 Quinazolines as mmp-13 inhibitors
专利摘要:
The present invention relates to compounds of formula (I), optionally, racemic forms thereof, isomers thereof, N-oxides thereof, and pharmaceutically acceptable salts thereof, wherein R 1 is hydrogen, amino, alkyl, alkenyl , Aminoalkyl, aryl, arylalkyl, heterocycle, and cycloalkylalkyl, (optionally substituted), W represents oxygen, sulfur, or = N-R ', wherein R' is as defined herein. , X 1 , X 2 and X 3 represent nitrogen or -CR 6 , where R 6 is as defined in the specification, and Y represents oxygen, sulfur, -NH, or -N (C 1 -C 6 ) alkyl. Z represents oxygen, sulfur, -NR 7 (where R 7 is as defined herein), and optionally a carbon atom, n is an integer from 1 to 8, and Z 1 is -CR 8 R 9 (wherein R 8 and R 9 represents the same as defined in the specification), a is an aromatic or non-aromatic, heterocyclic or non-heterocyclyl Denotes a ring system, m is an integer from 0 to 7, R 2 group (s) are as defined herein, R 3 is hydrogen, alkyl, alkenyl, alkynyl, or a group of the following formula (wherein, Z 2 , B, R 5 , P and q are as defined in the specification). Agents comprising such compounds are useful as specific inhibitors of type-13 substrate metalloproteases. 公开号:KR20030074827A 申请号:KR10-2003-7010659 申请日:2002-02-11 公开日:2003-09-19 发明作者:샤를 앙드리앙자라；니콜 챈텔-바비언；베르나르 고딜리에르；앙리 자코벨리；대니얼 프레드 오트와인；윌리엄 체스터 패트；리 팜；캐더린로즈 코스틀랜；마이클 윌리엄 윌슨 申请人:워너-램버트 캄파니 엘엘씨； IPC主号:
专利说明:
QUINAZOLINES AS MMP-13 INHIBITORS as an MMP-13 inhibitor [2] Matrix metalloprotease (MMPs) are enzymes involved in the regeneration of extracellular matrix tissues such as cartilage, tendons and joints. MMPs break down extracellular matrix tissue, which is compensated for by simultaneous regeneration in non-pathological physiological conditions. [3] Under normal physiological conditions, the activity of these extremely aggressive peptidases is controlled by special proteins that inhibit MMPs, such as tissue inhibitors of metalloprotease (TIMPs). [4] Local equilibrium of MMP and TIMP activity is important for the regeneration of extracellular matrix. The change in equilibrium results in an excess of active MMP relative to the inhibitor, which leads to pathological degradation of cartilage, which is particularly observed in rheumatoid arthritis and osteoarthritis. [5] In pathological situations, irreversible degradation of articular cartilage occurs, such as in rheumatoid diseases such as rheumatoid arthritis or osteoarthritis. In this pathology, cartilage breakdown predominates, causing tissue collapse and loss of function. [6] To date, more than 20 different substrate metalloproteases have been identified and classified into four groups, respectively, collagenase, gelatinase, stromelysin, and membrane-type MMPs (MT-MMPs). [7] Substrate metalloprotease-13 (MMP-13) is a collagenase type MMP that constitutes the predominant collagenase observed in osteoarthritis in which chondrocytes exhibit a pathology that directs the breakdown of cartilage. [8] Prior art includes arthritis, rheumatoid arthritis, osteoarthritis, osteoporosis, periodontal disease, inflammatory bowel disease, psoriasis, multiple sclerosis, heart failure, atherosclerosis, asthma, chronic obstructive pulmonary disease (COPD), age-related macular degeneration (ARMD) and cancer There is a need for new MMP inhibitors, more particularly MMP-13 inhibitors, for preventing and / or correcting non-uniformity of regeneration of the same extracellular matrix tissue. [9] MMP-inhibitor compounds are known. Most of the MMP-inhibitors as described by Montana and Baxter (2000) or Clark et al. Are not selective for a single MMP. [10] There is a need in the prior art for novel inhibitors active against substrate metalloprotease-13 to enrich the therapeutic agents that can be used to treat extracellular matrix disruption and pathologies associated with cancer. [1] The present invention relates to novel substituted quinazolines useful for the manufacture of a medicament for treating indications associated with treatment with a substrate metalloprotease-13 (MMP-13) inhibitor. The medicament is particularly suitable for the treatment of certain proliferative symptoms such as cancer as well as certain inflammatory symptoms such as rheumatoid arthritis or osteoarthritis. [11] Summary of the Invention [12] The present invention relates to substituted quinazolines of formula (I), optionally, racemic forms thereof, isomers thereof, N-oxides thereof, and pharmaceutically acceptable salts thereof: [13] [14] Where: [15] R 1 is hydrogen, amino, or [16] (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, mono (C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, di ( C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, aryl, aryl (C 1 -C 6 ) alkyl, heterocycle, and 3- to 6-membered cycloalkyl (C 1 -C 6 ) alkyl, wherein The groups may be unsubstituted or substituted with amino, (C 1 -C 6 ) alkyl, cyano, halo (C 1 -C 6 ) alkyl, C (═O) OR 4 , OR 4 and SR 4, where R 4 is hydrogen or (C 1 -C 6 ) alkyl; substituted with one or more groups which may be the same or different). [17] W represents an oxygen atom, a sulfur atom, or a = NR 'group where R' represents (C 1 -C 6 ) alkyl, hydroxyl, or cyano, [18] X 1 , X 2 and X 3 are independently of each other a nitrogen atom or a —CR 6 group wherein R 6 is hydrogen, (C 1 -C 6 ) alkyl, amino, mono (C 1 -C 6 ) alkylamino, di (C 1 -C 6 ) alkylamino, hydroxyl, (C 1 -C 6 ) alkoxy and halogen), provided that no more than two of X 1 , X 2 and X 3 simultaneously represent nitrogen atoms. Indicates, [19] Y represents a group selected from an oxygen atom, a sulfur atom, -NH, and -N (C 1 -C 6 ) alkyl, [20] Z represents an oxygen atom, a sulfur atom [21] -NR 7 group, where R 7 represents a group selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl, and heteroaryl), or [22] When Y is an oxygen atom, a sulfur atom, or a -N (C 1 -C 6 ) alkyl group, Z is optionally substituted or (C 1 -C 6 ) alkyl, aryl, aryl (C 1 -C 6 ) alkyl, Optionally represents a carbon atom substituted with an aromatic or non-aromatic heterocycle or cycloalkyl, [23] n is an integer from 1 to 8, [24] Z 1 is -CR 8 R 9 , wherein R 8 and R 9 are independently of each other hydrogen, (C 1 -C 6 ) alkyl, halo (C 1 -C 6 ) alkyl, halogen, amino, OR 4 , SR 4 or C (= O) OR 4, where R 4 represents hydrogen or (C 1 -C 6 ) alkyl] [25] when n is 2 or more, the hydrocarbon chain Z 1 optionally contains one or more multiple bonds and / or a sulfur atom in which one of the carbon atoms in the hydrocarbon chain Z 1 is an oxygen atom, unsubstituted or substituted with one or two oxygen atoms, Or a nitrogen atom unsubstituted or substituted with (C 1 -C 6 ) alkyl, [26] When one of the carbon atoms in the hydrocarbon chain Z 1 is unsubstituted or substituted with a sulfur atom substituted with one or two oxygen atoms, the -C (= Y) -Z- group may be optionally absent in general formula (I), [27] A is a 5 or 6 membered monocycle comprising 1 to 4 heteroatoms selected from aromatic or non-aromatic, nitrogen, oxygen and sulfur, and [28] Represents a group selected from the group consisting of two aromatic or non-aromatic bicycles which may be the same or different and comprise 0-4 heteroatoms selected from nitrogen, oxygen and sulfur, [29] m is an integer from 0 to 7, [30] R 2 groups may be the same or different and may be (C 1 -C 6 ) alkyl, halogen, —CN, N0 2 , SCF 3 , -CF 3 , -OCF 3 , -NR 10 R 11 , -OR 10 ,- SR 10 , -SOR 10 , -SO 2 R 10 ,-(CH 2 ) k SO 2 NR 1O R 11 , -X 5 (CH 2 ) k C (= O) OR 10 ,-(CH 2 ) k C ( = O) OR 10 , -X 5 (CH 2 ) k C (= 0) NR 1O R 11 ,-(CH 2 ) k C (= 0) NR 1O R 11 , and -X 4 -R 12 . , [31] Wherein X 5 represents a group selected from oxygen, sulfur optionally substituted with one or two oxygen atoms, and nitrogen substituted with hydrogen or (C 1 -C 6 ) alkyl, [32] k is an integer from 0 to 3, [33] R 10 and R 11 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, [34] X 4 represents a group selected from a single bond, —CH 2 —, an oxygen atom, sulfur optionally substituted with one or two oxygen atoms, and a nitrogen substituted with hydrogen or (C 1 -C 6 ) alkyl, [35] R 12 is substituted with one or more groups, which may be aromatic or nonaromatic, heterocyclic or non-heterocyclic, unsubstituted or the same or different groups selected from (C 1 -C 6 ) alkyl, halogen, hydroxyl and amino A 5- or 6-membered ring, and when the ring is heterocyclic, it contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur; [36] R 3 is hydrogen, [37] (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, wherein the group is unsubstituted or amino, cyano, halo (C 1 -C 6 ) alkyl , Cycloalkyl, -C (= 0) NR 10 R 11 , -C (= 0) OR 10 , OR 10 , and SR 10 , wherein R 10 and R 11 can be the same or different and are hydrogen or (C 1 -C 6 ) alkyl which is substituted with one or more groups which may be the same or different), or [38] Is a group of the formula [39] [40] Where p is an integer from 0 to 8, [41] Z 2 is —CR 13 R 14 wherein R 13 and R 14 are independently of each other hydrogen, (C 1 -C 6 ) alkyl, phenyl, halo (C 1 -C 6 ) alkyl, halogen, amino, OR 4 , SR 4 and —C (═O) OR 4, wherein R 4 represents hydrogen or (C 1 -C 6 ) alkyl, and when p is 2 or more, the hydrocarbon chain Z 2 optionally contains one or more multiple bonds Or one of the carbon atoms in the hydrocarbon chain Z 2 is replaced by an oxygen atom, a sulfur atom unsubstituted or substituted with one or two oxygen atoms, or a nitrogen atom unsubstituted or substituted with (C 1 -C 6 ) alkyl Can be, [42] B is an aromatic or non-aromatic five or six membered monocycle comprising 0 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and [43] Represents a group selected from a bicycle consisting of two aromatic or non-aromatic, five or six membered rings, which may be the same or different and include 0 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, [44] q is an integer from 0 to 7, [45] R 5 groups may be the same or different and may be selected from (C 1 -C 6 ) alkyl, halogen, —CN, NO 2 , —CF 3 , —OCF 3 , — (CH 2 ) k NR 15 R 16 , —N ( R 15 ) C (= O) R 16 , -N (R 15 ) C (= O) OR 16 , -N (R 15 ) SO 2 R 16 , -N (SO 2 R 15 ) 2 , -OR 15 , -S (O) k1 R 15 , -SO 2 -N (R 15 )-(CH 2 ) k2 -NR 16 R 17 ,-(CH 2 ) k SO 2 NR 15 R 16 , -X 7 (CH 2 ) k C (= 0) OR 15 ,-(CH 2 ) k C (= 0) OR 15 , -C (= 0) O- (CH 2 ) k2 -NR 15 R 16 , -C (= 0) O- (CH 2 ) k 2 -C (= 0) OR 18 , -X 7 (CH 2 ) k C (= 0) NR 15 R 16 ,-(CH 2 ) k C (= 0) NR 15 R 16 , -R 19 -C (= 0) OR 15 , -X 6 -R 20 , and -C (= 0) -R 21 -NR 15 R 16 , wherein [46] X 7 represents a group selected from an oxygen atom, sulfur optionally substituted with one or two oxygen atoms, and nitrogen substituted with hydrogen or (C 