83 (4H, m). FAB-Mass: 424 (M + +1) IR (KBr) (cm- 1 ): 1541, 1504, 1479, 1433, 1340, 1244, 1209, 989. Example 126 (dl) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (1-phenylethyl) -1-piperazinthiocarboamide (Compound 126) Yield: 81% Melting point: 98-99 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.41-7.25 (5H, m), 7.24 (1H, s), 7.10 (1H, s), 5.93 (1H, brd, J = 7.3 Hz), 5.85 (1H, dq, J = 7.3 Hz, 6.6 Hz), 4.09-4.06 (4H, m), 4.01 (3H, s), 3.97 (3H, s), 3.86-3.83 (4H, m ), 1.63 (3H, doublet, J = 6.6 Hz). FAB-Mass: 438 (M + +1) IR (KBr) (cm −1 ): 1576, 1506, 1475, 1429, 1348, 1240, 1211, 1136, 991, 700. Example 127 (S) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (1-phenylethyl) -1-piperazinecarboamide (Compound 127) Yield: 77% Melting Point: 191-192 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.37-7.26 (5H, m), 7.25 (1H, s), 7.09 (1H, s), 5.06 (1H, dq, J = 6.9 Hz, 6.6 Hz), 4.98 (1H, brd, J = 6.6 Hz), 4.02 (3H, s), 3.97 (3H, s), 3.66-3.63 (8H, m), 1.52 (3H, d, J = 6.9 Hz). FAB-Mass: 422 (M + +1) IR (KBr) (cm −1 ): 1618, 1574, 1535, 1504, 1473, 1437, 1394, 1348, 1250, 1213, 1134, 993. Example 128 (R) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (1-phenylethyl) -1-piperazinecarboamide (Compound 128) Yield: 72% Melting point: 189-190 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.36-7.23 (5H, m), 7.27 (1H, s), 7.09 (1H, s), 5.06 (1H, dq, J = 7.3 Hz, 6.6 Hz), 4.81 (1H, d, J = 7.3 Hz), 4.02 (3H, s), 3.98 (3H, s), 3.69-3.61 (8H, m), 1.53 (3H, d, J = 6.6 Hz). FAB-Mass: 422 (M + +1) IR (KBr) (cm −1 ): 1574, 1535, 1504, 1473, 1437, 1394, 1348, 1331, 1252, 1213, 1134, 993. Example 129 (S) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (1-phenylethyl) -1-piperazinthiocarboamide (Compound 129) Yield: 88% Melting point: 98-100 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.40-7.28 (5H, m), 7.24 (1H, s), 7.10 (1H, s), 5.85-5.81 (2H, m ), 4.09-4.06 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.87-3.83 (4H, m), 1.63 (3H, d, J = 6.3 Hz). FAB-Mass: 438 (M + +1) IR (KBr) (cm- 1 ): 1506, 1475, 1429, 1348, 1240, 1209. Example 130 (R) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (1-phenylethyl) -1-piperazinthiocarboamide (Compound 130) Yield: 82% Melting point: 99-101 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.41-7.26 (5H, m), 7.24 (1H, s), 7.10 (1H, s), 5.93-5.81 (2H, m ), 4.09-4.07 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.87-3.83 (4H, m), 1.63 (3H, d, J = 6.6 Hz). FAB-Mass: 438 (M + +1) IR (KBr) (cm −1 ): 1576, 1506, 1475, 1429, 1346, 1240, 1209, 1136, 991, 935, 849, 700. Example 131 (S) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (1-methoxycarbonyl-2-phenylethyl) -1-piperazincaramide (Compound 131) Yield: 71% Melting Point: 167-168 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.34-7.23 (5H, m), 7.14 (1H, s), 7.08 (1H, s), 4.98 (1H, brd, J = 7.3 Hz), 4.83 (1H, dt, J = 7.3 Hz, 5.6 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.76 (3H, s), 3.67-3.65 (4H, m), 3.61-3.57 (4H, m), 3.16 (2H, d, J = 5.6 Hz). FAB-Mass: 480 (M + +1) IR (KBr) (cm −1 ): 1749, 1624, 1576, 1541, 1504, 1475, 1437, 1350, 1211, 993. Example 132 4- (6,7-dimethoxy-4-quinazolinyl) -N- (1-naphthylmethyl) -1-piperazinthiocarboamide (Compound 132) Yield: 100% Melting Point: 164-165 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.58 (1H, s), 8.02 (1H, d, J = 7.6 Hz), 7.88-7.79 (2H, m), 7.57-7.29 (4H, m), 7.19 (1H, s), 7.05 (1H, s), 5.97 (1H, brt, J = 4.3 Hz), 5.28 (2H, d, J = 4.3 Hz), 4.05-4.01 (4H, m), 3.98 (3H , s), 3.95 (3H, s), 3.80-3.76 (4H, m). FAB-Mass: 474 (M + +1) IR (KBr) (cm −1 ): 1574, 1537, 1506, 1429, 1344, 1249, 1207, 1134, 989, 933, 879, 858, 791, 768. Example 133 4- (6,7-dimethoxy-4-quinazolinyl) -N-diphenylmethyl-1-piperazinthiocarboamide (Compound 133) Yield: 89% Melting point: 128-129 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.36-7.23 (11H, m), 7.09 (1H, s), 7.00 (1H, d, J = 7.3 Hz), 6.27 ( 1H, brd, J = 7.3 Hz, 4.13-4.08 (4H, m), 4.00 (3H, s), 3.96 (3H, s), 3.86-3.82 (4H, m). FAB-Mass: 500 (M + +1) IR (KBr) (cm -1 ): 1574, 1504, 1473, 1450, 1427, 1340, 1236, 1207, 993, 698. Example 134 (dl) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (1,2-diphenylethyl) -1-piperazinthiocarboamide (Compound 134) Yield: 97% Melting Point: 168-169 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.33-7.18 (9H, m), 7.11-7.07 (3H, m), 5.97-5.91 (2H, m), 4.05-3.93 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.81-3.79 (4H, m), 3.36-3.18 (2H, m). FAB-Mass: 514 (M + +1) IR (KBr) (cm −1 ): 1576, 1531, 1504, 1473, 1429, 1342, 1236, 1211, 993, 933, 856, 702. Example 135 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-phenylpropyl) -1-piperazinthiocarboamide (Compound 135) Yield: 74% Melting Point: 147-148 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.34-7.21 (6H, m), 7.08 (1H, s), 5.53 (1H, brt, J = 4.9 Hz), 4.02 ( 3H, s), 3.98 (3H, s), 3.87-3.74 (10H, m), 2.75 (2H, t, J = 7.3 Hz), 2.04 (2H, tt, J = 7.3 Hz, 6.6 Hz). FAB-Mass: 452 (M + +1) IR (KBr) (cm- 1 ): 1549, 1504, 1473, 1450, 1429, 1350, 1240, 1211, 991. Example 136 N- (2-Anthryl) -1- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 136) Yield: 100% 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 8.37 (1H, s), 8.29 (1H, s), 7.98-7.93 (3H, m), 7.70-7.54 (2H, m ), 7.48-7.38 (3H, m), 7.26 (1H, s), 7.06 (1H, s), 4.13-4.03 (4H, m), 4.02 (3H, s), 3.96 (3H, s), 3.86- 3.79 (4H, m). FAB-Mass: 510 (M + +1) Example 137 4- (6,7-dimethoxy-4-quinazolinyl) -N-methyl-N-phenyl-1-piperazinecarboamide (Compound 137) Virtually the same procedure as in Example 116 was repeated except that the matching N-methyl-N-phenylcarbamoyl chloride was used instead of diphenylcarbamoyl chloride to afford the desired compound. Yield: 95% Melting Point: 187-188 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.39-7.31 (2H, m), 7.22 (1H, s), 7.21-7.11 (3H, m), 7.02 (1H, s ), 4.01 (3H, s), 3.95 (3H, s), 3.46 (8H, m), 3.28 (3H, s). FAB-Mass: 408 (M + +1) IR (KBr) (cm- 1 ): 1633, 1570, 1506, 1430, 1344, 991. In Examples 138-149 below, the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used instead of phenyl isocyanate to afford the desired compound. Example 138 N-cyclohexylmethyl-4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 138) Yield: 73% Melting Point: 170-171 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.25 (1H, s), 7.12 (1H, s), 5.86 (1H, brt, J = 5.3 Hz), 4.12-4.08 ( 4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.88-3.84 (4H, m), 3.56 (2H, dd, J = 6.6 Hz, 5.3 Hz), 1.78-1.65 (6H, m ), 1.32-1.14 (3H, m), 1.05-0.92 (2H, m). FAB-Mass: 430 (M + +1) IR (KBr) (cm −1 ): 2924, 2852, 1578, 1541, 1506, 1477, 1427, 1338, 1247, 1209, 1136, 993, 933, 852. Example 139 4- (6,7-dimethoxy-4-quinazolinyl) -N-[(3αα, 4β, 5β, 7β, 7αα) -hexahydro-4,7-methano-5- (1H-indenyl) ] -1-piperazinthiocarboamide (Compound 139) Yield: 90% Melting point: 130-133 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.26 (1H, s), 7.11 (1H, s), 5.77-5.70 (2H, m), 5.41 (1H, m), 4.29 (1H, m), 4.06 (4H, m), 4.03 (3H, s), 3.98 (3H, s), 3.87-3.83 (4H, m), 3.16-0.97 (10H, m). FAB-Mass: 466 (M + +1) IR (KBr) (cm -1 ): 1574, 1504, 1473, 1429, 1346, 1240, 1209, 993, 935, 856. Example 140 (dl) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-tetrahydropyranyl) -1-piperazincarboamide (Compound 140) Yield: 87% Melting point: 199-200 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.26 (1H, s), 7.09 (1H, s), 5.44 (1H, d, J = 8.9 Hz), 5.09 (1H, ddd, J = 10.6 Hz, 8.9 Hz, 2.0 Hz), 4.05-4.03 (4H, m), 3.99 (3H, s), 3.68-3.59 (9H, m), 1.93-1.81 (2H, m), 1.68- 1.38 (4 H, m). FAB-Mass: 402 (M + +1) IR (KBr) (cm −1 ): 2935, 2862, 1624, 1541, 1535, 1502, 1479, 1431, 1350, 1247, 1211, 1134, 1078, 1032, 997, 939, 872. Example 141 (dl) -4- (6,7-dimethoxy-4-quinazolinyl) -N-tetrahydrofurfuryl-1-piperazinthiocarboamide (Compound 141) Yield: 88% Melting point: 195-196 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.26 (1H, s), 7.11 (1H, s), 6.17 (1H, brt, J = 5.9 Hz), 4.21-4.08 ( 6H, m), 4.03 (3H, s), 3.99 (3H, s), 3.92-3.74 (6H, m), 3.45 (1H, m), 2.09-1.88 (3H, m), 1.62 (1H, m) . FAB-Mass: 418 (M + +1) IR (KBr) (cm −1 ): 1574, 1543, 1504, 1471, 1417, 1350, 1240, 1209, 1136, 1066, 989, 931, 875, 843. Example 142 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-morpholinoethyl) -1-piperazinthiocarboamide (Compound 142) Yield: 70% Melting point: 79-81 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.26 (1H, s), 7.12 (1H, s), 6.55 (1H, brt, J = 3.6 Hz), 4.10-4.06 ( 4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.89-3.86 (4H, m), 3.77-3.70 (6H, m), 2.66-2.62 (2H, m), 2.52-2.49 ( 4H, m). FAB-Mass: 447 (M + +1) IR (KBr) (cm −1 ): 1578, 1506, 1477, 1429, 1350, 1238, 1209, 1114, 991. Example 143 N-cinamoyl-4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 143) Yield: 30% Melting point: 184-186 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, brs), 8.70 (1H, s), 7.74 (1H, d, J = 15.5 Hz), 7.55-7.51 (2H, m), 7.43- 7.38 (3H, m), 7.29 (1H, s), 7.10 (1H, s), 6.57 (1H, d, J = 15.5 Hz), 4.39-4.30 (2H, m), 4.04 (3H, s), 4.00 (3H, s), 3.97-3.90 (6H, m). FAB-Mass: 464 (M + +1) IR (KBr) (cm −1 ): 1668, 1618, 1578, 1502, 1477, 1429, 1354, 1336, 1242, 1209, 1184, 1134, 987. Example 144 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-toryl) -1-piperazinecarboamide (Compound 144) Yield: 79% Melting Point: 218-219 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.27 (1H, d, J = 7.3 Hz), 7.26 (1H, s), 7.20-7.13 (2H, m), 7.10 ( 1H, s), 6.86 (1H, m), 6.76 (1H, brs), 4.02 (3H, s), 3.99 (3H, s), 3.72 (8H, m), 2.31 (3H, s). FAB-Mass: 408 (M + +1) IR (KBr) (cm -1 ): 1632, 1545, 1506, 1477, 1425, 1400, 1350, 1248, 1209, 995. Example 145 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-toryl) -1-piperazinthiocarboamide (Compound 145) Yield: 78% Melting point: 199-201 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.72 (1H, brs), 7.24 (1H, s), 7.21 (1H, dd, J = 7.6 Hz, 2.6 Hz), 7.08 (1H, s), 7.00-6.96 (3H, m), 4.06-4.04 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.83-3.79 (4H, m), 2.33 (3H , s). FAB-Mass: 424 (M + +1) IR (KBr) (cm −1 ): 1576, 1533, 1502, 1473, 1446, 1421, 1385, 1335, 1240, 1211, 1134, 1018, 991, 931, 851. Example 146 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-tolyl) -1-piperazinthiocarboamide (Compound 146) Yield: 82% Melting point: 204-205 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.82 (1H, brs), 7.23 (1H, s), 7.13 (2H, d, J = 8.6 Hz), 7.10 (1H, s), 7.10 (2H, d, J = 8.6 Hz), 4.08-4.05 (4H, m), 4.00 (3H, s), 3.98 (3H, s), 3.83-3.79 (4H, m), 2.31 (3H , s). FAB-Mass: 424 (M + +1) IR (KBr) (cm −1 ): 1578, 1541, 1504, 1473, 1446, 1390, 1342, 1244, 1209, 991. Example 147 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methylbenzyl) -1-piperazinthiocarboamide (Compound 147) Yield: 89% Melting point: 202-204 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.28 (1H, s), 7.26 (2H, d, J = 7.9 Hz), 7.17 (2H, d, J = 7.9 Hz) , 7.10 (1H, s), 5.84 (1H, brt, J = 4.3 Hz), 4.85 (2H, d, J = 4.3 Hz), 4.10-4.07 (4H, m), 4.02 (3H, s), 3.98 ( 3H, s), 3.86-3.82 (4H, m), 2.35 (3H, s). FAB-Mass: 438 (M + +1) IR (KBr) (cm −1 ): 1539, 1504, 1477, 1431, 1348, 1238, 1205, 991. Example 148 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-ethylphenyl) -1-piperazinecarboamide (Compound 148) Yield: 78% Melting Point: 207-208 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.27-7.24 (2H, m), 7.21-7.16 (2H, m), 7.11 (1H, s), 6.91 (1H, m ), 6.63 (1H, brs), 4.03 (3H, s), 4.00 (3H, s), 3.74 (8H, m), 2.62 (2H, q, J = 7.6 Hz), 1.22 (3H, t, J = 7.6 Hz). FAB-Mass: 421 (M + +1) IR (KBr) (cm −1 ): 1637, 1543, 1504, 1475, 1429, 1240, 1209, 996. Example 149 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-ethylphenyl) -1-piperazinthiocarboamide (Compound 149) Yield: 79% Melting point: 195-197 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.61 (1H, brs), 7.31-7.22 (2H, m), 7.08 (1H, s), 7.01-6.99 (3H, m ), 4.07-4.03 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.83-3.79 (4H, m), 2.63 (2H, q, J = 7.4 Hz), 1.22 (3H, t, J = 7.4 Hz). FAB-Mass: 438 (M + +1) IR (KBr) (cm −1 ): 1578, 1533, 1506, 1473, 1421, 1335, 1240, 1211, 1134, 1018, 991, 930, 849. Example 150 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-isopropylphenyl) -1-piperazinecarboamide (Compound 150) To a solution of 2.05 g (9.39 mmol) of di-tert-butyldicarbonate in 30 ml of dichloromethane, 108 mg (0.88 mmol) of 4- (N, N-dimethylamino) pyridine are added. The mixture is stirred at room temperature for 5 minutes, 1.26 ml (8.95 mmol) of 3-isopropylaniline are added, followed by further stirring at room temperature for 30 minutes. 548 mg (2.00 mmol) of 6,7-dimethoxy-4-piperazinylquinazoline obtained according to the method described in South African Patent No. 67 06512 (1968) are added to the reaction mixture and stirred for 30 minutes at room temperature. The solvent is evaporated and the residue is recrystallized from silica gel chromatography and ethyl acetate to give the title compound as colorless crystals. Yield: 63% Melting point: 196-197 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.27-7.20 (4H, m), 7.12 (1H, s), 6.94 (1H, dd, J = 7.3 Hz, 1.6 Hz) , 6.42 (1H, brs), 4.04 (3H, s), 4.00 (3H, s), 3.76 (8H, m), 2.89 (1H, m), 1.25 (6H, d, J = 6.9 Hz). FAB-Mass: 436 (M + +1) IR (KBr) (cm- 1 ): 1637, 1521, 1449, 1429, 1238, 1211, 993, 795. Example 151 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-isopropylphenyl) -1-piperazinthiocarboamide (Compound 151) A solution of 696 mg (3.00 mmol) of commercially available 1,1'-thiocarbonyl-di-2 (1H) -pyridone in 10 ml of dichloromethane was slowly dissolved in 0.42 ml (2.98 mmol) of 3-isopropylaniline. Add. After stirring for 1 hour at room temperature, 6,7-dimethoxy-4-piperazinylquinazoline obtained according to the method described in South African Patent No. 67 06512 (1968) is added to the reaction mixture and stirred for another hour at room temperature. do. Water is added to the reaction mixture and extracted with chloroform. The organic layer is washed with saturated aqueous sodium chloride solution and dried over magnesium chloride. The solvent is evaporated and the residue is purified by recrystallization with silica gel chromatography and chloroform-diisopropyl ether to obtain the target compound as colorless crystals. Yield: 39% Melting point: 169-171 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.32-7.24 (3H, m), 7.09 (1H, s), 7.06-7.00 (3H, m), 4.07-4.04 (4H m), 4.03 (3H, s), 3.99 (3H, s), 3.84-3.80 (4H, m), 2.9 (1H, m), 1.25 (6H, d, J = 6.9 Hz). FAB-Mass: 452 (M + +1) IR (KBr) (cm- 1 ): 1539, 1506, 1479, 1429, 1238, 1209, 993, 797. Example 152 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-isopropylphenyl) -1-piperazinthiocarboamide (Compound 152) Virtually the same procedure as in Example 1 was repeated except that the matching 4-isopropylphenylisothiocyanate was used instead of phenylisocyanate to afford the desired compound. Yield: 84% Melting point: 194-195 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.56 (1H, brs), 7.28 (1H, s), 7.26 (2H, d, J = 8.3 Hz), 7.12 (2H, d, J = 8.3 Hz), 7.09 (1H, s), 4.08-4.04 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.84-3.81 (4H, m), 2.89 (1H) m), 1.23 (6H, d, J = 6.9 Hz). FAB-Mass: 452 (M + +1) IR (KBr) (cm −1 ): 1578, 1541, 1510, 1475, 1446, 1425, 1390, 1342, 1250, 1211, 1136, 1016, 991, 937. Example 153 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-isopropylbenzyl) -1-piperazinecarboamide (Compound 153) Virtually the same procedure as in Example 119 was repeated except that the matching 4-isopropylbenzylamine was used instead of 2- (4-chlorophenyl) ethylamine to afford the desired compound. Yield: 31% Melting point: 135-136 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.27 (2H, d, J = 8.3 Hz), 7.27 (1H, s), 7.21 (2H, d, J = 8.3 Hz) , 7.09 (1H, s), 4.88 (1H, brt, J = 5.3 Hz), 4.43 (2H, d, J = 5.3 Hz), 4.03 (3H, s), 3.98 (3H, s), 3.70-3.63 ( 8H, m), 2.90 (1H, m), 1.24 (6H, d, J = 6.9 Hz). FAB-Mass: 450 (M + +1) IR (KBr) (cm −1 ): 1628, 1545, 1502, 1471, 1431, 1352, 1254, 1207, 1134, 993, 852, 798. Example 154 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-isopropylbenzyl) -1-piperazinthiocarboamide (Compound 154) To a solution of 0.181 ml (2.37 mmol) of thiophosgene in 10 ml of dichloromethane, 353.1 mg (2.37 mmol) of 4-isopropylbenzylamine and 0.76 ml (5.45 mmol) of triethylamine were slowly added with ice cooling. The mixture was stirred at the same temperature for 1.5 hours and 500 mg (1.82 mmol) of 6,7-dimethoxy-4-piperazinylquinazoline obtained according to the method described in South African Patent No. 67 06512 (1968) was added. After that, the mixture is stirred overnight at room temperature. The solvent is evaporated and the residue is purified by silica gel chromatography to give the title compound as colorless crystals. Yield: 86% Melting point: 178-179 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.35-7.20 (5H, m), 7.10 (1H, s), 5.91 (1H, br), 4.85 (2H, d, J = 4.6 Hz), 4.12-4.07 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.86-3.82 (4H, m), 2.90 (1H, m), 1.24 (6H, d, J = 6.9 Hz). FAB-Mass: 466 (M + +1) IR (KBr) (cm -1 ): 2872, 1541, 1506, 1475, 1429, 1346, 1236, 1205, 1136, 991, 935. Example 155 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-isobutylphenyl) -1-piperazinecarboamide (Compound 155) Virtually the same procedure as in Example 164 was repeated except that the matching 4-isobutylbenzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 61% Melting Point: 215-217 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.28 (2H, d, J = 7.6 Hz), 7.26 (1H, s), 7.11 (1H, s), 7.09 (2H, d, J = 7.6 Hz), 6.37 (1H, brs), 4.04 (3H, s), 4.00 (3H, s), 3.75 (8H, m), 2.43 (2H, d, J = 6.9 Hz), 1.83 ( 1H, m), 0.89 (6H, d, J = 6.9 Hz). FAB-Mass: 398 (M + +1) IR (KBr) (cm- 1 ): 1643, 1573, 1502, 1415, 1245, 1211, 1133, 993, 846. Example 156 N- (4-tert-butylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 156) In fact the same procedure as in Example 117 was repeated except that the matching 4-tert-butylaniline was used instead of 4-morpholinoaniline to give the desired compound. Yield: 20% Melting Point: 109-111 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.43 (1H, brs), 7.37-7.28 (5H, m), 7.13 (1H, s), 4.03 (3H, s), 4.00 (3H, s), 3.77-3.75 (8H, m), 1.30 (9H, s). FAB-Mass: 450 (M + +1) IR (KBr) (cm- 1 ): 1662, 1508, 1475, 1429, 1354, 1246, 1211, 993. Example 157 N- (4-tert-butylbenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 157) Virtually the same procedure as in Example 154 was repeated except that the matching 4-tert-butylbenzylamine was used instead of 4-isopropylbenzylamine to afford the desired compound. Yield: 91% Melting point: 104-105 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.37 (2H, d, J = 8.3 Hz), 7.29 (2H, d, J = 8.3 Hz), 7.22 (1H, s) , 7.10 (1H, s), 6.11 (1H, brt, J = 4.3 Hz), 4.86 (2H, d, J = 4.3 Hz), 4.12-4.06 (4H, m), 4.00 (3H, s), 3.98 ( 3H, s), 3.86-3.82 (4H, m), 1.31 (9H, s). FAB-Mass: 480 (M + +1) IR (KBr) (cm- 1 ): 1508, 1475, 1431, 1350, 1240, 1209. Example 158 N- (4-difluoromethoxyphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 158) In fact the same procedure as in Example 164 was repeated except that the matching 4-difluoromethoxybenzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 15% Melting point: 190-192 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.37 (2H, d, J = 8.9 Hz), 7.27 (1H, s), 7.11 (1H, s), 7.08 (2H, d, J = 8.9 Hz), 6.50 (1H, brs), 6.46 (1H, t, J = 7.4 Hz), 4.04 (3H, s), 4.00 (3H, s), 3.76 (8H, m). FAB-Mass: 460 (M + +1) IR (KBr) (cm −1 ): 1646, 1573, 1538, 1508, 1436, 1234, 1209, 1132, 1027, 993, 927, 846, 777. Example 159 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-trifluoromethylphenyl) -1-piperazinthiocarboamide (Compound 159) Virtually the same procedure as in Example 1 was repeated except that the matching 4-trifluoromethylphenylisothiocyanate was used instead of phenylisocyanate to afford the desired compound. Yield: 82% Melting Point: 117-119 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 8.18 (1H, brs), 7.56 (2H, d, J = 8.6 Hz), 7.33 (2H, d, J = 8.6 Hz) , 7.23 (1H, s), 7.09 (1H, s), 4.12-4.07 (4H, m), 4.00 (3H, s), 3.98 (3H, s), 3.86-3.83 (4H, m). FAB-Mass: 478 (M + +1) IR (KBr) (cm −1 ): 1581, 1508, 1479, 1430, 1325, 1207, 1162, 1113, 1066, 993. Example 160 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-trifluoromethylbenzyl) -1-piperazinecarboamide (Compound 160) Virtually the same procedure as in Example 119 was repeated except that the matching 4-trifluoromethylbenzylamine was used instead of 2- (4-chlorophenyl) ethylamine to afford the desired compound. Yield: 60% Melting point: 195-197 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.59 (2H, d, J = 8.3 Hz), 7.44 (2H, d, J = 8.3 Hz), 7.25 (1H, s) , 7.09 (1H, s), 5.10 (1H, brt, J = 5.6 Hz), 4.52 (2H, d, J = 5.6 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.71-3.65 ( 8H, m). FAB-Mass: 476 (M + +1) IR (KBr) (cm −1 ): 1620, 1504, 1475, 1429, 1327, 1255, 1211, 1161, 1111, 1066, 993. Example 161 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-trifluoromethylbenzyl) -1-piperazinthiocarboamide (Compound 161) Virtually the same procedure as in Example 154 was repeated except that the matching 4-trifluoromethylbenzylamine was used instead of 4-isopropylbenzylamine to afford the desired compound. Yield: 99% Melting Point: 216-217 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.61 (2H, d, J = 7.9 Hz), 7.47 (2H, d, J = 7.9 Hz), 7.24 (1H, s) , 7.10 (1H, s), 6.07 (1H, brt, J = 5.3 Hz), 5.01 (2H, d, J = 5.3 Hz), 4.14-4.10 (4H, m), 4.02 (3H, s), 3.98 ( 3H, s), 3.89-3.85 (4H, m). FAB-Mass: 492 (M + +1) IR (KBr) (cm −1 ): 1531, 1500, 1473, 1429, 1329, 1234, 1207, 1159, 1113, 1066, 989. Example 162 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-trifluoromethylphenyl) -1-piperazinecarboamide (Compound 162) Virtually the same procedure as in Example 1 was repeated except that the matching 3-trifluoromethylphenylisocyanate was used instead of phenylisocyanate to afford the desired compound. Yield: 100% Melting point: 180-181 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.67 (1H, brs), 7.61 (1H, d, J = 8.3 Hz), 7.41-7.28 (3H, m), 7.24 ( 1H, s), 7.09 (1H, s), 4.01 (3H, s), 3.99 (3H, s), 3.77-3.71 (8H, m). FAB-Mass: 462 (M + +1) IR (KBr) (cm −1 ): 1647, 1554, 1502, 1471, 1431, 1335, 1244, 1207, 1124, 993. Example 163 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-trifluoromethylphenyl) -1-piperazinthiocarboamide (Compound 163) Virtually the same procedure as in Example 164 was repeated except that the matching 3-trifluoromethylphenylisothiocyanate was used instead of phenylisocyanate to afford the desired compound. Yield: 86% Melting point: 171-172 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.54 (1H, brs), 7.48-7.41 (3H, m), 7.27 (1H, s), 7.27 (1H, d, J = 2.3 Hz), 7.10 (1H, s), 4.16-4.11 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.89-3.85 (4H, m). FAB-Mass: 478 (M + +1) IR (KBr) (cm −1 ): 1576, 1543, 1506, 1477, 1431, 1333, 1238, 1211, 1165, 1119, 995. Example 164 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-vinylphenyl) -1-piperazinecarboamide (Compound 164) To 20 ml of toluene, 1.39 ml (10.0 mmol) of triethylamine and 2.15 ml (10.0 mmol) of diphenylphosphoryl azide are added to a suspension of 1.48 g (10.0 mmol) of 4-vinylbenzoic acid. The mixture was heated at 70 ° C. for 2 hours with stirring, after addition of 548 mg (2.00 mmol) of 6,7-dimethoxy-4-piperazinylquinazoline obtained by South African Patent No. 67 06512 (1968). Heat at reflux for one hour. After cooling the reaction mixture to room temperature, water is added and extracted with chloroform. The organic layer is washed with saturated aqueous sodium chloride solution and dried over magnesium chloride. The solvent is evaporated and the residue is purified by silica gel chromatography and recrystallized from ethyl acetate to give the title compound as colorless crystals. Yield: 54% Melting Point: 214-216 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.36 (4H, s), 7.27 (1H, s), 7.11 (1H, s), 6.65 (1H, dd, J = 17.5 Hz, 10.9 Hz), 6.50 (1H, brs), 5.67 (1H, d, J = 17.5 Hz), 5.18 (1H, d, J = 10.9 Hz), 4.03 (3H, s), 4.00 (3H, s) , 3.75 (8H, m). FAB-Mass: 420 (M + + +1) IR (KBr) (cm −1 ): 1619, 1577, 1504, 1477, 1421, 1303, 1236, 1211, 1039, 991, 939, 910. Example 165 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-isopropenylbenzyl) -1-piperazinecarboamide (Compound 165) In fact the same procedure as in Example 263 was repeated except that a matching 4-isopropylbenzylamine was used instead of 2-picorylamine to afford the desired compound. Yield: 17% Melting point: 123-124 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.47 (2H, d, J = 8.3 Hz), 7.31 (2H, d, J = 8.3 Hz), 7.26 (1H, s) , 7.10 (1H, s), 5.37 (1H, s), 5.09 (1H, s), 4.79 (1H, br), 4.46 (2H, d, J = 5.6 Hz), 4.03 (3H, s), 3.99 ( 3H, s), 3.71-3.68 (4H, m), 3.66-3.63 (4H, m), 2.15 (3H, s). FAB-Mass: 476 (M + +1) IR (KBr) (cm −1 ): 1621, 1540, 1506, 1429, 1351, 1253, 1209, 991, 846. Example 166 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-isopropenylbenzyl) -1-piperazinthiocarboamide (Compound 166) Virtually the same procedure as in Example 154 was repeated except that the corresponding 4-isopropylphenylbenzylamine was used instead of 4-isopropylbenzylamine to afford the desired compound. Yield: 21% 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.47 (2H, d, J = 8.5 Hz), 7.33 (2H, d, J = 8.5 Hz), 7.26 (1H, s) , 7.11 (1H, s), 5.70 (1H, br), 5.36 (1H, s), 5.11 (1H, s), 4.89 (2H, d, J = 4.6 Hz), 4.11-4.07 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.88-3.84 (4H, m), 2.16 (3H, s). Example 167 4- (6,7-dimethoxy-4-quinazolinyl) -N- {4- [1- (2-methyl-1-propenyl)] benzyl} -1-piperazinecarboamide (Compound 167) In fact the same procedure as in Example 263 was repeated except that the corresponding 4- [1- (2-methyl-1-propenyl)] benzylamine was used instead of 2-picorylamine to afford the desired compound. Yield: 16% Melting Point: 168-169 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.28 (2H, d, J = 8.3 Hz), 7.26 (1H, s), 7.21 (2H, d, J = 8.3 Hz) , 7.10 (1H, s), 6.25 (1H, s), 4.78 (1H, brt, J = 4.9 Hz), 4,45 (2H, d, J = 4.9 Hz), 4.03 (3H, s), 3.99 ( 3H, s), 3.71-3.68 (4H, m), 3.66-3.63 (4H, m), 1.91 (3H, s), 1.86 (3H, s). FAB-Mass: 462 (M + +1) IR (KBr) (cm- 1 ): 1623, 1542, 1504, 1436, 1427, 1253, 1209, 991, 848. Example 168 4- (6,7-dimethoxy-4-quinazolinyl) -N- {4- [1- (2-methyl-1-propenyl)] benzyl} -1-piperazinethiocarboamide (Compound 168 ) Virtually the same procedure as in Example 154 was repeated except that the matching 4- [1- (2-methyl-1-propenyl)] benzylamine was used instead of 4-isopropylbenzylamine to afford the desired compound. Yield: 31% 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.31 (2H, d, J = 8.3 Hz), 7.26 (1H, s), 7.22 (2H, d, J = 8.3 Hz) , 7.11 (1H, s), 6.25 (1H, s), 5.70 (1H, br), 4.87 (2H, d, J = 4.6 Hz), 4.11-4.07 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.88-3.85 (4H, m), 1.91 (3H, s), 1.87 (3H, s). In Examples 169-171 below, substantially the same procedure as in Example 1 was repeated except that a matching isothiocyanate was used in place of phenylisocyanate to afford the desired compound. Example 169 4- (6,7-dimethoxy-4-quinazolinyl) -N- [trans-4- (4-propylcyclohexyl) phenyl] -1-piperazinthiocarboamide (Compound 169) Yield: 83% Melting point: 106-109 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.53 (1H, brs), 7.25 (1H, s), 7.18 (2H, d, J = 8.6 Hz), 7.10 (2H, d, J = 8.6 Hz), 7.08 (1H, s), 4.07-4.03 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.84-3.80 (4H, m), 2.43 (1H , tt, J = 12.2 Hz, 3.0 Hz), 1.91-1.84 (4H, m), 1.48-1.15 (7H, m), 1.10-0.95 (2H, m), 0.90 (3H, t, J = 7.3 Hz) . FAB-Mass: 534 (M + +1) IR (KBr) (cm −1 ): 2920, 1576, 1506, 1473, 1427, 1236, 1209, 1134, 1014, 991, 854. Example 170 4- (6,7-dimethoxy-4-quinazolinyl) -N- {4- [1- (4-hexylbicyclo [2.2.2] octyl)] phenyl} -1-piperazinthiocarboamide (Compound 170) Yield: 70% Melting Point: 148-149 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.45 (1H, brs), 7.28 (2H, d, J = 6.9 Hz), 7.28 (2H, d, J = 6.9 Hz) , 7.25 (1H, s), 7.08 (1H, s), 4.06-4.03 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.84-3.80 (4H, m), 1.83-1.74 (6H, m), 1.49-1.44 (6H, m), 1.31-1.13 (10H, m), 0.89 (3H, t, J = 6.6 Hz). FAB-Mass: 602 (M + +1) IR (KBr) (cm −1 ): 2927, 2854, 1508, 1483, 1473, 1454, 1430, 1332, 1238, 1215, 1138, 995, 941, 854. Example 171 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-fluorobenzyl) -1-piperazinthiocarboamide (Compound 171) Yield: 75% Melting point: 100-102 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.32 (1H, m), 7.28 (1H, s), 7.27-6.95 (4H, m), 6.09 (1H, brt, J = 5.0 Hz), 4.93 (2H, d, J = 5.0 Hz), 4.14-4.10 (4H, m), 4.02 (3H, s), 3.99 (3H, s), 3.88-3.85 (4H, m). FAB-Mass: 442 (M + +1) IR (KBr) (cm −1 ): 1579, 1506, 1481, 1450, 1435, 1338, 1250, 1206, 1138, 991. Example 172 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-fluorobenzyl) -1-piperazinecarboamide (Compound 172) Virtually the same procedure as in Example 263 was repeated except that the corresponding 4-fluorobenzylamine was used instead of 2-picorylamine to afford the desired compound. Yield: 53% Melting point: 200-201 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.31 (2H, m), 7.26 (1H, s), 7.10 (1H, s), 7.04 (2H, m), 4.86 ( 1H, brt, J = 5.6 Hz), 4.43 (2H, d, J = 5.6 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.70-3.68 (4H, m), 3.65-3.63 (4H , m). FAB-Mass: 426 (M + +1) IR (KBr) (cm −1 ): 1576, 1506, 1475, 1429, 1350, 1240, 1209, 1136, 991. In Examples 173-182 below, the procedure was substantially the same as in Example 1 except that a matching isocyanate or isothiocyanate was used in place of phenylisocyanate to obtain the desired compound. Example 173 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-fluorobenzyl) -1-piperazinthiocarboamide (Compound 173) Yield: 78% Melting Point: 217-218 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.33 (2H, m), 7.23 (1H, s), 7.10 (1H, s), 7.02 (2H, m), 6.14 ( 1H, brt, J = 5.0 Hz), 4.88 (2H, d, J = 5.0 Hz), 4.12-4.07 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.87-3.83 (4H , m). FAB-Mass: 442 (M + +1) IR (KBr) (cm −1 ): 1533, 1506, 1477, 1452, 1431, 1406, 1327, 1236, 1211, 1136, 991, 937, 864. Example 174 (dl) -4- (6,7-dimethoxy-4-quinazolinyl) -N- [1- (4-fluorophenyl) ethyl] -1-piperazinthiocarboamide (Compound 174) Yield: 84% Melting point: 95-97 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.61 (1H, s), 7.34 (2H, dd, J = 6.9 Hz, 5.0 Hz), 7.22 (1H, s), 7.10 (1H, s), 7.00 (2H, dd, J = 8.9 Hz, 6.9 Hz), 6.13 (1H, brd, J = 7.6 Hz), 5.84 (1H, dq, J = 7.6 Hz, 6.9 Hz), 4.09-4.07 (4H, m), 4.01 (3H, s), 3.97 (3H, s), 3.86-3.85 (4H, m), 1.60 (3H, d, J = 6.9 Hz). FAB-Mass: 456 (M + +1) IR (KBr) (cm- 1 ): 1576, 1508, 1475, 1429, 1348, 1209, 993, 839. Example 175 N- (3-chlorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 175) Yield: 79% Melting Point: 222-224 ℃ 1 H-NMR (CDCl 3 + DMSO-d 6 ) δ (ppm): 8.78 (1H, brs), 8.67 (1H, s), 7.35 (2H, m), 7.28-7.26 (2H, m), 7.16- 7.13 (2H, m), 4.17-4.16 (4H, m), 4.04 (3H, s), 4.01 (3H, s), 3.87-3.85 (4H, m). FAB-Mass: 446 (M + +3), 444 (M + +1) IR (KBr) (cm −1 ): 1522, 1508, 1479, 1426, 1317, 1238, 1213, 994. Example 176 N- (2-chlorobenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 176) Yield: 89% Melting Point: 175-176 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.51 (1H, dd, J = 6.9 Hz, 2.3 Hz), 7.37 (1H, dd, J = 6.6 Hz, 1.7 Hz), 7.30-7.23 (3H, m), 7.10 (1H, s), 6.32 (1H, brt, J = 5.6 Hz), 5.01 (2H, d, J = 5.6 Hz), 4.12-4.07 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.87-3.83 (4H, m). FAB-Mass: 460 (M + +3), 458 (M + +1) IR (KBr) (cm −1 ): 1549, 1504, 1481, 1429, 1348, 1240, 1207, 1136, 991, 847. Example 177 N- (3-chlorobenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 177) Yield: 98% Melting Point: 117-119 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.60 (1H, s), 7.30-7.20 (5H, m), 7.08 (1H, s), 6.30 (1H, brt, J = 5.3 Hz), 4.89 ( 2H, d, J = 5.3 Hz), 4.12-4.07 (4H, m), 3.99 (3H, s), 3.96 (3H, s), 3.85-3.82 (4H, m). FAB-Mass: 460 (M + +3), 458 (M + +1) IR (KBr) (cm −1 ): 1576, 1506, 1483, 1437, 1406, 1354, 1329, 1254, 1205, 991, 858. Example 178 N- (4-chlorobenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 178) Yield: 76% Melting point: 203-204 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.32-7.18 (5H, m), 7.09 (1H, s), 5.04 (1H, brt, J = 5.6 Hz), 4.43 ( 2H, d, J = 5.6 Hz), 4.02 (3H, s), 3.98 (3H, s), 3.70-3.68 (4H, m), 3.65-3.63 (4H, m). FAB-Mass: 444 (M + +3), 442 (M + +1) IR (KBr) (cm -1 ): 1626, 1541, 1504, 1475, 1429, 1350, 1255, 1211, 993. Example 179 N- (4-chlorobenzoyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 179) Yield: 15% Melting point: 166-168 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.78 (1H, br), 8.69 (1H, s), 7.82 (2H, d, J = 8.2 Hz), 7.47 (2H, d, J = 8.2 Hz) , 7.28 (1H, s), 7.10 (1H, s), 4.41 (2H, m), 4.03 (3H, s), 4.00 (3H, s), 3.89 (6H, m). FAB-Mass: 474 (M + +3), 472 (M + +1) IR (KBr) (cm −1 ): 1670, 1579, 1504, 1425, 1350, 1242, 1211, 1096, 1016, 991, 851, 750. Example 180 N- [2- (4-chlorophenyl) ethyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 180) Yield: 74% Melting point: 106-109 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.29 (2H, d, J = 8.3 Hz), 7.25 (1H, s), 7.17 (2H, d, J = 8.3 Hz) , 7.10 (1H, s), 5.73 (1H, brt, J = 5.3 Hz), 4.02 (3H, s), 4.01-3.91 (6H, m), 3.98 (3H, s), 3.85-3.81 (4H, m ), 2.97 (2H, t, J = 6.9 Hz). FAB-Mass: 474 (M + +3), 472 (M + +1) IR (KBr) (cm -1 ): 1579, 1506, 1487, 1429, 1344, 1240, 1213, 1012, 993. Example 181 N- (3-bromophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 181) Yield: 81% Melting point: 220-222 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.51 (1H, brs), 7.37 (1H, dd, J = 2.0 Hz, 1.7 Hz), 7.32-7.14 (4H, m) , 7.09 (1H, s), 4.10-4.06 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.86-3.83 (4H, m). FAB-Mass: 490 (M + +3), 488 (M + +1) IR (KBr) (cm −1 ): 1572, 1508, 1477, 1425, 1315, 1236, 1213, 993, 870. Example 182 N- (4-bromophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 182) Yield: 78% Melting Point: 170-171 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.63 (1H, brs), 7.45 (2H, d, J = 8.6 Hz), 7.24 (1H, s), 7.11 (2H, d, J = 8.6 Hz), 7.09 (1H, s), 4.10-4.07 (4H, m), 4.01 (3H, s), 3.99 (3H, s), 3.85-3.82 (4H, m). FAB-Mass: 490 (M + +3), 488 (M + +1) IR (KBr) (cm- 1 ): 1504, 1473, 1425, 1344, 1209. Example 183 N- (4-bromophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -N-methyl-1-piperazinecarboamide (Compound 183) 1.01 g (2.15 mmol) of N- (4-bromophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide obtained in Example 45 was diluted with dimethylform. 