1 -C 6 ) alkyl, [47] k is an integer from 0 to 3, [48] k 1 is an integer from 0 to 2, [49] k 2 is an integer from 1 to 4, [50] R 15 , R 16 and R 17 , which may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, [51] R 18 is (C 1 -C 6) alkyl, -R 21 -NR 15 R 16, - R 21 -NR 15 -C (= O) -R 21 -NR 16 R 17, and -C (= O) OR A group selected from 21 -NR 15 R 16 , wherein R 21 is a linear or branched (C 1 -C 6 ) alkylene group and R 15 , R 16 and R 17 are as defined above, [52] R 19 represents a (C 3 -C 6 ) cycloalkyl group, [53] X 6 represents a group selected from a single bond, —CH 2 —, an oxygen atom, sulfur optionally substituted with one or two oxygen atoms, and a nitrogen atom substituted with a hydrogen atom or a (C 1 -C 6 ) alkyl group, [54] R 20 is unsubstituted or (C 1 -C 6 ) alkyl, halogen, hydroxyl, oxo, cyano, tetrazole, amino, and —C (═O) OR 4 , wherein R 4 is hydrogen or (C Aromatic or non-aromatic, heterocyclic or non-heterocyclic, 5- or 6-membered ring, which is substituted with one or more groups which may be the same or different, selected from 1 -C 6 ) alkyl) Heterocyclic, it contains from 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, [55] However, in the case where X 1 represents a nitrogen atom, X 2 can not represent a carbon atom substituted with a methyl group or an NH-CH 3. [56] The compounds of the present invention are useful as inhibitors, in particular selective inhibitors of the enzyme substrate metalloprotease-13 (MMP-13). [57] The invention also relates to compounds which are mainly used as intermediates in the synthesis of compounds of formula (I). The intermediate compound has the formula (III) [58] [59] here, [60] R 3 has the same meaning as defined for the compound of formula (I). [61] The invention also relates to compounds which are mainly used as intermediates in the synthesis of compounds of formula (I) having the formula (IV): [62] [63] here, [64] R 1 and R 3 have the same meanings as defined for the compound of formula (I). [65] The present invention also provides [66] R 2 , R 3 , Z 1 , A, n and m are as defined for the compound of formula (I), [67] X 1 , X 2 , X 3 are each a -CR 6 group, where R 6 is a hydrogen atom, [68] Y is O, [69] Z is -NR 7 where R 7 is as defined for the compound of formula (I), [70] A method for preparing a compound of formula (I) wherein W is O. [71] The method comprises reacting a compound of formula (II) with a pyridine and a compound of formula (V) to obtain a compound of formula (VI), reacting the compound of formula (VI) in the presence of Li0H so that R 3 is Characterized in that it comprises the step of obtaining a compound of formula (III) as mentioned. [72] [73] [74] Wherein R 3 is as defined above for the compound of formula (I). [75] [76] Where R 3 is as defined above. [77] <Formula III> [78] [79] The next step in the synthesis process involves the use of an acid activator such as O-[(ethoxycarbonyl) cyanomethylene amino] -N, N, N ', N'-tetramethyluronium tetrafluoroborate (TOTU). In the presence of the obtained compound of formula (III) is reacted with a compound of formula (VII) so that R 1 represents hydrogen and X 1 , X 2 and X 3 each represent -CR 6 where R 6 represents a hydrogen atom Y is O, Z is NR 7 , W is O, and A, R 2 , Z 1 , n and m yield the compound of formula (I) as defined above: [80] [81] here, [82] R 7 is selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, [83] A, R 2 , Z 1 , n and m are as defined above for the compound of formula (I). [84] In particular, when W is O, Y is O and Z is O, the compound of formula (III) is reacted with a compound of formula (XVI) to give a compound of formula (XVII), and in the presence of base (XVII) ) Is reacted with a compound of formula (VIII), XR 1 , wherein R 1 is as defined for compound of formula (I), X is a leaving group such as halogen, [85] X 1 , X 2 and X 3 are each -CR 6 , where R 6 is as defined above, W is O, Y is O, Z is 0, R 1 , R 2 , R 3 , Z 1 , A, n and m can yield compounds of formula (I) as defined above: [86] <Formula III> [87] [88] Wherein R 3 is as defined for the compound of formula (I). [89] [90] Wherein Z 1 , A, R 2 , n and m are as defined for compounds of formula (I). [91] [92] Where A, R 2 , R 3 , Z 1 , m and n are as defined for compounds of formula (I), wherein X 1 , X 2 and X 3 are each -CR 6 (wherein R 6 represents a hydrogen atom; It is displayed. [93] In particular, when X 2 and X 3 are each -CR 6 (where R 6 represents a hydrogen atom), X 1 is N, Z is O and Y is O, the compound of formula (XIX) is pyridine and Reacting with a compound of formula (V), O = C = NR 3 , wherein R 3 is as defined for the compound of formula (I) to obtain a compound of formula (XX), Reacting the compound in the presence of KMnO 4 to obtain a compound of formula (XXI), reacting the compound of formula (XXI) in the presence of SOCl 2 and CHCl 3 to obtain a compound of formula (XXII), and Reacting a compound of formula (XXII) with a compound of formula (XVI) wherein A, R 2 , R 3 , Z 1 , m and n are as defined above and X 2 and X 3 are Each having -CR 6, wherein R 6 represents a hydrogen atom, and R 3 is as defined for Formula (I). To give a compound of formula (I) having the corresponding definition: [94] [95] [96] Where R 3 is as defined above. [97] [98] Where R 3 is as defined above. [99] [100] Where R 3 is as defined above. [101] <Formula XVI> [102] [103] Wherein A, R 2 , Z 1 , n and m are as defined for compounds of formula (I). [104] [105] Wherein A, R 2 , R 3 , Z 1 , m and n are as defined above, X 2 and X 3 are each -CR 6 (where R 6 represents a hydrogen atom), and R 3 is of formula (I As defined for. [106] The invention also relates to pharmaceutical compositions comprising a compound of formula (I) and a pharmaceutically acceptable excipient. [107] The invention also relates to the preparation of a compound of formula (I) for the preparation of a medicament for treating a disease or indication relating to a method of treatment by inhibition of a substrate metalloprotease, more particularly type-13 substrate metalloprotease (MMP-13). It is about a use. [108] The invention also relates to a method of treatment by inhibition of a matrix metalloprotease, more particularly type-13 substrate metalloprotease (MMP-13), comprising administering to a patient an effective amount of a compound of formula (I) A method for treating a disease or indication. [109] Detailed description of the invention [110] The inventors have identified that the novel compounds according to the invention are substrate metalloprotease inhibitors, more particularly that the novel compounds are MMP-13 inhibitors. [111] One subject of the invention relates to the substituted quinazoline of the formula (I) or racemic forms thereof, isomers thereof, N-oxides thereof, and pharmaceutically acceptable salts thereof. [112] <Formula I> [113] [114] Wherein R 1 , R 2 , R 3 , X 1 , X 2 , X 3 , W, Y, Z, Z 1 , n and m are as defined above in the compound of formula (I). [115] The present invention is particularly [116] R 1 represents hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl or 3- to 6-membered cycloalkyl (C 1 -C 6 ) alkyl, [117] W represents an oxygen atom or a sulfur atom, [118] X 1 represents a nitrogen atom or -CR 6 , where R 6 represents a hydrogen atom, [119] X 2 and X 3 each represent —CR 6 (where R 6 represents a hydrogen atom), [120] Y represents an oxygen atom, [121] Z represents an oxygen atom or —NR 7 where R 7 represents a hydrogen atom. [122] The present invention also provides [123] n is an integer from 1 to 6, [124] Z 1 represents -CR 8 R 9 (wherein R 8 represents a hydrogen atom and R 9 represents a hydrogen atom or a methyl group), [125] when n is 2 or more, the hydrocarbon chain Z 1 optionally comprises a double bond, or [126] One of the carbon atoms in the hydrocarbon chain Z 1 may be replaced with an oxygen atom or a sulfur atom which is unsubstituted or substituted with one or two oxygens, [127] A is phenyl, pyridyl, thienyl, imidazolyl, furyl, piperidyl, 1,3-benzodioxyl, benzodioxyyl, benzothienyl, benzofuryl, benzofurazanyl, 2,1,3- Group selected from benzothiadiazolyl, and indolyl, [128] m is an integer from 0 to 7, [129] R 2 groups may be the same or different and may be (C 1 -C 6 ) alkyl, halogen, -CN, -CF 3 , -OCF 3 , -NR 10 R 11 , -OR 10 , -SR 10 , -SO 2 R 10, - (CH 2) k SO 2 NR 1O R 11, -X 5 (CH 2) k C (= O) OR 10, - (CH 2) k C (= O) OR 10, -X 5 ( CH 2 ) k C (= 0) NR 10 R 11 ,-(CH 2 ) k C (= 0) NR 10 R 11 , and -X 4 -R 12 , wherein [130] Wherein X 5 represents O, S or NH, k is an integer from 0 to 3, R 10 and R 11 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, X 4 Represents a single bond, —CH 2 —, or an oxygen atom, and R 12 is unsubstituted or substituted with one or more groups which may be the same or different, selected from (C 1 -C 6 ) alkyl, halogen, hydroxyl and amino Indicating [131] It relates to a compound of formula (I). [132] The present invention also provides [133] R 3 is hydrogen, (C 1 -C 6 ) alkyl or a group of formula wherein p is an integer from 0 to 3, [134] [135] Z 2 represents —CR 13 R 14 , wherein R 13 and R 14 independently of one another represent a group selected from hydrogen, methyl, or phenyl, [136] when p is 2 or more, the hydrocarbon chain Z 2 optionally contains one double bond, or [137] One of the carbon atoms of the carbon atoms in the hydrocarbon chain Z 2 is an oxygen atom, a sulfur atom unsubstituted or substituted with one or two oxygen atoms, a nitrogen atom unsubstituted or substituted with a (C 1 -C 6 ) alkyl, or carbonyl group Replaced, [138] B is phenyl, pyridyl, thienyl, imidazolyl, furyl, 1,3-benzodioxyl, benzodioxyyl, benzothienyl, benzofuryl, 2,1,3-benzothiadiazolyl, benzofurazanyl , A group selected from naphthyl and indolyl, [139] q is an integer from 0 to 3, [140] R 5 groups may be the same or different and may be selected from (C 1 -C 6 ) alkyl, halogen, —CN, NO 2 , —CF 3 , —OCF 3 , — (CH 2 ) k NR 15 R 16 , —N ( R 15 ) C (= O) R 16 , -N (R 15 ) COR 16 , -N (R 15 ) SO 2 R 16 , -N (SO 2 R 15 ) 2 , -OR 15 , -S (O) k1 R 15 , -SO 2 -N (R 15 )-(CH 2 ) k2 -NR 16 R 17 ,-(CH 2 ) k SO 2 NR 15 R 16 , -X 7 (CH 2 ) k C (= O ) OR 15 ,-(CH 2 ) k C (= O) OR 15 , -C (= O) O- (CH 2 ) k2 -NR 15 R 16 , -X 7 (CH 2 ) k C (= O) NR 15 R 16 , and — (CH 2 ) k C (═O) NR 15 R 16 , wherein [141] X 7 is S, O or NH, [142] k is an integer from 0 to 3, [143] k 1 is an integer from 0 to 2, [144] k 2 is an integer from 1 to 4, [145] R 15 , R 16 and R 17 relate to compounds of formula (I), which may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl. [146] More particularly, the present invention [147] R 1 is hydrogen, amino, [148] (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, mono (C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, di ( C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, aryl, aryl (C 1 -C 6 ) alkyl, heterocycle, and 3- to 6-membered cycloalkyl (C 1 -C 6 ) alkyl ( Wherein the group is unsubstituted or amino, (C 1 -C 6 ) alkyl, cyano, halo (C 1 -C 6 ) alkyl, C (═O) OR 4 , OR 4 and SR 4, where R 4 is hydrogen Or (C 1 -C 6 ) alkyl] which is substituted with one or more groups which may be the same or different, and [149] W represents an oxygen atom, a sulfur atom, or a = NR 'group where R' is (C 1 -C 6 ) alkyl, hydroxyl, or cyano), [150] X 1 represents a nitrogen atom or a -CR 6 group, wherein R 6 represents a hydrogen atom, [151] X 2 and X 3 independently of one another represent a —CR 6 group wherein R 6 represents a group selected from hydrogen, (C 1 -C 6 ) alkyl, amino, hydroxyl and halogen), [152] Y represents an oxygen atom, [153] Z represents an oxygen atom or a -NR 7 group wherein R 7 represents a group selected from hydrogen and (C 1 -C 6 ) alkyl [154] n is an integer from 1 to 6, [155] Z 1 represents —CR 8 R 9 , wherein R 8 and R 9 are, independently of each other, a group selected from hydrogen, (C 1 -C 6 ) alkyl, and hydroxyl, [156] when n is 2 or more, the hydrocarbon chain Z 1 optionally contains one or more multiple bonds, or [157] One of the carbon atoms in the hydrocarbon chain Z 2 may be replaced with an oxygen atom, an unsubstituted or substituted sulfur atom, or a nitrogen atom unsubstituted or substituted with (C 1 -C 6 ) alkyl, [158] A is phenyl, pyridyl, thienyl, imidazolyl, furyl, 1,3-benzodioxyl, benzodioxyyl, benzothienyl, benzofuryl, benzofurazanyl, 2,1,3-benzothiadiazolyl A group selected from, and indolyl, [159] m is an integer from 0 to 3, [160] R 2 groups may be the same or different and may be (C 1 -C 6 ) alkyl, halogen, -CN, -CF 3 , -OCF 3 , -NR 10 R 11 , -OR 10 , -SR 10 , -SO 2 R 10, - (CH 2) k SO 2 NR 1O R 11, -X 5 (CH 2) k C (= O) OR 10, - (CH 2) k C (= O) OR 10, -X 5 ( CH 2 ) k C (= 0) NR 10 R 11 ,-(CH 2 ) k C (= 0) NR 10 R 11 , and -X 4 -R 12 , wherein [161] X 5 here represents O, S or NH, [162] k is an integer from 0 to 3, [163] R 10 and R 11 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, [164] X 4 represents —CH 2 — or an oxygen atom, [165] R 12 represents phenyl which is unsubstituted or substituted with one or more groups which may be the same or different selected from (C 1 -C 6 ) alkyl, halogen and hydroxyl, [166] R 3 is hydrogen, (C 1 -C 6 ) alkyl, and [167] Is a group of the formula [168] [169] Where p is an integer from 0 to 6, [170] Z 2 represents —CR 13 R 14 , wherein R 13 and R 14 independently of one another represent hydrogen, (C 1 -C 6 ) alkyl and hydroxy, [171] When p is 2 or more, the hydrocarbon chain Z 2 optionally contains one or more multiple bonds, or a sulfur atom in which one of the carbon atoms in the hydrocarbon chain Z 2 is an oxygen atom, unsubstituted or substituted with one or two oxygen atoms, or unsubstituted Or a nitrogen atom substituted with (C 1 -C 6 ) alkyl, [172] B is phenyl, pyridyl, thienyl, imidazolyl, furyl, 1,3-benzodioxyl, benzodioxyyl, benzothienyl, benzofuryl, 2,1,3-benzothiadiazolyl, benzofurazanyl , A group selected from naphthyl and indolyl, [173] q is an integer from 0 to 3, [174] R 5 groups may be the same or different and may be selected from (C 1 -C 6 ) alkyl, halogen, —CN, NO 2 , —CF 3 , —OCF 3 , — (CH 2 ) k NR 15 R 16 , —N ( R 15 ) C (= O) R 16 , -N (R 15 ) COR 16 , -N (R 15 ) SO 2 R 16 , -N (SO 2 R 15 ) 2 , -OR 15 , -S (O) k1 R 15 , -SO 2 -N (R 15 )-(CH 2 ) k2 -NR 16 R 17 ,-(CH 2 ) k SO 2 NR 15 R 16 , -X 7 (CH 2 ) k C (= O ) OR 15 ,-(CH 2 ) k C (= O) OR 15 , -C (= O) O- (CH 2 ) k 2-NR 15 R 16 , -X 7 (CH 2 ) k C (= O ) NR 15 R 16 ,-(CH 2 ) k C (= 0) NR 15 R 16 and -X 6 -R 20 , wherein [175] X 7 is S, O or NH, [176] k is an integer from 0 to 3, [177] k 1 is an integer from 0 to 2, [178] k 2 is an integer from 1 to 4, [179] R 15 , R 16 and R 17 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, [180] X 6 represents a single bond, -CH 2- , an oxygen atom, or a sulfur atom unsubstituted or substituted with one or two oxygen atoms, [181] R 20 is aromatic or non-aromatic, heterocyclic or non-heterocyclic, unsubstituted or substituted with one or more groups which may be the same or different, selected from (C 1 -C 6 ) alkyl, halogen, hydroxyl and amino. And a 5 or 6 membered ring, when the ring is heterocyclic, comprising 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur. [182] The present invention also provides [183] R 1 is hydrogen, mono (C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, di (C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, (C 1 -C 6 ) Alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, aryl, aryl (C 1 -C 6 ) alkyl, and 3- to 6-membered cycloalkyl (C 1 -C 6 ) alkyl Represents a group selected from [184] W represents an oxygen atom or a sulfur atom, [185] X 1 represents a nitrogen atom or a —CH group, [186] X 2 and X 3 represent a -CH group, [187] Y represents a group selected from an oxygen atom, a sulfur atom, -NH, and -N (C 1 -C 6 ) alkyl, [188] Z represents an oxygen atom or an -NH group, [189] n is an integer from 1 to 3, [190] Z 1 represents —CR 8 R 9 , wherein R 8 and R 9 independently of one another represent a group selected from hydrogen, (C 1 -C 6 ) alkyl and hydroxy, [191] When n is 2 or more, the hydrocarbon chain Z 1 optionally contains one double bond, or one of the carbon atoms in the hydrocarbon chain Z 1 is an oxygen atom, an unsubstituted or substituted with one or two oxygen atoms, or —NH Can be replaced with [192] A is phenyl, pyridyl, thienyl, imidazolyl, furyl, 1,3-benzodioxolyl, benzodioxyyl, benzothienyl, benzofuryl, 2,1,3-benzothiadiazolyl, benzofurazanyl , A group selected from naphthyl and indolyl, [193] m is an integer from 0 to 3, [194] R 2 groups may be the same or different and may be (C 1 -C 6 ) alkyl, halogen, -CN, -CF 3 , -OCF 3 , -NR 10 R 11 , -OR 10 , -SR 10 , -SO 2 R 10, - (CH 2) k SO 2 NR 1O R 11, -X 5 (CH 2) k C (= O) OR 10, - (CH 2) k C (= O) OR 10, -X 5 ( CH 2 ) k C (= 0) NR 10 R 11 ,-(CH 2 ) k C (= 0) NR 10 R 11 , and -X 4 -R 12 , wherein [195] X 5 here represents O, S or NH, [196] k is an integer from 0 to 3, [197] R 10 and R 11 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, [198] X 4 represents -CH 2- , or an oxygen atom, and R 12 represents a phenyl group which is unsubstituted or substituted with one or more groups which may be the same or different selected from (C 1 -C 6 ) alkyl, halogen and hydroxyl. , [199] R 12 represents phenyl which is unsubstituted or substituted with one or more groups which may be the same or different selected from (C 1 -C 6 ) alkyl, halogen and hydroxyl, [200] R 3 is a group of the formula [201] [202] Where p is an integer from 0 to 3, [203] Z 2 represents —CR 13 R 14 , wherein R 13 and R 14 independently of one another represent hydrogen, (C 1 -C 6 ) alkyl and hydroxy, [204] When p is 2 or more, the hydrocarbon chain Z 2 optionally contains one double bond, or a sulfur atom in which one of the carbon atoms in the hydrocarbon chain Z 2 is an oxygen atom, unsubstituted or substituted with one or two oxygen atoms, or unsubstituted Or a nitrogen atom substituted with (C 1 -C 6 ) alkyl); [205] B is phenyl, pyridyl, thienyl, imidazolyl, furyl, 1,3-benzodioxyl, benzodioxyyl, benzothienyl, benzofuryl, 2,1,3-benzothiadiazolyl, benzofurazanyl , A group selected from naphthyl and indolyl, [206] q is an integer from 0 to 3, [207] R 5 groups may be the same or different and may be selected from (C 1 -C 6 ) alkyl, halogen, —CN, NO 2 , —CF 3 , —OCF 3 , — (CH 2 ) k NR 15 R 16 , —N ( R 15 ) C (= O) R 16 , -N (R 15 ) C (= O) OR 16 , -N (R 15 ) SO 2 R 16 , -N (SO 2 R 15 ) 2 , -OR 15 , -S (O) k1 R 15 , -SO 2 -N (R 15 )-(CH 2 ) k2 -NR 16 R 17 ,-(CH 2 ) k SO 2 NR 15 R 16 , -X 7 (CH 2 ) k C (= 0) OR 15 ,-(CH 2 ) k C (= 0) OR 15 , -C (= 0) O- (CH 2 ) k2 -NR 15 R 16 , -X 7 (CH 2 ) k C (= 0) NR 15 R 16 ,-(CH 2 ) k C (= 0) NR 15 R 16 , and -X 6 -R 20 , wherein [208] X 7 is S, O or NH, [209] k is an integer from 0 to 3, [210] k 1 is an integer from 0 to 2, [211] k 2 is an integer from 1 to 4, [212] R 15 , R 16 and R 17 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, [213] X 6 represents a single bond, -CH 2- , an oxygen atom or a sulfur atom which is unsubstituted or substituted with one or two oxygen atoms, [214] R 20 is aromatic or non-aromatic, heterocyclic or non-heterocyclic, unsubstituted or substituted with one or more groups which may be the same or different, selected from (C 1 -C 6 ) alkyl, halogen, hydroxyl and amino. And a 5 or 6 membered ring, when the ring is heterocyclic, comprising 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur. [215] The present invention also provides [216] R 1 represents hydrogen, (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, aryl (C 1 -C 6 ) alkyl, 3- to 6-membered cycloalkyl (C 1 -C 6 ) alkyl Indicate, [217] W represents an oxygen atom, [218] X 1 represents a -CH group or a nitrogen atom, [219] X 2 and X 3 each represent a -CH group, [220] Y represents an oxygen atom, [221] Z represents an oxygen atom or an -NH group, [222] n is an integer from 1 to 3, [223] Z 1 represents —CR 8 R 9 , wherein R 8 and R 9 independently of one another represent a group selected from hydrogen and methyl, [224] When n is 2 or more, the hydrocarbon chain Z 1 optionally contains one double bond, or one of the carbon atoms in the hydrocarbon chain Z 1 is an oxygen atom, an unsubstituted or substituted one or two oxygen atoms, or —NH Can be replaced with [225] A represents a group selected from phenyl, pyridyl, thienyl, imidazolyl, furyl, and 1,3-benzodioxolyl, [226] m is an integer from 0 to 3, [227] R 2 groups may be the same or different and may be (C 1 -C 6 ) alkyl, halogen, -CN, -CF 3 , -OCF 3 , -NR 10 R 11 , -OR 10 , -SR 10 , -SO 2 R 10, - (CH 2) k SO 2 NR 1O R 11, -X 5 (CH 2) k C (= O) OR 10, - (CH 2) k C (= O) OR 10, -X 5 ( CH 2 ) k C (= 0) NR 10 R 11 and- (CH 2 ) k C (= 0) NR 10 R 11 , [228] X 5 here represents O, S or NH, [229] k is an integer from 0 to 3, [230] R 10 and R 11 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, [231] R 3 is a group of the formula [232] [233] Where p is an integer from 0 to 3, [234] Z 2 represents —CR 13 R 14 , wherein R 13 and R 14 represent, independently of each other, a group selected from hydrogen and methyl, [235] When p is 2 or more, the hydrocarbon chain Z 2 optionally contains one double bond, or a sulfur atom in which one of the carbon atoms in the hydrocarbon chain Z 2 is an oxygen atom, unsubstituted or substituted with one or two oxygen atoms, or unsubstituted Or a nitrogen atom substituted with (C 1 -C 6 ) alkyl, [236] B represents a group selected from phenyl, pyridyl, thienyl, imidazole, furyl and 1,3-benzodioxolyl, [237] q is an integer from 0 to 3, [238] R 5 groups may be the same or different and may be selected from (C 1 -C 6 ) alkyl, halogen, —CN, NO 2 , —CF 3 , —OCF 3 , — (CH 2 ) k NR 15 R 16 , —N ( R 15 ) C (= O) R 16 , -N (R 15 ) C (= O) OR 16 , -N (R 15 ) SO 2 R 16 , -N (SO 2 R 15 ) 2 , -OR 15 , -S (O) k1 R 15 , -SO 2 -N (R 15 )-(CH 2 ) k2 -NR 16 R 17 ,-(CH 2 ) k SO 2 NR 15 R 16 , -X 7 (CH 2 ) k C (= 0) OR 15 ,-(CH 2 ) k C (= 0) OR 15 , -C (= 0) O- (CH 2 ) k2 -NR 15 R 16 , -X 7 (CH 2 ) k C (= 0) NR 15 R 16 , and-(CH 2 ) k C (= 0) NR 15 R 16 , wherein [239] X 7 is S, O or NH, [240] k is an integer from 0 to 3, [241] k 1 is an integer from 0 to 2, [242] k 2 is an integer from 1 to 4, [243] R 15 , R 16 and R 17 relate to compounds of formula (I), which may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl. [244] The invention also relates to compounds of formula (I), wherein R 1 represents a hydrogen atom or a (C 1 -C 6 ) alkyl group. [245] The invention further relates to compounds of formula (I) wherein W represents an oxygen atom, Y represents an oxygen atom, Z represents an NH group, Z 1 represents a methylene group and n is equal to zero. [246] The present invention also relates to compounds of formula (I), wherein X 1 represents a -CH group or a nitrogen atom and X 2 and X 3 each represent a -CH group. [247] The invention also relates to compounds of formula (I), wherein X 1 and X 3 each represent a -CH group and X 2 represents a -CH group or a nitrogen atom. [248] The invention also relates to compounds of formula (I), wherein X 1 and X 3 represent a -CH group and X 2 represents a nitrogen atom. [249] The invention also provides that A is a group selected from phenyl, pyridyl, 1,3-benzodioxolyl and benzofurazanyl, m is 0 or 1, and R 2 is (C 1 -C 6 ) alkoxy, hydroxy, halogen And a compound selected from (C 1 -C 6 ) thioalkoxy. [250] The present invention also provides [251] R 3 is a group of the formula [252] [253] Where p is 1, [254] Z 2 is a methylene group, [255] B represents a group selected from phenyl, pyridyl, 1,3-benzodioxolyl and benzofurazanyl, [256] q is an integer from 0 to 2, [257] R 5 is halogen, -CN,-(CH 2 ) k NR 15 R 16 , -S (O) k1 R 15 ,-(CH 2 ) k SO 2 NR 15 R 16 ,-(CH 2 ) k C (= O) OR 15 , -X 6 -R 20 and-(CH 2 ) k C (= 0) NR 15 R 16 , wherein [258] k is an integer from 0 to 1, [259] k 1 is an integer from 0 to 2, [260] R 15 and R 16 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, [261] X 6 represents a single bond, [262] R 20 represents a 5 membered heterocyclic ring which contains 3 to 4 heteroatoms selected from oxygen and nitrogen and a methyl group and is optionally substituted with a methyl or oxo group. [263] Among the groups defined above, the following substituents are particularly preferred: [264] Halogen: F, Cl, Br, I, preferably F, Br and Cl; [265] -(C 1 -C 6 ) alkyl: linear or branched containing 1 to 6, preferably 1 to 3 carbon atoms; [266] — (C 1 -C 6 ) alkoxy: linear or branched containing 1 to 6, preferably 1 to 3 carbon atoms; [267] -(C 3 -C 6 ) alkenyl: contains 3 to 6, preferably 3 or 4 carbon atoms, more particularly allyl; [268] -(C 3 -C 6 ) alkynyl: contains 3 to 6, preferably 3 or 4 carbon atoms, more particularly propargyl; [269] Aryl: contains 5 to 10, preferably 5 or 6 carbon atoms; [270] Heteroaryl: An aryl group with one or several hetero atoms selected from nitrogen, oxygen and sulfur in between. "Interrupted" means that a heteroatom can replace the carbon atom of the ring. Examples of the group containing a hetero atom are, among others, thienyl, pyridyl and benzofurazanyl; [271] Heterocycle: an aromatic or nonaromatic, 5- or 6-membered monocycle comprising 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur; [272] Aryl (C 1 -C 6 ) alkyl, wherein alkyl contains 1 to 6, preferably 1 to 4 carbon atoms; [273] Cycloalkyl: contains from 3 to 8, preferably from 3 to 6 carbon atoms; [274] Cycloalkyl (C 1 -C 6 ) alkyl: wherein alkyl comprises 1 to 6, preferably 1 to 3 carbon atoms and cycloalkyl comprises 3 to 6 carbon atoms. [275] Multiple bonds represent double bonds or triple bonds. [276] Preferred among the compounds of the present invention are those described in Examples 1 to 227 below. [277] More particularly, preferred compounds of the invention are compounds of formula (I) [278] 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] pyrimidine- 3-ylmethyl] -benzoic acid [279] 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6 carboxylic acid (1,3-benzodi Oxol-5-ylmethyl) -amide [280] 4- [6- (4-Fluoro-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid [281] 1-methyl-2,4-dioxo-3- [4- (5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl) -benzyl] -1,2 , 3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [282] 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethethyl] -hemicalcium benzoate salt [283] Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] pyrimidine -3-ylmethyl] -benzoate [284] 4- [6- (3-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid [285] 1-methyl-2,4-dioxo-3- [4- (2H-tetrazol-5-yl) -benzyl] -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4 -Methoxy-benzylamide [286] Methyl 2-hydroxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl Methyl] -benzoate [287] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 3-methoxy-benzylamide [288] 4- {6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin- 3-ylmethyl} -benzoic acid [289] 2-hydroxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoic acid [290] Methyl 4- [6- (3-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate [291] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 3-methoxy-benzylamide [292] 4-pyridylmethyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6carboxylate [293] Methyl 4- {6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazoline -3-ylmethyl} -benzoate [294] 1-methyl-3- [4- (5-methyl-1,2,4-oxadiazol-3-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro -Quinazolin-6-carboxylic acid 4-methoxy-benzylamide [295] 1-methyl-3- [4- (3-methyl-1,2,4-oxadiazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro -Quinazolin-6-carboxylic acid 4-methoxy-benzylamide [296] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1 2, 3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy-pyridine-4 -Ylmethyl) -amide [297] 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H] quinazolin-3-ylmethyl] -benzoic acid [298] 1- {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Phenyl} -cyclopropanecarboxylic acid [299] 4-pyridylmethyl 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [300] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 3-methoxy-benzylamide [301] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide [302] 3- (4-Dimethylcarbamoyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzyl amides [303] 1-methyl-3- [4- (2-methyl-2H-tetrazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6 -Carboxylic acid 4-methoxy-benzylamide [304] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy-pyridine- 4-ylmethyl) -amide [305] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridine-3- Monomethyl) -amide [306] Benzo [1,3] dioxol-5-ylmethyl-3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [307] 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide [308] 1-methyl-3- (4-methylcarbamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzylamide [309] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [310] 4- [6- (4-Hydroxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid [311] Methyl 4- [6- (4-fluoro-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate [312] 3- (4-chlorobenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amides [313] 1-methyl-3- [4- (1-methyl-1H-tetrazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6 -Carboxylic acid 4-methoxy-benzylamide [314] 3- (4-methoxybenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxybenzylamide [315] 4-pyridylmethyl 3- (benzo [1,3] dioxol-5-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [316] Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate [317] 1-methyl-2,4-dioxo-3-pyridin-4-ylmethyl-1,2,3,4-tetrahydro-quinazolincarboxylic acid 4-methoxy-benzylamide [318] 3- (4-Amino-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [319] 1-methyl-3- (4-nitro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [320] 2-methoxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoic acid [321] 1-methyl-3- (4-methylsulfamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzylamide [322] 1-Methyl-2,4-dioxo-3- (4-sulfamoyl-benzyl) -1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [323] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [324] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides [325] 3- (4-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides [326] 2-methyl-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] Benzoic acid [327] 3- (4-cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [328] 4- {1-Methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3-ylmethyl}- Benzoic acid [329] 3- (3-Fluoro-4-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy Benzylamine [330] 4- [1-Ethyl-6- (4-methoxy-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid [331] 3- (benzo [1,3] dioxol-5-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3 ] Dioxol-5-ylmethyl) amide [332] 3- (2'-cyano-biphenyl-4-ylmeethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4- Methoxy-benzylamide [333] 4- [1-Methyl-6- (4-methylsulfanyl-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid [334] 4- {6-[(benzofurazane-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl } -Benzoic acid [335] Methyl 2-methyl-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoate [336] 3- (4-acetylamino-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [337] 3- (benzo [1,3] dioxol-5-ylmethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide [338] 3- (4-dimethylcarbamoylmethyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzyl amides [339] Benzo [1,3] dioxol-5-ylmethyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [340] {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -phenyl} Acetic acid [341] (4- {1-methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3-ylmethyl} -Phenyl) -acetic acid [342] 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxybenzylamide [343] Methyl {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -phenyl }-acetate [344] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides [345] 2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-yl Methyl) amide [346] 