171.9 mg (4.30 mmol) of 60% sodium hydride was added to a solution dissolved in 15 ml of amide while cooling with ice, and stirred at room temperature for 30 minutes. 0.27 ml (4.34 mmol) of methyl iodide is added to the reaction mixture and stirred at room temperature overnight. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel column chromatography to obtain the target compound of colorless crystals. Yield: 81% 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.47 (2H, d, J = 8.6 Hz), 7.24 (1H, s), 7.04 (2H, d, J = 8.6 Hz) , 7.02 (1H, s), 4.02 (3H, s), 3.97 (3H, s), 3.51-3.43 (8H, m), 3.25 (3H, s). FAB-Mass: 488 (M + +3), 486 (M + +1) Example 184 N- (4-bromobenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 184) Virtually the same procedure as in Example 119 was repeated except that the matching 4-bromobenzylamine was used instead of 2- (4-chlorophenyl) ethylamine to afford the desired compound. Yield: 55% Melting point: 211-212 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.45 (2H, d, J = 7.2 Hz), 7.25 (1H, s), 7.21 (2H, d, J = 7.2 Hz) , 7.09 (1H, s), 4.99 (1H, brt, J = 5.6 Hz), 4.41 (2H, d, J = 5.6 Hz), 4.03 (3H, s), 3.98 (3H, s), 3.70-3.63 ( 8H, m). FAB-Mass: 488 (M + +3), 486 (M + +1) IR (KBr) (cm −1 ): 1626, 1574, 1539, 1504, 1473, 1429, 1352, 1255, 1209, 1134, 993. Example 185 N- (4-bromobenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 185) Triethylamine in a solution of 502.3 mg (1.42 mmol) of 4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinethiocarboxylic acid chloride obtained in Reference Example 6 in 10 ml of dimethylformamide. 1.00 ml (7.17 mmol) and 950 mg (4.27 mmol) of 4-bromobenzylaminehydrochloride are added. The mixture is stirred at room temperature overnight in an argon atmosphere. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel column chromatography to give the title compound as colorless crystals. Yield: 76% Melting Point: 217-218 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.61 (1H, s), 7.43 (2H, d, J = 8.2 Hz), 7.22 (2H, d, J = 8.2 Hz), 7.21 (1H, s) , 7.09 (1H, s), 6.29 (1H, brt, J = 5.0 Hz), 4.87 (2H, d, J = 5.0 Hz), 4.11-4.09 (4H, m), 4.01 (3H, s), 3.98 ( 3H, s), 3.87-3.83 (4H, m). FAB-Mass: 504 (M + +3), 502 (M + +1) IR (KBr) (cm −1 ): 1533, 1498, 1473, 1425, 1394, 1319, 1234, 1207, 1134, 989, 935, 864, 795. In Examples 186-197 below, substantially the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used in place of phenylisocyanate to obtain the target compound. Example 186 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-iodinephenyl) -1-piperazinecarboamide (Compound 186) Yield: 93% Melting point: 205-208 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.77 (1H, brs), 7.38-7.32 (2H, m), 7.24 (1H, s), 7.08 (1H, s), 7.00-6.93 (2H, m), 4.01 (3H, s), 3.98 (3H, s), 3.72 (8H, m). FAB-Mass: 520 (M + +1) IR (KBr) (cm −1 ): 1637, 1578, 1506, 1475, 1419, 1238, 1209, 995. Example 187 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-fluoro-4-methylphenyl) -1-piperazinecarboamide (Compound 187) Yield: 87% 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 7.67 (1H, brs), 7.27 (2H, m), 7.12 (1H, s), 7.05 (2H, m), 4.03 ( 3H, s), 4.01 (3H, s), 3.76-3.73 (8H, m), 2.20 (3H, s). FAB-Mass: 426 (M + +1) Example 188 N- (3-chloro-4-methylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 188) Yield: 91% Melting Point: 217-218 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.45 (1H, brs), 7.42 (1H, s), 7.23 (1H, s), 7.18 (1H, d, J = 8.2 Hz), 7.08 (1H, s), 7.07 (1H, d, J = 8.2 Hz), 4.00 (3H, s), 3.97 (3H, s), 3.72-3.70 (8H, m), 2.26 (3H, s ). FAB-Mass: 424 (M + +3), 422 (M + +1) IR (KBr) (cm- 1 ): 1641, 1576, 1502, 1471, 1429, 1400, 1244, 1207, 993. Example 189 N- (4-chloro-3-trifluoromethylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinethiocarboamide (Compound 189) Yield: 79% 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.71 (1H, brs), 8.56 (1H, s), 7.91 (1H, d, J = 2.3 Hz), 7.72 (1H, dd, J = 8.6 Hz, 2.3 Hz), 7.66 (1H, d, J = 8.6 Hz), 7.25 (1H, s), 7.24 (1H, s), 4.16 (4H, m), 3.94 (3H, s), 3.94 (3H, s), 3.87 (4H, m). FAB-Mass: 514 (M + +3), 512 (M + +1) Example 190 N- (3-chloro-4-methylbenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 190) Yield: 85% Melting point: 108-110 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.35-7.12 (3H, m), 7.23 (1H, s), 7.10 (1H, s), 6.13 (1H, brt, J = 5.3 Hz), 4.93 (2H, d, J = 5.3 Hz), 4.12-4.07 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.87-3.83 (4H, m). FAB-Mass: 474 (M + +3), 472 (M + +1) IR (KBr) (cm -1 ): 1576, 1504, 1477, 1429, 1350, 1240, 1209, 1136, 993. Example 191 N- (4-bromo-3-methylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 191) Yield: 74% Melting point: 160-161 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.49 (1H, d, J = 8.3 Hz), 7.36 (1H, brs), 7.27 (1H, s), 7.24 (1H, d, J = 2.6 Hz), 7.09 (1H, s), 6.92 (1H, dd, J = 8.3 Hz, 2.6 Hz), 4.10-4.06 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.86-3.82 (4H, m), 2.38 (3H, s). FAB-Mass: 504 (M + +3), 502 (M + +1) IR (KBr) (cm- 1 ): 1576, 1504, 1477, 1429, 1319, 1209, 993. Example 192 N- (3,4-difluorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 192) Yield: 82% 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.42 (1H, m), 7.30-7.24 (2H, m), 7.09 (1H, s), 7.05-6.97 (2H, m ), 4.01 (3H, s), 3.99 (3H, s), 3.73 (8H, m). FAB-Mass: 430 (M + +1) Example 193 N- (3-chloro-4-fluorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 193) Yield: 93% Melting point: 200-201 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.52 (1H, dd, J = 6.6 Hz, 2.6 Hz), 7.25 (1H, s), 7.21 (1H, ddd, J = 8.9 Hz, 6.9 Hz, 2.6 Hz), 7.11 (1H, brs), 7.10 (1H, s), 7.03 (1H, dd, J = 8.9 Hz, 8.6 Hz), 4.02 (3H, s), 3.99 (3H, s), 3.73 (8H, m). FAB-Mass: 448 (M + +3), 446 (M + +1) IR (KBr) (cm −1 ): 1645, 1535, 1506, 1473, 1454, 1412, 1244, 1209, 1136, 993, 852, 814. Example 194 N- (4-bromo-3-chlorophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 194) Yield: 89% Melting point: 169-172 ℃ 1 H-NMR (CDCl 3 + DMSO-d 6 ) δ (ppm): 9.07 (1H, brs), 8.67 (1H, s), 7.59-7.50 (2H, m), 7.28-7.23 (2H, m), 7.14 (1H, s), 4.21-4.19 (4H, m), 4.05 (3H, s), 4.01 (3H, s), 3.88-3.87 (4H, m). FAB-Mass: 526 (M + +5), 524 (M + +3), 522 (M + +1) IR (KBr) (cm- 1 ): 1525, 1504, 1471, 1429, 1417, 1313, 1209, 1018, 993. Example 195 N- (3,4-dichlorobenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 195) Yield: 91% Melting point: 197-200 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.43 (1H, d, J = 2.0 Hz), 7.40 (1H, d, J = 8.3 Hz), 7.24 (1H, s) , 7.21 (1H, dd, J = 8.3 Hz, 2.0 Hz), 7.10 (1H, s), 6.20 (1H, brt, J = 5.0 Hz), 4.90 (2H, d, J = 5.0 Hz), 4.15-4.10 (4H, m), 4.02 (3H, s), 3.99 (3H, s), 3.89-3.85 (4H, m). FAB-Mass: 494 (M + +3), 492 (M + +1) IR (KBr) (cm −1 ): 1579, 1506, 1475, 1446, 1429, 1396, 1346, 1327, 1248, 1207, 1140, 993. Example 196 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methoxyphenyl) -1-piperazinthiocarboamide (Compound 196) Yield: 84% Melting point: 196-197 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.46 (1H, brs), 7.28 (1H, s), 7.15 (2H, d, J = 8.9 Hz), 7.10 (1H, s), 6.88 (2H, d, J = 8.9 Hz), 4.09-4.07 (4H, m), 4.02 (3H, s), 3.99 (3H, s), 3.85-3.82 (4H, m), 3.80 (3H , s). FAB-Mass: 440 (M + +1) IR (KBr) (cm −1 ): 1539, 1508, 1431, 1336, 1240, 1209, 1039, 993, 867. Example 197 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-methoxybenzyl) -1-piperazinthiocarboamide (Compound 197) Yield: 85% Melting point: 146-147 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.29 (1H, m), 7.27 (1H, s), 7.11 (1H, s), 6.96-6.92 (2H, m), 6.86 (1H, dd, J = 8.3 Hz, 1.7 Hz), 5.73 (1H, brt, J = 4.6 Hz), 4.87 (2H, d, J = 4.6 Hz), 4.11-4.07 (4H, m), 4.03 ( 3H, s), 3.99 (3H, s), 3.88-3.84 (4H, m), 3.82 (3H, s). FAB-Mass: 454 (M + +1) IR (KBr) (cm- 1 ): 1541, 1500, 1477, 1435, 1352, 1327, 1244, 1207, 991. Example 198 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methoxybenzyl) -1-piperazinecarboamide (Compound 198) Virtually the same procedure as in Example 263 was repeated except that the corresponding 4-methoxybenzylamine was used instead of 2-picorylamine to afford the desired compound. Yield: 34% Melting Point: 147-148 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.27 (2H, d, J = 7.6 Hz), 7.26 (1H, s), 7.09 (1H, s), 6.88 (2H, d, J = 7.6 Hz), 4.77 (1H, brt, J = 5.3 Hz), 4.40 (2H, d, J = 5.3 Hz), 4.03 (3H, s), 3.98 (3H, s), 3.81 (3H, s), 3.70-3.67 (4H, m), 3.64-3.61 (4H, m). FAB-Mass: 438 (M + +1) IR (KBr) (cm −1 ): 1623, 1575, 1540, 1504, 1429, 1351, 1243, 1209, 1133, 1029, 993, 848. Example 199 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methoxybenzyl) -1-piperazinthiocarboamide (Compound 199) Virtually the same procedure as in Example 1 was repeated except that the corresponding 4-methoxybenzylisothiocyanate was used in place of phenylisocyanate to afford the desired compound. Yield: 72% Melting point: 201-204 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.30 (2H, d, J = 8.6 Hz), 7.27 (1H, s), 7.10 (1H, s), 6.90 (2H, d, J = 8.6 Hz), 5.69 (1H, brt, J = 4.3 Hz), 4.82 (2H, d, J = 4.3 Hz), 4.10-4.06 (4H, m), 4.03 (3H, s), 3.98 ( 3H, s), 3.87-3.83 (4H, m), 3.82 (3H, s). FAB-Mass: 454 (M + +1) IR (KBr) (cm- 1 ): 1506, 1477, 1449, 1431, 1346, 1248, 1209, 991. Example 200 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-ethoxybenzyl) -1-piperazinecarboamide (Compound 200) Virtually the same procedure as in Example 263 was repeated except that the corresponding 4-ethoxybenzylamine was used instead of 2-picorylamine to afford the desired compound. Yield: 39% Melting Point: 176-177 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.26 (1H, s), 7.25 (2H, d, J = 8.3 Hz), 7.09 (1H, s), 6.87 (2H, d, J = 8.3 Hz), 4.75 (1H, brt, J = 5.3 Hz), 4.39 (2H, d, J = 5.3 Hz), 4.04 (2H, q, J = 6.9 Hz), 4.02 (3H, s) , 3.98 (3H, s), 3.69-3.67 (4H, m), 3.64-3.62 (4H, m), 1.41 (3H, t, J = 6.9 Hz). FAB-Mass: 452 (M + +1) IR (KBr) (cm- 1 ): 1629, 1575, 1527, 1429, 1234, 1209, 1043, 995. Example 201 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-propoxyphenyl) -1-piperazinecarboamide (Compound 201) Virtually the same procedure as in Example 164 was repeated except that the corresponding 4-propoxybenzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 67% Melting Point: 218-220 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.26 (1H, s), 7.25 (2H, d, J = 8.5 Hz), 7.11 (1H, s), 6.86 (2H, d, J = 8.5 Hz), 6.35 (1H, brs), 4.03 (3H, s), 4.00 (3H, s), 3.89 (2H, t, J = 6.6 Hz), 3.74 (8H, m), 1.79 ( 2H, m), 1.02 (3H, t, J = 6.8 Hz). FAB-Mass: 452 (M + +1) IR (KBr) (cm −1 ): 1637, 1573, 1508, 1473, 1419, 1234, 1211, 1133, 993. Example 202 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-isopropoxyphenyl) -1-piperazinecarboamide (Compound 202) Virtually the same procedure as in Example 164 was repeated except that the matching 4-isopropoxybenzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 67% Melting point: 220-222 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.26 (1H, s), 7.25 (2H, d, J = 8.6 Hz), 7.11 (1H, s), 6.85 (2H, d, J = 8.6 Hz), 6.35 (1H, brs), 4.49 (1H, m), 4.03 (3H, s), 4.00 (3H, s), 3.74 (8H, m), 1.31 (6H, d, J = 5.9 Hz). FAB-Mass: 452 (M + +1) IR (KBr) (cm −1 ): 1637, 1573, 1535, 1504, 1473, 1234, 1211, 1133, 993. Example 203 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-trifluoromethoxybenzyl) -1-piperazinecarboamide (Compound 203) In fact the same procedure as in Example 263 was repeated except that a matching 4-trifluoromethoxybenzylamine was used instead of 2-picorylamine to afford the desired compound. Melting Point: 176-177 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.37 (2H, d, J = 8.4 Hz), 7.26 (1H, s), 7.19 (2H, d, J = 8.4 Hz) , 7.10 (1H, s), 4.93 (1H, brt, J = 5.3 Hz), 4.47 (2H, d, J = 5.3 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.71-3.69 ( 4H, m), 3.66-3.64 (4H, m). FAB-Mass: 492 (M + +1) IR (KBr) (cm- 1 ): 1629, 1573, 1540, 1504, 1473, 1430, 1249, 1209, 1135, 993. Example 204 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-trifluoromethoxybenzyl) -1-piperazinthiocarboamide (Compound 204) Virtually the same procedure as in Example 154 was repeated except that a matching 4-trifluoromethoxybenzylamine was used instead of 4-isopropylbenzylamine to afford the desired compound. Yield: 95% Melting point: 131-132 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.40 (2H, d, J = 8.6 Hz), 7.24 (1H, s), 7.20 (2H, d, J = 8.6 Hz) , 7.10 (1H, s), 6.00 (1H, brt, J = 4.9 Hz), 4.94 (2H, d, J = 4.9 Hz), 4.13-4.07 (4H, m), 4.02 (3H, s), 3.98 ( 3H, s), 3.88-3.84 (4H, m). FAB-Mass: 508 (M + +1) IR (KBr) (cm −1 ): 1508, 1477, 1431, 1350, 1263, 1213, 1163, 991. Example 205 N- (3,4-dimethoxybenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 205) Virtually the same procedure as in Example 1 was repeated except that a matching 3,4-dimethoxybenzylisothiocyanate was used in place of phenylisocyanate to afford the desired compound. Yield: 82% Melting point: 196-197 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.28 (1H, s), 7.11 (1H, s), 6.90-6.83 (3H, m), 5.78 (1H, brt, J = 4.6 Hz), 4.82 (2H, d, J = 4.6 Hz), 4.11-4.07 (4H, m), 4.03 (3H, s), 3.98 (3H, s), 3.88 (3H, s), 3.88 (3H , s), 3.87-3.83 (4H, m). FAB-Mass: 484 (M + +1) IR (KBr) (cm −1 ): 1516, 1504, 1477, 1431, 1352, 1263, 1236, 1209, 1137, 1028, 991, 849. Example 206 N- [2- (3,4-dimethoxyphenyl) ethyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 206) Virtually the same procedure as in Example 1 was repeated except that the corresponding 2- (3,4-dimethoxyphenyl) ethylisothiocyanate was used instead of phenylisocyanate to afford the desired compound. Yield: 71% Melting point: 98-100 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.25 (1H, s), 7.10 (1H, s), 6.84-6.75 (3H, m), 5.69 (1H, brt, J = 5.3 Hz), 4.03 (3H, s), 4.01-3.93 (6H, m), 3.98 (3H, s), 3.88 (3H, s), 3.87 (3H, s), 3.84-3.80 (4H, m) , 2.93 (2H, t, J = 7.3 Hz). FAB-Mass: 498 (M + +1) IR (KBr) (cm −1 ): 1576, 1506, 1475, 1429, 1344, 1261, 1236, 1211, 1138, 1028, 993. Example 207 N- (3-cyclopentyloxy-4-methoxyphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 207) Virtually the same procedure as in Example 154 was repeated except that the corresponding 3-cyclopentyloxy-methoxyaniline was used in place of 4-isopropylbenzylamine to afford the desired compound. Yield: 77% 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.78 (1H, brs), 7.23 (1H, s), 7.09 (1H, s), 6.84 (1H, d, J = 2.3 Hz), 6.80 (1H, d, J = 8.6 Hz), 6.71 (1H, dd, J = 8.6 Hz, 2.3 Hz), 4.69 (1H, m), 4.09-4.04 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.95-3.81 (4H, m), 3.81 (3H, s), 1.98-1.76 (6H, m), 1.58 (2H, m). FAB-Mass: 524 (M + +1) In Examples 208-212 below, virtually the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used in place of phenyl isocyanate to afford the desired compound. Example 208 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3,4-methylenedioxybenzyl) -1-piperazinthiocarboamide (Compound 208) Yield: 72% Melting Point: 113-114 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.24 (1H, s), 7.10 (1H, s), 6.87 (1H, d, J = 1.3 Hz), 6.81 (1H, dd, J = 7.9 Hz, 1.3 Hz), 6.77 (1H, d, J = 7.9 Hz), 5.95 (2H, s), 5.89 (1H, brt, J = 5.0 Hz), 4.79 (2H, d, J = 5.0 Hz), 4.11-4.07 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.87-3.83 (4H, m). FAB-Mass: 468 (M + +1) IR (KBr) (cm −1 ): 1579, 1504, 1483, 1452, 1352, 1238, 1215, 1038, 991, 935, 849. Example 209 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3,4-ethylenedioxyphenyl) -1-piperazinthiocarboamide (Compound 209) Yield: 81% Melting point: 165-166 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.56 (1H, brs), 7.24 (1H, s), 7.09 (1H, s), 6.81 (1H, dd, J = 8.6 Hz, 2.3 Hz), 6.74 (1H, d, J = 2.3 Hz), 6.67 (1H, d, J = 8.6 Hz), 4.23-4.22 (4H, m), 4.07-4.04 (4H, m), 4.01 ( 3H, s), 3.98 (3H, s), 3.83-3.81 (4H, m). FAB-Mass: 468 (M + +1) IR (KBr) (cm −1 ): 1533, 1508, 1479, 1433, 1340, 1246, 1207, 1068, 991. Example 210 4- (6,7-dimethoxy-4-quinazolinyl) -N- [2- (6,7,9,10,12,13,15,16-octahydro-5,8,11,14, 17-pentaoxabenzocyclopentadecenyl)]-1-piperazinecarboamide (Compound 210) Yield: 15% Melting Point: 163-164 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.25 (1H, s), 7.19 (1H, s), 7.09 (1H, s), 6.79-6.76 (2H, m), 6.65 (1H, brs), 4.14-4.09 (4H, m), 4.03 (3H, s), 4.00 (3H, s), 3.91-3.86 (4H, m), 3.75 (16H, m). FAB-Mass: 584 (M + +1) IR (KBr) (cm −1 ): 1633, 1572, 1512, 1506, 1477, 1425, 1352, 1242, 1211, 1134, 996, 856, 800. Example 211 4- (6,7-dimethoxy-4-quinazolinyl) -N- [2- (6,7,9,10,12,13,15,16,18,19-decahydro-5,8, 11,14,17,20-hexaoxabenzocyclooctadecenyl)]-1-piperazinecarboamide (Compound 211) Yield: 39% 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.28-7.26 (2H, m), 7.20 (1H, brs), 7.11 (1H, s), 6.89 (1H, dd, J = 8.6Hz, 2.0Hz), 6.72 (1H, d, J = 8.6Hz), 4.09 (4H, m), 4.03 (3H, s), 4.00 (3H, s), 3.86 (4H, m), 3.74- 3.67 (20 H, m). FAB-Mass: 628 (M + +1) Example 212 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3,4,5-trimethoxyphenyl) -1-piperazinecarboamide (Compound 212) Yield: 100% Melting point: 198-199 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.26 (1H, s), 7.11 (1H, s), 6.78 (1H, brs), 6.72 (2H, s), 4.02 ( 3H, s), 3.99 (3H, s), 3.82 (6H, s), 3.82 (3H, s), 3.74 (8H, m). FAB-Mass: 484 (M + +1) IR (KBr) (cm −1 ): 1630, 1606, 1506, 1452, 1425, 1236, 1209, 1126, 997. Example 213 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3,4,5-trimethoxybenzyl) -1-piperazinecarboamide (Compound 213) Virtually the same procedure as in Example 119 was repeated except that the corresponding 3,4,5-trimethoxybenzylamine was used instead of 2- (4-chlorophenyl) ethylamine to afford the desired compound. Yield: 53% 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.28 (1H, s), 7.10 (1H, s), 6.56 (2H, s), 4.93 (1H, brt, J = 5.3 Hz), 4.40 (2H, d, J = 5.3 Hz), 4.03 (3H, s), 3.98 (3H, s), 3.86 (3H, s), 3.81 (6H, s), 3.68-3.67 (8H, m ). FAB-Mass: 498 (M + +1) Example 214 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-hydroxymethylbenzyl) -1-piperazinecarboamide (Compound 214) 1.50 mg (5.48 mmol) of 6,7-dimethoxy-4-piperazinylquinazoline obtained according to the method described in South African Patent No. 67 06512 (1968) was dissolved in 40 ml of dimethylformamide in 4- ( 1.10 g (6.56 mmol) of chloromethyl) phenyl isocyanate were added, followed by stirring at room temperature overnight. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel column chromatography to give the target compound of colorless crystals. Yield: 25% Melting Point: 228-229 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.38-7.32 (5H, m), 7.11 (1H, s), 6.68 (1H, br), 4.64 (2H, s), 4.03 (3H, s), 4.00 (3H, s), 3.73 (8H, m), 1.74 (1H, br). FAB-Mass: 424 (M + +1) IR (KBr) (cm −1 ): 3125, 1657, 1597, 1529, 1508, 1470, 1423, 1360, 1308, 1230, 1205, 991, 931, 854. Example 215 (dl) -4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (1-hydroxyethyl) phenyl] -1-piperazinecarboamide (Compound 215) N- (4-acetylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl)-obtained in Example 87 above in a suspension of 38 mg (1.0 mmol) of sodium borohydride in 50 ml of isopropyl alcohol. After 1-piperazinecarboamide is added, it is stirred overnight at room temperature. The solvent is evaporated and the residue is taken up in chloroform. The solution is washed sequentially with 1N hydrochloric acid, water, saturated aqueous sodium bicarbonate solution and aqueous sodium chloride solution, and dried over magnesium chloride. After evaporation of the solvent, the residue is purified by silica gel chromatography and recrystallization from ethyl acetate to give the title compound as colorless crystals. Yield: 98% Melting point: 228-230 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.36 (2H, d, J = 9.2 Hz), 7.32 (2H, d, J = 9.2 Hz), 7.28 (1H, s) , 7.12 (1H, s), 6.43 (1H, brs), 4.87 (1H, q, J = 6.3 Hz), 4.04 (3H, s), 4.00 (3H, s), 3.75 (8H, m), 1.48 ( 3H, d, J = 6.3 Hz). FAB-Mass: 398 (M + +1) IR (KBr) (cm −1 ): 3330, 1664, 1577, 1506, 1475, 1417, 1241, 1211, 1137, 993. Example 216 N- (4-acetoxyphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 216) Virtually the same procedure as in Example 164 was repeated except that the corresponding 4-acetoxybenzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 67% Melting point: 197-199 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.39 (2H, d, J = 8.9 Hz), 7.28 (1H, s), 7.12 (1H, s), 7.04 (2H, d, J = 8.9 Hz), 6.45 (1H, brs), 4.04 (3H, s), 4.00 (3H, s), 3.75 (8H, m), 2.29 (3H, s). FAB-Mass: 452 (M + + +1) IR (KBr) (cm -1 ): 1730, 1631, 1505, 1450, 1429, 1241, 1211, 993, 916, Example 217 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-methylthiophenyl) -1-piperazinecarboamide (Compound 217) Virtually the same procedure as in Example 1 was repeated except that the corresponding 3-methylthiophenylisocyanate was used instead of phenylisocyanate to afford the desired compound. Yield: 96% Melting point: 180-181 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.56 (1H, s), 7.35 (1H, brs), 7.26 (1H, s), 7.12 (1H, s), 7.05-7.03 (2H, m), 6.97 (1H, m), 6.76 (1H, m), 3.89 (3H, s), 3.86 (3H, s), 3.61-3.59 (8H, m), 2.30 (3H, s). FAB-Mass: 440 (M + +1) IR (KBr) (cm −1 ): 1641, 1583, 1537, 1504, 1477, 1421, 1242, 1209, 993. Example 218 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methylthiophenyl) -1-piperazinthiocarboamide (Compound 218) Virtually the same procedure as in Example 154 was repeated except that the corresponding 4-methylthioaniline was used instead of 4-isopropylbenzylamine to afford the desired compound. Yield: 77% Melting point: 214-216 ° C 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.41 (1H, brs), 8.55 (1H, s), 7.28 (2H, d, J = 8.9 Hz), 7.25 (1H, s), 7.23 ( 1H, s), 7.21 (2H, d, J = 8.9 Hz), 4.13-4.02 (4H, m), 3.94 (3H, s), 3.94 (3H, s), 3.90-3.85 (4H, m), 2.47 (3H, s). FAB-Mass: 456 (M + +1) IR (KBr) (cm- 1 ): 1514, 1433, 1336, 1238, 1211, 993. Example 219 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-ethylthiophenyl) -1-piperazinecarboamide (Compound 219) Virtually the same procedure as in Example 164 was repeated except that the corresponding 4-ethylthiobenzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 77% Melting Point: 208-209 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.32 (4H, s), 7.27 (1H, s), 7.11 (1H, s), 6.45 (1H, brs), 4.03 ( 3H, s), 4.00 (3H, s), 3.75 (8H, m), 2.89 (2H, q, J = 7.3 Hz), 1.28 (3H, t, J = 7.3 Hz). FAB-Mass: 454 (M + +1) IR (KBr) (cm −1 ): 1641, 1573, 1502, 1448, 1436, 1236, 1211, 1135, 991, 846. Example 220 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-trifluoromethylthiophenyl) -1-piperazinthiocarboamide (Compound 220) Virtually the same procedure as in Example 154 was repeated except that the matching 4-trifluoromethylthioaniline was used in place of 4-isopropylbenzylamine to afford the desired compound. Yield: 87% Melting point: 128-131 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 8.17 (1H, brs), 7.59 (2H, d, J = 7.9 Hz), 7.29 (2H, d, J = 7.9 Hz) , 7.23 (1H, s), 7.08 (1H, s), 4.10-4.07 (4H, m), 4.00 (3H, s), 3.98 (3H, s), 3.86-3.83 (4H, m). FAB-Mass: 510 (M + +1) IR (KBr) (cm −1 ): 1578, 1506, 1477, 1458, 1427, 1346, 1238, 1209, 1155, 1128, 1109, 989, 851. Example 221 N- (4-aminophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 221) 50 g of the 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-nitrophenyl) -1-piperazinecarboamide obtained in Example 77 (3.7 mmol) in 50 ml of ethanol Suspension was added, and a suspension of 500 mg of 10% palladium-carbon suspended in 10 ml of water and 10 ml of ethanol was added, followed by stirring at room temperature under hydrogen vapor for 5 hours. The crystals were separated by filtration through celite and the solvent was evaporated. The residue is then recrystallized from silica gel chromatography and ethyl acetate to give the title compound as colorless crystals. Yield: 29% Melting Point: 215-217 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.26 (1H, s), 7.13 (2H, d, J = 9.0 Hz), 7.11 (1H, s), 6.65 (2H, d, J = 9.0 Hz), 6.26 (1H, brs), 4.03 (3H, s), 3.99 (3H, s), 3.72 (8H, m), 3.56 (2H, brs). FAB-Mass: 409 (M + +1) IR (KBr) (cm- 1 ): 1556, 1508, 1406, 1257, 1213, 910, 835, 711. Example 222 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-dimethylaminophenyl) -1-piperazinecarboamide (Compound 222) Virtually the same procedure as in Example 164 was repeated except that the corresponding 4-dimethylaminobenzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 63% Melting Point: 252-254 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.26 (1H, s), 7.20 (2H, d, J = 8.9 Hz), 7.11 (1H, s), 6.71 (2H, d, J = 8.9 Hz), 6.31 (1H, brs), 4.03 (3H, s), 4.00 (3H, s), 3.72 (8H, m), 2.91 (6H, s). FAB-Mass: 437 (M + +1) IR (KBr) (cm −1 ): 1631, 1523, 1504, 1483, 1450, 1348, 1255, 1209, 1135, 993, 937, 848. Example 223 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-dimethylaminobenzyl) -1-piperazinecarboamide (Compound 223) Virtually the same procedure as in Example 263 was repeated except that the corresponding 4-dimethylaminobenzylamine was used instead of 2-picorylamine to afford the desired compound. Yield: 28% Melting point: 188-190 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.26 (1H, s), 7.21 (2H, d, J = 9.0 Hz), 7.09 (1H, s), 6.72 (2H, d, J = 9.0 Hz), 4.66 (1H, brt, J = 5.2 Hz), 4.36 (2H, d, J = 5.2 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.70-3.67 ( 4H, m), 3.63-3.61 (4H, m), 2.95 (6H, s). FAB-Mass: 451 (M + +1) IR (KBr) (cm −1 ): 1646, 1575, 1521, 1506, 1475, 1430, 1351, 1247, 1213, 1133, 993. Example 224 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-dimethylaminobenzyl) -1-piperazinthiocarboamide (Compound 224) Virtually the same procedure as in Example 185 was repeated except that the corresponding 4-dimethylaminobenzylamine was used instead of 4-bromobenzylamine to afford the desired compound. Yield: 71% Melting Point: 177-178 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.24 (2H, d, J = 8.6 Hz), 7.24 (1H, s), 7.10 (1H, s), 6.71 (2H, d, J = 8.6 Hz), 5.73 (1H, brt, J = 4.3 Hz), 4.75 (2H, d, J = 4.3 Hz), 4.08-4.04 (4H, m), 4.02 (3H, s), 3.98 ( 3H, s), 3.85-3.81 (4H, m), 2.95 (6H, s). FAB-Mass: 467 (M + +1) IR (KBr) (cm −1 ): 1522, 1504, 1475, 1431, 1352, 1327, 1211, 991. Example 225 N- (4-diethylaminophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 225) Virtually the same procedure as in Example 164 was repeated except that the corresponding 4-diethylaminobenzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 32% Melting Point: 221-223 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.26 (1H, s), 7.17 (2H, d, J = 9.0 Hz), 7.12 (1H, s), 6.64 (2H, d, J = 9.0 Hz), 6.22 (1H, brs), 4.03 (3H, s), 4.00 (3H, s), 3.73 (8H, m), 3.32 (4H, q, J = 6.9 Hz), 1.13 ( 6H, t, J = 6.9 Hz). FAB-Mass: 465 (M + +1) IR (KBr) (cm −1 ): 1633, 1575, 1506, 1475, 1423, 1351, 1245, 1211, 1133, 993. Example 226 N- (3-acetamidophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 226) Virtually the same procedure as in Example 1 was repeated except that a matching 3-acetamidophenylisothiocyanate was used instead of phenylisocyanate to afford the desired compound. Yield: 92% Melting Point: 207-208 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 8.07 (1H, brs), 7.90 (1H, s), 7.56 (1H, brs), 7.25 (1H, s), 7.19 ( 1H, m), 7.11 (1H, m), 7.09 (1H, s), 6.97 (1H, d, J = 7.9 Hz), 4.02 (4H, m), 4.02 (3H, s), 3.99 (3H, s ), 3.79 (4H, m), 2.10 (3H, s). FAB-Mass: 467 (M + +1) IR (KBr) (cm −1 ): 1662, 1574, 1506, 1481, 1429, 1336, 1242, 1225, 1211, 991. Example 227 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (N, N-dimethylaminomethyl) phenyl] -1-piperazinecarboamide (Compound 227) Virtually the same procedure as in Example 100 was repeated except that the corresponding dimethylamine was used instead of piperidine to afford the desired compound. Yield: 56% Melting point: 213-215 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.42 (2H, d, J = 8.3 Hz), 7.32 (2H, d, J = 8.3 Hz), 7.26 (1H, s) , 7.11 (1H, s), 6.78 (1H, brs), 4.04 (3H, s), 4.00 (3H, s), 3.76 (8H, m), 3.60 (2H, s), 2.38 (6H, s). FAB-Mass: 451 (M + +1) IR (KBr) (cm −1 ): 1646, 1575, 1504, 1473, 1429, 1241, 1211, 1133, 993, 858, 848. Example 228 N- [4- (N-tert-butoxycarbonylaminomethyl) phenyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 228) Virtually the same procedure as in Example 1 was repeated except that the corresponding 4- (N-tert-butoxycarbonylaminomethyl) was used instead of phenylisocyanate to afford the desired compound. Yield: 93% Melting point: 123-126 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.93 (1H, brs), 7.24 (1H, s), 7.22 (2H, d, J = 8.9 Hz), 7.16 (2H, d, J = 8.9 Hz), 7.09 (1H, s), 5.18 (1H, br), 4.26 (2H, d, J = 5.6 Hz), 4.07 (4H, m), 4.01 (3H, s), 3.98 ( 3H, s), 3.82-3.79 (4H, m), 1.45 (9H, s). FAB-Mass: 539 (M + +1) IR (KBr) (cm -1 ): 1695, 1583, 1531, 1506, 1479, 1429, 1336, 1252, 1207. Example 229 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-phenylazophenyl) -1-piperazinecarboamide (Compound 229) Virtually the same procedure as in Example 164 was repeated except that the corresponding 4-phenylazobenzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 65% Melting Point: 244-246 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 7.94-7.87 (4H, m), 7.59-7.42 (5H, m), 7.28 (1H, s), 7.11 (1H, s ), 6.73 (1 H, brs), 4.04 (3 H, s), 4.01 (3 H, s), 3.78 (8 H, m). FAB-Mass: 498 (M + +1) IR (KBr) (cm- 1 ): 1645, 1506, 1473, 1436, 1242, 1211, 993, 846. Example 230 N- (4-azidophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 230) Virtually the same procedure as in Example 1 was repeated except that a matching 4-azidophenylisothiocyanate was used in place of phenylisocyanate to afford the desired compound. Yield: 86% 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.57 (1H, brs), 7.27 (2H, d, J = 8.6 Hz), 7.22 (1H, s), 7.10 (1H, s), 7.01 (2H, d, J = 8.6 Hz), 4.16-4.09 (4H, m), 4.02 (3H, s), 3.99 (3H, s), 3.87-3.83 (4H, m). FAB-Mass: 451 (M + +1) Example 231 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-nitrobenzyl) -1-piperazinthiocarboamide (Compound 231) Virtually the same procedure as in Example 185 was repeated except that the corresponding 4-nitrobenzylamine was used instead of 4-bromobenzylamine to afford the desired compound. Yield: 85% Melting point: 214-216 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 8.17 (2H, d, J = 8.6 Hz), 7.51 (2H, d, J = 8.6 Hz), 7.26 (1H, s) , 7.11 (1H, s), 6.16 (1H, brt, J = 5.3 Hz), 5.09 (2H, d, J = 5.3 Hz), 4.17-4.14 (4H, m), 4.03 (3H, s), 3.99 ( 3H, s), 3.91-3.87 (4H, m). IR (KBr) (cm −1 ): 1502, 1475, 1427, 1346, 1327, 1234, 1205, 1134, 989, 860. In Examples 232-242 below, virtually the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used in place of phenyl isocyanate to obtain the target compound. Example 232 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-nitrobenzoyl) -1-piperazinthiocarboamide (Compound 232) Yield: 27% Melting Point: 103-105 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.34 (2H, d, J = 8.9 Hz), 8.06 (2H, d, J = 8.9 Hz), 7.29 (1H, brs) , 7.27 (1H, s), 7.10 (1H, s), 4.41 (2H, m), 4.03 (3H, s), 4.00 (3H, s), 3.91 (6H, m). FAB-Mass: 483 (M + +1) IR (KBr) (cm −1 ): 1579, 1506, 1475, 1427, 1348, 1244, 1211, 991, 833, 717. Example 233 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methyl-3-nitrophenyl) -1-piperazinecarboamide (Compound 233) Yield: 94% 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.04 (1H, brs), 8.58 (1H, s), 8.27 (1H, s), 7.75 (1H, d, J = 8.5 Hz), 7.38 ( 1H, d, J = 8.5 Hz), 7.25 (1H, s), 7.20 (1H, s), 3.94 (4H, m), 3.71 (4H, m), 3.36 (3H, s), 3.36 (3H, s ), 2.45 (3H, s). FAB-Mass: 453 (M + +1) Example 234 N- (4-chloro-2-nitrophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 234) Yield: 89% Melting point: 205-206 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 10.10 (1H, brs), 8.66 (1H, s), 8.57 (1H, d, J = 9.2 Hz), 8.18 (1H, d, J = 2.3 Hz) , 7.59 (1H, dd, J = 9.2 Hz, 2.3 Hz), 7.26 (1H, s), 7.15 (1H, s), 4.04 (3H, s), 4.02 (3H, s), 4.00-3.82 (8H, m). FAB-Mass: 475 (M + +3), 473 (M + +1) IR (KBr) (cm −1 ): 1686, 1660, 1578, 1508, 1429, 1358, 1335, 1267, 1238, 1209, 991. Example 235 N- (4-chloro-3-nitrophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 235) Yield: 74% 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.81 (1H, brs), 8.56 (1H, s), 8.15 (1H, d, J = 2.3 Hz), 7.76-7.67 (2H, m), 7.25 (1H, s), 7.24 (1H, s), 4.16 (4H, m), 3.94 (3H, s), 3.94 (3H, s), 3.87 (4H, m). FAB-Mass: 491 (M + +3), 489 (M + +1) Example 236 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3,4-dinitrophenyl) -1-piperazinecarboamide (Compound 236) Yield: 82% Melting point: 273-274 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.60 (1H, brs), 8.87 (2H, s), 8.58 (1H, s), 8.40 (1H, s), 7.25 (1H, s), 7.20 (1H, s), 3.94 (3H, s), 3.94 (3H, s), 3.76-3.74 (8H, m). FAB-Mass: 484 (M + +1) IR (KBr) (cm -1 ): 1645, 1535, 1502, 1471, 1427, 1346, 1252, 1209, 1136, 991, 729. Example 237 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4,5-dimethyl-2-nitrophenyl) -1-piperazinecarboamide (Compound 237) Yield: 76% Melting point: 213-215 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 10.28 (1H, brs), 8.70 (1H, s), 8.43 (1H, s), 7.98 (1H, s), 7.28 (1H, s), 7.13 ( 1H, s), 4.04 (3H, s), 4.02 (3H, s), 3.85-3.78 (8H, m), 2.34 (3H, s), 2.27 (3H, s). FAB-Mass: 467 (M + +1) IR (KBr) (cm -1 ): 1686, 1578, 1508, 1448, 1329, 1246, 1209, 993. Example 238 N- (3-cyanophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 238) Yield: 79% Melting point: 169-170 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.58-7.54 (2H, m), 7.48-7.45 (2H, m), 7.27 (1H, s), 7.27 (1H, brs ), 7.11 (1H, s), 4.17-4.15 (4H, m), 4.03 (3H, s), 4.00 (3H, s), 3.91-3.87 (4H, m). FAB-Mass: 435 (M + +1) IR (KBr) (cm- 1 ): 2220, 1578, 1541, 1506, 1479, 1429, 1313, 1240, 1211, 993. Example 239 N- (4-cyanophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 239) Yield: 90% Melting Point: 274-275 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.15 (1H, brs), 8.58 (1H, s), 7.70 (4H, s), 7.24 (1H, s), 7.19 (1H, s), 3.94 (3H, s), 3.94 (3H, s), 3.71-3.70 (8H, m). FAB-Mass: 419 (M + +1) IR (KBr) (cm −1 ): 2222, 1659, 1593, 1524, 1429, 1385, 1360, 1319, 1248, 1234, 1209, 1136, 996, 933, 837. Example 240 N- (4-cyanobenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 240) Yield: 87% Melting point: 186-187 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.58 (2H, d, J = 8.4 Hz), 7.45 (2H, d, J = 8.4 Hz), 7.24 (1H, s) , 7.11 (1H, s), 6.37 (1H, brt, J = 5.4 Hz), 5.03 (2H, d, J = 5.4 Hz), 4.16-4.12 (4H, m), 4.02 (3H, s), 3.98 ( 3H, s), 3.89-3.85 (4H, m). FAB-Mass: 449 (M + +1) IR (KBr) (cm −1 ): 2220, 1543, 1502, 1475, 1414, 1387, 1333, 1236, 1207, 1134, 1014, 989, 931. Example 241 N- (3-acetylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 241) Yield: 71% Melting Point: 192-193 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.80 (1H, brs), 7.75 (1H, d, J = 7.6 Hz), 7.54-7.43 (3H, m), 7.26 ( 1H, s), 7.10 (1H, s), 4.15-4.11 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.88-3.86 (4H, m), 2.60 (3H, s) . FAB-Mass: 452 (M + +1) IR (KBr) (cm −1 ): 1666, 1541, 1506, 1473, 1448, 1425, 1302, 1236, 1203, 1188, 991. Example 242 N- (4-acetylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 242) Yield: 79% Melting point: 256-257 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.69 (1H, brs), 8.55 (1H, s), 7.90 (2H, d, J = 8.3 Hz), 7.52 (2H, d, J = 8.3 Hz), 7.25 (1H, s), 7.24 (1H, s), 4.13 (4H, m), 3.94 (3H, s), 3.94 (3H, s), 3.85 (4H, m), 2.54 (3H, s ). FAB-Mass: 452 (M + +1) IR (KBr) (cm −1 ): 1678, 1574, 1506, 1429, 1358, 1319, 1269, 1240, 1211, 1136, 993, 941, 870. Example 243 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-trifluoroacetylphenyl) -1-piperazinecarboamide (Compound 243) Virtually the same procedure as in Example 164 was repeated except that the corresponding 4-trifluoroacetylbenzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 15% Melting Point: 144-146 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.05 (2H, d, J = 8.4 Hz), 7.59 (2H, d, J = 8.4 Hz), 7.28 (1H, s) , 7.11 (1H, s), 6.80 (1H, brs), 4.04 (3H, s), 4.01 (3H, s), 3.79 (8H, m). FAB-Mass: 490 (M + +1) IR (KBr) (cm −1 ): 1654, 1641, 1589, 1577, 1506, 1473, 1423, 1232, 1207, 1168, 991, 939, 769. Example 244 N- (4-butyrylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 244) Virtually the same procedure as in Example 154 was repeated except that the corresponding 4-butyrylaniline was used in place of 4-isopropylbenzylamine to afford the desired compound. Yield: 86% Melting Point: 218-219 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.69 (1H, brs), 8.55 (1H, s), 7.91 (2H, d, J = 8.9 Hz), 7.51 (2H, d, J = 8.9 Hz), 7.25 (1H, s), 7.24 (1H, s), 4.14-4.12 (4H, m), 3.94 (3H, s), 3.94 (3H, s), 3.86-3.85 (4H, m), 2.96 (2H, t, J = 7.3 Hz), 1.64 (2H, tq, J = 7.3 Hz, 7.3 Hz), 0.93 (3H, t, J = 7.3 Hz). FAB-Mass: 480 (M + +1) IR (KBr) (cm −1 ): 1680, 1576, 1508, 1462, 1429, 1313, 1238, 1211, 993. Example 245 N- (4-benzoylphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 245) Virtually the same procedure as in Example 164 was repeated except that the corresponding 4-benzoylbenzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 55% Melting point: 240-241 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.34 (1H, brs), 8.58 (1H, s), 7.76 (2H, d, J = 8.6 Hz), 7.72 (4H, m), 7.58 ( 1H, m), 7.54 (2H, d, J = 8.6 Hz), 7.24 (1H, s), 7.20 (1H, s), 3.94 (3H, s), 3.94 (3H, s), 3.73-3.71 (8H , m). FAB-Mass: 498 (M + +1) IR (KBr) (cm −1 ): 1637, 1616, 1508, 1473, 1438, 1238, 1211, 991, 848. Example 246 N- (3-carboxyphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 246) Virtually the same procedure as in Example 1 was repeated except that the corresponding 3-carboxyphenylisothiocyanate was used in place of phenylisocyanate to afford the desired compound. Yield: 96% 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.62 (1H, brs), 8.55 (1H, s), 7.94 (1H, s), 7.72 (1H, d, J = 7.6 Hz), 7.48 ( 1H, d, J = 8.3 Hz), 7.32 (1H, dd, J = 8.3 Hz, 7.6 Hz), 7.25 (1H, s), 7.23 (1H, s), 4.16 (4H, m), 3.94 (3H, s), 3.94 (3H, s), 3.85 (4H, m). FAB-Mass: 454 (M + +1) IR (KBr) (cm- 1 ): 3360, 1549, 1506, 1431, 1394, 1338, 1211. Example 247 N- (4-carboxyphenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 247) 390 mg (0.84 mmol) of 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-ethoxycarbonylphenyl) -1-piperazincaramide obtained in Example 89 was added thereto. To a solution dissolved in 10 ml of 1,4-dioxane, 70.4 mg (1.68 mmol) of lithium hydroxide monohydrate and 1 ml of water were added, followed by stirring at room temperature for 4.5 hours. To this mixture is further added 70.4 mg (1.68 mmol) of lithium hydroxide monohydrate and stirred at room temperature overnight. After evaporating the solvent and adding water to the residue, the mixture is adjusted to pH 4 with 4N hydrochloric acid. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel column chromatography to give the title compound as colorless crystals. Yield: 100% 1 H-NMR (DMSO-d 6 ) δ (ppm): 8.86 (1H, brs), 8.57 (1H, s), 7.87 (2H, d, J = 8.3 Hz), 7.50 (2H, d, J = 8.3 Hz), 7.24 (1H, s), 7.20 (1H, s), 3.94 (3H, s), 3.94 (3H, s), 3.70 (4H, m), 3.42 (4H, m). FAB-Mass: 438 (M + +1) IR (KBr) (cm- 1 ): 3360, 1601, 1506, 1412, 1385, 1246, 1213, 993. In Examples 248 and 249 below, virtually the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used in place of phenyl isocyanate to afford the desired compound. Example 248 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-ethoxycarbonylphenyl) -1-piperazincaramide (Compound 248) Yield: 92% Melting Point: 187-188 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.92 (1H, d, J = 1.7 Hz), 7.78-7.71 (2H, m), 7.36 (1H, m), 7.26 ( 1H, s), 7.11 (1H, s), 7.06 (1H, brs), 4.25 (2H, q, J = 7.3 Hz), 4.02 (3H, s), 3.99 (3H, s), 3.75 (8H, m ), 1.37 (3H, t, J = 7.3 Hz). FAB-Mass: 466 (M + +1) IR (KBr) (cm −1 ): 1699, 1668, 1539, 1506, 1489, 1431, 1352, 1300, 1242, 1209, 997, 760. Example 249 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methoxycarbonylphenyl) -1-piperazinthiocarboamide (Compound 249) Yield: 75% Melting Point: 208-209 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 8.02 (2H, d, J = 8.9 Hz), 7.55 (1H, brs), 7.27 (1H, s), 7.22 (2H, d, J = 8.9 Hz), 7.08 (1H, s), 4.09-4.05 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.91 (3H, s), 3.86-3.82 (4H , m). FAB-Mass: 468 (M + +1) IR (KBr) (cm −1 ): 1716, 1578, 1527, 1508, 1477, 1431, 1284, 1211, 991. Example 250 (dl) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methylsulfinylphenyl) -1-piperazinecarboamide (Compound 250) 646.8 mg (1.47 mmol) of 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methylthiophenyl) -1-piperazinecarboamide obtained according to Example 69 above were diluted with 381.4 mg (2.21 mmol) of m-chloroperbenzoic acid was added to a solution dissolved in 15 ml of methane while cooling with ice, and then stirred for 6 hours at the same temperature in an argon atmosphere. 0.1 N sodium thiosulfate aqueous solution is added to the reaction mixture, followed by further stirring at room temperature for 30 minutes. The organic layer is separated, washed with saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfide. The solvent is evaporated and the residue is purified by silica gel column chromatography to give the title compound as colorless crystals. Yield: 72% 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.58 (1H, brs), 7.56 (2H, d, J = 6.3 Hz), 7.29 (1H, s), 7.28 (2H, d, J = 6.3 Hz), 7.11 (1H, s), 4.03 (3H, s), 4.00 (3H, s), 3.77-3.73 (8H, m), 2.72 (3H, s). FAB-Mass: 456 (M + +1) IR (KBr) (cm- 1 ): 1670, 1541, 1508, 1481, 1433, 1242, 1213, 1026, 993. Example 251 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-mesylphenyl) -1-piperazinecarboamide (Compound 251) 780.0 mg (1.78 mmol) of 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-methylthiophenyl) -1-piperazinecarboamide obtained according to Example 69 and m- Except that chloroperbenzoic acid was used, in fact the same procedure as in Example 250 was repeated to afford the title compound as colorless crystals. Yield: 44% Melting point: 266-269 ℃ 1 H-NMR (CDCl 3 + DMSO-d 6 ) δ (ppm): 9.07 (1H, brs), 8.57 (1H, s), 7.77 (4H, m), 7.22 (1H, s), 7.17 (1H, s), 3.97 (3H, s), 3.97 (3H, s), 3.76-3.71 (8H, m), 3.08 (3H, s). FAB-Mass: 472 (M + +1) IR (KBr) (cm −1 ): 1653, 1591, 1533, 1504, 1471, 1419, 1321, 1298, 1236, 1209, 1147, 991, 770. Example 252 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-mesylbenzyl) -1-piperazinthiocarboamide (Compound 252) Virtually the same procedure as in Example 185 was repeated except that a matching 4-mesylbenzylamine was used instead of 4-bromobenzylamine to afford the desired compound. Yield: 83% 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.65 (2H, d, J = 8.2 Hz), 7.38 (2H, d, J = 8.2 Hz), 7.25 (1H, s) , 7.13 (1H, s), 6.89 (1H, brt, J = 5.6 Hz), 5.06 (2H, d, J = 5.6 Hz), 4.20-4.16 (4H, m), 4.03 (3H, s), 4.00 ( 3H, s), 3.90-3.87 (4H, m), 3.01 (3H, s). Example 253 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-sulfamoylbenzyl) -1-piperazinthiocarboamide (Compound 253) Virtually the same procedure as in Example 185 was repeated except that the corresponding 4-sulfamoylbenzylamine was used instead of 4-bromobenzylamine to afford the desired compound. Yield: 66% 1 H-NMR (DMSO-d 6 ) δ (ppm): 8.54 (1H, s), 8.41 (1H, brt, J = 4.3 Hz), 7.76 (2H, d, J = 7.9 Hz), 7.47 (2H, d, J = 7.9 Hz), 7.31 (2H, brs), 7.24 (1H, s), 7.23 (1H, s), 4.87 (2H, d, J = 4.3 Hz), 4.07-4.05 (4H, m), 3.93 (3H, s), 3.93 (3H, s). 3.82-3. 81 (4H, m). FAB-Mass: 503 (M + +1) Example 254 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-piperidinosulfonylphenyl) -1-piperazinthiocarboamide (Compound 254) Virtually the same procedure as in Example 1 was repeated except that the corresponding 4-piperidinosulfonylphenylisothiocyanate was used in place of phenylisocyanate to afford the desired compound. Yield: 100% Melting point: 149-150 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 8.16 (1H, brs), 7.55 (2H, d, J = 8.6 Hz), 7.42 (2H, d, J = 8.6 Hz) , 7.25 (1H, s), 7.12 (1H, s), 4.20-4.17 (4H, m), 4.02 (3H, s), 4.01 (3H, s), 3.91-3.89 (4H, m), 2.99-2.95 (4H, m), 1.63 (4H, m), 1.44-1.42 (2H, m). FAB-Mass: 557 (M + +1) IR (KBr) (cm −1 ): 1593, 1579, 1504, 1477, 1427, 1327, 1242, 1213, 1163, 1093, 991, 737. Example 255 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-furyl) -1-piperazinecarboamide (Compound 255) In fact the same procedure as in Example 265 was repeated except that a matching 2-furoyl chloride was used instead of nicotinoyl chloride to afford the desired compound. Yield: 32% Melting point: 213-215 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.84 (1H, d, J = 1.7 Hz), 7.31 (1H, dd, J = 1.7 Hz, 1.3 Hz), 7.27 (1H) , s), 7.11 (1H, s), 6.33 (1H, d, J = 1.3 Hz), 6.27 (1H, brs), 4.04 (3H, s), 4.00 (3H, s), 3.73 (8H, m) . FAB-Mass: 384 (M + +1) IR (KBr) (cm −1 ): 1637, 1556, 1504, 1475, 1430, 1349, 1336, 1255, 1209, 991. Example 256 4- (6,7-dimethoxy-4-quinazolinyl) -N-fufuryl-1-piperazinecarboamide (Compound 256) Virtually the same procedure as in Example 263 was repeated except that a matching fufurylamine was used in place of 2-picorylamine to afford the desired compound. Yield: 63% Melting Point: 168-170 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.37 (1H, d, J = 1.6 Hz), 7.26 (1H, s), 7.09 (1H, s), 6.34 (1H, dd, J = 3.1 Hz, 1.6 Hz), 6.26 (1H, d, J = 3.1 Hz), 4.84 (1H, brt, J = 5.3 Hz), 4.46 (2H, d, J = 5.3 Hz), 4.03 (3H , s), 3.99 (3H, s), 3.70-3.67 (4H, m), 3.65-3.62 (4H, m). FAB-Mass: 398 (M + +1) IR (KBr) (cm −1 ): 1633, 1542, 1504, 1475, 1430, 1344, 1332, 1238, 1211, 991, 856, 738. Example 257 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-thienyl) -1-piperazinecarboamide (Compound 257) Virtually the same procedure as in Example 265 was repeated except that the matching 3-thiophenecarbonyl chloride was used in place of nicotinic acid chloride to afford the desired compound. Yield: 81% Melting Point: 239-241 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.31 (1H, dd, J = 3.1 Hz, 1.3 Hz), 7.27 (1H, s), 7.23 (1H, dd, J = 5.1 Hz, 3.1 Hz), 7.11 (1H, s), 7.00 (1H, dd, J = 5.1 Hz, 1.3 Hz), 6.72 (1H, brs), 4.04 (3H, s), 4.00 (3H, s), 3.74 (8 H, m). FAB-Mass: 398 (M + +1) IR (KBr) (cm −1 ): 1637, 1535, 1504, 1473, 1411, 1251, 1211, 993, 846, 773. Example 258 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-thienylmethyl) -1-piperazinecarboamide (Compound 258) Virtually the same procedure as in Example 164 was repeated except that the matching 3-thiophenecarboxylic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 48% Melting point: 178-179 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.31 (1H, dd, J = 5.0 Hz, 3.0 Hz), 7.26 (1H, s), 7.19 (1H, dd, J = 3.0 Hz, 1.3 Hz), 7.09 (1H, dd, J = 5.0 Hz, 1.3 Hz), 7.08 (1H, s), 4.78 (1H, brt, J = 5.1 Hz), 4.48 (2H, d, J = 5.1 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.70-3.68 (4H, m), 3.64-3.62 (4H, m). FAB-Mass: 414 (M + +1) IR (KBr) (cm −1 ): 1637, 1556, 1504, 1475, 1430, 1349, 1336, 1255, 1209, 991. Example 259 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-thienylmethyl) -1-piperazinecarboamide (Compound 259) Virtually the same procedure as in Example 263 was repeated except that the corresponding 2-thienylmethylamine was used instead of 2-picorylamine to afford the desired compound. Yield: 42% Melting Point: 168-170 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.27-7.23 (2H, m), 7.10 (1H, s), 7.01-6.95 (2H, m), 4.85 (1H, br ), 4.65 (2H, d, J = 4.0 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.70-3.68 (4H, m), 3.65-3.63 (4H, m). FAB-Mass: 414 (M + +1) IR (KBr) (cm −1 ): 1626, 1544, 1502, 1431, 1350, 1282, 1207, 993, 856. Example 260 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-methoxycarbonyl-3-thienyl) -1-piperazinthiocarbonamide (Compound 260) Virtually the same procedure as in Example 1 was repeated except that the corresponding 3-isothiocyanatothiophene-2-carboxylic acid methyl ester was used in place of phenylisocyanate to afford the desired compound. Yield: 75% Melting Point: 226-228 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 10.82 (1H, brs), 8.77 (1H, d, J = 5.6 Hz), 8.68 (1H, s), 7.48 (1H, d, J = 5.6 Hz) , 7.28 (1H, s), 7.13 (1H, s), 4.32-4.28 (4H, m), 4.04 (3H, s), 4.01 (3H, s), 3.95-3.91 (4H, m), 3.90 (3H , s). FAB-Mass: 474 (M + +1) IR (KBr) (cm −1 ): 1682, 1589, 1502, 1473, 1458, 1425, 1333, 1254, 1203, 1134, 1092, 991, 781. Example 261 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-methoxycarbonyl-4-methyl-3-thienyl) -1-piperazinthiocarbonamide (Compound 261) Virtually the same procedure as in Example 1 was repeated except that the corresponding 3-isothiocyanato-4-methylthiophene-2-carboxylic acid methyl ester was used instead of phenylisocyanate to afford the desired compound. Yield: 78% Melting Point: 113-116 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.54 (1H, brs), 7.29 (1H, s), 7.17 (1H, s), 7.13 (1H, s), 4.30- 4.26 (4H, m), 4.04 (3H, s), 4.01 (3H, s), 3.93-3.89 (4H, m), 3.85 (3H, s), 2.27 (3H, s). FAB-Mass: 488 (M + +1) IR (KBr) (cm −1 ): 1700, 1572, 1504, 1475, 1431, 1346, 1279, 1242, 1209, 991. Example 262 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-pyridyl) -1-piperazinthiocarboamide (Compound 262) Virtually the same procedure as in Example 154 was repeated except that the corresponding 2-aminopyridine was used in place of 4-isopropylbenzylamine to afford the desired compound. Yield: 30% Melting Point: 208-210 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.90 (1H, brs), 8.55 (1H, s), 8.29 (1H, dd, J = 5.3 Hz, 1.3 Hz), 7.71 (1H, ddd, J = 8.1Hz, 7.1Hz, 1.3Hz), 7.61 (1H, d, J = 8.1Hz), 7.24 (1H, s), 7.23 (1H, s), 7.05 (1H, dd, J = 7.1Hz, 5.3 Hz), 4.11 (3H, s), 3.93 (8H, m), 3.83 (3H, s). FAB-Mass: 411 (M + +1) IR (KBr) (cm −1 ): 1577, 1519, 1504, 1477, 1421, 1303, 1236, 1039, 991, 939, 769. Example 263 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-picoryl) -1-piperazinecarboamide (Compound 263) 2-pico in 954 mg (3.30 mmol) of 4-methoxyphenyl-4-nitrophenylcarbonate obtained according to the method described in Synthetic Communications, 26, 331 (1996) in 20 ml of acetonitrile. A solution of 324 mg (3.00 mmol) of rylamine was added to acetonitrile and then stirred at room temperature for 3 hours. To this mixture 548 mg (2.00 mmol) of 6,7-dimethoxy-4-piperazinylquinazoline and 1,8-diazabicyclo [5.4 obtained according to the method described in South African Patent No. 67 06512 (1968). 0.328 ml (2.19 mmol) of .0] -7-undecene are added and then heated to reflux for 3 hours. The reaction mixture is cooled to room temperature, the solvent is evaporated and chloroform is added to the residue. The reaction mixture is washed three times with 10% aqueous sodium hydroxide solution, washed with saturated aqueous sodium chloride solution and then dried over magnesium chloride. After evaporation of the solvent, the residue is purified by silica gel chromatography and recrystallization with ethyl acetate to give the title compound as colorless crystals. Yield: 49% Melting point: 181-182 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 8.55 (1H, d, J = 4.3 Hz), 7.68 (1H, m), 7.30 (1H, d, J = 8.9 Hz) , 7.26 (1H, s), 7.20 (1H, m), 7.12 (1H, s), 6.03 (1H, brt, J = 4.6 Hz), 4.58 (2H, d, J = 4.6 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.71 (8H, m). FAB-Mass: 395 (M + +1) IR (KBr) (cm −1 ): 1631, 1569, 1546, 1504, 1473, 1436, 1344, 1263, 1236, 1209, 1132, 987, 854, 752. Example 264 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-picoryl) -1-piperazinthiocarboamide (Compound 264) Virtually the same procedure as in Example 185 was repeated except that the corresponding 2-picorylamine was used instead of 4-bromobenzylamine to afford the desired compound. Yield: 56% Melting Point: 175-176 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 8.54 (1H, d, J = 5.0 Hz), 7.74-7.68 (2H, m), 7.33-7.22 (3H, m), 7.14 (1H, s), 4.97 (2H, d, J = 3.6 Hz), 4.21-4.17 (4H, m), 4.03 (3H, s), 4.00 (3H, s), 3.91-3.87 (4H, m) . IR (KBr) (cm −1 ): 1576, 1545, 1504, 1477, 1427, 1352, 1242, 1207, 1136, 989, 933, 843. Example 265 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-pyridyl) -1-piperazinecarboamide (Compound 265) To 50 ml of diethyl ether, 50 ml of an aqueous solution of 12.0 g (185 mmol) of sodium azide was added to a suspension of 5.9 g (33 mmol) of nicotinoyl chloride hydrochloride while cooling with ice, followed by vigorous stirring at room temperature. The organic layer is separated and the water layer is extracted with ether. The organic layers are then combined, washed with saturated aqueous sodium chloride solution and dried over magnesium chloride. The solvent is dried below 30 ° C. and the residue is dissolved in 40 ml of toluene. To this solution was added 548 mg (2.00 mmol) of 6,7-dimethoxy-4-piperazinylquinazoline obtained according to the method described in South African Patent No. 67 06512 (1968) and for 3 hours at 70 ° C. Stir while heating. After the reaction mixture is cooled to room temperature and the solvent is evaporated, the residue is purified by silica gel chromatography and recrystallization with ethyl acetate to give the title compound as colorless crystals. Yield: 25% Melting point: 208-209 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.48 (1H, d, J = 2.7 Hz), 8.30 (1H, dd, J = 4.8 Hz, 1.6 Hz), 8.00 (1H) , m), 7.26 (1H, s), 7.25 (1H, m), 7.11 (1H, s), 6.66 (1H, brs), 4.03 (3H, s), 4.00 (3H, s), 3.77 (8H, m). FAB-Mass: 395 (M + +1) IR (KBr) (cm −1 ): 1672, 1575, 1546, 1504, 1483, 1430, 1234, 1201, 1133, 993. Example 266 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-picoryl) -1-piperazinecarboamide (Compound 266) Virtually the same procedure as in Example 119 was repeated except that the matching 3-picorylamine was used instead of 2- (4-chlorophenyl) ethylamine to afford the desired compound. Yield: 12% Melting point: 188-189 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.57 (1H, d, J = 2.3 Hz), 8.53 (1H, dd, J = 5.0 Hz, 1.7 Hz), 7.70 (1H) , ddd, J = 7.9 Hz, 2.3 Hz, 1.7 Hz), 7.30-7.26 (2H, m), 7.09 (1H, s), 5.04 (1H, brt, J = 5.6 Hz), 4.49 (2H, d, J = 5.6 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.71-3.64 (8H, m). FAB-Mass: 409 (M + +1) IR (KBr) (cm −1 ): 1626, 1574, 1537, 1504, 1487, 1435, 1346, 1242, 1213, 1136, 993, 849, 716. Example 267 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-pyridyl) -1-piperazincarboamide (Compound 267) Virtually the same procedure as in Example 265 was repeated except that the corresponding carboxylic acid chloride was used instead of nicotinoyl chloride to afford the desired compound. Yield: 76% Melting Point: 141-143 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.46 (2H, d, J = 4.9 Hz), 7.37 (2H, d, J = 4.9 Hz), 7.26 (1H, s) , 7.11 (1 H, s), 6.71 (1 H, brs), 4.04 (3 H, s), 4.01 (3 H, s), 3.77 (8 H, m). FAB-Mass: 395 (M + +1) IR (KBr) (cm −1 ): 1660, 1579, 1546, 1508, 1475, 1430, 1240, 1213, 989, 939, 852, 827. Example 268 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-pyridyl) -1-piperazinthiocarboamide (Compound 268) Virtually the same procedure as in Example 154 was repeated except that the corresponding 4-aminopyridine was used in place of 4-isopropylbenzylamine to afford the desired compound. Yield: 43% Melting Point: 218-220 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.52 (2H, d, J = 6.3 Hz), 7.28 (1H, s), 7.26 (1H, brs), 7.08 (1H, s), 7.07 (2H, d, J = 6.3 Hz), 4.10-4.07 (4H, m), 4.04 (3H, s), 4.00 (3H, s), 3.88-3.64 (4H, m). FAB-Mass: 411 (M + +1) IR (KBr) (cm −1 ): 1580, 1508, 1479, 1425, 1405, 1344, 1251, 1207, 1141, 991, 944, 852, 821. Example 269 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-picoryl) -1-piperazinecarboamide (Compound 269) Virtually the same procedure as in Example 119 was repeated except that the corresponding 4-picorylamine was used instead of 2- (4-chlorophenyl) ethylamine to afford the desired compound. Yield: 45% 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 8.53 (2H, d, J = 5.3 Hz), 7.28 (1H, s), 7.23 (2H, d, J = 5.3 Hz) , 7.10 (1H, s), 5.35 (1H, brt, J = 5.9 Hz), 4.48 (2H, d, J = 5.9 Hz), 4.02 (3H, s), 3.99 (3H, s), 3.70-3.69 ( 8H, m). FAB-Mass: 409 (M + +1) Example 270 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-picoryl) -1-piperazinthiocarboamide (Compound 270) Virtually the same procedure as in Example 1 was repeated except that a matching 4-picorylisothiocyanate was used in place of phenylisocyanate to afford the desired compound. Yield: 59% Melting Point: 236-239 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 8.57 (2H, d, J = 5.7 Hz), 7.27 (2H, d, J = 5.7 Hz), 7.26 (1H, s) , 7.11 (1H, s), 6.09 (1H, brt, J = 5.3 Hz), 5.00 (2H, d, J = 5.3), 4.16-4.12 (4H, m), 4.03 (3H, s), 3.99 (3H , s), 3.91-3.87 (4H, m). FAB-Mass: 425 (M + +1) IR (KBr) (cm −1 ): 1577, 1535, 1504, 1479, 1430, 1336, 1241, 1211, 1135, 993, 935, 865, 798. In Examples 271-273 below, virtually the same procedure as in Example 265 was repeated except that a matching carboxylic acid halide was used instead of nicotinoyl chloride to afford the desired compound. Example 271 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-methyl-5-pyridyl) -1-piperazincarboamide (Compound 271) Yield: 6% Melting point: 240-241 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.35 (1H, d, J = 2.6 Hz), 7.88 (1H, dd, J = 8.8 Hz, 2.6 Hz), 7.27 (1H) , s), 7.12 (1H, d, J = 8.8 Hz), 7.11 (1H, s), 6.46 (1H, brs), 4.04 (3H, s), 4.01 (3H, s), 3.77 (8H, m) , 2.52 (3H, s). FAB-Mass: 409 (M + +1) IR (KBr) (cm- 1 ): 1676, 1618, 1504, 1448, 1429, 1236, 1209, 993. Example 272 N- (2-chloro-5-pyridyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 272) Yield: 53% Melting Point: 238-240 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.27 (1H, d, J = 2.6 Hz), 8.01 (1H, dd, J = 8.5 Hz, 2.6 Hz), 7.29 (1H) , d, J = 8.5 Hz), 7.26 (1H, s), 7.11 (1H, s), 6.62 (1H, brs), 4.04 (3H, s), 4.00 (3H, s), 3.77 (8H, m) . FAB-Mass: 431 (M + +3), 429 (M + +1) IR (KBr) (cm- 1 ): 1637, 1571, 1508, 1465, 1351, 1240, 1213, 995. Example 273 N- (2-cyano-5-pyridyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 273) Yield: 12% Melting point: 275-277 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.38 (1H, brs), 8.83 (1H, d, J = 2.3 Hz), 8.58 (1H, s), 8.14 (1H, dd, J = 8.9 Hz, 2.3 Hz), 7.91 (1H, d, J = 8.9 Hz), 7.25 (1H, s), 7.20 (1H, s), 3.93 (3H, s), 3.93 (3H, s), 3.73 (8H, m). FAB-Mass: 420 (M + +1) IR (KBr) (cm- 1 ): 2233, 1666, 1575, 1523, 1427, 1236, 1211, 1135, 993. Example 274 N- (2,6-dichloro-4-pyridyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 274) Virtually the same procedure as in Example 1 was repeated except that the corresponding 2,6-dichloro-4-pyridylisocyanate was used instead of phenylisocyanate to afford the desired compound. Yield: 56% Melting point: 267-270 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.61 (1H, brs), 7.44 (2H, s), 7.28 (1H, s), 7.09 (1H, s), 4.03 ( 3H, s), 4.00 (3H, s), 3.75 (8H, m). FAB-Mass: 467 (M + +5), 465 (M + +3), 463 (M + +1) IR (KBr) (cm- 1 ): 1682, 1578, 1504, 1477, 1431, 1248, 1215, 1163, 1099, 991, 845. Example 275 N- (3-chloro-5-trifluoromethyl-2-picoryl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 275) In fact the same procedure as in Example 119 was repeated except that the corresponding 3-chloro-5-trifluoromethyl-2-picorylamine