1-methyl-3- (4-methylsulfamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzylamide [347] Methyl 4- {1-methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3-ylmethyl} -Benzoate [348] 2-fluoro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoic acid [349] 3- (4-cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxyl Acid 4-methoxy-benzylamide [350] 4- [6- (3-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] pyrimidine- 3-ylmethyl] -benzoic acid [351] 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -hemi magnesium salt [352] Example 164 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4 dihydro-2H-pyrido [2,3-d] Pyrimidin-3-ylmethyl] -benzoic acid [353] 3- [4- (N-methylsulfonylamino) -benzyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-meth Oxy-benzylamide [354] Ethyl 2-fluoro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4 dihydro-2H-quinazolin-3-ylmethyl ] -Benzoate [355] 3- (4-dimethylsulfamoyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzylamide [356] 3- (4-methoxybenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol- 5-ylmethyl) amide. [357] The present invention also relates to pharmaceutically acceptable salts of compounds of formula (I). Investigations into pharmaceutically acceptable salts are described in J. Chem. Pharm. Sci., 1977, vol. 66: 1-19. However, "pharmacologically acceptable salts of compounds of formula (I) with basicity" include hydrobromic acid, hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid, succinic acid, tartaric acid, citric acid, maleic acid, hydroxymaleic acid, Compound addition salts of formula (I) formed from non-toxic inorganic or organic acids such as benzoic acid, fumaric acid, toluenesulfonic acid, isethionic acid and the like. Various quaternary ammoniums of compounds of formula (I) are also included in this class of compounds. In addition, "pharmacologically acceptable salts of compounds of formula (I) with acidity" are, for example, hydroxides of alkali metals and alkaline earth metals (sodium, potassium, magnesium and calcium), amines (dibenzylethylenediamine, trimethyl Amine, piperidine, pyrrolidine, benzylamine, etc.) or compounds of formula (I) formed from non-toxic inorganic or organic bases such as quaternary ammonium hydroxides such as tetraammonium hydroxide. [358] As mentioned above, the compounds of formula (I) of the present invention are substrate metalloprotease inhibitors, and more particularly inhibitors of the MMP-13 enzyme. [359] In this regard, it is recommended to use them in the treatment of diseases or signs associated with treatment by MMP-13 inhibition. For example, any pathology associated with the destruction of extracellular matrix tissue, in particular arthritis, rheumatoid arthritis, osteoarthritis, osteoporosis, periodontal disease, inflammatory bowel disease, psoriasis, multiple sclerosis, heart failure, atherosclerosis, asthma, chronic obstructive pulmonary It may be advisable to use the compounds of the invention in the treatment of pathological phenomena such as disease (COPD), age-related macular degeneration (ARMD) and certain cancers. [360] Selectivity of Compounds of Formula (I) for MMP-13 Enzymes [361] Most of the substrate metalloprotease inhibitors described in the prior art are non-selective inhibitors that can simultaneously inhibit several substrate metalloproteases. For example, compounds such as CGS-27.023A and AG-3340 (Montana and Baxter (2000)) may contain MMP-1, MMP-2, MMP-3, MMP-9 and MMP-13. Suppress all That is, the compound of the prior art inhibits both collagen degrading enzyme, gelatin degrading enzyme and stromelysin type MMP. [362] According to the invention the compound of formula (I) is a selective inhibitor of MMP-13. "Selective inhibitors of MMP-13" is more IC 50 values for MMP-13 MMP low IC 50 is more than five times the IC 50 for the other MMP non-MMP-13, preferably a non-MMP-13 for, Refers to compounds of formula (I) that are 10, 15, 20, 30, 40, 50, 100 or 1000 times lower. [363] MMPs other than MMP-13 refer to substrate metalloproteases selected from MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-12 and MMP-14. [364] In particular, according to the invention, compounds of formula (I), more particularly compounds of the class shown as examples in the description of the invention, have an IC 50 value for the enzyme MMP-13 which is different from that of the substrate metalloprotease, in particular MMP. -1, 1000 times lower than the IC 50 value for MMP-2, MMP-3, MMP-7, MMP-9, MMP-12 and MMP-14. [365] As a result, the compounds of formula (I) according to the present invention are particularly useful for the treatment of diseases mainly associated with physiological imbalances between MMP-13 enzymes and their natural tissue inhibitors. [366] Pharmaceutical Formulations of Compounds of the Invention [367] Subject of the invention is also a pharmaceutical composition comprising a compound of formula (I) as defined above and a pharmaceutically acceptable excipient. [368] The invention also relates to diseases or signs associated with treatment by inhibition of matrix metalloproteases, arthritis, rheumatoid arthritis, osteoarthritis, osteoporosis, periodontal disease, inflammatory bowel disease, psoriasis, multiple sclerosis, heart failure, atherosclerosis, asthma, chronic obstructive pulmonary Formulas as defined above for the manufacture of a medicament for the treatment of a disease or indication associated with treatment by disease (COPD), age-related macular degeneration (ARMD) and inhibition of type-13 matrix metalloprotease (MMP-13) (such as cancer) It relates to the use of the compound of I). [369] The invention also relates to an imbalance of MMP, more particularly MMP-13 activity, comprising administering to a patient in need thereof a pharmaceutically effective amount of an MMP-inhibitor according to the invention or a pharmaceutical composition comprising said compound. It relates to a method of treating pathology. [370] Among the various pathologies associated with the imbalance of MMP activity, the MMP-13-inhibitor of formula (I) according to the present invention can be used for all pathologies caused by the degradation of extracellular matrix tissue, more particularly rheumatoid arthritis, osteoarthritis, osteoporosis, It is particularly useful for the treatment of periodontal disease, inflammatory bowel disease, psoriasis, multiple sclerosis, heart failure, atherosclerosis, asthma, chronic obstructive pulmonary disease (COPD), age-related macular degeneration (ARMD) and cancer. [371] In a very preferred manner, the compounds of formula (I) defined according to the invention will preferably be used for the treatment of arthritis, osteoarthritis and rheumatoid arthritis. [372] The compounds of the present invention are administered in the form of compositions suitable for the nature and severity of the indications to be treated. The daily dosage in humans is typically from 2 mg to 1 g of compound and can be absorbed in one or more unit doses. The compositions are prepared by methods conventional to those skilled in the art and generally comprise from 0.5% to 60% by weight of the active principal compound (compound of formula (I)) and from 40% to 99.5% by weight of a pharmaceutically acceptable vehicle. [373] Accordingly, the compositions of the present invention are prepared in a form compatible with the desired route of administration. For example, the following forms of constraints may be considered, but are not limited to: [374] 1) Oral Dosage Form: [375] Drinkable solutions, suspensions, sachets of powder for drinkable solutions, packing containers of powder for drinkable suspensions, gas-resistant gel capsules, sustained release, emulsions, HPMR capsules or gel capsules, sublingual melt freeze-driers. [376] 2) Extra-intestinal Dosage Form: [377] Intravenous route: [378] Aqueous solutions using one or more solubilizers, water / cosolvent solutions, colloidal suspensions, emulsions, nanoparticle suspensions that can be used for sustained release injection, dispersions and liposomes. [379] Subcutaneous / Muscular Pathway: [380] In addition to formulations that can be used intravenously and also in the subcutaneous and muscular routes, suspensions, dispersions, sustained release gels and sustained release implants can also be used. [381] 3) Topical Dosage Forms: [382] Preferred among conventional topical dosage forms are creams, gels (polymerized gelled aqueous phases), dressings that adhere directly to the skin, and patches, sprays, and solutions that can be used to treat dermatitis without percutaneous penetration of the active ingredient. . [383] 4) Pulmonary Dosage Forms: [384] Forms such as solutions for aerosols, powders for inhalers and other suitable forms are preferred in this category. [385] 5) Forms for Nasal Administration: [386] In this context it relates to a drop solution. [387] 6) Forms for rectal administration: [388] Among them, suppositories and gels will be selected. [389] It is also contemplated to use a form that allows administration of an ophthalmic solution of the active substance or administration of a vaginal solution. [390] Another important category of pharmaceutical compositions that can be used in the present invention relates to forms for improving the solubility of the active ingredient. [391] For example, it is conceivable to use formulations comprising an aqueous solution of cyclodextrin, and more particularly hydroxypropyl-p-cyclodextrin. Detailed investigations of this type of pharmaceutical form are given in Journal of Pharmaceutical Sciences, 85 (11), 1142-1169 (1996) and incorporated herein by reference. [392] The various pharmaceutical forms recommended above are described in detail in "Pharmacie galenique" by A. Lehir (published by Masson, 1992 (6th edit 10n)) and incorporated herein by reference. [393] Intermediate compound [394] The present invention also relates to intermediate compounds of formula (III). [395] <Formula III> [396] [397] R 3 here has the same meaning as defined for the compound of formula (I). [398] According to another aspect, the invention also relates to an intermediate compound of formula (IV): [399] <Formula IV> [400] [401] Wherein R 1 and R 3 have the same meanings as defined for the compound of formula (I). [402] Process for the Preparation of Compounds of Formula (I) [403] Throughout this application, the following abbreviations have the following meanings: [404] DEAD: diethyl azodicarboxylate [405] DIPEA: N, N-diisopropylethylamine [406] DMF: N, N-dimethylformamide [407] NMP: 1-methyl-2-pyrrolidone [408] THF: tetrahydrofuran [409] TOTU: O-[(ethoxycarbonyl) cyanomethyleneamino] -N, N, N ', N'-tetramethyluronium tetrafluoroborate [410] EDCI: 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrogen chloride [411] HOBT: 1-hydroxybenzotriazole hydrate [412] The compounds according to the invention can be carried out by various synthetic methods. Some of these synthesis methods are described below: [413] A) General way: [414] Processes for the preparation of compounds of formula (I) are described in the following reaction schemes: [415] [416] Wherein R 7 is hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl or heteroaryl, R ″ is (C 1 -C 6 ) alkyl, aryl, aryl ( C 1 -C 6 ) alkyl, aromatic or non-aromatic heterocycle or cycloalkyl, R 1 , R 2 , R 3 , X 1 , X 2 , X 3 , A, W, Y, Z 1 , n and m are It has the same meaning as defined for the compound of formula (I). [417] B) Synthesis Method 1 [418] The compounds of the present invention can be prepared first by the method shown in Scheme 1 below. [419] Scheme 1 [420] [421] Wherein each general substituent is as defined for the compound of formula (I). [422] Intermediate compounds of formula (II) that make up the starting materials for the synthetic methods illustrated in Scheme 1 above may be prepared according to Scheme 2: [423] Scheme 2 [424] [425] Intermediate compounds of formula (II) constituting the starting material in the method for synthesizing compounds of formula (I) as illustrated in Scheme 1 above may also be prepared according to Scheme 3 below. [426] Scheme 3 [427] [428] Compounds of formula (III) may be prepared according to the process described in Scheme 1 above from compounds of formula (II) according to the following synthetic scheme 4: [429] Scheme 4 / Method A [430] [431] Wherein R 3 is as defined above for the compound of formula (I). [432] According to another aspect, an intermediate compound of formula (III) may be prepared according to the synthetic method illustrated in Scheme 1 above according to reaction B as illustrated in the following synthetic scheme 5: [433] Scheme 5 / Method B [434] [435] Where R 3 is as defined for the compound of formula (I). [436] According to another aspect, an intermediate compound of formula (III), wherein R 3 is a benzyl radical, can be obtained according to the synthesis method illustrated in Scheme 1 above according to Method C illustrated in Scheme 6 below: [437] Scheme 6 / Method C [438] [439] As a result, the subject of the invention is also a process for the preparation of compounds of formula (I): [440] <Formula I> [441] [442] Wherein R 1 , R 2 , R 3 , Z 1 , A, n and m are as defined in the Summary of the Invention, X 1 , X 2 and X 3 are CH, Y is O and Z is NR 7 , W is O, [443] The method comprises reacting a compound of formula (II) with pyridine and a compound of formula (V) to obtain a compound of formula (VI), followed by reacting the compound of formula (VI) in the presence of Li0H Obtaining the compound of (III). [444] <Formula II> [445] [446] <Formula V> [447] [448] Where R 3 is as defined in the Summary of the Invention. [449] <Formula VI> [450] [451] Where R 3 is as defined above. [452] <Formula III> [453] [454] Where R 3 is as defined above. [455] The synthesis method also reacts the compound of formula (III) obtained above with a compound of formula (VII) in the presence of an acid activator such as TOTU, wherein R 1 represents hydrogen and X 1 , X 2 and X 3 Each is -CR 6 , where R 6 represents a hydrogen atom, Y is O, Z is NR 7 , W is O, and A, R 2 , Z 1 , n and m are as defined above; It is characterized by obtaining the compound of I): [456] <Formula VII> [457] [458] here, [459] R 7 is selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, [460] A, R 2 , Z 1 , n and m are as defined above for the compound of formula (I). [461] The invention also relates to compounds of formula (I) wherein R 1 , R 2 , R 3 , A, Z 1 , m and n are as defined for compounds of formula (I), wherein X 1 , X 2 and X 3 are CH, W is O, Y is O, and Z is NR 7 ). [462] The process comprises reacting a compound of formula (VI) with a compound of formula XR 1 in which R 1 is as defined in the Summary of the Invention and X is a leaving group such as halogen, in the presence of a base to give a compound of formula (IX) It characterized in that it comprises the steps of: [463] <Formula VI> [464] [465] Where R 3 is as defined in the Summary of the Invention. [466] [467] Wherein R 1 and R 3 are as defined above. [468] The method is also characterized in that the compound of formula (IX) is reacted in the presence of Li 0 H to give a compound of formula (IV): [469] <Formula IX> [470] [471] <Formula IV> [472] [473] Wherein R 1 and R 3 are as defined above. [474] The process is also characterized in that the compound of formula (IV) is reacted with a compound of formula (VII) in the presence of an acid activator such as TOTU to give a compound of formula (I): [475] <Formula IV> [476] [477] Where R 3 is as defined above. [478] <Formula VII> [479] [480] Wherein R 7 is hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are in the Summary of the Invention. As defined. [481] <Formula I> [482] [483] Wherein R 1 , R 2 , R 3 , A, Z 1 , m and n are as defined in the Summary of the Invention, X 1 , X 2 and X 3 are each -CH, W is O and Z is NR 7 to be. [484] Another aspect of the invention relates to compounds of formula (I) wherein R 1 , R 2 , R 3 , W, X 1 , X 2 , X 3 , A, Z 1 , m and n are as defined in the Summary of the Invention. Same method) [485] The process reacts a compound of formula (I) wherein R 1 is H with compound XR 1 of formula (VIII) in the presence of a base, as defined in the Summary of the R 1 Invention, wherein X is a leaving group such as halogen To obtain a compound of formula (I) wherein R < 1 > [486] [487] C. Synthesis Method 2 [488] Compounds of the invention can also be obtained by the method shown in Scheme 7: [489] Scheme 7 [490] [491] Wherein each general substituent is as defined for the compound of formula (I). [492] The invention also relates to compounds of formula (I) wherein X 1 , X 2 and X 3 are CH, W is O, Y is O, Z is NR 7 , R 1 , R 3 , A, R 2 , Z 1 , m and n are as defined for the compound of formula (I)) [493] The compound of formula (XI) is reacted with AlCl 3 in a solvent such as benzene to obtain a compound of formula (XII): [494] [495] Where R 1 is as defined above. [496] [497] Where R 1 is as defined above. [498] The process for the preparation of the compound of formula (I) is further characterized by obtaining the compound of formula (XII) in the presence of Li0H and dioxane / H 2 O to obtain a compound of formula (XIII): [499] [500] Where R 1 is as defined above. [501] The process for preparing the compound of formula (I) also comprises the step of reacting a compound of formula (XIII) with a compound of formula (VII) in the presence of an acid activator such as TOTU to obtain a compound of formula (XIV) Features: [502] <Formula VII> [503] [504] Wherein R 7 is hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are in the Summary of the Invention. As defined. [505] [506] Wherein X 1 , X 2 and X 3 are CH, W is O, Y is O and R 7 , A, R 2 , Z 1 , m and n are as defined above. [507] The process for the preparation of the compound of formula (I), wherein the compound of formula (XIV) is a compound of formula (XV), XR 3 , wherein R 3 is as defined in the Summary of the Invention and X is a leaving group such as halogen Reacted with a compound of formula (I) wherein X 1 , X 2 and X 3 are CH, W is O, Y is O, Z is NR 7 , R 7 , R 1 , A, R 2 , Z 1 , m and n are as defined in the compound of formula (I)). [508] D. Manufacturing Method 3 [509] Compounds of formula (I) of the present invention may also be obtained by the method shown in Scheme 8: [510] Scheme 8 [511] [512] In the above scheme, each general substituent is as defined above for the compound of formula (I). [513] Accordingly, the present invention also relates to a process for the preparation of compounds of formula (I) as defined above, wherein X 1 , X 2 and X 3 are CH, W is O, Y is O and Z is O A compound of formula (III) is reacted with a compound of formula (XVI) to obtain a compound of formula (XVII): [514] <Formula III> [515] [516] Where R 3 is as defined for the compound of formula (I). [517] <Formula XVI> [518] [519] Where A, R 2 , Z 1 , m and n are as defined for compounds of formula (I). [520] <Formula XVII> [521] [522] Wherein A, R 2 , R 3 , Z 1 , m and n are as defined in the Summary of the Invention, X 1 , X 2 and X 3 are CH and W is O. [523] According to the above process for the preparation of the compound of formula (I), the process also comprises the compound of formula (XVII) in the presence of a base, the compound of formula (VIII), XR 1 , wherein R 1 is as defined in the Summary of the Invention, X is reacted with a leaving group such as halogen) to react compounds of formula (I), wherein X 1 , X 2 and X 3 are CH, W is O, Y is O, Z is 0, A, R 2 , R 3 , R 1 , Z 1 , m and n are as defined in the Summary of the Invention). [524] The present invention also relates to a process for the preparation of a compound of formula (I) as defined above, wherein a compound of formula (IV) is reacted with a compound of formula (XVI), wherein X 1 , X 2 and X 3 is CH, W is O, Y is O, and Z is 0). [525] E. Manufacturing Method 4 [526] The compounds of the present invention and most particularly the compounds of the present invention which constitute the pyridine ester can be obtained by the method shown in Scheme 9: [527] Scheme 9 [528] [529] Wherein each general substituent on the intermediate compound has the same meaning as defined for the compound of formula (I). [530] As a result, the subject matter also relates to a process for the preparation of compounds of formula (I) wherein X 2 and X 3 are CH, X 1 is N, Z is O and Y is O, The process is carried out by reacting a compound of formula (XIX) with a pyridine and a compound of formula (V), O = C = NR 3 , where R 3 is as defined for the compound of formula (I) Characterized by including the steps of: [531] <Formula XIX> [532] [533] <Formula XX> [534] [535] Where R 3 is as defined above. [536] The process for preparing the compound of formula (I) further comprises the step of reacting the compound of formula (XX) in the presence of KMn0 4 to obtain a compound of formula (XXI): [537] <Formula XXI> [538] [539] Where R 3 is as defined above. [540] The process for preparing the compound of formula (I) further comprises the step of reacting the compound of formula (XXI) in the presence of SOCl 2 and CHCl 3 to obtain a compound of formula (XXII): [541] <Formula XXII> [542] [543] Where R 3 is as defined above. [544] The process for preparing the compound of formula (I) comprises the step of reacting a compound of formula (XXII) with