was used instead of 2- (4-chlorophenyl) ethylamine to afford the desired compound. It was. Yield: 40% 1 H-NMR (CDCl 3 ) δ (ppm): 8.83 (1H, s), 8.62 (1H, s), 8.01 (1H, s), 7.27 (1H, br), 7.27 (1H, s), 7.10 ( 1H, s), 5.06 (2H, d, J = 4.0 Hz), 4.07 (3H, s), 4.03-3.97 (8H, m), 4.01 (3H, s). Example 276 N- (3-chloro-5-trifluoromethyl-2-picoryl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 276) Virtually the same procedure as in Example 185 was repeated except that the matching 3-chloro-5-trifluoromethyl-2-picorylamine was used instead of 4-bromobenzylamine to afford the desired compound. Yield: 76% Melting point: 182-183 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.76 (1H, d, J = 1.7 Hz), 8.67 (1H, s), 8.00 (1H, d, J = 1.7 Hz), 7.60 (1H, br) , 7.27 (1H, s), 7.14 (1H, s), 5.10 (2H, d, J = 2.6 Hz), 4.27-4.18 (4H, m), 4.04 (3H, s), 4.00 (3H, s), 3.98-3.89 (4H, m). FAB-Mass: 529 (M + +3), 527 (M + +1) IR (KBr) (cm −1 ): 1506, 1475, 1448, 1429, 1354, 1329, 1234, 1209, 1134, 1122, 1095, 1061, 993. Example 277 N- (2,6-dihydroxy-4-pyrimidinyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 277) Virtually the same procedure as in Example 1 was repeated except that the corresponding 2,6-dihydroxy-4-pyrimidinylisothiocyanate was used in place of phenylisocyanate to afford the desired compound. Yield: 40% Melting point: 283-285 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 11.25 (1H, br), 10.85 (1H, br), 8.65 (1H, brs), 8.54 (1H, s), 7.46 (1H, s), 7.24 (1H, s), 7.23 (1H, s), 4.11 (4H, m), 3.94 (3H, s), 3.94 (3H, s), 3.83 (4H, m). FAB-Mass: 444 (M + +1) IR (KBr) (cm- 1 ): 1682, 1504, 1483, 1433, 1346, 1207, 991. Example 278 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-methyl-2-pyrazinylmethyl) -1-piperazinecarboamide (Compound 278) Virtually the same procedure as in Example 263 was repeated except that the corresponding 3-methyl-2-pyrazinylmethylamine was used instead of 2-picorylamine to afford the desired compound. Yield: 59% Melting point: 202-204 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.52 (1H, s), 8.39 (1H, s), 7.26 (1H, s), 7.10 (1H, s), 5.65 ( 1H, brt, J = 4.9 Hz, 4.58 (2H, d, J = 4.9 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.69 (8H, m), 2.57 (3H, s). FAB-Mass: 424 (M + +1) IR (KBr) (cm- 1 ): 1648, 1504, 1450, 1423, 1243, 1205, 993. Example 279 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2,3,4,5-tetrahydro-2-oxo-3-furyl) -1-piperazinecarboamide (Compound 279 ) Virtually the same procedure as in Example 1 was repeated except that the corresponding 2,3,4,5-tetrahydro-2-oxo-3-furylisocyanate was used instead of phenylisocyanate to afford the desired compound. Yield: 73% Melting Point: 147-148 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.27 (1H, s), 7.11 (1H, s), 6.47 (1H, d, J = 5.6 Hz), 5.40 (1H, m), 4.51 (1H, m), 4.31 (1H, m), 4.17-4.09 (4H, m), 4.04 (3H, s), 4.00 (3H, s), 3.88-3.80 (4H, m), 3.13 (1 H, m), 2.17 (1 H, m). FAB-Mass: 418 (M + +1) IR (KBr) (cm −1 ): 1774, 1578, 1508, 1481, 1427, 1348, 1211, 1140, 1020, 991, 941. Example 280 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (1-pyrrolyl) phenyl] -1-piperazinecarboamide (Compound 280) In fact the same procedure as in Example 164 was repeated except that the corresponding 4- (1-pyrrolyl) benzoic acid was used instead of 4-vinylbenzoic acid to afford the desired compound. Yield: 98% Melting Point: 224-226 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.44 (2H, d, J = 8.9 Hz), 7.33 (2H, d, J = 8.9 Hz), 7.26 (1H, s) , 7.12 (1H, s), 7.04 (2H, d, J = 2.2 Hz), 6.59 (1H, brs), 6.33 (2H, d, J = 2.2 Hz), 4.04 (3H, s), 4.00 (3H, s), 3.77 (8H, m). FAB-Mass: 459 (M + +1) IR (KBr) (cm −1 ): 1656, 1523, 1427, 1328, 1309, 1232, 1205, 991, 846, 723. Example 281 4- (6,7-dimethoxy-4-quinazolinyl) -N- {4- [5- (1,2,3-thiadiazolyl)] phenyl} -1-piperazinthiocarboamide (compound 281) Virtually the same procedure as in Example 154 was repeated except that the corresponding 4- [5- (1,2,3-thiadiazoryl) benzylamine was used instead of 4-isopropylbenzylamine to afford the desired compound. Yield: 96% Melting Point: 225-226 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.58 (1H, s), 8.54 (1H, s), 8.38 (1H, br), 8.09 (2H, d, J = 7.9 Hz), 7.49 ( 2H, d, J = 7.9 Hz), 7.24 (1H, s), 7.23 (1H, s), 4.89 (2H, br), 4.08-3.99 (4H, m), 3.93 (3H, s), 3.93 (3H , s), 3.88-3.81 (4H, m). FAB-Mass: 508 (M + +1) IR (KBr) (cm −1 ): 1508, 1479, 1456, 1427, 1363, 1346, 1238, 1132, 991. Example 282 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (4-picoryl) phenyl] -1-piperazinthiocarboamide (Compound 282) Virtually the same procedure as in Example 154 was repeated except that the corresponding 4-picorynyline was used in place of 4-isopropylbenzylamine to afford the desired compound. Yield: 67% Melting point: 198-200 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 8.50 (2H, d, J = 4.6 Hz), 7.49 (1H, brs), 7.27 (1H, s), 7.19-7.09 ( 7H, m), 4.13-4.08 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.95 (2H, s), 3.87-3.83 (4H, m). FAB-Mass: 501 (M + +1) IR (KBr) (cm- 1 ): 1502, 1475, 1419, 1344, 1230, 1209, 991. Example 283 4- (6,7-dimethoxy-4-quinazolinyl) -N- [2- (1-pyrrolyl) -5-pyridyl] -1-piperazinecarboamide (Compound 283) In fact the same procedure as in Example 265 was repeated except that the matching 2- (1-pyrrolyl) pyridine-5-carboxylic acid chloride was used in place of nicotinoyl chloride to afford the desired compound. Yield: 60% Melting Point: 252-254 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 8.27 (1H, d, J = 2.5 Hz), 8.06 (1H, dd, J = 8.9 Hz, 2.5 Hz), 7.45 (2H , d, J = 2.2 Hz, 7.30 (1H, d, J = 8.9 Hz), 7.28 (1H, s), 7.12 (1H, s), 6.51 (1H, brs), 6.35 (2H, d, J = 2.2 Hz), 4.04 (3H, s), 4.01 (3H, s), 3.78 (8H, m). FAB-Mass: 460 (M + +1) IR (KBr) (cm −1 ): 1646, 1540, 1502, 1429, 1245, 1234, 1211, 993. Example 284 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-thiocyanatophenyl) -1-piperazinthiocarboamide (Compound 284) Virtually the same procedure as in Example 154 was repeated except that the corresponding 4-thiocyanatoaniline was used in place of 4-isopropylbenzylamine to afford the desired compound. Yield: 58% 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.74 (1H, brs), 7.50 (2H, d, J = 8.6 Hz), 7.34 (2H, d, J = 8.6 Hz) , 7.25 (1H, s), 7.10 (1H, s), 4.26-4.11 (4H, m), 4.02 (3H, s), 3.99 (3H, s), 3.88-3.85 (4H, m). FAB-Mass: 467 (M + +1) In Examples 285 and 286 below, 4- (1-piperazinyl) quinazoline is used instead of 6,7-dimethoxy-4-piperazinylquinazoline, and a matching isothiocyanate is used in place of phenylisocyanate Except for that, in fact the same procedure as in Example 1 was repeated to obtain the target compound. Example 285 N-benzyl-4- (4-quinazolinyl) -1-piperazinthiocarboamide (Compound 285) Yield: 52% Melting point: 68-70 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.90-7.83 (2H, m), 7.74 (1H, m), 7.47 (1H, m), 7.34-7.21 (5H, m ), 6.70 (1H, brt, J = 5.3 Hz), 4.90 (2H, d, J = 5.3 Hz), 4.11-4.08 (4H, m), 3.94-3.91 (4H, m). FAB-Mass: 364 (M + +1) IR (KBr) (cm −1 ): 1568, 1539, 1500, 1444, 1402, 1348, 1012, 939, 773, 698. Example 286 N- (3-Picoryl) -4- (4-quinazolinyl) -1-piperazinthiocarboamide (Compound 286) Yield: 61% Melting Point: 193-194 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 8.43-8.39 (2H, m), 7.91-7.83 (2H, m), 7.78-7.71 (2H, m), 7.48 (1H) , ddd, J = 7.9 Hz, 7.3 Hz, 0.7 Hz), 7.29-7.21 (2H, m), 4.93 (2H, d, J = 5.3 Hz), 4.18-4.14 (4H, m), 3.97-3.93 (4H , m). FAB-Mass: 365 (M + +1) IR (KBr) (cm- 1 ): 1568, 1537, 1495, 1400, 1346, 1325, 1236, 1005, 775. In Examples 287 and 288 below, 5-methyl-4- (1-piperazinyl) quinazolin is used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline, and instead of phenylisocyanate Virtually the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used to afford the desired compound. Example 287 4- (5-methyl-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 287) Yield: 80% Melting Point: 187-188 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.72 (1H, d, J = 8.3 Hz), 7.61 (1H, dd, J = 8.3 Hz, 6.9 Hz), 7.36-7.23 (6H, m), 7.03 (1H, m), 6.95-6.88 (4H, m), 3.72-3.53 (6H, m), 3.42-3.38 (2H, m), 2.73 (3H, s). FAB-Mass: 440 (M + +1) IR (KBr) (cm −1 ): 1641, 1541, 1508, 1489, 1419, 1250, 1217, 997. Example 288 N-benzyl-4- (5-methyl-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 288) Yield: 84% Melting point: 165-167 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.55 (1H, s), 7.69-7.58 (2H, m), 7.31-7.19 (6H, m), 6.60 (1H, brt, J = 5.0 Hz), 4.87 (2H, doublet, J = 5.0 Hz), 3.98-3.94 (4H, m), 3.70-3.61 (2H, br), 3.48 (2H, br), 2.72 (3H, s). FAB-Mass: 378 (M + +1) IR (KBr) (cm −1 ): 1541, 1491, 1439, 1414, 1341, 1236, 1009, 818, 700. In Examples 289-291 below, 5-chloro-4- (1-piperazinyl) quinazoline is used instead of 6,7-dimethoxy-4-piperazinylquinazoline, and the corresponding isocyanate or Except that the isothiocyanate was used, in fact the same procedure as in Example 1 was repeated to give the desired compound. Example 289 4- (5-chloro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazincarboamide (Compound 289) Yield: 33% 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.82 (1H, d, J = 7.3 Hz), 7.64 (1H, dd, J = 7.9 Hz, 7.3 Hz), 7.51 (1H) , dd, J = 7.9 Hz, 1.3 Hz), 7.33-7.27 (4H, m), 7.06 (1H, m), 6.98-6.95 (4H, m), 6.62 (1H, brs), 3.82-3.54 (8H, m). FAB-Mass: 462 (M + +3), 460 (M + +1) Example 290 N-benzyl-4- (5-chloro-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 290) Yield: 90% 1 H-NMR (CDCl 3 ) δ (ppm): 8.58 (1H, s), 7.77 (1H, dd, J = 8.3 Hz, 1.3 Hz), 7.62 (1H, dd, J = 8.3 Hz, 7.6 Hz), 7.49 (1H, dd, J = 7.6 Hz, 1.3 Hz), 7.33-7.24 (5H, m), 6.34 (1H, brt, J = 5.0 Hz), 4.88 (2H, d, J = 5.0 Hz), 4.01 ( 4H, m). FAB-Mass: 400 (M + +3), 398 (M + +1) Example 291 4- (5-Chloro-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide dihydrochloride (Compound 291) Yield: 30% Melting Point: 150-152 ℃ (HCl) 1 H-NMR (free base, CDCl 3 ) δ (ppm): 8.61 (1H, s), 8.47 (1H, dd, J = 4.9 Hz, 1.7 Hz), 8.41 (1H, d, J = 2.3 Hz), 7.79 (1H, dd, J = 8.6 Hz, 1.3 Hz), 7.78 (1H, dd, J = 7.9 Hz, 2.3 Hz, 1.7 Hz), 7.63 (1H, dd, J = 8.6 Hz, 7.6 Hz), 7.50 ( 1H, dd, J = 7.6Hz, 1.3Hz), 7.25 (1H, dd, J = 7.9Hz, 4.9Hz), 6.66 (1H, brt, J = 5.0Hz), 4.93 (2H, d, J = 5.0Hz ), 4.06 (4H, m), 3.86-3.72 (2H, br), 3.70-3.57 (2H, br). FAB-Mass: 401 (M + +3), 399 (M + +1) IR (KBr hydrochloric acid) (cm -1 ): 1605, 1539, 1414, 1389, 1360, 1327, 1279, 683. In Example 292-295 below, 6-methyl-4- (1-piperazinyl) quinazolin is used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin and instead of phenylisocyanate Virtually the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used to afford the desired compound. Example 292 4- (6-Methyl-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazincarboamide (Compound 292) Yield: 85% Melting Point: 244-246 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 7.81 (1H, d, J = 8.6 Hz), 7.64 (1H, d, J = 1.3 Hz), 7.58 (1H, dd, J = 8.6 Hz, 1.3 Hz), 7.35 (2H, d, J = 8.9 Hz), 7.36-7.23 (3H, m), 7.04 (1H, m), 6.96-6.92 (4H, m), 3.77-3.75 ( 8H, m), 2.51 (3H, s). FAB-Mass: 440 (M + +1) IR (KBr) (cm −1 ): 1641, 1605, 1580, 1508, 1489, 1263, 1234, 833, 750, 694. Example 293 4- (6-methyl-4-quinazolinyl) -N- (4-nitrophenyl) -1-piperazincarboamide (Compound 293) Yield: 52% Melting point: 126-129 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 8.13 (2H, d, J = 9.2 Hz), 7.87 (1H, s), 7.81 (1H, d, J = 7.6 Hz) 7.62 (1H, d, J = 7.6 Hz), 7.60 (2H, d, J = 9.2 Hz), 3.82 (8H, m), 2.53 (3H, s). FAB-Mass: 393 (M + +1) IR (KBr) (cm- 1 ): 1672, 1558, 1512, 1500, 1479, 1419, 1335, 1304, 1261. Example 294 N-benzyl-4- (6-methyl-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 294) Yield: 46% 1 H-NMR (CDCl 3 + DMSO-d 6 ) δ (ppm): 8.64 (1H, s), 7.80-7.49 (4H, m), 7.38-7.21 (5H, m), 4.95 (2H, d, J = 5.3 Hz), 4.17-4.13 (4H, m), 3.94-3.90 (4H, m), 2.52 (3H, s). Example 295 4- (6-Methyl-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 295) Yield: 71% Melting point: 128-129 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 8.51-8.49 (2H, m), 7.82-7.76 (2H, m), 7.66 (1H, d, J = 1.7 Hz), 7.59 (1H, dd, J = 8.6 Hz, 1.7 Hz), 7.28 (1H, m), 6.46 (1H, brt, J = 5.3 Hz), 4.96 (2H, d, J = 5.3 Hz), 4.16-4.12 ( 4H, m), 3.96-3.92 (4H, m), 2.52 (3H, s). FAB-Mass: 379 (M + +1) IR (KBr) (cm −1 ): 1574, 1539, 1512, 1479, 1446, 1431, 1406, 1387, 1356, 1331. In Example 296-299 below, 6-fluoro-4- (1-piperazinyl) quinazolin is used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin and instead of phenylisocyanate Virtually the same procedure as in Example 1 was repeated except that isocyanate or isothiocyanate was used to obtain the desired compound. Example 296 4- (6-Fluoro-4-quinazolinyl) -N- (4-isopropylphenyl) -1-piperazinecarboamide (Compound 296) Yield: 39% Melting Point: 139-140 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.77 (1H, s), 7.95 (1H, m), 7.59-7.51 (2H, m), 7.28 (2H, d, J = 8.6 Hz), 7.18 ( 2H, d, J = 8.6 Hz), 6.34 (1H, brs), 3.86-3.82 (4H, m), 3.77-3.73 (4H, m), 2.88 (1H, m), 1.23 (6H, d, J = 6.9 Hz). FAB-Mass: 394 (M + + +1) IR (KBr) (cm- 1 ): 1645, 1538, 1506, 1419, 1247, 1238, 995, 908, 838, 829. Example 297 4- (6-Fluoro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 297) Yield: 42% Melting point: 186-187 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.77 (1H, s), 7.97 (1H, m), 7.59-7.51 (2H, m), 7.37-7.26 (4H, m), 7.10 (1H, m ), 7.00-6.96 (4H, m), 6.43 (1H, brs), 3.86-3.82 (4H, m), 3.77-3.73 (4H, m). FAB-Mass: 444 (M + +1) IR (KBr) (cm −1 ): 1641, 1589, 1571, 1542, 1506, 1415, 1230, 995, 908, 837. Example 298 N- (4-acetylphenyl) -4- (6-fluoro-4-quinazolinyl) -1-piperazinecarboamide (Compound 298) Yield: 25% Melting point: 184-185 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.77 (1H, s), 7.95 (1H, m), 7.94 (2H, d, J = 8.9 Hz), 7.60-7.48 (2H, m), 7.51 ( 2H, d, J = 8.9 Hz), 6.69 (1H, brs), 3.87-3.84 (4H, m), 3.80-3.77 (4H, m), 2.58 (3H, s). FAB-Mass: 394 (M + +1) IR (KBr) (cm −1 ): 1648, 1645, 1544, 1513, 1419, 1355, 1242, 993, 838. Example 299 4- (6-Fluoro-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 299) Yield: 36% Melting point: 170-172 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.72 (1H, s), 8.59 (1H, d, J = 1.6 Hz), 8.56 (1H, dd, J = 4.9 Hz, 1.6 Hz), 7.95 (1H) , m), 7.77 (1H, ddd, J = 7.2 Hz, 1.6 Hz, 1.6 Hz), 7.57 (1 H, m), 7.52 (1 H, m), 7.30 (1 H, m), 5.86 (1 H, brt, J = 4.9 Hz) 4.97 (2H, d, J = 4.9 Hz), 4.14-4.11 (4H, m), 3.98-3.94 (4H, m). FAB-Mass: 383 (M + +1) IR (KBr) (cm -1 ): 1556, 1508, 1405, 1257, 1213, 1018, 910, 835, 711. In Examples 300-302 below, 6-chloro-4- (1-piperazinyl) quinazolin is used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin and instead of phenylisocyanate Virtually the same procedure as in Example 1 was repeated except that matching isocyanates were used to afford the desired compound. Example 300 4- (6-Chloro-4-quinazolinyl) -N- (4-isopropylphenyl) -1-piperazinecarboamide (Compound 300) Yield: 29% Melting Point: 192-193 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.76 (1H, s), 7.90-7.87 (2H, m), 7.70 (1H, dd, J = 9.2 Hz, 2.3 Hz), 7.28 (2H, d, J = 9.0 Hz), 7.17 (2H, d, J = 9.0 Hz), 6.35 (1H, brs), 3.89-3.86 (4H, m), 3.78-3.73 (4H, m), 2.88 (1H, m), 1.23 (6H, doublet, J = 6.9 Hz). FAB-Mass: 412 (M + +3), 410 (M + +1) IR (KBr) (cm- 1 ): 1643, 1594, 1535, 1502, 1419, 1245, 991, 835. Example 301 4- (6-Chloro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazincarboamide (Compound 301) Yield: 35% Melting point: 116-120 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.89 (1H, s), 7.90 (1H, d, J = 1.3 Hz), 7.85 (1H, dd, J = 8.1 Hz, 1.3 Hz), 7.43 (1H) , d, J = 8.1 Hz), 7.35-7.28 (4H, m), 7.10 (1H, m), 7.01-6.97 (4H, m), 6.36 (1H, brs), 3.93-3.89 (4H, m), 3.77-3.73 (4H, m). FAB-Mass: 462 (M + +3), 460 (M + +1) IR (KBr) (cm- 1 ): 1648, 1539, 1506, 1488, 1417, 1224, 993, 946. Example 302 N- (4-acetylphenyl) -4- (6-chloro-4-quinazolinyl) -1-piperazincarboamide (Compound 302) Yield: 18% Melting Point: 207-208 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.77 (1H, s), 7.94 (2H, d, J = 8.9 Hz), 7.92-7.82 (2H, m), 7.51 (2H, d, J = 8.9 Hz), 7.45 (1H, m), 6.64 (1H, brs), 3.96-3.92 (4H, m), 3.82-3.78 (4H, m) 2.59 (3H, s). FAB-Mass: 412 (M + +3), 410 (M + +1) IR (KBr) (cm -1 ): 1677, 1668, 1527, 1495, 1270, 1234, 1172, 993, 950, 839, 777. Example 303 4- (6-Bromo-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 303) Substantially the same as in Example 60 except that 6-bromo-4- (1-piperazinyl) quinazolin was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline The procedure was repeated to yield the target compound. Yield: 29% Melting point: 169-170 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.77 (1H, s), 8.05 (1H, d, J = 1.0 Hz), 7.87-7.79 (2H, m), 7.37-7.28 (4H, m), 7.08 (1H, m), 7.02-6.96 (4H, m), 6.44 (1H, brs), 3.90-3.85 (4H, m), 3.79-3.63 (4H, m). FAB-Mass: 506 (M + +3), 504 (M + +1) IR (KBr) (cm- 1 ): 1633, 1531, 1504, 1489, 1416, 1227, 833. In Examples 304-306 below, 6-iodine-4- (1-piperazinyl) quinazolin instead of phenylisocyanate in place of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin is phenyl Virtually the same procedure as in Example 1 was repeated except that matching isocyanates or isocyanates were used instead of isocyanates to afford the desired compounds. Example 304 4- (6-iodine-4-quinazolinyl) -N- (4-isopropylphenyl) -1-piperazinecarboamide (Compound 304) Yield: 14% Melting Point: 211-212 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.76 (1H, s), 8.26 (1H, d, J = 1.8 Hz), 8.00 (1H, dd, J = 8.9 Hz, 1.8 Hz), 7.66 (1H) , d, J = 8.9 Hz, 7.28 (2H, d, J = 8.6 Hz), 7.17 (2H, d, J = 8.6 Hz), 6.36 (1H, brs), 3.90-3.86 (4H, m), 3.76 -3.72 (4H, m), 2.88 (1H, m), 1.23 (6H, d, J = 6.9 Hz). FAB-Mass: 502 (M + +1) IR (KBr) (cm −1 ): 1643, 1594, 1556, 1531, 1496, 1417, 1245, 991, 831. Example 305 4- (6-iodine-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 305) Yield: 43% Melting point: 184-185 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.76 (1H, s), 8.27 (1H, d, J = 2.0 Hz), 8.00 (1H, dd, J = 8.9 Hz, 2.0 Hz), 7.66 (1H) , d, J = 8.9 Hz), 7.36-7.28 (4H, m), 7.08 (1H, m), 7.01-6.97 (4H, m), 6.40 (1H, brs), 3.91-3.87 (4H, m), 3.77-3.73 (4H, m). FAB-Mass: 552 (M + +1) IR (KBr) (cm −1 ): 1637, 1540, 1508, 1488, 1413, 1226, 1012, 993, 840. Example 306 N- (4-acetylphenyl) -4- (6-iodine-4-quinazolinyl) -1-piperazincarboamide (Compound 306) Yield: 7% 1 H-NMR (CDCl 3 ) δ (ppm): 8.78 (1H, s), 8,27 (1H, d, J = 1.6 Hz), 8.01 (1H, dd, J = 8.9 Hz, 1.6 Hz), 7.93 (2H, d, J = 8.5 Hz), 7.67 (1H, d, J = 8.9 Hz), 7.50 (2H, d, J = 8.5 Hz), 6.68 (1H, brs), 3.92-3.88 (4H, m) , 3.80-3.76 (4H, m), 2.58 (3H, s). FAB-Mass: 502 (M + +1) In Examples 307-310 below, 6-methoxy-4- (1-piperazinyl) quinazolin instead of phenylisocyanate in place of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin Virtually the same procedure as in Example 1 was repeated except that matching isocyanates or isocyanates were used instead of phenylisocyanates to afford the desired compounds. Example 307 4- (6-methoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazincarboamide (Compound 307) Yield: 100% Melting Point: 139-140 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.86 (1H, d, J = 8.9 Hz), 7.43 (1H, dd, J = 8.9 Hz, 2.3 Hz), 7.35-7.25 (4H, m), 7.14 (1H, d, J = 2.3 Hz), 7.07-7.01 (2H, m), 6.96-6.93 (4H, m), 3.90 (3H, s), 3.74 (8H, m). FAB-Mass: 456 (M + +1) IR (KBr) (cm- 1 ): 1637, 1539, 1508, 1489, 1417, 1227, 843. Example 308 4- (6-methoxy-4-quinazolinyl) -N- (4-nitrophenyl) -1-piperazinecarboamide (Compound 308) Yield: 76% Melting Point: 228-229 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.12 (2H, d, J = 9.2 Hz), 7.89 (1H, brs), 7.85 (1H, d, J = 8.9 Hz) , 7.59 (2H, d, J = 9.2 Hz), 7.44 (1H, dd, J = 8.9 Hz, 2.6 Hz), 7.15 (1H, d, J = 2.6 Hz), 3.92 (3H, s), 3.80-3.79 (8H, m). FAB-Mass: 409 (M + +1) IR (KBr) (cm -1 ): 1651, 1541, 1502, 1475, 1417, 1325, 1240, 1109, 985, 841. Example 309 N-benzyl-4- (6-methoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 309) Yield: 79% Melting point: 68-70 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.59 (1H, s), 7.82 (1H, d, J = 9.2 Hz), 7.43 (1H, dd, J = 9.2 Hz, 2.3 Hz), 7.35-7.24 (5H, m), 7.15 (1H, d, J = 2.3 Hz), 6.68 (1H, brt, J = 4.6 Hz), 4.91 (2H, d, J = 4.6 Hz), 4.10-4.09 (4H, m) , 3.91 (3H, s), 3.89-3.87 (4H, m). FAB-Mass: 394 (M + +1) IR (KBr) (cm- 1 ): 1541, 1508, 1448, 1335, 1228. Example 310 4- (6-methoxy-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 310) Yield: 81% Melting Point: 139-140 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.59 (1H, s), 8.42-8.40 (2H, m), 7.80-7.75 (2H, m), 7.41 (1H, dd, J = 8.9 Hz, 2.3 Hz), 7.34 (1H, br), 7.24 (1H, dd, J = 7.9 Hz, 4.9 Hz), 7.14 (1H, d, J = 2.3 Hz), 4.94 (2H, d, J = 5.3 Hz), 4.16 -4.14 (4H, m), 3.90 (3H, s), 3.90-3.87 (4H, m). FAB-Mass: 395 (M + +1) IR (KBr) (cm −1 ): 1549, 1502, 1425, 1406, 1257, 1227, 1016, 943, 849, 714. Example 311 4- (6-Nitro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazincarboamide (Compound 311) In fact the same procedure as in Example 60 except that 6-nitro-4- (1-piperazinyl) quinazolin was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline Was repeated to obtain the target compound. Yield: 98% Melting Point: 170-171 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.89 (1H, brs), 8.77 (1H, s), 8.51 (1H, d, J = 8.9 Hz), 8.29 (1H, s), 7.98 (1H, d, J = 8.9 Hz), 7.47-7.44 (2H, m), 7.34-7.28 (2H, m), 7.06 (1H, m), 6.97-6.94 (4H, m), 4.14-4.11 (4H, m) , 4.09-4.06 (4H, m). FAB-Mass: 471 (M + +1) IR (KBr) (cm -1 ): 1633, 1581, 1506, 1416, 1356, 1325, 1225, 847, 748. In Examples 312-315 below, 7-methyl-4- (1-piperazinyl) quinazolin instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline is substituted for phenylisocyanate In fact, the same procedure as in Example 1 was repeated except that an isocyanate or isothiocyanate was used to obtain the target compound. Example 312 4- (7-methyl-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazincarboamide (Compound 312) Yield: 93% Melting point: 184-185 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.72 (1H, s), 7.79 (1H, d, J = 8.6 Hz), 7.69 (1H, s), 7.37-7.26 (5H, m), 7.06 ( 1H, m), 6.99-6.93 (4H, m), 6.86 (1H, brs), 3.84-3.81 (4H, m), 3.75-3.68 (4H, m), 2.53 (3H, s). FAB-Mass: 440 (M + +1) IR (KBr) (cm- 1 ): 1626, 1525, 1508, 1489, 1421, 1227. Example 313 4- (7-methyl-4-quinazolinyl) -N- (4-nitrophenyl) -1-piperazinecarboamide (Compound 313) Yield: 65% Melting point: 251-254 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 8.08 (1H, brs), 8.06 (2H, d, J = 9.2 Hz), 7.74 (1H, d, J = 9.3 Hz) , 7.62 (1H, d, J = 1.3 Hz), 7.57 (2H, d, J = 9.2 Hz), 7.29 (1H, dd, J = 9.3 Hz, 1.3 Hz), 3.78 (8H, m), 2.48 (3H , s). FAB-Mass: 393 (M + +1) IR (KBr) (cm −1 ): 1680, 1597, 1551, 1498, 1450, 1416, 1390, 1331, 1304, 1234, 1198, 1111, 993, 752. Example 314 N-benzyl-4- (7-methyl-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 314) Yield: 78% Melting Point: 177-178 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.81 (1H, m), 7.65 (1H, m), 7.39-7.26 (6H, m), 6.87 (1H, br), 4.96 (2H, d, J = 4.0 Hz), 4.15-4.13 (4H, m), 3.95 (4H, m), 2.55 (3H, s). FAB-Mass: 378 (M + +1) IR (KBr) (cm −1 ): 1566, 1541, 1495, 1448, 1414, 1338, 1219, 1012, 694. Example 315 4- (7-Methyl-4-quinazolinyl) -N- (3-picoryl) -1-piperazinethiocarboamide dihydrochloride (Compound 315) Yield: 87% Melting Point: 180-183 ℃ (HCl) 1 H-NMR (free base, CDCl 3 ) δ (ppm): 8.63 (1H, s), 8.47-8.45 (2H, m), 7.81-7.76 (2H, m), 7.64 (1H, s), 7.32- 7.23 (2H, m), 6.82 (1H, brt, J = 5.3 Hz), 4.95 (2H, d, J = 5.3 Hz), 4.16-4.12 (4H, m), 3.97-3.93 (4H, m), 2.52 (3H, s). FAB-Mass: 379 (M + +1) IR (HCl, KBr) (cm -1 ): 1525, 1473, 1444, 1419, 1396, 1360, 1323. In Examples 316 and 317 below, 7-chloro-4- (1-piperazinyl) quinazolin instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline is substituted for phenylisocyanate In fact, the same procedure as in Example 1 was repeated except that an isocyanate or isothiocyanate was used to obtain the target compound. Example 316 4- (7-chloro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 316) Yield: 13% FAB-Mass: 462 (M + +3), 460 (M + +1) Example 317 N-benzyl-4- (7-chloro-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 317) Yield: 79% Melting point: 70-71 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.88 (1H, d, J = 2.0 Hz), 7.83 (1H, d, J = 8.9 Hz), 7.41 (1H, dd, J = 8.9 Hz, 2.0 Hz), 7.36-7.29 (5H, m), 5.84 (1H, brt, J = 4.9 Hz), 4.89 (2H, d, J = 4.9 Hz), 4.12-4.07 (4H, m) , 4.00-3.96 (4H, m). FAB-Mass: 400 (M + +3), 398 (M + +1) IR (KBr) (cm- 1 ): 1562, 1537, 1495, 1454, 1439, 1335. In Examples 318-320 below, instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, 7-isopropoxy-4- (1-piperazinyl) quinazoline was substituted for phenyl isocyanate. Virtually the same procedure as in Example 1 was repeated except that the corresponding isocyanate or isothiocyanate was used to obtain the desired compound. Example 318 4- (7-isopropoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 318) Yield: 23% Melting point: 181-182 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 8.02 (1H, d, J = 8.9 Hz), 7.37-7.27 (5H, m), 7.19 (1H, dd, J = 8.9 Hz, 2.6 Hz), 7.11-6.94 (5H, m), 6.71 (1H, brs), 5.60 (1H, m), 3.77-3.70 (4H, m), 3.48-3.45 (4H, m), 1.46 (6H , d, J = 6.3 Hz). FAB-Mass: 484 (M + +1) IR (KBr) (cm −1 ): 1660, 1614, 1572, 1531, 1508, 1491, 1429, 1219, 1113, 837, 750, 689. Example 319 4- (7-isopropoxy-4-quinazolinyl) -N- (4-nitrophenyl) -1-piperazinecarboamide (Compound 319) Yield: 23% 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 8.15 (2H, d, J = 8.9 Hz), 8.03 (1H, d, J = 8.9 Hz), 7.70 (2H, d, J = 8.9 Hz), 7.35-7.13 (3H, m), 5.60 (1H, m), 4.05 (4H, m), 3.80-3.78 (4H, m), 1.46 (6H, d, J = 6.3 Hz). FAB-Mass: 437 (M + +1) Example 320 N-benzyl-4- (7-isopropoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 320) Yield: 24% 1 H-NMR (CDCl 3 ) δ (ppm): 8.60 (1H, s), 8.00 (1H, d, J = 9.2 Hz), 7.37-7.29 (5H, m), 7.10 (1H, dd, J = 9.2 Hz, 2.3 Hz), 6.98 (1H, d, J = 2.3 Hz), 6.26 (1H, brt, J = 5.0 Hz), 5.57 (1H, m), 4.89 (2H, d, J = 5.0 Hz), 4.70 -4.06 (4H, m), 3.54-3.51 (4H, m), 1.45 (6H, d, J = 6.3 Hz). FAB-Mass: 422 (M + +1) Example 321 4- (7-amino-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 321) 455.6 mg (0.97 mmol) of 4- (7-nitro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazincaramide obtained in Example 322 was dissolved in 10 ml of ethanol. To the solution, a suspension of 100 g of 10% palladium-carbon is added to 5 ml of ethanol and 2 ml of water and stirred for 4 hours at room temperature under hydrogen vapor. The catalyst is separated by filtration using celite and the solvent is evaporated. The residue is purified by silica gel chromatography to give the title compound as colorless crystals. Yield: 45% 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.77 (1H, d, J = 8.3 Hz), 7.55 (1H, brs), 7.35-7.29 (4H, m), 7.07- 6.97 (7H, m), 6.35 (2H, brs), 3.84-3.82 (4H, m), 3.75-3.73 (4H, m). Example 322 4- (7-nitro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 322) In fact the same procedure as in Example 60 except that a corresponding 7-nitro-4- (1-piperazinyl) quinazolin was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline Was repeated to obtain the target compound. Yield: 24% Melting point: 146-148 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.82 (1H, s), 8.73 (1H, d, J = 2.3 Hz), 8.21 (1H, dd, J = 8.9 Hz, 2.3 Hz), 8.04 (1H , d, J = 8.9 Hz), 7.35-7.27 (4H, m), 7.06 (1H, m), 6.98-6.94 (4H, m), 6.80 (1H, brs), 3.95-3.92 (4H, m), 3.78-3.74 (4H, m). FAB-Mass: 471 (M + +1) IR (KBr) (cm −1 ): 1635, 1587, 1541, 1529, 1508, 1489, 1417, 1346, 1227, 996, 808, 743. Example 323 4- (7-methoxycarbonyl-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecaramide (Compound 323) Example 60, except that 7-methoxycarbonyl-4- (1-piperazinyl) quinazoline was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline The same procedure was repeated to obtain the target compound. Yield: 32% 1 H-NMR (CDCl 3 ) δ (ppm): 8.78 (1H, s), 8.57 (1H, d, J = 1.7 Hz), 8.06 (1H, dd, J = 8.6 Hz, 1.7 Hz), 7.93 (1H) , d, J = 8.6 Hz), 7.36-7.25 (4H, m), 7.06 (1H, m), 7.02-6.93 (5H, m), 3.99 (3H, s), 3.90-3.86 (4H, m), 3.77-3.74 (4H, m). FAB-Mass: 484 (M + +1) Example 324 4- (7-carboxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 324) 1.50 g (3.11 mmol) of 4- (7-methoxycarbonyl-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecaramide obtained in Example 323 was added to methanol 20. 20 ml of 1 N aqueous sodium hydroxide solution was added to the solution dissolved in ml, and the mixture was stirred while heating to 50 ° C. for 3.5 hours. The mixture is acidified with concentrated hydrochloric acid, the precipitated crystals are collected by filtration, washed with ethanol, then chloroform and recrystallized from methanol to give the target compound as colorless crystals. Yield: 37% 1 H-NMR (DMSO-d 6 ) δ (ppm): 8.93 (1H, s), 8.71 (1H, brs), 8.37-8.34 (2H, m), 8.11 (1H, d, J = 8.9 Hz), 7.52-7.49 (2H, m), 7.39-7.33 (2H, m), 7.09 (1H, m), 6.97-6.94 (4H, m), 4.24 (4H, m), 3.77-3.76 (4H, m). FAB-Mass: 470 (M + +1) Example 325 N- (4-acetylphenyl) -4- (8-chloro-4-quinazolinyl) -1-piperazincarboamide (Compound 325) In fact the same procedure as in Example 87 except that a matching 8-chloro-4- (1-piperazinyl) quinazolin was used in place of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin Was repeated to obtain the target compound. Yield: 23% Melting Point: 208-209 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.89 (1H, s), 7.93 (2H, d, J = 8.9 Hz), 7.91-7.82 (2H, m), 7.50 (2H, d, J = 8.9 Hz), 7.45 (1H, m), 6.66 (1H, brs), 3.94-3.90 (4H, m), 3.80-3.76 (4H, m), 2.58 (3H, s). FAB-Mass: 412 (M + +3), 410 (M + +1) IR (KBr) (cm −1 ): 1677, 1668, 1596, 1527, 1494, 1270, 1234, 1172, 993, 950, 838, 777. In Examples 326-328 below, instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, 8-methoxy-4- (1-piperazinyl) quinazolin is substituted for phenylisocyanate Virtually the same procedure as in Example 1 was repeated except that the matching isocyanate was used to give the desired compound. Example 326 N- (4-isopropylphenyl) -4- (8-methoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 326) Yield: 6% Melting point: 102-104 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.82 (1H, s), 7.48-7.39 (2H, m), 7.28 (2H, d, J = 8.6 Hz), 7.17 (2H, d, J = 8.6 Hz), 7.12 (1H, m), 6.35 (1H, brs), 4.07 (3H, s), 3.86-3.83 (4H, m), 3.74-3.72 (4H, m), 2.87 (1H, m), 1.23 (6H, doublet, J = 6.9 Hz). FAB-Mass: 405 (M + +1) IR (KBr) (cm −1 ): 1635, 1498, 1454, 1417, 1241, 1024, 991, 958, 827, 760. Example 327 4- (8-methoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 327) Yield: 21% Melting point: 108-109 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.82 (1H, s), 7.49-7.39 (2H, m), 7.36-7.25 (4H, m), 7.16-7.05 (2H, m), 7.00-6.97 (4H, m), 6.43 (1H, brs), 4.07 (3H, s), 3.87-3.83 (4H, m), 3.76-3.72 (4H, m). FAB-Mass: 456 (M + +1) IR (KBr) (cm −1 ): 1641, 1538, 1498, 1415, 1224, 1024, 991, 754. Example 328 N- (4-acetylphenyl) -4- (8-methoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 328) Yield: 6% Melting Point: 239-240 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.82 (1H, s), 7.93 (2H, d, J = 8.6 Hz), 7.50 (2H, d, J = 8.6 Hz), 7.45-7.23 (2H, m), 7.15 (1H, dd, J = 6.3 Hz, 2.6 Hz), 6.70 (1H, brs), 4.07 (3H, s), 3.88-3.84 (4H, m), 3.79-3.75 (4H, m), 2.58 (3 H, s). FAB-Mass: 405 (M + +1) IR (KBr) (cm −1 ): 1675, 1662, 1527, 1490, 1419, 1386, 1272, 1226, 1172, 995, 950, 775. Example 329 4- (6,7-difluoro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 205) 446.7 mg (1.27 mmol) of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butyl ester obtained according to Reference Example 7 was dissolved in 3 ml of dichloromethane, 3 ml of trifluoroacetic acid was added with ice cooling, followed by stirring at the same temperature for 4 hours. After evaporation of the solvent, the residue is azeotropically distilled twice with toluene and the residue obtained is taken up in 10 ml of dimethylformamide. 