a compound of formula (XVI) to obtain a compound of formula (XXIV): [545] <Formula XVI> [546] [547] Wherein A, R 2 , Z 1 , m and n are as defined for compounds of formula (I). [548] <XXIV> [549] [550] Wherein X 2 and X 3 are CH and A, n, m, Z 1 , R 2 and R 3 are as defined in the Summary of the Invention. [551] Compounds of the invention constituting pyridine amide can be prepared by the process shown in Scheme 10 below: [552] Scheme 10 [553] [554] As a result, the subject matter of the present invention also relates to compounds of formula (I) wherein X 2 and X 3 are CH, X 1 is N, Z is -NR 7 [where R 7 is defined in compounds of formula (I) And W is O and Y is O). [555] The method reacts the compound of formula (XXV) with N, N'-dimethylformamide dimethyl acetal under DMF reflux in the first step and with N-iodosuccinimide in the second step to Obtaining a compound, and then reacting the compound of formula (XXVI) with ethyl acrylate in the presence of palladium diacetate, CuI and base to obtain a compound of formula (XXVII), followed by the compound of formula (XXVII) Reacting in the presence of to obtain a compound of formula (XXVIII), [556] The compound (XXVIII) is reacted with a compound of formula (VII) in the presence of an acid activator such as TOTU to give a compound of formula (XXIX), [557] Or reacting a compound of formula (XXVIII) with AlCl 3 in the first step in the presence of benzene and in the second step with a compound of formula (VII) in the presence of an acid activator such as TOTU to give a compound of formula (XXX) And then reacting the compound of formula (XXX) with a compound of formula R 3 -X, wherein R 3 is as defined in formula (I), in the presence of a base to obtain a compound of formula (XXXI). It is characterized by. [558] [559] [560] [561] [562] <Formula VII> [563] [564] Wherein R 7 is selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are of the invention As defined in the summary. [565] [566] Wherein A, R 2 , R 7 , Z 1 , m and n are as defined above and X 2 and X 3 each represent a —CH group. [567] <Formula VII> [568] [569] Wherein R 7 is selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are of the invention As defined in the summary. [570] [571] Wherein A, R 2 , R 7 , Z 1 , m and n are as defined above and X 2 and X 3 are each a —CH group. [572] [573] Compounds of the invention constituting pyridine amides and in particular pyrido [3,4-d] pyrimidine derivatives can also be prepared according to the method shown in Scheme 11 below: [574] Scheme 11 [575] [576] As a result, the subject matter of the present invention also relates to compounds of formula (I) wherein X 1 and X 3 are CH, X 2 is N, Z is -NR 7 wherein R 7 is as defined in formula (I) ], W is O, and Y is O). [577] The process involves reacting a compound of formula (XXXII) with selenium dioxide in the presence of acetic acid in the first step, with dimethylhydrazine in the second step and with N, N'-dimethylformamide dimethylacetal under reflux in the third step. Obtaining a compound of formula (XXXIII), followed by reacting the compound of formula (XXXIII) with methyl acrylate in the presence of palladium diacetate to obtain a compound of formula (XXXIV), followed by Reacting with benzene and acetic acid to obtain a compound of formula (XXXV), followed by reacting the compound of formula (XXXV) in the presence of a base to obtain a compound of formula (XXXVI), [578] [579] [580] [581] [582] [583] Reacting the compound of formula (XXXVI) with a compound of formula (VII) in the presence of an acid activator such as TOTU to obtain a compound of formula (XXXVII), [584] <Formula VII> [585] [586] Wherein R 7 is selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are of the invention As defined in the summary. [587] [588] Wherein A, R 2 , R 7 , Z 1 , m and n are as defined above and X 1 and X 3 each represent a —CH group. [589] Or reacting a compound of formula (XXXVI) with AlCl 3 in the presence of benzene in the first step and a compound of formula (VII) in the presence of an acid activator such as TOTU in the second step to obtain a compound of formula (XXXVIII) And then reacting the compound of formula (XXXVIII) with a compound of formula R 3 -X in which R 3 is as defined for the compound of formula (I) in the presence of a base to obtain a compound of formula (XXXIX). Shall be: [590] <Formula VII> [591] [592] Wherein R 7 is selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are of the invention As defined in the summary. [593] [594] Wherein A, R2, R7, Z1, m and n are as defined above and X1 and X3 each represent a -CH group. [595] [596] The invention is illustrated by, but not limited to, the following examples. [597] Example [598] Preparation Example A: Dimethyl 4-aminoisophthalate [599] Preparation Example according to Scheme 2: [600] Step 1-2: 4-nitroisophthalic acid [601] 25 g (138 mmol) of 5-methyl-2-nitrobenzoic acid were suspended in 300 ml of water. 5 g (89.1 mmol) of KOH were added and dissolved. The medium was heated to 90 ° C. and 158 g of KMnO 4 (414 mmol) was added in portions and washed with H 2 O. After 3 hours, the reaction medium was filtered through celite and the filtrate was acidified to pH 1 with concentrated HCl. The precipitate obtained was filtered off and removed in vacuo. [602] Weight = 15.3 g; Yield = 53% [603] NMR: DMSO 1 H δ (ppm) 5.62-5.70 (d, 1H); 7.88 (d, 1 H); 8.16 (s, 1 H) [604] Step 2-2: Dimethyl 4-nitroisophthalate [605] 12.75 g (60.4 mmol) of 4-nitroisophthalic acid and 13 ml of H 2 SO 4 and 100 ml of methanol at this stage were kept at reflux overnight. After cooling, methanol was removed under reduced pressure. The residue was dissolved in 400 ml of EtOAc. The organic phase was washed with 50 ml of H 2 0 followed by 50 ml of 5% NaHCO 3 solution. Drying over MgSO 4 gave a crystalline residue. [606] Weight = 12.17 g Yield = 84% [607] NMR: DMSO 1 H δ (ppm) 3.86 (s, 3H); 3.91 (s, 3 H); 8.16 (d, 1 H); 8. 29-8. 34 (m, 2 H) [608] Step 3-2: Dimethyl 4-aminoisophthalate [609] The compound obtained in this step was reduced with hydrogen in the presence of palladium as catalyst. [610] Filter through celite and concentrate to afford: [611] Weight = 5.12 g; Yield = 70%; m.p. = 127-128 C [612] NMR: CDCl 3 1 H δ (ppm) 3.87 (s, 3H); 3.88 (s, 3 H); 6.30 (brs, 2 H); 6.65 (d, 1 H); 7.89 (dd, 1 H); 8.57 (d, 1H) [613] Preparation according to Scheme 3—J. Org. Chem., 1997, 62 (12), 4088-4096] [614] Step 1-3: Dimethyl 4-amino-1-hydroxycyclohexa-3,5-diene-1,3-dicarboxylate [615] 526 ml of benzene and 20 ml of methyl acrylate are added to a 1-liter three-necked flask equipped with a reflux condenser, placed under an inert atmosphere, protected from moisture, and then 10 g (70.8 mmol) of methyl 5-amino 2-furan carboxylate was added. The mixture was refluxed and maintained for 24 hours. The reaction medium was dried on a rotary evaporator at 50 ° C. under vacuum of 20 mmHG. The residue obtained by flash chromatography was purified in dichloromethane as a solvent, gradually increasing the ethyl acetate content. The product was obtained as follows: [616] Weight = 15 g of yellow precipitate; Yield = 93% [617] [618] Step 2-3: Dimethyl 4-aminoisophthalate [619] 15 g (66 mmol) of the compound obtained in steps 1-3 and 600 ml of benzene were added to a 1-liter three-necked flask equipped with a reflux condenser, placed under an inert atmosphere and protected from moisture. 13.8 g (12 ml, 98 mmol) of BF3 etherate were added with stirring. The mixture was refluxed for 2 minutes, then cooled to room temperature, saturated NaHCO 3 solution (pH 9) was added and then left to stand to separate phases. The aqueous phase was reextracted with dichloromethane. The combined organic phases were dried over sodium sulfate. After removing the solvent in vacuo, 13.8 g of the residue was chromatographed using dichloromethane as the elution solvent. The product was obtained as follows: [620] Weight = 8.5 g of crystalline residue; Yield = 62% [621] [622] Preparation Example B 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [623] Preparation Example according to Scheme 4 [624] Step 1-4: Methyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [625] 4 g (19.1 mmol) of the compound of Preparation A and 40 ml of pyridine were continuously added to a 50 ml three-necked flask equipped with a reflux condenser and protected from moisture, followed by 3.2 g (24 mmol) of benzyl isocyanate. . The colorless solution was stirred and heated to 95-100 ° C. After 6 hours at this temperature, 1 ml of benzyl isocyanate was added and stirring was continued at 100 ° C. overnight. The next day, the reaction medium was cooled down and added to a mixture of 400 ml of water and ice, then stirring was continued for about 30 minutes and the residue obtained was filtered. The product was reslurried under reflux in 150 ml of ethanol. After cooling, the product was filtered off. The product was obtained as follows: [626] Weight = 3.7 g; Yield = 62% [627] [628] Step 2-4: 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [629] 1.5 g (4.84 mmol) methyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylate, 14 ml dioxane and 48 ml H 2 O was introduced into a 100 ml round bottom flask equipped with a reflux condenser. 0.41 g (9.68 mmol) of hydrated lithium hydroxide was added to the suspension with stirring. The mixture was refluxed and maintained for about 1 hour (solution). After cooling in an ice bath, the medium was acidified to pH 1 with concentrated hydrochloric acid. The very fine precipitate obtained was filtered to give: [630] Weight = 1.3 g; Yield = 96% [631] [632] Preparation according to Scheme 5: [633] Step 1-5: Dimethyl 4- (3-benzylureido) isophthalate [634] 10 g (48 mmol) of the compound of Preparation A, 200 ml of anhydrous toluene, about 100 mg of animal charcoal and then 12 g (40 mmol) of triphosgen in 1-liter 1 equipped with a reflux condenser It was introduced into an old flask and protected from moisture. The suspension was stirred and kept at reflux temperature of toluene for 2 hours. The reaction medium was filtered through an infusorial earth and then concentrated to dryness at 50 ° C. under vacuum of about 20 mm Hg. The obtained residue was dissolved in 200 ml of anhydrous toluene and stirred. [635] 4.7 ml (43 mmol) benzylamine were added to the solution over a few minutes. A precipitate formed immediately. 