0.89 ml (6.39 mmol) of triethylamine and 0.27 ml (1.28 mmol) of 4-phenoxyphenylisocyanate are added to the solution, followed by stirring at room temperature overnight. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel chromatography to obtain the target compound as colorless crystals. Yield: 98% Melting Point: 177-178 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.74 (1H, s), 7.71-7.62 (2H, m), 7.36-7.26 (4H, m), 7.05 (1H, m), 6.98-6.94 (4H m), 6.69 (1 H, br s), 3.83-3.72 (8 H, m). FAB-Mass: 462 (M + +1) IR (KBr) (cm- 1 ): 1633, 1578, 1508, 1489, 1423, 1227. In Examples 330 and 331 below, virtually the same procedure as in Example 329 was repeated except that a matching isothiocyanate was used in place of 4-phenoxyphenylisocyanate to afford the desired compound. Example 330 N-benzyl-4- (6,7-difluoro-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 330) Yield: 94% Melting Point: 119-120 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.70-7.61 (2H, m), 7.36-7.29 (5H, m), 5.90 (1H, brt, J = 4.9 Hz), 4.89 (2H, doublet, J = 4.9 Hz), 4.12-4.06 (4H, m), 3.95-3.92 (4H, m). FAB-Mass: 400 (M + +1) IR (KBr) (cm −1 ): 1578, 1539, 1514, 1481, 1446, 1381, 1335, 698. Example 331 4- (6,7-difluoro-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 331) Yield: 93% Melting Point: 177-178 ℃ 1 H-NMR (DMSO-d6) δ (ppm): 8.62 (1H, s), 8.55 (1H, s), 8.45 (1H, d, J = 4.6 Hz), 8.36 (1H, br), 8.12 (1H , dd, J = 11.6 Hz, 8.9 Hz, 7.83 (1H, dd, J = 11.6 Hz, 7.9 Hz), 7.74 (1H, d, J = 7.9 Hz), 7.35 (1H, dd, J = 7.9 Hz, 4.6 Hz), 4.82 (2H, d, J = 2.6 Hz), 4.06-4.05 (4H, m), 3.96-3.95 (4H, m). FAB-Mass: 401 (M + +1) IR (KBr) (cm- 1 ): 1581, 1514, 1481, 1446, 1327. Example 332 4- (7-ethoxy-6-fluoro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 332) Example in effect except that 7-ethoxy-6-fluoro-4- (1-piperazinyl) quinazolin was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline The same procedure as in 60 was repeated to obtain the target compound. Yield: 72% Melting point: 197-198 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.73 (1H, d, J = 12.9 Hz), 7.37-7.25 (5H, m), 7.05 (1H, m), 6.98- 6.93 (4H, m), 6.87 (1H, brs), 4.60 (2H, q, J = 7.3 Hz), 3.73-3.69 (4H, m), 3.30-3.26 (4H, m), 1.50 (3H, t, J = 7.3 Hz). FAB-Mass: 488 (M + +1) IR (KBr) (cm -1 ): 1649, 1533, 1500, 1431, 1417, 1379, 1356, 1221, 1003, 868, 744. In Examples 333 and 334 below, instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, 6-methoxy-7-methyl-4- (1-piperazinyl) quinazolin is Virtually the same procedure as in Example 1 was repeated except that a matching isocyanate was used instead of phenylisocyanate to afford the desired compound. Example 333 4- (6-methoxy-7-methyl-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 333) Yield: 31% Melting point: 188-189 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 7.71 (1H, s), 7.36-7.28 (4H, m), 7.10-7.04 (2H, m), 7.01-6.97 (4H m), 6.46 (1H, brs), 3.95 (3H, s), 3.77-3.76 (8H, m), 2.40 (3H, s). FAB-Mass: 470 (M + +1) IR (KBr) (cm- 1 ): 1632, 1537, 1506, 1489, 1417, 1225, 997. Example 334 N- (4-cyanophenyl) -4- (6-methoxy-7-methyl-4-quinazolinyl) -1-piperazinecarboamide (Compound 334) Yield: 51% Melting Point: 242-243 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.70 (1H, s), 7.59 (2H, d, J = 9.2 Hz), 7.54 (2H, d, J = 9.2 Hz) , 7.07 (1H, brs), 7.04 (1H, s), 3.94 (3H, s), 3.78 (8H, m), 2.41 (3H, s). FAB-Mass: 403 (M + +1) IR (KBr) (cm −1 ): 2227, 1666, 1595, 1525, 1417, 1385, 1319, 1238, 995, 837. In Examples 335-338 below, 4- (7-E) obtained according to Reference Example 8 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester The oxy-6-methoxy-4-quinazolinyl) -1-piperazincarboxylic acid tert-butylester is substantially identical except that 4-phenoxyphenylisocyanate, or instead of a matching isocyanate or isothiocyanate is used. The same procedure as in Example 329 was repeated to obtain the target compound. Example 335 4- (7-ethoxy-6-methoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 335) Yield: 100% Melting point: 174-175 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.36-7.24 (5H, m), 7.10 (1H, s), 7.06 (1H, m), 6.98-6.94 (4H, m ), 6.80 (1H, brs), 4.25 (2H, q, J = 6.9 Hz), 3.98 (3H, s), 3.74 (8H, m), 1.56 (3H, t, J = 6.9 Hz). FAB-Mass: 500 (M + +1) IR (KBr) (cm -1 ): 1630, 1541, 1508, 1491, 1421, 1232. Example 336 N- (4-bromophenyl) -4- (7-ethoxy-6-methoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 336) Yield: 100% Melting point: 210-212 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.40 (2H, d, J = 8.9 Hz), 7.29 (2H, d, J = 8.9 Hz), 7.24 (1H, s) , 7.09 (1H, s), 6.79 (1H, brs), 4.25 (2H, q, J = 6.9 Hz), 3.98 (3H, s), 3.73 (8H, m), 1.55 (3H, t, J = 6.9 Hz). FAB-Mass: 488 (M + +3) 486 (M + +1) IR (KBr) (cm- 1 ): 1641, 1524, 1500, 1450, 1425, 1400, 1230, 1206. Example 337 N-benzyl-4- (7-ethoxy-6-methoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 337) Yield: 97% Melting Point: 168-169 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.61 (1H, s), 7.36-7.28 (5H, m), 7.21 (1H, s), 7.10 (1H, s), 6.07 (1H, brt, J = 4.6 Hz), 4.90 (2H, d, J = 4.6 Hz), 4.23 (2H, q, J = 6.9 Hz), 4.12-4.06 (4H, m), 3.97 (3H, s), 3.86-3.82 (4H m), 1.55 (3H, t, J = 6.9 Hz). FAB-Mass: 438 (M + +1) IR (KBr) (cm −1 ): 1574, 1537, 1506, 1450, 1335, 1236, 1211, 1011, 937, 870. Example 338 4- (7-ethoxy-6-methoxy-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 338) Yield: 100% Melting point: 169-170 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.60 (1H, s), 8.47-8.44 (2H, m), 7.78 (1H, m), 7.27 (1H, dd, J = 7.9 Hz, 4.9 Hz) , 7.20 (1H, s), 7.09 (1H, s), 6.81 (1H, br), 4.95 (2H, d, J = 5.3 Hz), 4.23 (2H, q, J = 6.9 Hz), 4.16-4.12 ( 4H, m), 3.97 (3H, s), 3.95-3.82 (4H, m), 1.55 (3H, t, J = 6.9 Hz). FAB-Mass: 439 (M + +1) IR (KBr) (cm −1 ): 1579, 1539, 1506, 1487, 1463, 1435, 1400, 1336, 1244, 1211, 1189, 1009, 945, 860. Example 339 4- (7-isopropoxy-6-methoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 339) 4- (7-isopropoxy-6-methoxy- obtained according to Reference Example 9 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester Virtually the same procedure as in Example 329 was repeated except that 4-quinazolinyl) -1-piperazincarboxylic acid tert-butylester was used to afford the desired compound. Yield: 100% Melting Point: 157-160 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.38-7.23 (6H, m), 7.09 (1H, s), 7.02 (1H, m), 6.96-6.93 (4H, m ), 4.75 (1H, m), 3.95 (3H, s), 3.73-3.72 (8H, m), 1.47 (6H, d, J = 6.3 Hz). FAB-Mass: 514 (M + +1) IR (KBr) (cm −1 ): 1630, 1541, 1508, 1489, 1421, 1230, 1201, 1109, 941. Example 340 N-benzyl-4- (6-methoxy-7-methyl-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 340) 6-methoxy-7-methyl-4- (1-piperazinyl) quinazolin instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolinisocyanate of Example 125 replaces phenylisocyanate Virtually the same procedure as in Example 125 was repeated except that the same benzyl isothiocyanate was used to afford the desired compound. Yield: 37% 1 H-NMR (CDCl 3 ) δ (ppm): 8.60 (1H, s), 7.63 (1H, s), 7.35-7.26 (5H, m), 7.02 (1H, s), 6.19 (1H, brt, J = 4.9 Hz), 4.90 (2H, d, J = 4.9 Hz), 4.10-4.02 (4H, m), 3.92 (3H, s), 3.87-3.83 (4H, m), 2.38 (3H, s). In Examples 341 and 342 below, 4- (7-iso is obtained according to Reference Example 9 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester Propoxy-6-methoxy-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylesterphenylisocyanate is practically carried out except that a matching isothiocyanate is used in place of 4-phenoxyphenylisocyanate. The same procedure as in Example 329 was repeated to obtain the target compound. Example 341 N-benzyl-4- (7-isopropoxy-6-methoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 341) Yield: 84% Melting Point: 174-175 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.60 (1H, s), 7.34-7.23 (6H, m), 7.12 (1H, s), 5.81 (1H, br), 4.90 (2H, d, J = 5.0 Hz), 4.74 (1H, m), 4.08-4.04 (4H, m), 3.93 (3H, s), 3.84-3.80 (4H, m), 1.45 (6H, d, J = 5.9 Hz). FAB-Mass: 452 (M + +1) IR (KBr) (cm −1 ): 1576, 1543, 1504, 1481, 1456, 1429, 1379, 1340, 1240, 1203, 1109, 941, 876, 854. Example 342 4- (7-isopropoxy-6-methoxy-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 342) Yield: 61% Melting point: 205-206 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.59 (1H, s), 8.45 (1H, dd, J = 5.0 Hz, 1.7 Hz), 8.42 (1H, d, J = 2.0 Hz), 7.78 (1H) , ddd, J = 7.9 Hz, 2.0 Hz, 1.7 Hz), 7.26 (1H, dd, J = 7.9 Hz, 5.0 Hz), 7.20 (1H, s), 7.10 (1H, s), 7.03 (1H, brt, J = 5.3 Hz), 4.95 (2H, d, J = 5.3 Hz), 4.75 (1H, m), 4.17-4.13 (4H, m), 3.95 (3H, s), 3.86-3.82 (4H, m), 1.47 (6H, doublet, J = 5.9 Hz). FAB-Mass: 453 (M + +1) IR (KBr) (cm −1 ): 1576, 1545, 1504, 1483, 1458, 1431, 1410, 1342, 1242, 1207, 1107, 939. Example 343 4- (6-methoxy-7-methyl-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 219) 6-methoxy-7-methyl-4- (1-piperazinyl) quinazolin in place of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline is a 3-matched alternative to phenyl isocyanate Virtually the same procedure as in Example 1 was repeated except that picoryl isothiocyanate was used to afford the desired compound. Yield: 36% 1 H-NMR (CDCl 3 ) δ (ppm): 8.60 (1H, s), 8.46 (2H, m), 7.78 (1H, m), 7.63 (1H, s), 7.26 (1H, dd, J = 7.9 Hz, 5.0 Hz), 7.03 (1H, s), 7.02 (1H, br), 4.96 (2H, d, J = 5.3 Hz), 4.17-4.12 (4H, m), 3.92 (3H, s), 3.88- 3.84 (4H, m), 2.38 (3H, s). Example 344 4- (7-hydroxy-6-methoxy-4-quinazolinyl) -N- (4-nitrophenyl) -1-piperazinecarboamide (Compound 344) (1) 162.0 mg (0.36 mmol) of 4- (7-benzyloxy-6-methoxy-4-quinazolinyl) -1-piperazinecarboxylic acid obtained according to Reference Example 8 (6) was suspended in 10 ml of ethanol. To the resulting suspension, a suspension of 100 mg of 10% palladium-carbon suspended in 5 ml of water is added and stirred for 7.5 hours at room temperature under hydrogen vapor. The catalyst is separated by filtration using celite and the solvent is evaporated. The residue is taken up in 5 ml of dichloromethane, 5 ml of trifluoroacetic acid is added with ice cooling and then stirred at the same temperature for 2 hours. The solvent is evaporated, the residue is azeotropically distilled twice with toluene and the residue obtained is taken up in 5 ml of dichloromethane. 122.5 mg (1.80 mmol) of imidazole and 108.5 mg (0.72 mmol) of tert-butyldimethylsilyl chloride were added to the solution, followed by stirring at room temperature for 2 hours. To this mixture is added 500.0 mg (3.32 mmol) of tert-butyldimethyl chloride and stirred overnight. Saturated aqueous sodium chloride solution is added, the resulting mixture is extracted with chloroform and the organic layer is dried over anhydrous sodium sulfide. The solvent is evaporated and the residue is taken up in 5 ml of dimethylformamide, 88.6 mg (0.54 mmol) of 4-nitrophenylisocyanate are added and then stirred at room temperature for 40 minutes. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals were collected by filtration, washed with water, dried and purified by silica gel chromatography to obtain 4- (7-tert-butyldimethylsilyloxy-6-methoxy-4-quinazolinyl) -N- (4-nitro 45.6 mg (24%) of phenyl) -1-piperazinecarboamide are obtained. (2) To a solution of 22.8 mg (0.04 mmol) of the compound obtained in (1) above in 5 ml of THF, 0.04 ml (0.04 mmol) of a solution of 1 mol / 1 tetrabutylammonium fluoride in THF was added thereto, and the same temperature was obtained. Stir for 10 minutes. The reaction mixture is concentrated and saturated aqueous sodium chloride solution is added to the residue. The mixture is extracted with chloroform, the organic layer is washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfide and the solvent is evaporated to give the desired compound. Yield: 80% 1 H-NMR (CDCl 3 ) δ (ppm): 10.03 (1H, brs), 8.56 (1H, s), 8.14 (2H, d, J = 9.2 Hz), 8.06 (2H, d, J = 9.2 Hz) , 7.50 (1H, s), 7.08 (1H, s), 4.00 (4H, m), 3.93 (3H, s), 3.73-3.72 (4H, m). FAB-Mass: 425 (M + +1) Example 345 4- (7-benzyloxy-6-methoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 345) Matching 4- (7-benzyloxy-6 obtained according to Reference Example 8 (6) instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazincarboxylic acid tert-butylester Virtually the same procedure as in Example 329 was repeated except that -methoxy-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester was used to afford the desired compound. Yield: 83% Melting point: 220-221 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.50-7.46 (2H, m), 7.42-7.26 (8H, m), 7.11 (1H, s), 7.04 (1H, m ), 6.98-6.95 (4H, m), 6.77 (1H, brs), 5.27 (2H, s), 3.98 (3H, s), 3.72 (8H, m). IR (KBr) (cm- 1 ): 1633, 1504, 1489, 1416, 1250, 1000. In Example 346-349 below, 4- (6-e) obtained according to Reference Example 10 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester Toxy-7-methoxy-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester is used in place of 4-phenoxyphenyl isocyanate (used in Example 346), instead of matching isocyanate or isothiocyanate Except for the above, the procedure of Example 329 was virtually repeated to obtain the target compound. Example 346 4- (6-Ethoxy-7-methoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazincaramide (Compound 346) Yield: 100% Melting point: 213-214 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.37-7.27 (4H, m), 7.26 (1H, s), 7.12 (1H, s), 7.07 (1H, m), 7.01-6.95 (4H, m), 6.55 (1H, brs), 4.19 (2H, q, J = 6.9 Hz), 4.02 (3H, s), 3.74 (8H, m), 1.57 (3H, t, J = 6.9 Hz). FAB-Mass: 500 (M + +1) IR (KBr) (cm −1 ): 1635, 1541, 1508, 1489, 1473, 1446, 1423, 1394, 1248, 1219, 1201, 997, 858, 750. Example 347 N- (4-cyanophenyl) -4- (6-ethoxy-7-methoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 347) Yield: 95% Melting point: 178-179 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.59 (2H, d, J = 9.2 Hz), 7.54 (2H, d, J = 9.2 Hz), 7.26 (1H, s) , 7.11 (1H, s), 7.05 (1H, brs), 4.19 (2H, q, J = 6.9 Hz), 4.02 (3H, s), 3.76 (8H, m), 1.56 (3H, t, J = 6.9 Hz). FAB-Mass: 433 (M + +1) IR (KBr) (cm −1 ): 2220, 1660, 1593, 1504, 1471, 1434, 1317, 1244, 1207, 997. Example 348 N-benzyl-4- (6-ethoxy-7-methoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 348) Yield: 86% Melting Point: 170-171 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.46-7.29 (5H, m), 7.25 (1H, s), 7.11 (1H, s), 5.76 (1H, brt, J = 4.6 Hz), 4.91 (2H, d, J = 4.6 Hz), 4.17 (2H, q, J = 6.9 Hz), 4.11-4.07 (4H, m), 4.02 (3H, s), 3.86-3.82 (4H m), 1.56 (3H, t, J = 6.9 Hz). FAB-Mass: 438 (M + +1) IR (KBr) (cm −1 ): 1576, 1547, 1504, 1475, 1456, 1425, 1392, 1351, 1242, 1209, 1142, 1026, 935, 849. Example 349 4- (6-Ethoxy-7-methoxy-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 349) Yield: 80% Melting Point: 208-209 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 8.53-8.51 (2H, m), 7.78 (1H, ddd, J = 7.9 Hz, 2.0 Hz, 1.7 Hz), 7.29 (1 H) , dd, J = 7.9 Hz, 5.0 Hz), 7.24 (1H, s), 7.11 (1H, s), 6.32 (1H, brt, J = 5.3 Hz), 4.97 (2H, d, J = 5.3 Hz), 4.19 (2H, q, J = 6.9 Hz), 4.14-4.11 (4H, m), 4.01 (3H, s), 3.86-3.82 (4H, m), 1.56 (3H, t, J = 6.9 Hz). FAB-Mass: 439 (M + +1) IR (KBr) (cm −1 ): 1558, 1506, 1473, 1427, 1396, 1332, 1240, 1209, 1198, 997, 872, 717. In Examples 350 and 351 below, 4- (6-mesyl obtained according to Reference Example 11 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester Oxy-7-methoxy-4-quinazolinyl) -1-piperazincarboxylic acid tert-butylester was used instead of 4-phenoxynyl isocyanate (used in Example 350) in which isothiocyanate was used. Except that in fact the same procedure as in Example 329 was repeated to give the desired compound. Example 350 4- (6-Mesyloxy-7-methoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 350) Yield: 100% Melting Point: 228-229 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.84 (1H, s), 7.36-7.27 (5H, m), 7.07 (1H, m), 6.99-6.96 (4H, m ), 6.54 (1H, brs), 4.04 (3H, s), 3.87-3.85 (4H, m), 3.76-3.74 (4H, m), 3.25 (3H, s). FAB-Mass: 550 (M + +1) IR (KBr) (cm −1 ): 1620, 1539, 1506, 1487, 1417, 1350, 1223, 1167, 993, 876. Example 351 N-benzyl-4- (6-mesyloxy-7-methoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 351) Yield: 97% Melting point: 76-80 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.84 (1H, s), 7.38-7.31 (5H, m), 7.27 (1H, s), 5.73 (1H, br), 4.89 (2H, d, J = 4.6 Hz), 4.11-4.08 (4H, m), 4.03 (3H, s), 3.99-3.95 (4H, m), 3.23 (3H, s). FAB-Mass: 488 (M + +1) IR (KBr) (cm- 1 ): 1506, 1475, 1365, 1350, 1161. In Examples 352-354 below, instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, 6,7-diethoxy-4- (1-piperazinyl) quinazoline is phenylisocyanate In fact the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used to obtain the desired compound. Example 352 N- (4-cyanophenyl) -4- (6,7-diethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 352) Yield: 94% Melting point: 186-187 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.71 (1H, brs), 7.59 (2H, d, J = 8.9 Hz), 7.54 (2H, d, J = 8.9 Hz) , 7.21 (1H, s), 7.11 (1H, s), 4.22 (2H, q, J = 6.3 Hz), 4.18 (2H, q, J = 6.3 Hz), 3.78-3.74 (4H, m), 3.73- 3.70 (4H, m), 1.54 (3H, t, J = 6.3 Hz), 1.53 (3H, t, J = 6.3 Hz). FAB-Mass: 447 (M + +1) IR (KBr) (cm −1 ): 2980, 2216, 1641, 1591, 1516, 1471, 1419, 1402, 1315, 1246, 1205, 986. Example 353 N-benzyl-4- (6,7-diethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 353) Yield: 97% Melting point: 134-136 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.58 (1H, s), 7.32-7.26 (5H, m), 7.18 (1H, s), 7.11 (1H, s), 6.34 (1H, brt, J = 5.0 Hz), 4.90 (2H, d, J = 5.0 Hz), 4.24-4.14 (4H, m), 4.11-4.07 (4H, m), 3.87-3.79 (4H, m), 1.53 (3H, t, J = 6.9 Hz), 1.53 (3H, t, J = 6.9 Hz). FAB-Mass: 452 (M + +1) IR (KBr) (cm −1 ): 1574, 1573, 1506, 1475, 1344, 1242, 1205, 1012, 935, 868, 731. Example 354 4- (6,7-diethoxy-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 354) Yield: 92% Melting point: 90-92 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 8.58-8.54 (2H, m), 7.78 (1H, ddd, J = 7.9 Hz, 2.0 Hz, 2.0 Hz), 7.28 (1 H) , m), 7.23 (1H, s), 7.11 (1H, s), 6.05 (1H, brt, J = 5.3 Hz), 4.98 (2H, d, J = 5.3 Hz), 4.25 (2H, q, J = 6.9 Hz), 4.19 (2H, q, J = 7.3 Hz), 4.13-4.09 (4H, m), 3.86-3.82 (4H, m), 1.55 (3H, t, J = 7.3 Hz), 1.55 (3H, t, J = 6.9 Hz). FAB-Mass: 453 (M + +1) IR (KBr) (cm- 1 ): 1504, 1443, 1392, 1344, 1238, 1203, 1041, 1009, 941. Example 355 4- (6,7-dibenzyloxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 355) In fact Example 60 except that 6,7-dibenzyloxy-4- (1-piperazinyl) quinazolin was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline The same procedure was repeated to obtain the target compound. Yield: 65% Melting Point: 137-138 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.61 (1H, s), 7.53-7.50 (2H, m), 7.45-7.26 (13H, m), 7.09-6.96 (6H, m), 6.73 (1H) , brs), 5.34 (2H, s), 5.32 (2H, s), 3.55-3.53 (4H, m), 3.46-3.44 (4H, m). FAB-Mass: 638 (M + +1) IR (KBr) (cm −1 ): 1630, 1537, 1506, 1489, 1452, 1417, 1225, 993, 748, 694. Example 356 4- (6-amino-7-chloro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 356) 628.8 mg (1.25 mmol) of 4- (7-chloro-6-nitro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide obtained according to Example 357 was acetic acid. To the solution dissolved in 15 ml, 407.9 mg (6.24 mmol) of zinc powder were added, followed by stirring overnight at room temperature in an argon atmosphere. The zinc powder is separated by filtration with ceria and the filtrate is washed with a chloroform-methanol-triethylamine mixture. The solvent is evaporated and the residue is purified by silica gel chromatography to give the title compound as colorless crystals. Yield: 18% 1 H-NMR (CDCl 3 ) δ (ppm): 8.60 (1H, s), 7.93 (1H, s), 7.35-7.27 (4H, m), 7.10-7.04 (2H, m), 6.99-6.96 (4H m), 6.65 (1 H, brs), 4.62 (2 H, br), 3.73-3.72 (8 H, m). In Examples 357 and 358 below, 4- (7-chloro obtained according to Reference Example 12 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester -6-nitro-4-quinazolinyl) -1-piperazincarboxylic acid tert-butylester was practically carried out except that a matching isothiocyanate was used in place of phenoxyphenylisocyanate (used in Example 357). The same procedure as in Example 329 was repeated to obtain the target compound. Example 357 4- (7-chloro-6-nitro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 357) Yield: 60% Melting point: 190-191 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.78 (1H, s), 8.55 (1H, s), 8.06 (1H, s), 7.34-7.28 (4H, m), 7.06 (1H, m), 7.00-6.97 (4H, m), 6.40 (1H, brs), 4.08-4.04 (4H, m), 3.81-3.77 (4H, m). FAB-Mass: 505 (M + +1) IR (KBr) (cm −1 ): 1637, 1608, 1564, 1527, 1506, 1489, 1419, 1352, 1325, 1225, 1028, 991, 918, 827, 748, 690. Example 358 N-benzyl-4- (7-chloro-6-nitro-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 358) Yield: 84% Melting point: 93-95 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.54 (1H, s), 7.93 (1H, s), 7.31-7.23 (5H, m), 6.18 (1H, brt, J = 5.0 Hz), 4.85 (2H, d, J = 5.0 Hz), 4.12 (8H, m). FAB-Mass: 443 (M + +1) IR (KBr) (cm- 1 ): 1564, 1539, 1498, 1352. Example 359 4- (7-amino-6-nitro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 359) In fact Example 60 except that 7-amino-6-nitro-4- (1-piperazinyl) quinazolin was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline The same procedure was repeated to obtain the target compound. Yield: 8% 1 H-NMR (CDCl 3 ) δ (ppm): 8.88 (1H, s), 8.55 (1H, s), 7.35-7.27 (4H, m), 7.12 (1H, s), 7.07 (1H, m), 7.00-6.96 (4H, m), 6.52 (1H, s), 6.22 (2H, brs), 4.07-4.03 (4H, m), 3.81-3.77 (4H, m). FAB-Mass: 486 (M + +1) Example 360 4- (6-acetamido-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 360) To a solution of 464.1 mg (0.99 mmol) of Compound 311 in 15 ml of ethanol, 100 mg of 10% palladium-carbon was added and stirred at room temperature under hydrogen vapor for 4 hours. The catalyst is separated by filtration using celite and the solvent is evaporated. The residue is taken up in 15 ml of dichloromethane, 0.70 ml (5.02 mmol) of triethylamine and 0.19 ml of acetic anhydride are added, followed by stirring at room temperature overnight. Methanol is added to the mixture, the solvent is evaporated and the residue is purified by silica gel chromatography to give the title compound as colorless crystals. Yield: 20% 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 8.66 (1H, d, J = 2.3 Hz), 8.20 (1H, brs), 7.84 (1H, d, J = 8.9 Hz) , 7.47 (1H, dd, J = 8.9 Hz, 2.3 Hz), 7.36-7.27 (4H, m), 7.06 (1H, m), 6.98-6.94 (4H, m), 6.75 (1H, brs), 3.86- 3.84 (4H, m), 3.77-3.75 (4H, m), 2.24 (3H, s). FAB-Mass: 483 (M + +1) Example 361 N-benzyl-4- (7-ethylamino-6-nitro-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 361) Instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, 7-ethylamino-6-nitro-4- (1-piperazinyl) quinazolin obtained according to Reference Example 5 is 4 Virtually the same procedure as in Example 60 was repeated except that a matching isothiocyanate was used in place of phenoxyphenyl isocyanate to afford the desired compound. Yield: 77% 1 H-NMR (CDCl 3 ) δ (ppm): 8.91 (1H, s), 8.50 (1H, s), 7.66 (1H, brt, J = 4.6 Hz), 7.38-7.29 (5H, m), 7.01 ( 1H, s), 5.71 (1H, brt, J = 4.6 Hz), 4.89 (2H, d, J = 4.6 Hz), 4.14 (8H, m), 3.39 (2H, dq, J = 7.3 Hz, 4.6 Hz) , 1.42 (3H, t, J = 7.3 Hz). FAB-Mass: 452 (M + +1) Example 362 4- (7-acetamido-6-nitro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 362) Example in effect except that 7-acetamido-6-nitro-4- (1-piperazinyl) quinazolin was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline The same procedure as in 60 was repeated to obtain the target compound. Yield: 26% 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.47 (1H, s), 7.35-7.27 (4H, m), 7.15 (1H, s), 7.07 (1H, m), 6.99-6.96 (4H, m), 6.54 (1H, brs), 6.51 (1H, brs), 4.00 (4H, m), 3.69 (4H, m), 2.04 (3H, s). In Examples 363-366 below, 4- (4-benzo obtained according to Reference Example 13 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester [g] quinazolinyl) -1-piperazincarboxylic acid tert-butylester is practiced in practice except that a matching isocyanate or isothiocyanate is used in place of 4-phenoxyphenylisocyanate (used in Example 363). The same procedure as in Example 329 was repeated to obtain the target compound. Example 363 4- (4-benzo [g] quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 363) Yield: 24% Melting point: 105-108 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.75 (1H, s), 8.49 (1H, s), 8.46 (1H, s), 8.04-7.99 (2H, m), 7.64-7.50 (2H, m ), 7.38-7.26 (4H, m), 7.07 (1H, m), 7.00-6.97 (4H, m), 6.68 (1H, brs), 4.04-4.01 (4H, m), 3.83-3.79 (4H, m) ). FAB-Mass: 476 (M + +1) IR (KBr) (cm- 1 ): 1637, 1541, 1508, 1489, 1419, 1225. Example 364 4- (4-benzo [g] quinazolinyl) -N- (4-nitrophenyl) -1-piperazincarboamide (Compound 364) Yield: 35% Melting Point: 272-275 ℃ 1 H-NMR (DMSO-d6) δ (ppm): 9.32 (1H, brs), 8.73 (1H, s), 8.63 (1H, s), 8.40 (1H, s), 8.20-8.05 (2H, m) , 8.14 (2H, d, J = 9.3 Hz), 7.78 (2H, d, J = 9.3 Hz), 7.65-7.52 (2H, m), 4.02-4.00 (4H, m), 3.83 (4H, m). FAB-Mass: 429 (M + +1) IR (KBr) (cm −1 ): 1670, 1597, 1541, 1518, 1508, 1419, 1321, 1300, 1236, 1113, 847, 750. Example 365 4- (4-benzo [g] quinazolinyl) -N-benzyl-1-piperazinthiocarboamide (Compound 365) Yield: 42% Melting Point: 187-188 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 8.47 (1H, s), 8.40 (1H, s), 8.00-7.95 (2H, m), 7.61-7.48 (2H, m ), 7.38-7.27 (5H, m), 6.06 (1H, brt, J = 5.0 Hz), 4.91 (2H, d, J = 5.0 Hz), 4.17-4.11 (8H, m). FAB-Mass: 414 (M + +1) IR (KBr) (cm- 1 ): 1545, 1520, 1408, 1381, 1369, 1238, 1198, 1012, 748, 694. Example 366 4- (4-benzo [g] quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 366) Yield: 44% Melting point: 107-110 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.61 (1H, s), 8.45-8.41 (3H, m), 8.34 (1H, s), 7.97-7.93 (2H, m), 7.77 (1H, ddd) , J = 7.9 Hz, 2.0 Hz, 1.7 Hz), 7.59-7.46 (2H, m), 7.24 (1H, dd, J = 7.9 Hz, 5.0 Hz), 7.14 (1H, br), 4.95 (2H, d, J = 5.3 Hz), 4.20-4.17 (4H, m), 4.12-4.10 (4H, m). FAB-Mass: 415 (M + +1) IR (KBr) (cm −1 ): 1560, 1508, 1479, 1433, 1410, 1383, 1352, 941, 744, 716. In Examples 367-371 below, instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, 6,7-methylenedioxy-4- (1-piperazinyl) quinazolin is phenyl Virtually the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used in place of the isocyanate to afford the desired compound. Example 367 4- (6,7-methylenedioxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 367) Yield: 85% Melting point: 206-207 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.35-7.30 (4H, m), 7.27 (1H, s), 7.15 (1H, s), 7.06 (1H, m), 6.99-6.94 (4H, m), 6.68 (1H, brs), 6.12 (2H, s), 3.73-3.65 (8H, m). FAB-Mass: 470 (M + +1) IR (KBr) (cm −1 ): 1630, 1491, 1462, 1419, 1227, 1038, 1003, 916, 872, 849, 762. Example 368 4- (6,7-methylenedioxy-4-quinazolinyl) -N- (4-nitrophenyl) -1-piperazinecarboamide (Compound 368) Yield: 92% Melting point: 247-250 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 8.12 (2H, d, J = 8.9 Hz), 7.84 (1H, brs), 7.59 (2H, d, J = 8.9 Hz) , 7.20 (1H, s), 7.13 (1H, s), 6.13 (2H, s), 3.79-3.77 (4H, m), 3.66-3.65 (4H, m). FAB-Mass: 423 (M + +1) IR (KBr) (cm −1 ): 1672, 1612, 1554, 1495, 1466, 1425, 1329, 1300, 1236, 1111, 1034, 918, 849. Example 369 N- (4-cyanophenyl) -4- (6,7-methylenedioxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 369) Yield: 100% Melting point: 220-222 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.79 (1H, brs), 7.58 (2H, d, J = 8.9 Hz), 7.53 (2H, d, J = 8.9 Hz) , 7.20 (1H, s), 7.13 (1H, s), 6.14 (2H, s), 3.78-3.75 (4H, m), 3.65-3.63 (4H, m). FAB-Mass: 403 (M + +1) IR (KBr) (cm −1 ): 2222, 1687, 1610, 1591, 1524, 1493, 1464, 1441, 1369, 1311, 1227, 1174, 1036, 916, 835. Example 370 N-benzyl-4- (6,7-methylenedioxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 370) Yield: 99% Melting point: 176-177 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.60 (1H, s), 7.36-7.30 (5H, m), 7.20 (1H, s), 7.14 (1H, s), 6.12 (2H, s), 5.95 (1H, brt, J = 4.6 Hz), 4.90 (2H, d, J = 4.6 Hz), 4.08-4.04 (4H, m), 3.77-3.73 (4H, m). FAB-Mass: 408 (M + +1) IR (KBr) (cm- 1 ): 1545, 1493, 1461, 1369, 1246, 1034, 918. Example 371 4- (6,7-methylenedioxy-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 371) Yield: 100% Melting Point: 167-168 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.59 (1H, s), 8.48 (1H, dd, J = 5.0 Hz, 1.7 Hz), 8.45 (1H, d, J = 2.0 Hz), 7.78 (1H) , ddd, J = 7.9 Hz, 2.0 Hz, 1.7 Hz), 7.28 (1H, dd, J = 7.9 Hz, 5.0 Hz), 7.19 (1H, s), 7.14 (1H, s), 6.70 (1H, brt, J = 5.3 Hz), 6.13 (2H, s), 4.95 (2H, d, J = 5.3 Hz), 4.13-4.10 (4H, m), 3.78-3.74 (4H, m). FAB-Mass: 409 (M + +1) IR (KBr) (cm −1 ): 1545, 1491, 1470, 1432, 1394, 1333, 1267, 1038, 997, 914. In Examples 372-375 below, 4- (6,7 obtained according to Reference Example 14 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazincarboxylic acid tert-butylester -Ethylenedioxy-4-quinazolinyl) -1-piperazincarboxylic acid tert-butylester is used instead of 4-phenoxyphenyl isocyanate (is used in Example 372) or isothiocyanate Except that in fact the same procedure as in Example 329 was repeated to give the desired compound. Example 372 4- (6,7-ethylenedioxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 372) Yield: 91% Melting point: 227-228 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.37-7.25 (6H, m), 7.05 (1H, m), 6.99-6.94 (5H, m), 4.38-4.33 (4H m), 3.72 (8H, m). FAB-Mass: 484 (M + +1) IR (KBr) (cm −1 ): 1664, 1539, 1506, 1489, 1419, 1342, 1290, 1219, 1064, 901. Example 373 N- (4-cyanophenyl) -4- (6,7-ethylenedioxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 373) Yield: 76% Melting Point: 246-247 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.14 (1H, brs), 8.52 (1H, s), 7.70 (4H, s), 7.39 (1H, s), 7.23 (1H, s), 4.41-4.40 (4H, m), 3.70 (8H, m). FAB-Mass: 417 (M + +1) IR (KBr) (cm −1 ): 2218, 1686, 1591, 1568, 1508, 1471, 1443, 1414, 1335, 1311, 1286, 1230, 1198, 912, 849. Example 374 N-benzyl-4- (6,7-ethylenedioxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 374) Yield: 88% Melting Point: 103-105 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.58 (1H, s), 7.40-7.29 (7H, m), 5.84 (1H, brt, J = 4.6 Hz), 4.90 (2H, d, J = 4.6 Hz), 4.40-4.35 (4H, m), 4.09-4.06 (4H, m), 3.88-3.84 (4H, m). FAB-Mass: 422 (M + +1) IR (KBr) (cm −1 ): 1568, 1541, 1508, 1477, 1443, 1340, 1286, 1240, 1066, 1003, 914, 901. Example 375 4- (6,7-ethylenedioxy-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 375) Yield: 72% Melting point: 110-113 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.52 (1H, s), 8.47 (1H, dd, J = 5.3 Hz, 1.3 Hz), 8.43 (1H, d, J = 2.3 Hz), 7.78 (1H) , ddd, J = 7.6Hz, 2.3Hz, 1.3Hz), 7.30 (1H, s), 7.28 (1H, s), 7.25 (1H, dd, J = 7.6Hz, 5.3Hz), 6.97 (1H, brt, J = 4.9 Hz), 4.94 (2H, d, J = 4.9 Hz), 4.39-4.34 (4H, m), 4.14-4.10 (4H, m), 3.86-3.82 (4H, m). FAB-Mass: 423 (M + +1) IR (KBr) (cm −1 ): 1574, 1558, 1508, 1443, 1410, 1389, 1348, 1290, 1068, 918, 710. In Examples 376-378 below, instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, 6,8-dichloro-4- (1-piperazinyl) quinazolin is substituted for phenylisocyanate Virtually the same procedure as in Example 1 was repeated except that an isocyanate conforming to was used to obtain the desired compound. Example 376 4- (6,8-dichloro-4-quinazolinyl) -N- (4-isopropylphenyl) -1-piperazinecarboamide (Compound 376) Yield: 20% Melting Point: 234-236 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.86 (1H, s), 7.87 (1H, d, J = 2.0 Hz), 7.80 (1H, d, J = 2.0 Hz), 7.29 (2H, d, J = 8.6 Hz), 7.17 (2H, d, J = 8.6 Hz), 6.32 (1H, brs), 3.91-3.87 (4H, m), 3.76-3.72 (4H, m), 2.88 (1H, m), 1.23 (6H, doublet, J = 6.9 Hz). FAB-Mass: 446 (M + +3), 444 (M + +1) IR (KBr) (cm -1 ): 1637, 1596, 1527, 1490, 1421, 1238, 995, 827. Example 377 4- (6,8-dichloro-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 377) Yield: 13% Melting point: 195-196 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.86 (1H, s), 7.87 (1H, d, J = 2.3 Hz), 7.80 (1H, d, J = 2.3 Hz), 7.34-7.28 (4H, m), 7.08 (1H, m), 7.00-6.96 (4H, m), 6.35 (1H, brs), 3.92-3.88 (4H, m), 3.77-3.73 (4H, m). FAB-Mass: 496 (M + +3), 494 (M + +1) IR (KBr) (cm- 1 ): 1643, 1600, 1537, 1506, 1488, 1419, 1222, 993. Example 378 N- (4-acetylphenyl) -4- (6,8-dichloro-4-quinazolinyl) -1-piperazincarboamide (Compound 378) Yield: 11% Melting Point: 187-188 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.87 (1H, s), 7.94 (2H, d, J = 8.9 Hz), 7.88 (1H, d, J = 2.1 Hz), 7.80 (1H, d, J = 2.1 Hz), 7.49 (2H, d, J = 8.9 Hz), 6.61 (1H, brs), 3.93-3.89 (4H, m), 3.80-3.76 (4H, m), 2.58 (3H, s). FAB-Mass: 446 (M + +3), 444 (M + + +1) IR (KBr) (cm −1 ): 1672, 1652, 1591, 1508, 1498, 1419, 1247, 990. In Examples 379 and 380 below, instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, 6,7-diiodine-4- (1-piperazinyl) quinazolin is a phenylisocyanate. In fact the same procedure as in Example 1 was repeated except that a matching isocyanate was used to afford the desired compound. Example 379 4- (6,8-Diiode-4-quinazolinyl) -N- (4-isopropylphenyl) -1-piperazinecarboamide (Compound 379) Yield: 9% Melting point: 267-269 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.83 (1H, s), 8.59 (1H, d, J = 1.6 Hz), 8.22 (1H, d, J = 1.6 Hz), 7.28 (2H, d, J = 8.1 Hz), 7.17 (2H, d, J = 8.1 Hz), 6.30 (1H, brs), 3,91-3.87 (4H, m), 3.73-371 (4H, m), 2.88 (1H, m ), 1.23 (6H, d, J = 6.9 Hz). FAB-Mass: 627 (M + +1) IR (KBr) (cm −1 ): 1643, 1594, 1540, 1486, 1452, 1419, 1238, 995, 937, 827. Example 380 4- (6,8-Diiodine-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazincarboamide (Compound 380) Yield: 14% Melting Point: 242-244 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.84 (1H, s), 8.60 (1H, d, J = 1.6 Hz), 8.22 (1H, d, J = 1.6 Hz), 7.32 (4H, m) , 7.08 (1H, m), 7.01-6.97 (4H, m), 6.36 (1H, brs), 3.92-3.88 (4H, m), 3.76-3.72 (4H, m). FAB-Mass: 678 (M + +1) IR (KBr) (cm −1 ): 1641, 1600, 1538, 1506, 1488, 1419, 1222, 991. In Examples 381 and 382 below, instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, 6,8-dimethoxy-4- (1-piperazinyl) quinazolin is a phenyl isocyanate. In fact the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used to obtain the desired compound. Example 381 4- (6,8-dimethoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 381) Yield: 86% Melting Point: 109-110 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.72 (1H, s), 7.36-7.25 (4H, m), 7.10 (1H, brs), 7.04 (1H, dd, J = 7.9 Hz, 1.0 Hz) , 6.97-6.93 (4H, m), 6.78 (1H, d, J = 1.7 Hz), 6.68 (1H, d, J = 1.7 Hz), 4.00 (3H, s), 3.90 (3H, s), 3.72 ( 8H, m). FAB-Mass: 486 (M + +1) IR (KBr) (cm −1 ): 1620, 1539, 1506, 1414, 1225, 1159. Example 382 4- (6,8-dimethoxy-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 382) Yield: 72% (free base) Melting Point: 164-167 ° C. (Dehydrochloride) 1 H-NMR (free base, CDCl 3 ) δ (ppm): 8.62 (1H, s), 8.58 (1H, dd, J = 5.0 Hz, 1.7 Hz), 8.42 (1H, d, J = 2.0 Hz), 7.76 (1H, ddd, J = 7.9 Hz, 2.0 Hz, 1.7 Hz), 7.23 (1H, dd, J = 7.9 Hz, 5.0 Hz), 7.14 (1H, br), 6.80 (1H, d, J = 2.3 Hz ), 6.68 (1H, d, J = 2.3 Hz), 4.94 (2H, d, J = 5.0 Hz), 4.17-4.13 (4H, m), 3.98 (3H, s), 3.89 (3H, s), 3.84 -3.81 (4H, m). FAB-Mass: 425 (M + +1) IR (Dehydrochloride, KBr) (cm −1 ): 1531, 1470, 1400, 1357, 1323, 1163. In Examples 383-385 below, instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, 7,8-dimethoxy-4- (1-piperazinyl) quinazolin is phenylisocyanate In fact the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used to obtain the desired compound. Example 383 4- (7,8-dimethoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 383) Yield: 65% Melting point: 189-190 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 8.66 (1H, brs), 8.60 (1H, s), 7.83 (1H, d, J = 9.2 Hz), 7.50 (2H, d, J = 8.9 Hz), 7.43-7.32 (3H, m), 7.08 (1H, m), 6.97-6.93 (4H, m), 3.97 (3H, s), 3.91 (3H, s), 3.78-3.76 (4H, m) , 3.69-3.68 (4H, m). FAB-Mass: 486 (M + +1) IR (KBr) (cm −1 ): 1633, 1605, 1527, 1506, 1491, 1417, 1282, 1225, 1097, 1012, 997. Example 384 N-benzyl-4- (7,8-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 384) Yield: 52% Melting Point: 158-160 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.66 (1H, d, J = 9.2 Hz), 7.35-7.26 (5H, m), 7.18 (1H, d, J = 9.2 Hz), 6.10 (1H, br), 4.90 (2H, d, J = 4.3 Hz), 4.10-4.02 (4H, m), 4.05 (3H, s), 4.01 (3H, s), 3.99-3.91 (4H , m). FAB-Mass: 424 (M + +1) IR (KBr) (cm −1 ): 1552, 1495, 1404, 1325, 1284, 1244, 1097, 1005, 700. Example 385 4- (7,8-dimethoxy-4-quinazolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide hydrochloride (Compound 385) Yield: 38% Melting Point: 208-209 ℃ (HCl) 1 H-NMR (free base, CDCl 3 ) δ (ppm): 8.62 (1H, s), 8.44 (1H, d, J = 1.7 Hz), 8.43 (1H, dd, J = 5.0 Hz, 1.7 Hz), 7.76 (1H, ddd, J = 7.9 Hz, 1.7 Hz, 1.7 Hz), 7.66 (1H, d, J = 9.2 Hz), 7.24 (1H, dd, J = 7.9 Hz, 5.0 Hz), 7.20 (1H, d , J = 9.2 Hz), 7.12 (1H, br), 4.94 (2H, d, J = 5.3 Hz), 4.16-4.13 (4H, m), 4.03 (3H, s), 4.01 (3H, s), 3.95 -3.91 (4H, m). FAB-Mass: 425 (M + +1) IR (KBr) hydrochloride (cm -1 ): 1533, 1479, 1396, 1367, 1300, 1003. Example 386 4- (1,3-dihydro-1,3-dimethyl-2-oxo-2H-imidazo [4,5-g] quinazolin-8-yl) -N- (4-nitrophenyl) -1- Piperazinecarboamide (Compound 386) 1,3-dihydro-1,3-dimethyl-2-oxo-8- (1-pi) obtained according to Reference Example 1 instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline Virtually the same procedure as in Example 77 was repeated except that ferrazinyl) -2H-imidazo [4,5-g] quinazolin was used to afford the desired compound. Yield: 53% Melting point: 299-300 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.37 (1H, br), 8.61 (1H, s), 8.17 (2H, d, J = 9.2 Hz), 7.75 (2H, d, J = 9.2 Hz), 7.53 (1H, s), 7.50 (1H, s), 3.76-3.57 (8H, m), 3.47 (3H, s), 3.44 (3H, s). FAB-Mass: 463 (M + +1) IR (KBr) (cm −1 ): 1705, 1668, 1606, 1547, 1502, 1446, 1416, 1329, 1234, 1111, 996, 847, 752. In Examples 387 and 388 below, 4- (1,3) obtained according to Reference Example 5 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazincarboxylic acid tert-butylester -Dihydro-3-ethyl-1-methyl-2-oxo-2H-imidazo [4,5-g] quinazolin-8-yl) -1-piperazinecarboxylic acid tert-butyl ester is 4-phenoxy Virtually the same procedure as in Example 329 was repeated except that a matching isocyanate or isothiocyanate was used instead of phenylisocyanate (used in Example 387) to afford the desired compound. Example 387 4- (1,3-dihydro-3-ethyl-1-methyl-2-oxo-2H-imidazo [4,5-g] quinazolin-8-yl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 387) Yield: 96% Melting point: 250-251 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.73 (1H, s), 7.44 (1H, s), 7.38-7.31 (4H, m), 7.28 (1H, s), 7.05 (1H, m), 6.99-6.96 (4H, m), 6.73 (1H, brs), 4.03 (2H, q, J = 7.3 Hz), 3.77 (8H, m), 3.51 (3H, s), 1.39 (3H, t, J = 7.3 Hz). FAB-Mass: 524 (M + +1) IR (KBr) (cm −1 ): 1734, 1639, 1602, 1543, 1506, 1487, 1417, 1223, 997. Example 388 N-benzyl-4- (1,3-dihydro-3-ethyl-1-methyl-2-oxo-2H-imidazo [4,5-g] quinazolin-8-yl) -1-piperazincar Boamide (Compound 388) Yield: 57% Melting Point: 207-208 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.43 (1H, s), 7.38-7.30 (5H, m), 7.27 (1H, s), 5.83 (1H, brt, J = 4.6 Hz), 4.91 (2H, d, J = 4.6 Hz), 4.16-4.08 (4H, m), 4.03 (2H, q, J = 7.3 Hz), 3.91-3.87 (4H, m), 3.49 (3H , s), 1.39 (3H, t, J = 7.3 Hz). FAB-Mass: 462 (M + +1) IR (KBr) (cm −1 ): 1722, 1552, 1539, 1489, 1454, 1427, 1404, 1377, 1352, 1248, 849. Example 389 4- (1,3-dihydro-1,3-dipropyl-2-oxo-2H-imidazo [4,5-g] quinazolin-8-yl) -N- (4-phenoxyphenyl)- 1-piperazinecarboamide (Compound 389) 1,3-dihydro-1,3-dipropyl-2-oxo-8- (1-, obtained according to Reference Example 3 instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline Virtually the same procedure as in Example 60 was repeated except that piperazinyl) -2H-imidazo [4,5-g] quinazolin was used to afford the desired compound. Yield: 62% Melting Point: 179-180 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 8.70 (1H, brs), 8.61 (1H, s), 7.60 (1H, s), 7.54-7.47 (3H, m), 7.39-7.33 (2H , m), 7.09 (1H, m), 6.97-6.94 (4H, m), 4.00-3.91 (4H, m), 3.71 (8H, m), 2.51-2.50 (4H, m), 1.79-1.69 (6H , m). FAB-Mass: 566 (M + +1) IR (KBr) (cm- 1 ): 1722, 1643, 1601, 1487, 1414, 1225, 993, 849, 748. Example 390 4- (1,3-Dibutyl-1,3-dihydro-2-oxo-2H-imidazo [4,5-g] quinazolin-8-yl) -N- (4-phenoxyphenyl)- 1-piperazincarboamide (Compound 390) 1,3-dibutyl-1,3-dihydro-2-oxo-8- (1-, obtained according to Reference Example 4 instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline Virtually the same procedure as in Example 60 was repeated except that piperazinyl) -2H-imidazo [4,5-g] quinazolin was used to afford the desired compound. Yield: 50% Melting point: 134-136 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 8.70 (1H, brs), 8.61 (1H, s), 7.58 (1H, s), 7.53-7.48 (3H, m), 7.39-7.33 (2H , m), 7.09 (1H, m), 6.97-6.94 (4H, m), 4.03-3.94 (4H, m), 3.71 (8H, m), 1.73-1.66 (4H, m), 1.34-1.29 (4H) m), 0.96-0.88 (6H, m). FAB-Mass: 594 (M + +1) IR (KBr) (cm- 1 ): 1726, 1643, 1504, 1487, 1414, 1225. Example 391 4- (6,7-dimethoxy-2-methyl-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 391) In practice, except that 6,7-dimethoxy-2-methyl-4- (1-piperazinyl) quinazoline was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline The same procedure as in Example 60 was repeated to obtain the target compound. Yield: 93% Melting point: 146-147 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 7.37-7.27 (4H, m), 7.21 (1H, s), 7.08 (1H, s), 7.04-6.95 (5H, m), 6.80 (1H, brs ), 4.00 (3H, s), 3.97 (3H, s), 3.72 (8H, m), 2.66 (3H, s). FAB-Mass: 500 (M + +1) IR (KBr) (cm −1 ): 1639, 1508, 1489, 1417, 1244, 1225, 1167, 991, 851. Example 392 4- (2-Chloro-6,7-dimethoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 392) 2.4 g (5.88 mmol) of 4- (2-chloro-6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butyl ester obtained according to Reference Example 15 was dissolved in 20 ml of dichloromethane. 20 ml of trifluoroacetic acid is added to the solution with ice cooling, followed by stirring at the same temperature for 1.5 hours. The reaction mixture is concentrated and azeotropically distilled with toluene and the obtained residue is taken up in 30 ml of difetylformamide. 4.09 ml (29.3 mmol) of triethylamine and 1.24 ml (5.88 mmol) of 4-4-phenoxyphenylisocyanate were added to the solution, followed by stirring at room temperature overnight. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel chromatography to obtain the target compound as colorless crystals. Yield: 73% Melting point: 178-179 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 7.36-7.28 (4H, m), 7.20 (1H, s), 7.11-6.97 (5H, m), 7.08 (1H, s), 6.50 (1H, brs ), 4.01 (3H, s), 3.99 (3H, s), 3.88-3.85 (4H, m), 3.76-3.73 (4H, m). FAB-Mass: 522 (M + +3), 520 (M + +1) IR (KBr) (cm −1 ): 1632, 1506, 1487, 1416, 1244, 1214, 1142, 997, 953, 868, 849, 749. Example 393 4- (6,7-dimethoxy-2-morpholino-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 393) In fact the same procedure as in Example 329 was repeated except that 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester obtained according to Reference Example 16 was used. The desired compound was obtained. Yield: 79% Melting point: 114-116 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 7.36-7.27 (5H, m), 7.07 (1H, m), 7.05-6.96 (5H, m), 6.41 (1H, brs), 3.99 (3H, s ), 3.93 (3H, s), 3.83-3.82 (8H, m), 3.71-3.70 (8H, m). FAB-Mass: 571 (M + +1) IR (KBr) (cm −1 ): 1641, 1554, 1508, 1489, 1419, 1379, 1240, 993. In Examples 394-396 below, 4- (1-piperazinyl) quinoline in place of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin is an isocyanate or isothio that matches instead of phenylisocyanate Except that cyanate was used, in fact the same procedure as in Example 1 was repeated to give the desired compound. Example 394 N- (4-phenoxyphenyl) -4- (4-quinolyl) -1-piperazinecarboamide (Compound 394) Yield: 93% Melting Point: 145-146 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.73 (1H, d, J = 5.0 Hz), 8.07 (1H, d, J = 8.3 Hz), 8.01 (1H, dd, J = 7.3 Hz, 1.3 Hz ), 7.67 (1H, ddd, J = 8.3 Hz, 7.3 Hz, 1.3 Hz), 7.51 (1H, dd, J = 7.3 Hz, 7.3 Hz), 7.38-7.24 (4H, m), 7.18 (1H, brs) , 7.05 (1H, m), 6.97-6.93 (4H, m), 6.82 (1H, d, J = 5.0 Hz), 3.80-3.76 (4H, m), 3.21-3.18 (4H, m). FAB-Mass: 425 (M + +1) IR (KBr) (cm −1 ): 1639, 1582, 1506, 1487, 1419, 1396, 1340, 1219, 997, 918, 833, 766, 692. Example 395 N-benzyl-4- (4-quinolyl) -1-piperazinthiocarboamide (Compound 395) Yield: 96% Melting point: 75-79 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, d, J = 5.0 Hz), 8.03-7.98 (2H, m), 7.66 (1H, ddd, J = 8.3 Hz, 7.3 Hz, 1.3 Hz ), 7.51 (1H, m), 7.35-7.23 (5H, m), 7.04 (1H, brt, J = 5.0 Hz), 6.76 (1H, d, J = 5.0 Hz), 4.95 (2H, d, J = 5.0 Hz), 4.17-4.14 (4H, m), 3.24-3.21 (4H, m). FAB-Mass: 363 (M + +1) IR (KBr) (cm −1 ): 1578, 1533, 1508, 1398, 1335, 1205, 1009, 926, 770. Example 396 N- (3-Picoryl) -4- (4-quinolyl) -1-piperazinthiocarboamide dihydrochloride (Compound 396) Yield: 86% Melting Point: 183-185 ° C. (HCl) 1 H-NMR (free base, CDCl 3 ) δ (ppm): 8.70 (1H, d, J = 5.0 Hz), 8.47 (1H, dd, J = 4.6 Hz, 1.6 Hz), 8.44 (1H, d, J = 2.0 Hz), 8.05-7.98 (2H, m), 7.78 (1H, ddd, J = 7.9 Hz, 2.0 Hz, 1.6 Hz), 7.70 (1H, ddd, J = 8.6 Hz, 8.3 Hz, 1.7 Hz), 7.51 (1H, ddd, J = 8.3 Hz, 8.3 Hz, 1.3 Hz), 7.25 (1H, dd, J = 7.9 Hz, 4.6 Hz), 6.85 (1H, br), 6.82 (1H, d, J = 5.0 Hz ), 4.95 (2H, d, J = 5.3 Hz), 4.20-4.16 (4H, m), 3.30-3.26 (4H, m). FAB-Mass: 364 (M + +1) IR (HCl, KBr) (cm −1 ): 1591, 1547, 1512, 1468, 1441, 1371, 1348, 1266, 1219, 1016, 777. Example 397 N- (4-phenoxyphenyl) -4- (2-trifluoromethyl-4-quinolyl) -1-piperazinecarboamide (Compound 397) In practice, except that commercially available 2-trifluoromethyl-4- (1-piperazinyl) quinoline was used in place of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline The same procedure as in Example 60 was repeated to obtain the target compound. Yield: 41% Melting point: 203-204 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.20 (1H, dd, J = 8.3 Hz, 1.3 Hz), 8.07 (1H, dd, J = 8.3 Hz, 1.3 Hz), 7.78 (1H, ddd, J) = 8.3Hz, 8.3Hz, 1.3Hz), 7.63 (1H, ddd, J = 8.3Hz, 8.3Hz, 1.3Hz), 7.37-7.26 (4H, m), 7.17 (1H, s), 7.06 (1H, m ), 7.00-6.97 (4H, m), 6.55 (1H, brs), 3.84-3.80 (4H, m), 3.37-3.34 (4H, m). FAB-Mass: 493 (M + +1) IR (KBr) (cm- 1 ): 1639, 1537, 1508, 1489, 1412, 1227, 1134, 995, 949, 771. Example 398 N-benzyl-4- (6-trifluoromethyl-4-quinolyl) -1-piperazinthiocarboamide (Compound 398) Virtually the same procedure as in Example 125 except that 6-trifluoromethyl-4- (1-piperazinyl) quinoline was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline Was repeated to obtain the target compound. Yield: 76% Melting Point: 158-159 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.79 (1H, d, J = 5.3 Hz), 8.29 (1H, d, J = 2.0 Hz), 8.13 (1H, d, J = 8.9 Hz), 7.82 (1H, dd, J = 8.9 Hz, 2.0 Hz), 7.35-7.23 (5H, m), 6.90 (1H, d, J = 5.3 Hz), 6.36 (1H, brt, J = 5.0 Hz), 4.90 (2H , d, J = 5.0 Hz), 4.16-4.13 (4H, m), 3.31-3.27 (4H, m). FAB-Mass: 431 (M + +1) IR (KBr) (cm −1 ): 1583, 1531, 1387, 1340, 1315, 1215, 1161, 1113, 1014, 854, 743. In Examples 399-402 below, 6-chloro-4- (1-piperazinyl) quinoline in place of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline corresponds to instead of phenylisocyanate Virtually the same procedure as in Example 1 was repeated except that isocyanate or isothiocyanate was used to obtain the desired compound. Example 399 4- (6-Chloro-4-quinolyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 399) Yield: 83% Melting point: 188-189 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.72 (1H, d, J = 5.0 Hz), 8.00 (1H, d, J = 8.9 Hz), 7.96 (1H, d, J = 2.3 Hz), 7.60 (1H, dd, J = 8.9 Hz, 2.3 Hz), 7.37-7.24 (4H, m), 7.07-6.98 (2H, m), 6.97-6.93 (4H, m), 6.85 (1H, d, J = 5.0 Hz), 3.80-3.76 (4H, m), 3.20-3.16 (4H, m). FAB-Mass: 459 (M + +1) IR (KBr) (cm- 1 ): 1639, 1537, 1506, 1489, 1417, 1371, 1236, 997, 838. Example 400 N-benzyl-4- (6-chloro-4-quinolyl) -1-piperazinthiocarboamide (Compound 400) Yield: 91% Melting Point: 173-174 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, d, J = 4.6 Hz), 7.96-7.93 (2H, m), 7.57 (1H, dd, J = 8.9 Hz, 2.0 Hz), 7.33 -7.23 (5H, m), 6.82 (1H, d, J = 4.6 Hz), 6.37 (1H, brt, J = 5.0 Hz), 4.90 (2H, d, J = 5.0 Hz), 4.12-4.09 (4H, m), 3.23-3.20 (4H, m). FAB-Mass: 399 (M + +3), 397 (M + +1) IR (KBr) (cm −1 ): 1579, 1531, 1495, 1450, 1387, 1369, 1360, 1333, 1275, 1225, 1205, 1142, 1011, 957, 926, 860, 843, 735. Example 401 N- (4-chlorobenzyl) -4- (6-chloro-4-quinolyl) -1-piperazinthiocarboamide (Compound 401) Yield: 99% Melting point: 89-90 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, d, J = 5.0 Hz), 7.94-7.91 (2H, m), 7.58 (1H, dd, J = 8.9 Hz, 2.0 Hz), 7.29 -7.21 (4H, m), 6.82 (1H, d, J = 5.0 Hz), 6.59 (1H, br), 4.87 (2H, d, J = 5.0 Hz), 4.16-4.12 (4H, m), 3.25- 3.21 (4H, m). FAB-Mass: 433 (M + +3), 431 (M + +1) IR (KBr) (cm −1 ): 1641, 1587, 1531, 1510, 1385, 1327, 1227, 1157, 1124, 999, 833. IR (KBr) (cm- 1 ): 1574, 1539, 1497, 1371, 1327, 1205, 1014, 841. Example 402 4- (6-Chloro-4-quinolyl) -N- (3-picoryl) -1-piperazinethiocarboamide dihydrochloride (Compound 402) Yield: 86% Melting Point: 162-164 ° C (HCl) 1 H-NMR (free base, CDCl 3 ) δ (ppm): 8.68 (1H, d, J = 5.0 Hz), 8.44-8.39 (2H, m), 7.97-7.94 (2H, m), 7.78 (1H, d, J = 7.9 Hz), 7.59 (1H, dd, J = 8.6 Hz, 2.0 Hz), 7.29-7.17 (2H, m), 6.85 (1H, d, J = 5.0 Hz), 4.94 (2H, d, J = 4.9 Hz), 4.21-4.17 (4H, m), 3.27-3.23 (4H, m). FAB-Mass: 400 (M + +3), 398 (M + +1) IR (HCl, KBr) (cm -1 ): 1605, 1585, 1539, 1506, 1471, 1410. Example 403 N-benzyl-4- (6-trifluoromethoxy-4-quinolyl) -1-piperazinthiocarboamide (Compound 403) Virtually the same procedure as in Example 1 except that 6-trifluoromethoxy-4- (1-piperazinyl) quinoline was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline Was repeated to obtain the target compound. Yield: 93% Melting point: 70-71 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.75 (1H, d, J = 5.0 Hz), 8.09 (1H, d, J = 9.3 Hz), 7.82 (1H, s), 7.53 (1H, d, J = 9.3 Hz), 7.36-7.30 (5H, m), 6.89 (1H, d, J = 5.0 Hz), 6.12 (1H, br), 4.91 (2H, d, J = 4.6 Hz), 4.16-4.12 ( 4H, m), 3.29-3.25 (4H, m). FAB-Mass: 447 (M + +1) IR (KBr) (cm −1 ): 1585, 1539, 1512, 1458, 1379, 1336, 1263, 1215, 1167, 1014. Example 404 N- (4-phenoxyphenyl) -4- (7-trifluoromethyl-4-quinolyl) -1-piperazincarboamide (Compound 404) Virtually the same procedure as in Example 60 except that 7-trifluoromethyl-4- (1-piperazinyl) quinoline was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline Was repeated to obtain the target compound. Yield: 100% Melting Point: 163-164 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.85 (1H, d, J = 5.0 Hz), 8.39 (1H, d, J = 1.7 Hz), 8.15 (1H, d, J = 8.9 Hz), 7.70 (1H, dd, J = 8.9 Hz, 1.7 Hz), 7.37-7.26 (4H, m), 7.09 (1H, m), 7.05-6.96 (5H, m), 6.59 (1H, brs), 3.83-3.79 ( 4H, m), 3.30-3.27 (4H, m). FAB-Mass: 493 (M + +1) In Examples 405 and 406 below, 7-chloro-4- (1-piperazinyl) quinoline instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline is substituted for phenylisocyanate Virtually the same procedure as in Example 1 was repeated except that isothiocyanate was used to afford the desired compound. Example 405 N-benzyl-4- (7-chloro-4-quinolyl) -1-piperazinthiocarboamide (Compound 405) Yield: 89% Melting Point: 84-86 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.59 (1H, d, J = 5.0 Hz), 7.93 (1H, d, J = 2.0 Hz), 7.89 (1H, d, J = 8.9 Hz), 7.39 (1H, dd, J = 8.9 Hz, 2.0 Hz), 7.31-7.20 (5H, m), 6.96 (1H, brt, J = 5.0 Hz), 6.74 (1H, d, J = 5.0 Hz), 4.90 (2H , d, J = 5.0 Hz), 4.12-4.11 (4H, m), 3.22-3.18 (4H, m). FAB-Mass: 399 (M + +3), 397 (M + +1) IR (KBr) (cm −1 ): 1537, 1504, 1427, 1379, 1335, 1250, 1011, 878, 824, 698. Example 406 4- (7-chloro-4-quinolyl) -N- (3-picoryl) -1-piperazinethiocarboamide dihydrochloride (Compound 406) Yield: 91% Melting Point: 170-173 ° C (HCl) 1 H-NMR (free base, CDCl 3 ) δ (ppm): 8.68 (1H, d, J = 5.0 Hz), 8.44 (1H, dd, J = 4.9 Hz, 1.7 Hz), 8.40 (1H, d, J = 2.0 Hz), 7.99 (1H, d, J = 2.0 Hz), 7.92 (1H, d, J = 8.9 Hz), 7.77 (1H, ddd, J = 7.9 Hz, 2.0 Hz, 1.7 Hz), 7.43 (1H , dd, J = 8.9 Hz, 2.0 Hz), 7.25 (1H, dd, J = 7.9 Hz, 4.9 Hz), 7.08 (1H, brt, J = 5.3 Hz), 6.81 (1H, d, J = 5.0 Hz) 4.94 (2H, d, J = 5.3 Hz), 4.20-4.16 (4H, m), 3.28-3.25 (4H, m). FAB-Mass: 400 (M + +3), 398 (M + +1) IR (HCl, KBr) (cm- 1 ): 1606, 1539, 1510, 1443, 1414, 1209, 1012. Example 407 N- (4-phenoxyphenyl) -4- (6,7-dimethoxy-4-quinolyl) -1-piperazinecarboamide (Compound 407) 4- (6,7-dimethoxy-4-quinolyl obtained according to Reference Example 17 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester In fact, the same procedure as in Example 329 was repeated except that tert-butylester was used to obtain the target compound. Yield: 57% Melting point: 204-206 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.59 (1H, d, J = 5.0 Hz), 7.40-7.26 (6H, m), 7.06 (1H, m), 6.98-6.93 (5H, m), 6.79 (1H, d, J = 5.0 Hz), 4.01 (3H, s), 4.00 (3H, s), 3.78 (4H, m), 3.19 (4H, m). FAB-Mass: 485 (M + +1) IR (KBr) (cm −1 ): 1633, 1583, 1541, 1508, 1487, 1423, 1248, 1217, 993, 843, 750. In Example 408-410 below, 4- (6,7 obtained according to Reference Example 18 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester Isothiocyanate where -dimethoxy-3-ethoxycarbonyl-4-quinolyl) -1-piperazinecarboxylic acid tert-butylester is substituted for 4-phenoxyphenylisocyanate (used in Example 408) Except where used, in fact the same procedure as in Example 329 was repeated to afford the desired compound. Example 408 4- (6,7-dimethoxy-3-ethoxycarbonyl-4-quinolyl) -N- (4-phenoxyphenyl) -1-piperazinecaramide (Compound 408) Yield: 100% Melting Point: 163-164 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.76 (1H, s), 7.52 (1H, brs), 7.37 (1H, s), 7.32 (1H, s), 7.29 (2H, d, J = 7.9 Hz), 7.22-7.16 (2H, m), 6.95 (1H, dd, J = 7.9 Hz, 1.0 Hz), 6.87-6.84 (4H, m), 4.31 (2H, q, J = 7.3 Hz), 3.94 ( 3H, s), 3.92 (3H, s), 3.70 (4H, m), 3.24 (4H, m), 1.32 (3H, t, J = 7.3 Hz). FAB-Mass: 557 (M + +1) IR (KBr) (cm −1 ): 1717, 1633, 1506, 1427, 1266, 1215, 1180, 999, 860. Example 409 N-benzyl-4- (6,7-dimethoxy-3-ethoxycarbonyl-4-quinolyl) -1-piperazinthiocarbonamide (Compound 409) Yield: 100% Melting point: 174-175 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.78 (1H, s), 7.40-7.26 (7H, m), 6.18 (1H, brt, J = 4.6 Hz), 4.91 (2H, d, J = 4.6 Hz), 4.40 (2H, q, J = 7.3 Hz), 4.08 (4H, m), 4.01 (3H, s), 4.00 (3H, s), 3.36-3.33 (4H, m), 1.41 (3H, t , J = 7.3 Hz). FAB-Mass: 495 (M + +1) IR (KBr) (cm- 1 ): 1701, 1537, 1497, 1475, 1427, 1263, 1203, 860. Example 410 4- (6,7-dimethoxy-3-ethoxycarbonyl-4-quinolyl) -N- (3-picoryl) -1-piperazinthiocarbonamide (Compound 410) Yield: 98% Melting point: 92-94 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.79 (1H, s), 8.48 (1H, dd, J = 5.0 Hz, 1.3 Hz), 8.47 (1H, d, J = 2.0 Hz), 7.80 (1H , ddd, J = 7.9 Hz, 2.0 Hz, 1.3 Hz), 7.41 (1H, s), 7.38 (1H, s), 7.28 (1H, dd, J = 7.9 Hz, 5.0 Hz), 6.65 (1H, brt, J = 5.3 Hz), 4.97 (2H, d, J = 5.3 Hz), 4.40 (2H, q, J = 7.3 Hz), 4.13 (4H, m), 4.03 (3H, s), 4.00 (3H, s) , 3.37-3.33 (4H, m), 1.41 (3H, t, J = 7.3 Hz). FAB-Mass: 496 (M + +1) IR (KBr) (cm- 1 ): 1712, 1502, 1478, 1427, 1263, 1205. Example 411 N- (4-phenoxyphenyl) -4- (8-trifluoromethyl-4-quinolyl) -1- piperazinecarboamide (Compound 411) Virtually the same procedure as in Example 60 except that 8-trifluoromethyl-4- (1-piperazinyl) quinoline was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline Was repeated to obtain the target compound. Yield: 100% Melting point: 214-215 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.88 (1H, d, J = 5.0 Hz), 8.24 (1H, d, J = 7.9 Hz), 8.04 (1H, d, J = 6.9 Hz), 7.55 (1H, dd, J = 7.9 Hz, 6.9 Hz), 7.37-7.26 (4H, m), 7.06 (1H, m), 6.99-6.93 (5H, m), 3.81-3.77 (4H, m), 3.22- 3.19 (4H, m). FAB-Mass: 493 (M + +1) IR (KBr) (cm −1 ): 1641, 1587, 1538, 1508, 1491, 1417, 1317, 1294, 1230, 1138, 999, 939, 825, 754. Example 412 4- (8-chloro-4-quinolyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 412) In fact the same procedure as in Example 60 was repeated except that 8-chloro-4- (1-piperazinyl) quinoline was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline. The desired compound was obtained. Yield: 99% Melting point: 174-175 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.82 (1H, d, J = 5.0 Hz), 7.93 (1H, d, J = 8.6 Hz), 7.79 (1H, d, J = 7.6 Hz), 7.43 -7.24 (6H, m), 7.04 (1H, dd, J = 7.3 Hz, 1.3 Hz), 6.96-6.90 (4H, m), 6.87 (1H, d, J = 5.0 Hz), 3.78-3.75 (4H, m), 3.18-3.15 (4H, m). FAB-Mass: 461 (M + +3), 459 (M + +1) IR (KBr) (cm −1 ): 1638, 1531, 1506, 1489, 1410, 1225, 996, 931, 831, 768. Example 413 4- (6-Methyl-5-nitro-2-trifluoromethyl-4-quinolyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 413) Except that 6-methyl-5-nitro-2-trifluoromethyl-4- (1-piperazinyl) quinoline was used in place of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline In fact, the same procedure as in Example 60 was repeated to obtain the target compound. Yield: 96% Melting point: 197-198 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.24 (1H, d, J = 8.6 Hz), 7.70 (1H, d, J = 8.6 Hz), 7.54 (1H, s), 7.35-7.25 (4H, m), 7.04 (1H, m), 6.98-6.93 (4H, m), 6.62 (1H, brs), 4.07-4.02 (2H, m), 3.33-3.23 (2H, m), 3.13-3.08 (2H, m), 2.93-2.84 (2H, m), 2.51 (3H, s). FAB-Mass: 552 (M + +1) IR (KBr) (cm −1 ): 1626, 1539, 1508, 1489, 1423, 1381, 1252, 1227, 1190, 1136, 1099, 989, 922, 841, 750. In Examples 414 and 415 below, 4- (1-prop obtained according to Reference Example 20 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester Virtually the same procedure as in Example 329 was repeated except that thalazinyl-l-piperazinecarboxylic acid tert-butylester was used in place of 4-phenoxyphenylisocyanate (which is used in Example 414). The compound was obtained. Example 414 N- (4-phenoxyphenyl) -4- (1-phthalazinyl) -1-piperazincarboamide (Compound 414) Yield: 98% (two stages) Melting point: 202-203 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 9.20 (1H, s), 8.08 (1H, dd, J = 8.6 Hz, 2.3 Hz), 7.95-7.83 (3H, m), 7.41-7.26 (4H, m), 7.07 (1H, m), 7.00-6.96 (4H, m), 6.82 (1H, brs), 3.84-3.81 (4H, m), 3.66-3.63 (4H, m). FAB-Mass: 426 (M + +1) IR (KBr) (cm −1 ): 1649, 1587, 1531, 1506, 1487, 1410, 1377, 1228, 1003, 835. Example 415 N- (4-nitrophenyl) -4- (1-phthalazinyl) -1-piperazincarboamide (Compound 415) Yield: 10% 1 H-NMR (DMSO-d 6 ) δ (ppm): 12.19 (1H, brs), 9.36 (1H, s), 8.27 (1H, dd, J = 8.6 Hz, 1.3 Hz), 8.17 (2H, d, J = 9.2 Hz), 8.04-7.84 (3H, m), 7.77 (2H, d, J = 9.2 Hz), 3.75 (4H, m), 3.15 (4H, m). In Examples 416 and 417 below, 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester instead of 4- (obtained according to Reference Example 20 (1) Example 329 is practically except that 4-chloro-1-phthalazinyl) -1-piperazinecarboxylic acid tert-butylester is used in which isocyanate is used instead of 4-phenoxyphenylisocyanate (used in Example 416). The same procedure was repeated to obtain the target compound. Example 416 4- (4-Chloro-1-phthalazinyl) -N- (4-phenoxyphenyl) -1-piperazincarboamide (Compound 416) Yield: 100% Melting point: 196-197 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.25 (1H, dd, J = 7.3 Hz, 3.0 Hz), 8.08 (1H, dd, J = 6.9 Hz, 2.3 Hz), 7.97-7.90 (2H, m ), 7.39-7.26 (4H, m), 7.04 (1H, m), 6.98-6.93 (4H, m), 6.88 (1H, brs), 3.82-3.78 (4H, m), 3.60-3.57 (4H, m) ). FAB-Mass: 462 (M + +3), 460 (M + +1) IR (KBr) (cm- 1 ): 1655, 1508, 1489, 1410, 1242, 997, 775. Example 417 4- (4-Chloro-1-phthalazinyl) -N- (4-nitrophenyl) -1-piperazinecarboamide (Compound 417) Yield: 68% 1 H-NMR (CDCl 3 ) δ (ppm): 9.21 (1H, brs), 8.24 (1H, m), 8.17 (1H, m), 8.11 (2H, d, J = 9.2 Hz), 8.09-7.98 ( 2H, m), 7.76 (2H, d, J = 9.2 Hz), 3.88-3.84 (4H, m), 3.57-3.53 (4H, m). FAB-Mass: 415 (M + +3), 413 (M + +1) Example 418 4- (4-benzyl-1-phthalazinyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 418) In fact the same procedure as in Example 60 was repeated except that 1-benzyl-4- (1-piperazinyl) phthalazine was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline. To obtain the target compound. Yield: 75% Melting point: 100-101 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.07-7.99 (2H, m), 7.81-7.70 (2H, m), 7.39-7.15 (10H, m), 7.03 (1H, m), 6.97-6.90 (4H, m), 4.60 (2H, s), 3.81-3.77 (4H, m), 3.57-3.53 (4H, m). FAB-Mass: 516 (M + +1) IR (KBr) (cm- 1 ): 1637, 1541, 1508, 1491, 1414, 1227, 995, 768. Example 419 4- (1,3-diethyl-1,3-dihydro-2-oxo-2H-imidazo [4,5-g] phthalazin-8-yl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 419) 4- (1,3-diethyl-1,3- obtained according to Reference Example 21 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazincarboxylic acid tert-butylester Virtually the same procedure as in Example 329, except that dihydro-2-oxo-2H-imidazo [4,5-g] phthalazin-5-yl) -1-piperazinecarboxylic acid tert-butylester was used. Repeatedly obtained the desired compound. Yield: 95% (two stages) Melting point: 125-128 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 9.18 (1H, s), 7.49 (1H, s), 7.40-7.28 (5H, m), 7.06 (1H, m), 7.01-6.98 (4H, m ), 6.77 (1H, brs), 4.13-4.04 (4H, m), 3.85-3.82 (4H, m), 3.63-3.60 (4H, m), 1.44 (3H, t, J = 7.3 Hz), 1.43 ( 3H, t, J = 7.3 Hz). FAB-Mass: 538 (M + +1) IR (KBr) (cm −1 ): 1728, 1714, 1645, 1506, 1491, 1471, 1414, 1223, 993, 752. Example 420 4- (1,3-Diethyl-1,3-dihydro-2-oxo-2H-imidazo [4,5-g] phthalazin-8-yl) -N- (4-nitrophenyl)- 1-piperazincarboamide (Compound 420) 4- (8-chloro-1,3-diethyl-1,3-dihydro-2-oxo-2H-imidazo [4,5-g] phthalazine- obtained according to Reference Example 21 (5)- 50 ml of trifluoroacetic acid was added to a solution of 758.4 mg (1.65 mmol) of 5-yl) -1-piperazinecarboxylic acid tert-butyl ester in 20 ml of dichloromethane while cooling with ice, followed by stirring at the same temperature for 5 hours. . The solvent is evaporated and the residue is azeotropically distilled twice with toluene. The obtained residue is taken up in 20 ml of acetic acid, 5 ml of water and 300 mg suspension of 10% palladium-carbon are added, followed by stirring overnight at room temperature under hydrogen vapor. The catalyst is separated by filtration using celite, the solvent is evaporated and the residue is azeotropically distilled with trimethylamine. The obtained residue was dissolved in 10 ml of dimethylformamide, 297.3 mg (1.81 mmol) of 4-nitrophenyl isocyanate was added, followed by stirring at room temperature for 2 hours. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel chromatography to obtain the target compound as colorless crystals. Yield: 53% 1 H-NMR (CDCl 3 ) δ (ppm): 9.18 (1H, s), 8.98 (1H, brs), 8.11 (2H, d, J = 7.3 Hz), 7.76 (2H, d, J = 7.3 Hz) , 7.53 (1H, s), 7.49 (1H, s), 4.13-4.03 (4H, m), 3.90-3.87 (4H, m), 3.57-3.54 (4H, m), 1.43 (3H, t, J = 7.3 Hz), 1.42 (3H, t, J = 7.3 Hz). FAB-Mass: 491 (M + +1) Example 421 4- (5-chloro-1,3-diethyl-1,3-dihydro-2-oxo-2H-imidazo [4,5-g] phthalazin-8-yl) -N- (4- Phenoxyphenyl) -1-piperazinecarboamide (Compound 421) 4- (8-chloro-1,3- obtained according to Reference Example 21 (5) instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester In practice, except that diethyl-1,3-dihydro-2-oxo-2H-imidazo [4,5-g] phthalazin-5-yl) -1-piperazinecarboxylic acid tert-butylester was used The same procedure as in Example 329 was repeated to obtain the target compound. Yield: 100% Melting Point: 172-173 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 7.67 (1H, s), 7.49 (1H, s), 7.38 (2H, d, J = 8.9 Hz), 7.32-7.27 (2H, m), 7.08- 7.02 (2H, m), 6.98-6.94 (4H, m), 4.16-4.05 (4H, m), 3.84-3.80 (4H, m), 3.57-3.53 (4H, m), 1.44 (3H, t, J = 7.3 Hz), 1.44 (3H, t, J = 7.3 Hz). FAB-Mass: 572 (M + +1) IR (KBr) (cm- 1 ): 1726, 1495, 1412, 1383, 1223. Example 422 4- (1-Isoquinolyl) -N- (4-phenoxyphenyl) -1-piperazinecarboamide (Compound 422) 4- (1-isoquinolinyl) -1-piperazine obtained according to Reference Example 19 instead of 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester Virtually the same procedure as in Example 329 was repeated except that carboxylic acid tert-butylester was used to afford the desired compound. Yield: 100% Melting Point: 122-123 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.14 (1H, d, J = 5.9 Hz), 8.08 (1H, d, J = 8.3 Hz), 7.76 (1H, d, J = 8.3 Hz), 7.61 (1H, dd, J = 8.3 Hz, 6.9 Hz), 7.52 (1H, dd, J = 8.3 Hz, 6.9 Hz), 7.35-7.24 (5H, m), 7.03 (1H, m), 6.96-6.91 (5H m), 3.76-3.72 (4H, m), 3.45-3.41 (4H, m). FAB-Mass: 425 (M + +1) IR (KBr) (cm- 1 ): 1637, 1541, 1508, 1489, 1406, 1225. In Examples 423-425 below, 6,7-dimethol obtained according to the method described in South African Patent No. 67 06512 (1968) instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin Virtually the same procedure as in Example 1 was repeated except that oxy-4- (1-piperazinyl) isoquinoline was used in place of phenylisocyanate, matching isocyanate or isothiocyanate to afford the desired compound. Example 423 4- (6,7-dimethoxy-1-isoquinolyl) -N- (4-phenoxyphenyl) -1-piperazincarboamide (Compound 423) Yield: 87% Melting point: 178-179 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.07 (1H, d, J = 5.6 Hz), 7.37-7.26 (5H, m), 7.21 (1H, d, J = 5.6 Hz), 7.05 (1H, s), 7.05 (1H, m), 6.98-6.95 (4H, m), 6.76 (1H, brs), 4.01 (3H, s), 4.00 (3H, s), 3.78-3.74 (4H, m), 3.42 -3.38 (4H, m). FAB-Mass: 485 (M + +1) IR (KBr) (cm −1 ): 1633, 1541, 1508, 1489, 1477, 1417, 1377, 1296, 1250, 1215, 1201, 991, 860, 752. Example 424 N-benzyl-4- (6,7-dimethoxy-1-isoquinolyl) -1-piperazinthiocarboamide (Compound 424) Yield: 76% Melting point: 171-172 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.02 (1H, d, J = 5.6 Hz), 7.34-7.24 (6H, m), 7.19 (1H, d, J = 5.6 Hz), 7.03 (1H, s), 6.18 (1H, br), 4.90 (2H, d, J = 3.3 Hz), 4.07 (4H, m), 3.98 (3H, s), 3.97 (3H, s), 3.42-3.40 (4H, m ). FAB-Mass: 423 (M + +1) IR (KBr) (cm −1 ): 1568, 1539, 1508, 1479, 1437, 1419, 1335, 1267, 1230, 1215, 1201, 1161, 987. Example 425 4- (6,7-dimethoxy-1-isoquinolyl) -N- (3-picoryl) -1-piperazinthiocarboamide dihydrochloride (Compound 425) Yield: 66% Melting Point: 195-197 ° C (HCl) 1 H-NMR (free base, CDCl 3 ) δ (ppm): 8.43-8.41 (2H, m), 8.01 (1H, d, J = 5.6 Hz), 7.78 (1H, ddd, J = 7.9 Hz, 2.0 Hz , 1.7 Hz), 7.33 (1H, s), 7.24 (1H, dd, J = 7.9 Hz, 5.0 Hz), 7.20 (1H, br), 7.19 (1H, d, J = 5.6 Hz), 7.04 (1H, s), 4.95 (2H, d, J = 5.3 Hz), 4.17-4.13 (4H, m), 3.99 (3H, s), 3.98 (3H, s), 3.43-3.40 (4H, m). FAB-Mass: 424 (M + +1) IR (HCl, KBr) (cm −1 ): 1610, 1535, 1510, 1477, 1446, 1411, 1394, 1381, 1281. In Examples 426 and 427 below, instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, 6,7-dimethoxy-4- (1-piperazinyl) cinonoline is substituted with phenyl isocyanate. In fact the same procedure as in Example 1 was repeated except that a matching isocyanate or isothiocyanate was used to obtain the desired compound. Example 426 4- (6,7-dimethoxy-4-shinolinyl) -N- (4-phenoxyphenyl) -1-piperazincaramide (Compound 426) Yield: 73% Melting point: 165-167 ℃ 1 H-NMR (DMSO-d 6 ) δ (ppm): 8.85 (1H, s), 8.73 (1H, brs), 7.65 (1H, s), 7.51 (2H, d, J = 8.6 Hz), 7.36 ( 2H, dd, J = 8.6Hz, 7.9Hz), 7.15 (1H, s), 7.09 (1H, m), 6.97-6.94 (4H, m), 4.01 (3H, s), 4.01 (3H, s), 3.77-3.74 (4H, m), 3.41-3.38 (4H, m). FAB-Mass: 486 (M + +1) IR (KBr) (cm −1 ): 1662, 1533, 1506, 1435, 1416, 1381, 1229, 997, 868. Example 427 4- (6,7-dimethoxy-4-shinolinyl) -N- (3-picoryl) -1-piperazinthiocarboamide (Compound 427) Yield: 89% Melting Point: 181-190 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 8.49 (1H, d, J = 2.0 Hz), 8.46 (1H, dd, J = 4.9 Hz, 1.7 Hz), 7.78 (1H) , ddd, J = 7.9 Hz, 2.0 Hz, 1.7 Hz), 7.60 (1H, s), 7.28-7.22 (2H, m), 7.07 (1H, s), 4.98 (2H, d, J = 5.0 Hz), 4.24-4.20 (4H, m), 4.05 (3H, s), 4.03 (3H, s), 3.39-3.36 (4H, m). FAB-Mass: 425 (M + +1) IR (KBr) (cm- 1 ): 1535, 1506, 1437, 1416, 1373, 1288, 1242, 984. In Examples 428-431 below, instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin, (dl) -6,7-dimethoxy-4- (trans-2,5-dimethyl ( Virtually the same procedure as in Example 1 was repeated except that 1-piperazinyl)) quinazolin was used in place of phenylisocyanate matching isocyanate or isothiocyanate to afford the desired compound. Example 428 (dl) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-phenoxyphenyl)-(trans-2,5-dimethyl) -1-piperazinecarboamide (compound 428) Yield: 51% Melting point: 182-184 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.38-7.26 (5H, m), 7.09-7.04 (2H, m), 7.00-6.96 (4H, m), 6.54 (1H) , brs), 4.70 (1H, m), 4.39 (1H, m), 4.03 (3H, s), 4.00 (3H, s), 3.88 (2H, m), 3.82-3.74 (2H, m), 1.38 ( 3H, d, J = 6.6 Hz), 1.33 (3H, d, J = 6.6 Hz). FAB-Mass: 514 (M + +1) IR (KBr) (cm- 1 ): 1641, 1539, 1508, 1489, 1429, 1333, 1221, 1169. Example 429 (dl) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-nitrophenyl)-(trans-2,5-dimethyl) -1-piperazinecarboamide (Compound 429 ) Yield: 100% Melting Point: 226-227 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 8.15 (2H, d, J = 9.2 Hz), 7.63 (2H, d, J = 9.2 Hz), 7.52 (1H, brs) , 7.24 (1H, s), 7.09 (1H, s), 4.71 (1H, m), 4.48 (1H, m), 4.01 (3H, s), 4.00 (3H, s), 3.90-3.89 (2H, m ), 3.85-3.73 (2H, m), 1.37 (3H, d, J = 6.6 Hz), 1.33 (3H, d, J = 6.6 Hz). FAB-Mass: 467 (M + +1) IR (KBr) (cm −1 ): 1647, 1541, 1504, 1417, 1331, 1244, 1109, 1039, 1001, 851, 750. Example 430 (dl) -N-benzyl-4- (6,7-dimethoxy-4-quinazolinyl)-(trans-2,5-dimethyl) -1-piperazinthiocarboamide (Compound 430) Yield: 88% Melting point: 102-103 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.61 (1H, s), 7.35-7.28 (5H, m), 7.20 (1H, s), 7.06 (1H, s), 6.39 (1H, brt, J = 5.0 Hz), 5.01 (2H, dd, J = 14.5 Hz, 5.0 Hz), 4.86 (1H, dd, J = 14.6 Hz, 5.0 Hz), 4.73 (1H, m), 4.24 (1H, m), 3.98 (3H, s), 3.98 (3H, s), 3.95-3.71 (3H, m), 1.35 (3H, d, J = 6.6 Hz), 1.27 (3H, d, J = 6.6 Hz). FAB-Mass: 452 (M + +1) IR (KBr) (cm −1 ): 1576, 1506, 1473, 1429, 1335, 1242, 1211, 1167, 1055, 1003. Example 431 (dl) -4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-picoryl)-(trans-2,5-dimethyl) -1-piperazinthiocarboamide (compound 431) Yield: 73% Melting point: 224-225 ° C 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 8.49 (1H, dd, J = 4.6 Hz, 1.3 Hz), 8.45 (1H, s), 7.79 (1H, d, J = 7.6 Hz), 7.28 (1H, dd, J = 7.6 Hz, 4.6 Hz), 7.23 (1H, s), 7.05 (1H, s), 6.56 (1H, br), 5.05 (2H, dd, J = 15.2 Hz , 5.3 Hz), 4.91 (1H, dd, J = 14.9 Hz, 5.0 Hz), 4.75 (1H, m), 4.26 (1H, m), 4.02 (3H, s), 3.99 (3H, s), 3.91 ( 3H, m), 1.35 (3H, d, J = 6.3 Hz), 1.28 (3H, d, J = 6.9 Hz). FAB-Mass: 453 (M + +1) IR (KBr) (cm- 1 ): 1547, 1508, 1475, 1427, 1406, 1328, 1242, 1001. In Examples 432-434 below, 6,7-dimethoxy-4- [cis-3,5-dimethyl (1-pipera) instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin Genyl)] quinazoline was virtually the same procedure as in Example 1 except that a matching isocyanate or isothiocyanate was used in place of phenylisocyanate to afford the desired compound. Example 432 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-nitrophenyl)-(cis-2,6-dimethyl) -1-piperazinecarboamide (Compound 432) Yield: 95% Melting Point: 237-238 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.74 (1H, s), 8.37 (1H, brs), 8.15 (2H, d, J = 9.2 Hz), 7.76 (2H, d, J = 9.2 Hz) , 7.37 (1H, s), 7.29 (1H, s), 4.60 (2H, m), 4.05 (3H, s), 4.02 (3H, s), 4.00 (2H, m), 3.21 (2H, dd, J = 12.9 Hz, 4.3 Hz), 1.66 (6H, d, J = 6.9 Hz). FAB-Mass: 467 (M + +1) IR (KBr) (cm −1 ): 1662, 1535, 1502, 1427, 1329. 1313, 1246, 1140, 1111, 1061, 1003, 851. Example 433 N-benzyl-4- (6,7-dimethoxy-4-quinazolinyl)-(cis-2,6-dimethyl) -1-piperazinthiocarboamide (Compound 433) Yield: 90% Melting point: 165-166 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 7.38-7.29 (6H, m), 7.27 (1H, s), 5.98 (1H, brt, J = 4.6 Hz), 5.06 ( 2H, m), 4.95 (2H, d, J = 4.6 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.97 (2H, m), 3.26 (2H, dd, J = 13.2 Hz, 4.3 Hz), 1.64 (6H, d, J = 6.9 Hz). FAB-Mass: 452 (M + +1) IR (KBr) (cm −1 ): 1537, 1506, 1475, 1454, 1427, 1335, 1236, 1136, 1003, 698. Example 434 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-picoryl)-(cis-2,6-dimethyl) -1-piperazinthiocarboamide (Compound 434) Yield: 93% Melting Point: 187-188 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.71 (1H, s), 8.54-8.51 (2H, m), 7.78 (1H, m), 7.32-7.28 (3H, m), 6.32 (1H, brt , J = 5.0Hz), 5.09 (2H, m), 5.01 (2H, d, J = 5.0Hz), 4.04 (3H, s), 4.00 (3H, s), 4.00 (2H, m), 3.27 (2H , dd, J = 13.2 Hz, 4.3 Hz), 1.65 (6H, d, J = 6.6 Hz). FAB-Mass: 453 (M + +1) IR (KBr) (cm −1 ): 1541, 1506, 1475, 1429, 1371, 1336, 1255, 1236, 1213, 1134, 1061, 1001, 918, 872, 849, 822, 716. In Examples 435-437 below, 6,7-dimethol obtained according to the method described in South African Patent No. 67 06512 (1968) instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazolin The procedure of Example 1 was substantially repeated to give the desired compound except that oxy-4-homo (1-piperazinyl) quinazoline was used in place of phenylisocyanate matching isocyanate or isothiocyanate. Example 435 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-phenoxyphenyl) -1-homopiperazinecarboamide (Compound 435) Yield: 95% Melting point: 93-96 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.58 (1H, s), 7.33-7.26 (4H, m), 7.21 (1H, s), 7.18 (1H, s), 7.05 (1H, m), 6.97-6.92 (4H, m), 6.71 (1H, brs), 4.04-3.84 (6H, m), 4.00 (3H, s), 3.96 (3H, s), 3.69-3.65 (2H, m), 2.17- 2.14 (2H, m). FAB-Mass: 500 (M + +1) IR (KBr) (cm -1 ): 1641, 1576, 1508, 1489, 1417, 1356, 1223, 851. Example 436 N-benzyl-4- (6,7-dimethoxy-4-quinazolinyl) -1-homopiperazinethiocarboamide (Compound 436) Yield: 89% Melting point: 86-88 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.50 (1H, s), 7.30-7.22 (5H, m), 7.17 (1H, s), 7.15 (1H, s), 6.25 (1H, brt, J = 5.0 Hz), 4.85 (2H, d, J = 5.0 Hz), 4.22-4.20 (2H, m), 4.09-4.05 (2H, m), 3.97 (3H, s), 3.95 (3H, s), 3.89 -3.85 (4H, m), 2.20-2.16 (2H, m). FAB-Mass: 438 (M + +1) IR (KBr) (cm- 1 ): 1576, 1506, 1454, 1429, 1354, 1250, 1207. Example 437 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3-picoryl) -1-homopiperazinthiocarboamide dihydrochloride (Compound 437) Yield: 61% Melting Point: 177-183 ℃ (HCl) 1 H-NMR (free base, CDCl 3 ) δ (ppm): 8.50 (1H, s), 8.44 (1H, dd, J = 4.9 Hz, 1.6 Hz), 8.38 (1H, d, J = 2.3 Hz), 7.65 (1H, ddd, J = 7.6 Hz, 2.3 Hz, 1.6 Hz), 7.30 (1H, s), 7.18 (1H, dd, J = 7.6 Hz, 4.9 Hz), 7.16 (1H, s), 6.64 (1H , brt, J = 5.3 Hz), 4.89 (2H, d, J = 5.3 Hz), 4.26-4.24 (2H, m), 4.11-4.07 (2H, m), 4.00 (3H, s), 3.97 (3H, s), 3.97 (2H, m), 3.90-3.86 (2H, m), 2.22-2.17 (2H, m). FAB-Mass: 439 (M + +1) IR (HCl, KBr) (cm -1 ): 1622, 1527, 1502, 1470, 1441, 1392, 1360, 1323, 1284, 1217. In Examples 438 and 439 below, substantially the same procedure as in Example 1 was repeated except that a matching isothiocyanate was used in place of phenyl isocyanate to afford the desired compound. Example 438 4- (6,7-Dimethoxy-4-quinazolinyl) -N-methoxycarbonylmethyl-1-piperazinthiocarbonamide (Compound 438) Yield: 82% 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.28 (1H, s), 7.11 (1H, s), 6.28 (1H, brt, J = 4.3 Hz), 4.49 (2H, d, J = 4.3 Hz), 4.16-4.08 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.88-3.84 (4H, m), 3.82 (3H, s). FAB-Mass: 406 (M + +1) Example 439 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-morpholinophenyl) -1-piperazinthiocarboamide (Compound 439) Yield: 64% 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.43 (1H, brs), 8.10 (1H, d, J = 7.4 Hz), 7.28 (1H, s), 7.20-7.08 ( 4H, m), 4.21-4.16 (4H, m), 4.04 (3H, s), 4.00 (3H, s), 3.92-3.84 (8H, m), 2.93-2.90 (4H, m). FAB-Mass: 495 (M + +1) In Examples 440-444, obtained according to the method described in US Pat. No. 3,723,434 (1973) instead of 4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboxylic acid chloride One 4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboxylic acid chloride is substantially the same as in Example 1 except that a matching amine is used instead of 4-bromobenzylamine. The procedure was repeated to yield the target compound. Example 440 4- (6,7-dimethoxy-4-quinazolinyl) -N-phenacyl-1-piperazincarboamide (Compound 440) Yield: 19% 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 8.01 (2H, d, J = 7.9 Hz), 7.64 (1H, m), 7.55-7.49 (2H, m), 7.28 ( 1H, s), 7.12 (1H, s), 5.75 (1H, brt, J = 3.9 Hz), 4.82 (2H, d, J = 3.9 Hz), 4.04 (3H, s), 4.01 (3H, s), 3.73 (8 H, s). FAB-Mass: 436 (M + +1) Example 441 N- (4-tert-butylbenzyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 441) Yield: 96% 1 H-NMR (CDCl 3 ) δ (ppm): 8.66 (1H, s), 7.39-7.21 (5H, m), 7.09 (1H, s), 5.38 (1H, brt, J = 5.3 Hz), 4.43 ( 2H, d, J = 5.3 Hz), 4.01 (3H, s), 3.98 (3H, s), 3.69-3.63 (8H, m), 1.31 (9H, s). FAB-Mass: 464 (M + +1) Example 442 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-mesylbenzyl) -1-piperazinecarboamide (Compound 442) Yield: 69% 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.80 (2H, d, J = 8.5 Hz), 7.45 (2H, d, J = 8.5 Hz), 7.28 (1H, s) , 7.10 (1H, s), 5.54 (1H, brt, J = 5.6 Hz), 4.54 (2H, d, J = 5.6 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.70 (8H, brs), 3.02 (3H, s). FAB-Mass: 486 (M + +1) Example 443 4- (6,7-dimethoxy-4-quinazolinyl) -N- (4-sulfamoylbenzyl) -1-piperazinecarboamide (Compound 443) Yield: 79% 1 H-NMR (DMSO-d 6 ) δ (ppm): 8.56 (1H, s), 7.76 (2H, d, J = 8.3 Hz), 7.45 (2H, d, J = 8.3 Hz), 7.30 (3H, br), 7.24 (1H, s), 7.17 (1H, s), 4.32 (2H, d, J = 5.6 Hz), 3.93 (3H, s), 3.92 (3H, s), 3.61-3.59 (8H, m ). FAB-Mass: 487 (M + +1) Example 444 N- (2,3-dihydrobenzo [1,4] dioxyylmethyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 444) Yield: 97% 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.25 (1H, s), 7.09 (1H, s), 6.90-6.82 (4H, m), 5.21 (1H, brt, J = 5.6 Hz), 4.31 (2H, m), 4.02 (3H, s), 4.06-3.95 (1H, m), 3.98 (3H, s), 3.74-3.63 (8H, m), 3.59-3.48 (2H, m). FAB-Mass: 466 (M + +1) In Examples 445-447 below, substantially the same procedure as in Example 185 was repeated except that a matching amine was used instead of 4-bromobenzylamine to afford the desired compound. Example 445 4- (6,7-dimethoxy-4-quinazolinyl) -N-phenacyl-1-piperazinthiocarboamide (Compound 445) Yield: 42% Melting point: 99-100 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.06 (2H, d, J = 7.3 Hz), 7.67 (1H, m), 7.54 (2H, m), 7.28 (1H, s), 7.13 (1H, s), 6.94 (1H, br), 5.19 (2H, d, J = 3.3 Hz), 4.20-4.16 (4H, m), 4.04 (3H, s), 4.01 (3H, s ), 3.91-3.87 (4H, m). FAB-Mass: 452 (M + +1) Example 446 N- [1- (4-chlorophenyl) cyclopropylmethyl] -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 446) Yield: 91% Melting point: 108-111 ℃ 1 H-NMR (CDCl 3 ) δ (ppm): 8.63 (1H, s), 7.32-7.22 (5H, m), 7.09 (1H, s), 5.56 (1H, brt, J = 4.3 Hz), 4.03 ( 3H, s), 4.00-3.91 (4H, m), 3.98 (3H, s), 3.88 (2H, d, J = 4.3 Hz), 3.84-3.80 (4H, m), 1.02 (2H, m), 0.93 (2H, m). FAB-Mass: 500 (M + +3), 498 (M + +1) Example 447 4- (6,7-dimethoxy-4-quinazolinyl) -N- [2- (4-imidazoryl) ethyl] -1-piperazinthiocarboamide (Compound 447) Yield: 35% 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.99 (1H, brs), 7.60 (1H, s), 7.29 (1H, s), 7.24 (1H, s), 7.12 ( 1H, s), 6.88 (1H, s), 4.16-4.13 (4H, m), 4.02 (3H, s), 3.99 (3H, s), 3.93-3.83 (6H, m), 2.91 (2H, t, J = 5.9 Hz). FAB-Mass: 428 (M + +1) In Examples 448-456 below, substantially the same procedure as in Example 154 was repeated except that a matching amine was used instead of 4-isopropylbenzylamine to afford the desired compound. Example 448 N-benzyl-4- (6,7-dimethoxy-4-quinazolinyl) -N-methyl-1-piperazinthiocarboamide (Compound 448) Yield: 58% 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 7.40-7.26 (6H, m), 7.12 (1H, s), 4.95 (2H, s), 4.03 (3H, s), 4.01 (3H, s), 3.75 (8H, m), 3.05 (3H, s). FAB-Mass: 438 (M + +1) Example 449 4- (6,7-Dimethoxy-4-quinazolinyl) -N- (4-morpholinophenyl) -piperazinthiocarboamide (Compound 449) Yield: 64% 1 H-NMR (CDCl 3 ) δ (ppm): 8.64 (1H, s), 7.72 (1H, brs), 7.24 (1H, s), 7.13 (2H, d, J = 8.9 Hz), 7.09 (1H, s), 6.86 (2H, d, J = 8.9 Hz), 4.08-4.06 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.85-3.82 (8H, m), 3.14-3.11 (4H, m). FAB-Mass: 495 (M + +1) Example 450 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (6-methyl-2-benzothiazolyl) phenyl] -1-piperazinthiocarboamide (Compound 450) Yield: 57% 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.69 (1H, brs), 8.56 (1H, s), 8.01 (2H, d, J = 8.3 Hz), 7.93 (1H, s), 7.91 ( 1H, d, J = 7.9 Hz, 7.57 (2H, d, J = 8.3 Hz), 7.36 (1H, d, J = 7.9 Hz), 7.26 (1H, s), 7.24 (1H, s), 4.17 ( 4H, m), 3.94 (3H, s), 3.94 (3H, s), 3.87 (4H, m), 2.46 (3H, s). FAB-Mass: 557 (M + +1) Example 451 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (2-pyridyl) phenyl] -1-piperazinthiocarboamide (Compound 451) Yield: 72% 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, d, J = 4.6 Hz), 8.65 (1H, s), 7.98-7.95 (2H, d, J = 8.6 Hz), 7.78-7.67 ( 3H, m), 7.31-7.20 (4H, m), 7.08 (1H, s), 4.16-4.06 (4H, m), 4.02 (3H, s), 3.98 (3H, s), 3.93-3.80 (4H, m). FAB-Mass: 487 (M + +1) Example 452 4- (6,7-dimethoxy-4-quinazolinyl) -N- (2-thienylmethyl) -1-piperazinthiocarboamide (Compound 452) Yield: 82% 1 H-NMR (CDCl 3 ) δ (ppm): 8.62 (1H, s), 7.24 (1H, dd, J = 5.3 Hz, 1.0 Hz), 7.23 (1H, s), 7.10 (1H, s), 7.05 (1H, dd, J = 3.6 Hz, 1.0 Hz), 6.96 (1H, dd, J = 5.3 Hz, 3.6 Hz), 6.18 (1H, brt, J = 4.6 Hz), 5.08 (2H, d, J = 4.6 Hz), 4.12-4.07 (4H, m), 4.01 (3H, s), 3.98 (3H, s), 3.86-3.82 (4H, m). FAB-Mass: 430 (M + +1) Example 453 4- (6,7-dimethoxy-4-quinazolinyl) -N- [2- (2-pyridyl) ethyl] -1-piperazinthiocarboamide (Compound 453) Yield: 82% 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 8.51 (1H, dd, J = 5.0 Hz, 1.7 Hz), 8.12 (1H, br), 7.63 (1H, ddd, J = 7.9 Hz, 7.6 Hz, 1.7 Hz), 7.26-7.18 (3H, m), 7.13 (1H, s), 4.15-4.06 (6H, m), 4.02 (3H, s), 4.00 (3H, s), 3.88 -3.85 (4H, m), 3.11 (2H, t, J = 5.9 Hz). FAB-Mass: 439 (M + +1) Example 454 N- (2,3-dihydrobenzo [1,4] dioxyylmethyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboamide (Compound 454) Yield: 98% 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.26 (1H, s), 7.11 (1H, s), 6.90-6.83 (4H, m), 6.20 (1H, brt, J = 5.3 Hz), 4.53 (1H, m), 4.36 (1H, dd, J = 11.6 Hz, 2.3 Hz), 4.27 (2H, m), 4.11-4.04 (4H, m), 4.03 (3H, s), 3.99 (3H, s), 3.95 (1H, m), 3.92-3.85 (4H, m). FAB-Mass: 482 (M + +1) Example 455 4- (6,7-dimethoxy-4-quinazolinyl) -N- {4- [1- (1,2,4-triazolyl)] phenyl} -1-piperazinthiocarboamide (Compound 455 ) Yield: 61% 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.57 (1H, brs), 9.25 (1H, s), 8.56 (1H, s), 8.23 (1H, s), 7.79 (2H, d, J = 8.6 Hz), 7.53 (2H, d, J = 8.6 Hz), 7.26 (1H, s), 7.24 (1H, s), 4.17-3.99 (4H, m), 3.94 (3H, s), 3.94 (3H , s), 3.88-3.89 (4H, m). Example 456 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (2-oxopyrrolidinyl) phenyl] -1-piperazinthiocarboamide (Compound 456) Yield: 58% 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.39 (1H, brs), 8.55 (1H, s), 7.59 (2H, d, J = 8.3 Hz), 7.31 (2H, d, J = 8.3 Hz), 7.25 (1H, s), 7.23 (1H, s), 4.13 (4H, m), 3.94 (3H, s), 3.94 (3H, s), 4.05-3.81 (6H, m), 2.49-2.46 (2H, m), 2.09-2.03 (2H, m). Example 457 N- (4-acetamidophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide (Compound 457) 10 ml of 514.0 mg (1.26 mmol) of N- (4-aminophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide obtained according to Example 221 above To this solution was added 0.18 ml (1.89 mmol) and 0.53 ml (3.78 mmol) triethylamine with ice cooling. The mixture is stirred overnight at room temperature, 0.18 ml (1.81 mmol) of acetic anhydride and 0.53 ml (3.78 mmol) of trimethylamine are added, followed by stirring overnight. Methanol is added to the reaction mixture and the solvent is evaporated. The residue is then purified by silica gel chromatography to give the title compound as colorless crystals. Yield: 34% 1 H-NMR (DMSO-d 6 ) δ (ppm): 9.79 (1H, brs), 8.57 (1H, s), 8.56 (1H, brs), 7.44 (2H, J = 8.9 Hz), 7.37 (2H, d, J = 8.9 Hz), 7.24 (1H, s), 7.20 (1H, s), 3.93 (3H, s), 3.93 (3H, s), 3.68 (8H, m), 1.90 (3H, s). FAB-Mass: 451 (M + +1) Example 458 4- (6,7-dimethoxy-4-quinazolinyl) -N- [4- (3-ethylthioureido) phenyl] -1-piperazinecarboamide (Compound 458) 514.0 mg (1.26 mmol) of N- (4-aminophenyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinecarboamide obtained according to Example 221 was diluted with dimethylformamide. To a solution dissolved in 10 ml, 0.13 ml (1.51 mmol) of ethyl isothiocyanate are added and stirred at room temperature overnight. 0.13 ml (1.51 mmol) of ethyl isothiocyanate are added to the mixture, followed by stirring overnight. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel chromatography to obtain the target compound as colorless crystals. Yield: 33% 1 H-NMR (CDCl 3 ) δ (ppm): 8.69 (1H, s), 7.71 (1H, brs), 7.42 (2H, d, J = 8.6 Hz), 7.28 (1H, s), 7.15 (2H, d, J = 8.6 Hz), 7.11 (1H, s), 6.82 (1H, brs), 6.01 (1H, br), 4.04 (3H, s), 4.01 (3H, s), 3.77 (8H, m), 3.65 (2H, m), 1.18 (3H, t, J = 7.3 Hz). FAB-Mass: 496 (M + +1) Example 459 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3,4-methylenedioxybenzyl) -1-piperazinecarboamide (Compound 459) 152.7 mg (0.33 mmol of 4- (6,7-dimethoxy-4-quinazolinyl) -N- (3,4-methylenedioxybenzyl) -1-piperazinthiocarboamide obtained according to example 208 ) Is suspended in 10 ml of ethanol, 1 ml of 10 N aqueous sodium hydroxide solution and 1 ml of 30% hydrogen peroxide aqueous solution are added, followed by stirring overnight. An aqueous sodium thiosulfate solution is added and neutralized by adding 4N hydrochloric acid to the reaction mixture. The mixture is extracted with dichloromethane and the organic layer is washed with water and dried over sodium sulfide. After evaporation of the solvent, the residue is purified by silica gel chromatography to give the title compound as colorless crystals. Yield: 20% 1 H-NMR (CDCl 3 ) δ (ppm): 8.67 (1H, s), 7.27 (1H, s), 7.10 (1H, s), 6.84-6.78 (3H, m), 5.95 (2H, s), 4.80 (1H, brt, J = 5.3 Hz), 4.37 (2H, d, J = 5.3 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.71-3.63 (8H, m). FAB-Mass: 452 (M + +1) Example 460 4- (6-methoxy-7-methyl-4-quinazolinyl) -N- (3,4-methylenedioxybenzyl) -1-piperazinthiocarboamide (Compound 460) Example 208, in fact, except that 6-methoxy-7-methyl-4- (1-piperazinyl) quinazolin was used instead of 6,7-dimethoxy-4- (1-piperazinyl) quinazoline The same procedure was repeated to obtain the target compound. Yield: 47% 1 H-NMR (CDCl 3 ) δ (ppm): 8.65 (1H, s), 7.68 (1H, s), 7.04 (1H, s), 6.87-6.77 (3H, m), 5.97 (2H, s), 5.95 (1H, brt, J = 4.6 Hz), 4.80 (2H, d, J = 4.6 Hz), 4.09-4.07 (4H, m), 3.93 (3H, s), 3.89-3.85 (4H, m), 2.40 (3H, s). FAB-Mass: 452 (M + +1) Example 461 4- (6-Amino-7-ethylamino-4-quinazolinyl) -N-benzyl-1-piperazinthiocarboamide (Compound 461) 100 ml of ethanol and 4.26 g (9.44 mmol) of N-benzyl-4- (7-ethylamino-6-nitro-4-quinazolinyl) -1-piperazinethiocarboamide obtained according to Experimental Example 361 and water To 10 ml suspension, 4.26 g (76.3 mmol) of iron powder and 430 mg (1.59 mmol) of ferric chloride hexahydrate are added with ice cooling, followed by heating under reflux for 4 hours in an argon atmosphere. The iron powder is separated by filtration using celite and the residue is purified by silica gel chromatography to give the title compound as colorless crystals. Yield: 92% 1 H-NMR (CDCl 3 ) δ (ppm): 8.54 (1H, s), 7.38-7.37 (5H, m), 7.07 (1H, s), 6.93 (1H, s), 5.76 (1H, brt, J = 4.6 Hz), 4.91 (2H, d, J = 4.6 Hz), 4.07-4.04 (4H, m), 3.78-3.74 (4H, m), 3.61 (1H, br), 3.30 (2H, m), 1.68 (2H, broad singlet), 1.37 (3H, t, J = 6.9 Hz). FAB-Mass: 422 (M + +1) Example 462 4- (6-acetamido-7-ethylamino-4-quinazolinyl) -N-benzyl-1-piperazinthiocarboamide (Compound 462) 528 mg (1.25 mmol) of 4- (6-amino-7-ethylamino-4-quinazolinyl) -N-benzyl-1-piperazinthiocarboamide obtained according to Example 461 were added to 15 ml of dimethylformamide. To this solution, 0.57 ml (4.09 mmol) of triethylamine and 0.31 ml (3.29 mmol) of acetic anhydride were added, followed by stirring overnight at room temperature in an argon atmosphere. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel chromatography to obtain the target compound as colorless crystals. Yield: 27% 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, brs), 8.42 (1H, s), 7.76 (1H, s), 7.32-7.23 (5H, m), 6.74 (1H, s), 6.28 (1H, brt, J = 5.0 Hz), 4.86 (2H, d, J = 5.0 Hz), 4.75 (1H, br), 3.93 (4H, m), 3.73 (4H, m), 3.06 (2H, m ), 2.20 (3H, s), 1.19 (3H, t, J = 7.3 Hz). FAB-Mass: 464 (M + +1) Example 463 4- (6-Benzamido-7-ethylamino-4-quinazolinyl) -N-benzyl-1-piperazinthiocarboamide (Compound 463) 504.9 mg (1.20 mmol) of 4- (6-amino-7-ethylamino-4-quinazolinyl) -N-benzyl-1-piperazinthiocarboamide obtained according to Example 461 was added to 15 ml of dichloromethane. To the dissolved solution, 0.50 ml (3.6 mmol) of triethylamine and 0.17 ml (1.44 mmol) of benzoyl chloride were added, followed by stirring at room temperature overnight in an argon atmosphere. After addition of water, the reaction mixture is extracted with dichloromethane and the organic layer is washed with water and dried over sodium sulfide. After evaporation of the solvent, the residue is purified by silica gel chromatography to give the title compound as colorless crystals. Yield: 38% 1 H-NMR (CDCl 3 ) δ (ppm): 9.23 (1H, br), 8.36 (1H, s), 7.97 (2H, d, J = 7.3 Hz), 7.57-7.22 (9H, m), 6.79 ( 1H, s), 6.31 (1H, brt, J = 4.6 Hz), 4.83 (2H, d, J = 4.6 Hz), 4.65 (1H, br), 4.06-3.86 (4H, m), 3.67 (4H, m ), 3.05 (2H, dq, J = 6.9 Hz, 4.6 Hz), 1.17 (3H, t, J = 6.9 Hz). FAB-Mass: 526 (M + +1) Example 464 N-benzyl-4- [7-ethylamino-6- (3-ethylureido) -4-quinazolinyl] -1-piperazinthiocarboamide (Compound 464) 502.5 mg (1.19 mmol) of 4- (6-amino-7-ethylamino-4-quinazolinyl) -N-benzyl-1-piperazinthiocarboamide obtained according to Example 461 was charged with 10 m of dimethylformamide. To the solution dissolved in, 0.10 ml (1.19 mmol) of ethyl isothiocyanate was added, followed by stirring at room temperature overnight. 0.10 ml (1.19 mmol) of ethylisothiocyanate are added to the mixture, which is stirred for 4 hours while heating to 80 ° C. The reaction mixture is cooled to room temperature, poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel chromatography to obtain the target compound as colorless crystals. Yield: 29% 1 H-NMR (DMSO-d 6 ) δ (ppm): 13.00 (1H, brs), 8.59 (1H, s), 7.77-7.74 (3H, m), 7.64 (1H, s), 7.36-7.31 (5H , m), 4.36 (2H, m), 4.00 (4H, m), 3.79 (4H, m), 3.55 (2H, m), 3.37-3.28 (2H, m), 1.29 (3H, t, J = 7.3 Hz), 1.13 (3H, t, J = 7.3 Hz). FAB-Mass: 509 (M + +1) Example 465 N-benzyl-4- [7-ethylamino-6-mesylamino-4-quinazolinyl] -1-piperazinthiocarboamide (Compound 465) 528 mg (1.25 mmol) of 4- (6-amino-7-ethylamino-4-quinazolinyl) -N-benzyl-1-piperazinthiocarboamide obtained according to Example 461 were added to 15 ml of dimethylformamide. 0.57 ml (4.09 mmol) of triethylamine and 0.31 ml (1.55 mmol) of methanesulfonyl chloride were added to the dissolved solution, and the mixture was stirred overnight at room temperature in an argon atmosphere. To this mixture is added 0.06 ml (0.31 mmol) of methanesulfonyl chloride, followed by stirring at room temperature overnight. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel chromatography to obtain the target compound as colorless crystals. Yield: 6% 1 H-NMR (CDCl 3 ) (ppm): 8.48 (1H, s), 7.76 (1H, s), 7.36-7.29 (5H, m), 6.80 (1H, s), 5.94 (1H, brt, J = 4.9 Hz), 5.27 (1H, br), 4.88 (2H, d, J = 4.9 Hz), 4.05-4.01 (4H, m), 3.89-3.86 (4H, m), 3.19 (2H, m), 3.01 ( 3H, s), 1.27 (3H, t, J = 6.9 Hz). FAB-Mass: 500 (M + +1) Example 466 N- (2-chloroethyl) -4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazincarboamide (Compound 466) Virtually the same procedure as in Example 1 was repeated except that 2-chloroethylisocyanate was used instead of phenylisocyanate to give the desired compound. Yield: 60% 1 H-NMR (CDCl 3 ) δ (ppm): 8.70 (1H, s), 7.26 (1H, s), 7.10 (1H, s), 5.14 (1H, brt, J = 5.3 Hz), 4.03 (3H, s), 3.99 (3H, s), 3.72-3.64 (12H, m). FAB-Mass: 382 (M + +3), 380 (M + +1) Example 467 N-benzyl-4- (3-ethyl-1,3-dihydro-2-thioxo-2H-imidazo [4,5-g] quinazolin-8-yl) -1-piperazinthiocarboamide (Compound 467) 502.7 mg (1.19 mmol) of 4- (6-amino-7-ethylamino-4-quinazolinyl) -N-benzyl-1-piperazinthiocarboamide obtained according to Example 461 was dissolved in 10 ml of ethanol. To the solution, 1.66 ml (11.9 mmol) of triethylamine and 10 ml (166 mmol) of carbon disulfide were added, followed by stirring at room temperature overnight in an argon atmosphere. The solvent is evaporated and the residue is purified by silica gel chromatography to give the title compound as colorless crystals. Yield: 41% 1 H-NMR (DMSO-d 6 ) δ (ppm): 13.00 (1H, br), 8.60 (1H, s), 8.32 (1H, brt, J = 5.6 Hz), 7.76 (1H, s), 7.65 ( 1H, s), 7.33-7.23 (5H, m), 4.83 (2H, d, J = 5.6 Hz), 4.36 (2H, q, J = 6.9 Hz), 4.07 (4H, m), 3.82 (4H, m ), 1.29 (3H, t, J = 6.9 Hz). FAB-Mass: 464 (M + +1) Example 468 N-benzyl-4- (3-ethyl-2-methyl-3H-imidazo [4,5-g] quinazolin-8-yl) -1-piperazinthiocarboamide (Compound 468) 528 mg (1.25 mmol) of 4- (6-amino-7-ethylamino-4-quinazolinyl) -N-benzyl-1-piperazinthiocarboamide obtained according to Example 461 were added to 15 ml of dimethylformamide. To the solution dissolved in 0.55 ml (4.09 mmol) of trimethylamine and 0.31 ml (3.29 mmol) of acetic anhydride were added, followed by stirring at room temperature overnight in an argon atmosphere. The reaction mixture is poured into moles and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel chromatography to give the target compound as colorless crystals. Yield: 5% 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.21 (1H, s), 7.79 (1H, s), 7.38-7.27 (5H, m), 5.95 (1H, brt, J = 4.6 Hz), 4.91 (2H, d, J = 4.6 Hz), 4.16-3.93 (8H, m), 3.09 (2H, q, J = 7.3 Hz), 2.69 (3H, s), 1.48 (3H, t , J = 7.3 Hz). FAB-Mass: 446 (M + +1) Example 469 N-benzyl-4- (3-ethyl-3H-imidazo [4,5-g] quinazolin-8-yl) -1-piperazinthiocarboamide (Compound 469) 504.4 mg (1.20 mmol) of 4- (6-amino-7-ethylamino-4-quinazolinyl) -N-benzyl-1-piperazinthiocarboamide obtained according to Example 461 was added to 10 ml of dimethylformamide. To the solution dissolved in, 0.29 ml (3.60 mmol) of pyridine and 0.13 ml (1.49 mmol) of oxalyl chloride were added with ice cooling, followed by stirring overnight at room temperature in an argon atmosphere. The mixture is then heated to 80 ° C. with stirring for 5 hours. The reaction mixture is cooled to room temperature, poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel chromatography to obtain the target compound as colorless crystals. Yield: 55% 1 H-NMR (CDCl 3 ) δ (ppm): 8.68 (1H, s), 8.36 (1H, s), 8.14 (1H, s), 7.91 (1H, s), 7.37-7.31 (5H, m), 6.16 (1H, brt, J = 4.6 Hz), 4.92 (2H, d, J = 4.6 Hz), 4.33 (2H, q, J = 7.3 Hz), 4.16-4.08 (4H, m), 4.00-3.97 (4H m), 1.26 (3H, t, J = 7.3 Hz). FAB-Mass: 432 (M + +1) Reference Example 1 1,3-dihydro-1,3-dimethyl-2-oxo-8- (1-piperazinyl) -2H-imidazo [4,5-g] quinazoline (1) 7.86 g (40.9 mmol) of 1,3-dihydro-2-oxo-1H-benzimidazole-5-carboxylic acid methyl ester obtained according to a known method (Japanese Published Unexamined Patent Application No. 207388/86) To the solution dissolved in 100 ml of acetic anhydride, 3.46 ml (86.4 mmol) of fuming nitric acid was added with ice cooling, followed by stirring at 0 ° C. for 3.5 hours. 6.13 ml (98.5 mmol) of methyl iodide are added to the reaction mixture and stirred for 1.5 hours at the same temperature. The reaction mixture was poured into cold water, the precipitated crystals were collected by filtration, washed with water and dried to afford 7.78 g (80%) of 1,3-dihydro-6-nitro-2-oxo-2H-benzimidazole- 5-carboxylic acid methyl ester is obtained. (2) To the solution of 7.78 g (32.8 mmol) of the obtained compound (1) in 100 ml of dimethylformamide, 3.94 g (98.5 mmol) of sodium hydride was added, followed by stirring at the same temperature for 1.5 hours. The reaction mixture is poured into water, the precipitated crystals are collected by filtration, washed with water and dried to afford 8.58 g (99%) of 1,3-dihydro-1,3-dimethyl-6-nitro-2-oxo-2H- Benzimidazole-5-carboxylic acid methyl ester is obtained. (3) 1.6 g of 10% palladium-carbon was added to a solution of 8.58 g (32.4 mmol) of the obtained compound (2) in 100 ml of ethanol, followed by stirring at room temperature under a hydrogen atmosphere for 5.5 hours. The catalyst was filtered off with a strainer and the filtrate was concentrated under reduced pressure to afford 6-amino-1,3-dihydro-1,3-dimethyl-2-oxo-2H-benzimidazole-5-carboxylic acid methyl ester. To obtain. (4) The solution obtained by dissolving the obtained compound (3) in 100 ml formamide was stirred at 190 ° C. for two hours. After cooling it, the solution is poured into water and sodium chloride is added. The precipitated crystals were collected by filtration and 4.73 g (64%, 2 steps) of 1,3-dihydro-1,3-dimethylimidazo-2H, 7H-imidazo [4,5-g] quinazolin- 2,8-dione is obtained. (5) The obtained compound (4) (4.73 g, 20.6 mmol) was dissolved in 50 ml of phosphorus oxcyclolide and heated under reflux for 1.5 hours. The reaction mixture is cooled, excess phosphorus oxcyclolide is evaporated and cold water is added. The precipitated crystals are collected by filtration, washed with water and dried to give 8-chloro-1,3-dihydro-1,3-dimethyl-2-oxo-2H-imidazo [4,5-g] quinazoline . (6) To the solution obtained by dissolving 17.72 g (206 mmol) of anhydrous piperazine in 100 ml of isopropyl alcohol, the compound obtained in (5) was added, followed by heating while refluxing. The reaction mixture is concentrated and saturated aqueous sodium chloride solution is added to the residue, followed by extraction with chloroform. The organic layer was washed with saturated aqueous sodium chloride solution and dried over sodium sulfide, and then the solvent was blown to obtain the target compound. Reference Example 2 1,3-diethyl-1,3-dihydro-2-oxo-8- (1-piperazinyl) -2H-imidazo [4,5-g] quinazoline Reference Example 1 Using 2,3-dihydro-6-nitro-2-oxo-2H-benzimidazole-5-carboxylic acid methyl ester and ethyl iodide obtained in (1), Reference Example 1 (2)-( A method similar to that described in 6) was repeated to afford the desired compound. Reference Example 3 1,3-dihydro-1,3-dipropyl-2-oxo-8- (1-piperazinyl) -2H-imidazo [4,5-g] quinazoline Reference Example 1 Using 1,3-dihydro-6-nitro-2-oxo-2H-benzimidazole-5-carboxylic acid methyl ester and propyl iodide obtained in (1), Reference Example 1 (2)-( A method similar to that described in 6) was repeated to afford the desired compound. Reference Example 4 1,3-dibutyl-1,3-dihydro-2-oxo-8- (1-piperazinyl) -2H-imidazo [4,5-g] quinazoline Reference Example 1 1,3-dihydro-6-nitro-2-oxo-2H-benzimidazole-5-carboxylic acid methyl ester obtained in (1) and butyl iodide were used, and Reference Example 1 (2)-( A method similar to that described in 6) was repeated to afford the desired compound. Reference Example 5 4- (1,3-dihydro-3-ethyl-1-methyl-2-oxo-2H-imidazo [4,5-g] quinazolin-8-yl) -1-piperazinecarboxylic acid tert-butylester (1) 7-ethylamino-6-nitroquinazolin-4 (3H) -one (5.42 g, 23.2 mmol) obtained according to the method described in WO 95-06648 in 60 ml of phosphorus oxcyclolide Melted to reflux and heated for 2 hours. The reaction mixture is cooled to room temperature, excess phosphorus oxcyclolide is evaporated and the residue is azeotropically distilled twice with toluene. The obtained residue was dissolved in 50 ml of THF, and the solution was slowly added dropwise with ice cooling to a solution of 19.95 g (232.0 mmol) of anhydrous piperazine in 50 ml of ethanol, followed by stirring at room temperature overnight. After the reaction mixture was concentrated, saturated aqueous sodium chloride solution was added, followed by extraction with chloroform. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfide, and then the solvent was dried to give 6.28 g (94%) of 7-ethylamino-6-nitro-4- (1-piperazinyl) quinazolin. . (2) To a solution of 1.08 g (3.75 mmol) of 7-ethylamino-6-nitro-4- (1-piperazinyl) quinazolin in 20 ml of dichloromethane, 2.61 ml (18.7 mmol) of triethylamine and di 1.33 ml (5.79 mmol) of -tert-butyldicarbonate are added with ice cooling, followed by stirring at room temperature overnight. The reaction mixture is longitudinally fed and purified by silica gel chromatography to yield 1.39 g (92%) of 4- (7-ethylamino-6-nitro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester. (3) To the suspension of 1.29 g (3.22 mmol) of the compound obtained in the above step (2) and 20 ml of ethanol, 300 mg of 10% palladium-carbon was added, followed by stirring at room temperature under hydrogen vapor for 6 hours. The catalyst is separated by filtration using celite and the solvent is evaporated. The obtained residue was dissolved in 20 ml of dimethylformamide, 2.25 ml (16.1 mmol) of trimethylamine and 1.05 g (6.48 mmol) of 1,1'-carbonyldiimidazole were added, followed by 80 ° C. for 4.5 hours in an argon atmosphere. Heated and stirred. The reaction mixture is cooled to room temperature, poured into water and sodium chloride is added. The precipitated crystals were collected by filtration, washed with water and dried to give 2.02 g (quant.) Of 4- (1,3-dihydro-3-ethyl-2-oxo-2H-imidazo [4,5-g] quina. Zolin-8-yl) -1-piperazinecarboxylic acid tert-butylester is obtained. (4) To a solution of 1.42 g (3.57 mmol) of the compound obtained in step (3), dissolved in 15 ml of dimethylformamide, 213.7 mg (14.8 mmol) of 60% sodium hydride was added with ice cooling, followed by 30 minutes at room temperature. Stir. 0.44 ml (7.07 mmol) of methyl iodide is added to the mixture and stirred overnight at room temperature. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water and dried to afford 748.6 mg (51%) of the title compound. Reference Example 6 4- (6,7-dimethoxy-4-quinazolinyl) -1-piperazinthiocarboxylic acid chloride 6,7-dimethoxy-4- (1-piperazinyl) obtained according to the method described in South African Patent No. 67 06512 (1968) in a solution of 3.06 ml (40.1 mmol) of thiophosgene in 100 ml of dichloromethane. A solution of 10 g (36.5 mmol) of quinazoline in 100 m of dichloromethane and 12.4 ml (89.1 mmol) of triethylamine are added slowly with ice cooling. The mixture is stirred for 2 hours at the same temperature in an argon atmosphere. The solvent is evaporated and the residue is purified by silica gel chromatography to give 6.65 g (52%) of the title compound. Reference Example 7 4- (6,7-difluoro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester (1) In a solution of 4.81 g (27.8 mmol) of commercially available 2-amino-4,5-difluorobenzoic acid in 20 ml of ethanol, 1.92 ml (19.4 mmol) of piperidine and 1,3,5 2.25 g (27.8 mmol) of triazine are added and then heated to reflux for 6.5 hours in an argon atmosphere. The reaction mixture is cooled to room temperature and the solvent is evaporated. Water is added to the residue and the mixture is neutralized with 4N hydrochloric acid. The precipitated crystals are collected by filtration, washed with water and dried to yield 4.37 g (86%) of 6,7-difluoro-4 (3H) -quinazolone. (2) The compound (1.89 g, 10.4 mmol) obtained in the step (1) was dissolved in 25 ml of phosphorus oxcyclolide and heated under reflux for 1.5 hours. After cooling the reaction mixture to room temperature and evaporating excess phosphorus oxcyclolide, the residue is azeotropically distilled twice with toluene. The obtained residue was dissolved in 20 ml THF and 5 ml dimethylformamide, 7.25 ml (52.0 mmol) of triethylamine and 4.84 g (26.0 mmol) of N-tert-butoxycarbonylpiperazine were added thereto under an argon atmosphere. Stir at room temperature for 3 hours. The solvent is evaporated and water is added to the residue. The precipitated crystals are collected by filtration, washed with water and dried to give 2.60 g (71%) of the title compound. Reference Example 8 4- (7-ethoxy-6-methoxy-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butyl ester (1) To a solution of 52.6 g (313 mmol) of commercially available vanillic acid in 250 ml of dimethylformamide, 129.8 g (939 mmol) of potassium carbonate and 78.2 ml (657 mmol) of benzyl bromide were slowly added with ice cooling. After that, the mixture is stirred at room temperature overnight in an argon atmosphere. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water and dried to afford 104.2 g (96%) of 4-benzyloxy-3-methoxybenzoic acid benzyl ester. (2) A solution of 22.5 g (64.7 mmol) of the compound obtained in step (1) in 200 ml of anhydrous acetic acid was cooled to -15 ° C, 6.11 ml (153 mmol) of fuming nitric acid was added, and then ice-cooled. Stir for 7.5 hours. The reaction mixture is poured into cold water and adjusted to pH 7 with aqueous sodium hydroxide solution. The precipitated crystals are collected by filtration, washed with water and dried to give 25.6 g (100%) of 4-benzyloxy-5-methoxy-2-nitrobenzoic acid benzyl ester. (3) To a solution of 10.2 g (25.9 mmol) of the compound obtained in the above step (2) in 120 ml of acetic acid, 9.6 g (146 mmol) of zinc powder was added while cooling with ice, followed by argon steam at room temperature for 2 hours. Stir. The zinc powder is separated by filtration with celite and the solvent is evaporated. Dichloromethane was added to the residue, and the mixture was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfide, and the solvent was evaporated to 9.2 g (97%) of 2-amino-4-benzyloxy-5-methoxybenzoic acid. Benzyl ester is obtained. (4) The compound (9.15 g, 25.2 mmol) obtained in the step (3) was dissolved in 100 ml of formamide, heated to 150 ° C, and stirred for 1.5 hours. The reaction mixture is cooled to room temperature and poured into water, then sodium chloride is added. The precipitated crystals are collected by filtration, washed with water and dried to yield 6.18 g (87%) of 7-benzyloxy-6-methoxy-4 (3H) -quinazolin. (5) The compound (6.83 g, 24.2 mmol) obtained in the above step (4) was dissolved in 80 ml of phosphorus oxcyclolide and heated under reflux for 3 hours. The reaction mixture is cooled to room temperature, excess phosphorus oxcyclolide is evaporated and the residue is azeotropically distilled twice with toluene. The obtained residue was taken up in dichloromethane, the solution was washed with saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfide, and then the solvent was evaporated to give 6.66 g (92%) of 7-benzyloxy-4-chloro-6-methoxyquina. Obtain sleepy. (6) 6.66 g (22.2 mmol) of the compound obtained in the step (5) was dissolved in 50 ml of THF, 15.5 ml (111 mmol) of triethylamine, and 12.4 g (66.5 mmol) of N-tert-butoxycarbonylpiperazine. After the addition, it is heated under reflux for 4 hours in an argon atmosphere. The reaction mixture is cooled to room temperature and the solvent is evaporated and water is added to the residue, followed by sodium chloride. The precipitated crystals were collected by filtration, washed with water and dried to afford 9.25 g (93%) of 4- (7-benzyloxy-6-methoxy-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butylester. To obtain. (7) 4.67 g (10.4 mmol) of the compound obtained in the step (6) was dissolved in 40 ml ethanol, 1 g of 10% palladium-carbon was added, and the mixture was stirred while heating at 40 ° C. for 4 hours under hydrogen vapor. . The catalyst is separated by filtration using celite and the solvent is evaporated. The residue is taken up in 30 ml of dimethylformamide, 1.72 g (12.4 mmol) of potassium carbide and 1.24 ml (12.4 mmol) of ethyl iodide are added, followed by stirring at room temperature overnight in an argon atmosphere. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water, dried and purified by silica gel chromatography to give 3.28 g (82%) of the title compound. Reference Example 9 4- (7-isopropoxy-6-methoxy-4-quinazolinyl) -1-piperazincarboxylic acid tert-butyl ester (7-benzyloxy-6-methoxy-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butyl ester and isopropyl iodide obtained in Reference Example 8 (6) were used, and Reference Example 8 (7) The procedure similar to the above was repeated to obtain the target compound. Reference Example 10 4- (6-Ethoxy-7-methoxy-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butyl ester Using a commercially available isovanic acid, a procedure similar to that described in Reference Example 8 (1)-(7) was repeated to obtain the desired compound. Reference Example 11 4- (7-methoxy-6-mesyloxy-4-quinazolinyl) -1-piperazincarboxylic acid tert-butyl ester (1) Using a commercially available isovanic acid and repeating a procedure similar to that described in Reference Example 8 (1)-(6), (6-benzyloxy-7-methoxy-4-quinazolinyl ) -1-piperazinecarboxylic acid tert-butyl ester was obtained. (2) Dissolve 965.4 mg (2.15 mmol) of the compound obtained in the step (1) in 20 ml of ethanol, add 200 mg of 10% palladium-carbon, and then stir while heating to 50 ° C. under hydrogen vapor for 12.5 hours. . The catalyst is separated by filtration using celite and the solvent is evaporated. The residue is then dissolved in 10 ml of dichloromethane, 0.90 ml (6.46 mmol) of triethylamine and 0.25 ml (3.23 mmol) of methanesulfonyl chloride are added followed by stirring overnight at room temperature in an argon atmosphere. 15 m of pyridine is added to the reaction mixture and stirred overnight. Methanol is added to the reaction mixture, the solvent is evaporated and the residue is purified by silica gel chromatography to give 609.6 mg (65%) of the title compound. Reference Example 12 4- (7-chloro-6-nitro-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butyl ester Using the 7-chloro-6-nitro-4 (3H) -quinazolone obtained according to the method described in WO 95-06648, the procedure similar to that described in Reference Example 7 (2) was repeated to obtain the target compound. Obtained (45%). Reference Example 13 4- (4-benzo [g] quinazolinyl) -1-piperazinecarboxylic acid tert-butyl ester J. Chem. Soc., 4191-4206 (1956)], using the 4 (3H) -benzo [g] quinazone obtained according to the method described in the above, and repeating a procedure similar to that described in Reference Example 7 (2) Was obtained (43%). Reference Example 14 4- (6,7-ethylenedioxy-4-quinazolinyl) -1-piperazinecarboxylic acid tert-butyl ester J. Org. Chem., 40, 356-363 (1975), using 6,7-ethylenedioxy-4 (3H) -quinazone obtained according to the method described in the above, and similar to that described in Reference Example 7 (2) The procedure was repeated to afford the desired compound (45%). Reference Example 15 4- (2-chloro-6,7-dimethoxy-4-quinazolinyl) -1-perazinecarboxylic acid tert-butyl ester In a solution of 4.62 g (17.8 mmol) of commercially available 2,4-dichloro-6,7-dimethoxyquinazoline in 50 ml of dimethyl formamide, 12.4 ml (89.1 mmol) of triethylamine and N-tert- 3.65 g (19.6 mmol) of butoxycarbonylpiperazine was added, followed by stirring overnight at room temperature in an argon atmosphere. The reaction mixture is poured into water and sodium chloride is added. The precipitated crystals are collected by filtration to afford 7.15 g (98%) of the title compound. Reference Example 16 4- (6,7-dimethoxy-2-morpholino-4-quinazolinyl) -1-piperazincarboxylic acid tert-butyl ester To a solution of 1.22 g (2.99 mmol) of the compound obtained according to Reference Example 15 in 15 ml of N-methylpyrrolidone was added 1.30 ml (14.9 mmol) of morpholine, followed by stirring while heating to 140 ° C. for 3 hours. . The reaction mixture is cooled to room temperature, poured into water and sodium chloride is added. The precipitated crystals are collected by filtration, washed with water and dried to give 850.9 mg (62%) of the title compound. Reference Example 17 4- (6,7-dimethoxy-4-quinolyl) -1-piperazinecarboxylic acid tert-butyl ester J. Am. Chem. Soc., 68, 1264-1266 (1946)], using the 4-hydroxy-6,7-dimethoxyquinoline obtained according to the method described in the above, and repeating the procedure similar to Reference Example 7 (2) to the target compound Was obtained (10%). Reference Example 18 4- (6,7-dimethoxy-3-ethoxycarbonyl-4-quinolyl) -1-piperazinecarboxylic acid tert-butyl ester J. Med. Chem., 14, 1060-1066 (1971), using a 4-chloro-6,7-dimethoxy-3-ethoxycarbonylquinoline obtained according to the method described in the above, and repeating a similar procedure as in Reference Example 15 To give the title compound (91%). Reference Example 19 4- (1-isoquinolyl) -1-piperazinecarboxylic acid tert-butyl ester Using commercially available 1,3-dichloroisoquinoline, a similar procedure to that described in Reference Example 19 was repeated to give the desired compound (77%, 2 steps). Reference Example 20 4- (1-phthalazinyl) -1-piperazinecarboxylic acid tert-butyl ester (1) To a solution of 2.09 g (10.5 mmol) of commercially available 1,4-dichlorophthalazine in 20 ml of N-methylpyrrolidone, 7.32 ml (52.5 mmol) of triethylamine and N-tert- 2.35 g (12.6 mmol) of butoxycarbonylpiperazine was added, followed by stirring under heating in an argon atmosphere at 70 ° C. for 2 hours. The reaction mixture is cooled to room temperature and poured into water, then sodium chloride is added. The precipitated crystals were collected by filtration, washed with water, dried and purified by silica gel chromatography to give 2.77 g (76%) of 4- (4-chloro-1-phthalazinyl) -1-piperazinecarboxylic acid tert-butyl ester Obtained. (2) 2.30 g (6.59 mmol) of the compound obtained in the step (1) was dissolved in 30 ml of acetic acid, 500 mg of 10% palladium-carbon was added, and the mixture was stirred while heating to 50 ° C. under hydrogen vapor for 3 hours. . The catalyst is separated by filtration using celite, the solvent is evaporated and the residue is azeotropically distilled twice with toluene. The obtained residue was purified by silica gel chromatography to give 801.6 mg (39%) of the title compound. Reference Example 21 4- (1,3-diethyl-1,3-dihydro-2-oxo-2H-imidazo [4,5-g] phthalazin-5-yl) -1-piperazinecarboxylic acid tert-butylester (1) 48 g (296 mmol) of 1,3-dihydro-5,6-dimethyl-2H-benzimidazol-2-one synthesized according to Tetrahedron Lett., 28, 1389-1392 (1987) To the solution dissolved in 200 ml of dimethylformamide, 25 g (625 mmol) of 60% sodium hydride was added with ice cooling, followed by stirring for 10 minutes. 50 ml (625 mmol) of ethyl iodide is added to the mixture, followed by stirring at the same temperature for 1 hour. The reaction mixture was poured into cold water and the precipitated crystals were collected by filtration, washed with water and dried to give 37.6 g (58%) of 1,3-diethyl-1,3-dihydro-5,6-dimethyl-2H-benz Obtain imidazol-2-one. (2) 47 g (215 mmol) of the compound obtained in the above step (1) was dissolved in a mixture of 500 ml of tert-butanol and 500 ml of water, and then 170 g (1.08 mol) of potassium permanganate was gradually added with stirring at 110 ° C. Add. After stirring for 1 hour at the same temperature, the mixture was filtered through celite while hot and the filtrate obtained was concentrated. The residue is then dissolved in water and 2N aqueous hydrochloric acid solution is added dropwise. The precipitated crystals were collected by filtration and washed with water to yield 40 g (67%) of 1,3-diethyl-1,3-dihydro-2-oxo-2H-benzimidazole-5,6-dicarboxylic acid. do. (3) 39.6 mg (142 mmol) of the compound obtained in the step (2) was dissolved in a mixture of 200 ml of acetic acid and 200 ml of water, and 35 ml (722 mmol) of hydrazine monohydrate was added with ice cooling, followed by 1 hour. While refluxing and heating. The reaction mixture was cooled to room temperature and the precipitated crystals were collected by filtration, washed with water and then with methanol and dried to give 27.6 g (71%) of 1,3-diethyl-1,3,5,6,7,8 -Hexahydro-2H, 6H, 7H-imidazo [4,5-g] phthalazine-2,5,8-trione is obtained. (4) 5,8-dichloro-1,3-diethyl-1,3-dihydro by using a compound obtained in the above step (3) and repeating a similar process as described in Reference Example 7 (2) -2H-imidazo [4,5-g] phthalazin-2-one was obtained (64%). (5) 1.81 g (89%) of 4- (8-chloro-1,3-di by using a compound obtained in the above Step (4) and repeating a similar process as described in Reference Example 19 (1) Ethyl-1,3-dihydro-2-oxo-2H-imidazo [4,5-g] phthalazin-5-yl) -1-piperazinecarboxylic acid tert-butylester was obtained. (6) To a solution of 954.8 mg (2.07 mmol) of the compound obtained in the step (5) was dissolved in 10 ml of acetic acid, a suspension of 200 mg of 10% palladium-carbon in 2 ml water and 3 ml acetic acid was added, followed by hydrogen Stir while heating to 50 ° C. under steam for 5.5 h. The crystals are separated by filtration using celite, the solvent is evaporated and the residue is purified by silica gel chromatography to give 453.1 mg (51%) of the title compound. Preparation Example 1 Tablet Tablets having the following composition were prepared by conventional methods. Compound 77 100 mg Lactose 60 mg Potato starch 30 mg 2 mg polyvinyl alcohol Magnesium Stearate 1 mg Tar Colorant Trace Preparation Example 2 Powder Powders having the following composition were prepared by conventional methods. Compound 77 150 mg Lactose 280 mg Preparation Example 3 Syrup Syrups having the following composition were prepared by conventional methods. Compound 77 100 mg 40 g of white refined sugar 40 mg of ethyl p-hydroxybenzoate Propyl p-hydroxybenzoate 10 mg Strawberry flavor 0.1 cc Water was added to give a volume of 100 cc. The present invention inhibits the phosphorylation of PDGF receptors to prevent abnormal cell proliferation and cell wandering, resulting in a heterocyclic ring containing nitrogen that can prevent or treat cell-proliferative diseases such as atherosclerosis, vascular occlusion, cancer and glomerulosclerosis. Provided are compounds and pharmaceutically suitable salts.
权利要求:
Claims (9) [1" claim-type="Currently amended] A nitrogen-containing heterocyclic compound represented by the following formula (I) and a pharmaceutically acceptable salt thereof: [Formula I] {Wherein V is oxygen or a sulfur atom; W is 1,4-piperazindiyl or 1,4-homopiperazindiyl, in which the carbon of the ring may be substituted with 1-4-alkyl groups which may be the same or different; R 1 is a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted alkenyl group, substituted or unsubstituted Unsubstituted alkynyl group, substituted or unsubstituted aryl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted heteroaryl group, or substituted or unsubstituted heteroarylalkyl group; R 2 is a substituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, substituted or Unsubstituted aryl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted heteroarylalkyl group, -COR 10 (R 10 has the same meaning as R 1 ) Or —SO 2 R 11 (R 11 is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alicyclic alkyl group, a substituted or unsubstituted alicyclic heterocyclic group, a substituted or unsubstituted alkenyl group, substituted Substituted or unsubstituted alkynyl groups, substituted or unsubstituted aryl groups, substituted or unsubstituted aralkyl groups, substituted or unsubstituted heteroaryl groups, or Substituted or unsubstituted heteroarylalkyl group); R 3 , R 4 , R 5 and R 6 may be the same or different and each is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a nitro group, a cyano group, -OR 12 [R 12 is equal to R 10 Have the same meaning, or -COR 13 (R 13 has the same meaning as R 10 ) or -SO 2 R 14 (R 14 has the same meaning as R 11 )], -NR 15 R 16 {R 15 is R It has the same meaning as 10, R 16 can have the same meaning as R 10, or or -SO 2 R 17 (R 17 has the same meaning as R 11) or [X 1 is an oxygen atom or a sulfur atom; R 18 has the same meaning as R 10 or -OR 19 (R 19 has the same meaning as R 11 ) or -NR 20 R 21 (R 20 has the same meaning as R 10 and R 21 has R Having the same meaning as 10 , or R 20 and R 21 combine with an adjacent nitrogen atom to represent a substituted or unsubstituted nitrogen-containing alicyclic heterocyclic group); Or R 15 and R 16 combine with an adjacent nitrogen atom to represent a substituted or unsubstituted nitrogen-containing heterocyclic group}, [m represents an integer from 0 to 2; if m is 0 then R 22 has the same meaning as R 10 ; when m is 1 then R 22 has the same meaning as R 11 ; If m is 2 then R 22 has the same meaning as R 11 , or -OR 23 (R 23 has the same meaning as R 10 ) or -NR 24 R 25 (R 24 and R 25 can be the same or different. Each having the same meaning as R 10 , or R 24 and R 25 taken together with an adjacent nitrogen atom to represent a substituted or unsubstituted nitrogen-containing alicyclic heterocyclic group)], or-COR 26 [R 26 is Have the same meaning as R 10 , or -OR 27 (R 27 has the same meaning as R 10 ) or -NR 28 R 29 (R 28 and R 29 can be the same or different, each with R 10 Or R 28 and R 29, in combination with adjacent nitrogen atoms, represent a substituted or unsubstituted nitrogen-containing alicyclic heterocyclic group); Or any two adjacent groups of R 3 , R 4 , R 5 and R 6 combine to represent methylenedioxy or ethylenedioxy; Or any two adjacent groups of R 3 , R 4 , R 5 and R 6 combine with two adjacent carbon atoms to form a substituted or unsubstituted phenyl ring; Or R 3 and R 4 , R 4 and R 5 , or R 5 and R 6 are bonded to two adjacent carbon atoms [A represents an oxygen atom, a sulfur atom or -NR 30- (R 30 has the same meaning as R 10 ); Q 1 has the same meaning as R 10 , or -NR 31 R 32 (R 31 and R 32 can be the same or different and each has the same meaning as R 10 , or R 31 and R 32 are adjacent nitrogen. Combined with an atom to represent a substituted or unsubstituted nitrogen-containing alicyclic heterocyclic group) or -SR 33 (R 33 has the same meaning as R 10 ); or (R 34 and R 35 may be the same or different and each has the same meaning as R 10 ; Q 2 represents an oxygen atom, a sulfur atom or = N-CN), or (R 36 has the same meaning as R 10 ); Z is a nitrogen atom or CR 7 [R 7 R 10 have meanings or have, or halogen atom, -OR 37, such as an (R 37 has the same meaning as R 10), -SR 38 (R 38 is R 10 and Has the same meaning) or -NR 39 R 40 (R 39 has the same meaning as R 10 , R 40 has the same meaning as R 10 , or R 39 and R 40 are bonded to an adjacent nitrogen atom to Or an unsubstituted nitrogen-containing alicyclic heterocyclic group). Y represents a nitrogen atom or CR 8 (R 8 has the same meaning as R 7 ); X represents a nitrogen atom or CR 9 [R 9 represents a hydrogen atom or -COOR 41 (R 41 has the same meaning as R 18 ), and Provided that at least one of X, Y and Z represents a nitrogen atom. [2" claim-type="Currently amended] A compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein W is 4-piperazindiyl. [3" claim-type="Currently amended] 3. A compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein X and Z are each nitrogen and Y is CH. [4" claim-type="Currently amended] 4. A compound according to claim 3 or a pharmaceutically acceptable salt thereof, wherein R 3 and R 6 are each hydrogen atoms, and R 4 and R 5 are each a halogen atom, a substituted or unsubstituted alkyl group or R 12 . [5" claim-type="Currently amended] The compound of claim 4, or a pharmaceutically acceptable salt thereof, wherein R 12 is methyl. [6" claim-type="Currently amended] 6. A compound according to claim 5, wherein R 1 is a hydrogen atom, R 2 is substituted or unsubstituted aryl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted heteroaryl group, or substituted or unsubstituted Compound or a pharmaceutically acceptable salt thereof. [7" claim-type="Currently amended] The compound according to claim 6 or a pharmaceutically acceptable salt thereof, wherein R 2 is a substituted or unsubstituted aryl group or heteroaryl group, and V is an oxygen atom. [8" claim-type="Currently amended] The compound according to claim 6, or a pharmaceutically acceptable salt thereof, wherein R 2 is a substituted or unsubstituted aralkyl group or a substituted or unsubstituted heteroarylalkyl group, and V is a sulfur atom. [9" claim-type="Currently amended] A pharmaceutical composition comprising a nitrogen-containing heterocyclic compound represented by formula (I) or a pharmaceutically acceptable salt thereof.
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同族专利:
公开号 | 公开日 US6169088B1|2001-01-02| CA2239227C|2007-10-30| US6750218B2|2004-06-15| US20020068734A1|2002-06-06| CN1208404A|1999-02-17| NZ330571A|1999-10-28| US20030229077A1|2003-12-11| US6207667B1|2001-03-27| KR100622323B1|2006-11-30| HK1016174A1|2011-04-29| US6472391B2|2002-10-29| DE69739986D1|2010-10-21| CN1169795C|2004-10-06| AT480521T|2010-09-15| AU4470897A|1998-04-24| ES2351684T3|2011-02-09| EP0882717A4|2002-06-19| WO1998014431A1|1998-04-09| AU719392B2|2000-05-11| EP0882717A1|1998-12-09| DK0882717T3|2010-12-13| EP0882717B1|2010-09-08| JP4073961B2|2008-04-09| CA2239227A1|1998-04-09|
引用文献:
公开号 | 申请日 | 公开日 | 申请人 | 专利标题
法律状态:
1996-10-01|Priority to JP26074396 1996-10-01|Priority to JP96-260743 1997-10-01|Application filed by 히라타 다다시, 교와 핫꼬 고교 가부시끼가이샤 1999-09-27|Publication of KR19990071843A 2006-11-30|Application granted 2006-11-30|Publication of KR100622323B1
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申请号 | 申请日 | 专利标题 JP26074396|1996-10-01| JP96-260743|1996-10-01| 相关专利
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