200 ml of toluene was added to facilitate stirring and the mixture was kept at room temperature overnight. The next day, the precipitate was filtered off and washed sequentially with toluene and ether. Drying in vacuo gave the product as follows: [636] Weight = 13.9 g; Yield = 84.6% [637] [638] Step 2-5: Methyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [639] 13.7 g (40 mmol) of the compound obtained in steps 1-5, 300 ml of methanol and then 1.3 g (24 mmol) of sodium methoxylated were introduced into a 1-liter 1-necked flask equipped with a reflux condenser and protected from moisture It was. The white suspension was juggled at reflux for 3 hours (suspension changed form). Half of the methanol was removed on a rotary evaporator at 50 ° C. under vacuum. The mixture was cooled down and cooled to pH 4 with 2 ml of concentrated hydrochloric acid. It was stirred for 15 minutes while cooling to obtain a crystalline residue, which was then filtered. [640] Weight = 12 g; Yield = 96.7% [641] [642] Step 3-5: 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [643] The product was obtained following the procedure of steps 2-4 of Preparation Example B using the compound obtained in step 205. [644] Preparation according to Scheme 6: [645] Step 1-6: 3-benzyl-6-bromo-lH-quinazolin-2,4-dione [646] 10 g (46.3 mmol) of 2-amino-5-bromobenzoic acid, 100 ml of anhydrous pyridine and 6.16 g (46.3 mmol) of benzyl isocyanate were introduced into a 250 ml one-necked flask equipped with a reflux condenser and protected from moisture. . The solution was kept at reflux with stirring for 36 hours. The reaction mixture was cooled down and H 2 0 was added until precipitation started to occur. The mixture was precipitated for about 1 hour, and the obtained precipitate was then filtered and washed. 8 g of crude product were purified by reslurried in reflux ethanol. [647] Weight: 3.4 g [648] [649] Step 2-6: 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6carbonitrile [650] 2.5 g (7.5 mmol) of the compound of steps 1-6, 1.215 g (13.6 mmol) of copper cyanide and 22.5 ml of 1-methyl-2-pyrrolidinone were introduced into a 50 ml three-necked flask equipped with a reflux condenser and And protected from moisture. The beige solution obtained was refluxed at an internal temperature of 200 ° C. for 1 hour 30 minutes. [651] The reaction medium was concentrated to dryness at 80 ° C. under vacuum of less than 1 mmHg. The residue was dissolved in 300 ml 2N NH 4 OH and extracted three times with dichloromethane. [652] The presence of insoluble matter was observed and the material was dissolved in 20 ml of 50/50 v / v MeOH / CH 2 Cl 2 mixture. The combined organic phases were washed with water. Concentrated in vacuo over Na 2 SO 4 and the obtained black residue was crystallized in 10 ml of CH 2 Cl 2 . The following product was obtained: [653] Weight: 1.2 g; Yield = 60% [654] [655] Step 3-6: 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [656] 1.4 g (5.05 mmol) of the compound of steps 2-6 and 35 ml of H 2 O were introduced into a one-necked flask equipped with a reflux condenser and 35 ml of H 2 SO 4 were carefully added. The suspension was kept at reflux with stirring for 3 hours. After cooling, the beige precipitate was filtered off and washed with water and then with methanol until neutral. [657] Weight: 1.5 g; Yield = 100% [658] [659] Preparation C: 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [660] Step 1: Methyl 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [661] 11.8 g (38.0 mmol) of the compound of Preparation B, 120 ml of dimethylformamide and 7.9 g (57 mmol) of K 2 CO 3 were introduced into a 250 ml three neck flask. The suspension was stirred at rt for 15 min. 27 g (12 ml, 190 mmol) of urododomethane were added over 2 minutes. The suspension was stirred at rt for 30-45 minutes. The solvent was removed in vacuo and the residue was dissolved in 500 ml of dichloromethane and washed three times with 300 ml of water. The organic phase is dried and the solvent is removed. The product was obtained as follows: [662] Weight = 12 g; Yield = 97. 4% [663] [664] Step 2: 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [665] 9.5 g (29. 3 mmol) of compound obtained in step 1 were used to obtain the product (10 g) in 100% yield following the procedure of steps 2-4 of Preparation B. [666] [667] Preparation Example D: 1-Methyl-3- (3-fluorobenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [668] Step 1: Methyl 3- (3-fluorobenzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylate [669] 5.5 g (26.3 mmol) of the compound of Preparation A and 50 ml of pyridine were introduced into a round bottom flask. 5.Og (33.1 mmol) of 3-fluorobenzyl isocyanate was added. [670] The mixture was kept under reflux for 6 hours and 0.8 g (5.3 mmol) of 3-fluorobenzyl isocyanate were added in one portion. The mixture was heated to reflux overnight. The mixture was cooled and water was added to precipitate the product and filtered. The product was reslurried in hot ethanol and filtered to give 6.7 g (yield: 78%) of the desired compound. [671] MS: m / z (APCI, AP +) 329.1 [M] + [672] CHN Analysis: Calcd (%): C, 62.20; H, 3.99; N, 8.53. [673] Found (%): C, 62.09; H, 3. 85; N, 8.42. [674] Step 2: Methyl 1-methyl-3- (3-fluorobenzyl) -2,4-dioxo-1,2,3,4 tetrahydroquinazolin-6-carboxylate [675] 1.8 g (5.5 mmol) of the product prepared in preceding 1 were dissolved in 30 ml of dimethylformamide and 1.8 g (8.1 mmol) cesium carbonate were added. After the mixture was stirred for 10 minutes, 1.1 g (8.1 mmol) of iodomethane were added. Stirring was continued overnight in Ceylon. Water (60 ml) was added and the product extracted with ethyl acetate (2 x 30 ml). The combined organic phases were washed with saturated aqueous NaCl solution (4 × 20 ml) and dried over MgSO 4 . The solid product was slurried and filtered in hot ethyl acetate to give 1.7 g (yield: 90%) of the title compound. [676] MS: m / z (APCI, AP +) 343.1 [M] + [677] CHN analysis: calculated (%): C, 63.16; H, 4. 42; N, 8.18. [678] Found (%): C, 63.02; H, 4. 26; N, 8.06. [679] Step 3: 1-methyl-3- (3-fluorobenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6 carboxylic acid [680] 0.71 g of a compound (yield: 76%) was obtained following the procedure of steps 2-4 of Preparation Example B using the compound obtained in the previous step 2. [681] MS: m / z (APCI, AP +) 329.0 [M] + [682] CHN analysis: calculated (%): C, 62.20; H, 3. 99; N, 8. 53. [683] Found (%): C, 61.94; H, 3.78; N, 8. 57. [684] Preparation Example E: 1-ethyl-3- (3-fluorobenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [685] Step 1: Methyl 1-ethyl-3- (3-fluorobenzyl) -2,4-dioxo-1,2,3,4 tetrahydroquinazolin-6-carboxylate [686] 2.0 g (6.1 mmol) of Preparation Example D, Step 1, were dissolved in 30 ml of dimethylformamide and 1.96 g (9.2 mmol) of cesium carbonate were added. After the mixture was stirred for 10 minutes, 1.4 g (9.2 mmol) of iodoethane were added. Stirring was continued overnight at room temperature. Water (60 ml) was added and the product extracted with ethyl acetate (2 x 30 ml). The combined organic extracts were washed with saturated aqueous NaCl solution (4 × 20 ml) and dried over MgSO 4 . The solid product was slurried in hot ethyl acetate and filtered to give 1.4 g (yield 67%) of the title compound. [687] MS: m / z (APCI, AP +) 357.1 [M] + [688] CHN analysis: calculated (%): C, 64.04; H, 4.81; N, 7.86. [689] Found (%): C, 63.72; H, 4.68; N, 7.75. [690] Step 2: 1-ethyl-3- (3-fluorobenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6 carboxylic acid [691] 1.1 g of compound (yield: 71%) was obtained according to the cuttlefish of Preparations B of Steps 2-4 using the compound obtained in Step 1 above. [692] MS: m / z (APCI, AP +) 343.0 [M] + [693] CHN analysis: calculated (%): C, 63.16; H, 4. 42; N, 8.18. [694] Found (%): C, 63.06; H, 4.41; N, 8.03. [695] Examples 1-461 illustrate the preparation of compounds of formula (I) which are particularly active according to the invention, but are not limiting. [696] Example 1 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid benzylamide [697] [698] 0.150 g (0.51 mmol) of Preparation B compound and 8.0 ml of dry dimethylformamide were introduced into a 25 ml one-necked flask protected from moisture. 0.054 g (56 μm, 0.51 mmol) benzylamine and 0.17 g (0.51 mmol) TOTU were added to the solution. This solution was cooled to 0 ° C. in the bath. 0.132 g (0.18 ml, 1.02 mmol) of N, N-diisopropylethylamine were then added. The mixture was warmed to rt and stirred overnight. After monitoring by TLC (90/10 CH 2 Cl 2 / MeOH), DMF was removed under reduced pressure. The obtained crystalline residue was dissolved in dichloromethane with the required amount of methanol to completely dissolve. The organic phase was washed successively with 40 ml of 1N HCl, saturated in 40 ml H 2 O, 40 ml of NaHCO 3 solution and finally with 40 ml of H 2 0. The organic phase is dried over Na 2 S0 4 and the solvent is removed in vacuo. 0.140 g of the product were obtained, which was recrystallized in 30 ml of acetonitrile: [699] Weight: 0.110 g; Yield = S6% [700] [701] Example 2 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (4-pyridylmethyl) amide [702] [703] The product was obtained in 46% yield (0.090 g) following the procedure of Example 1 using 4-picolylamine. [704] [705] Example 3 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide [706] [707] Crystallization from acetonitrile and the procedure of Example 1 using piperonylamine gave the product in 64% yield (0.140 g). [708] [709] Example 4 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (2-thienylmethyl) amide [710] The product was obtained in 40% yield (0.080 g) according to the procedure of Example 1 except for using 2-thienylamine and crystallization from acetonitrile. [711] TLC: CH 2 Cl 2 / MeOH 90/10 Rf = 0.65 [712] [713] Example 5 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (3-pyridylmethyl) amide [714] The procedure of Example 1 was followed except that 3- (aminomethyl) -pyridine was used, and crystallization from acetonitrile gave the product in 66% yield (0.130 g). [715] [716] Example 6 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxybenzylamide [717] The procedure of Example 1 was followed except that 4-methoxybenzylamine was used, and crystallization from acetonitrile gave the product in a yield of 47.2% (0.100 g). [718] [719] Example 7 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-chlorobenzylamide [720] Crystallization from acetnitrile and following the procedure of Example 1, except using 4-chlorobenzylamine, gave the product in 19% (0.040 g) yield. [721] [722] Example 8: 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methylbenzylamide [723] Crystallization from acetnitrile and following the procedure of Example 1, except using 4-methylbenzylamine, gave the product in 19% (0.040 g) yield. [724] TLC: CH 2 Cl 2 / MeOH 95/5 [725] [726] Example 9: 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-yl Methyl) amide [727] 0.500 g (1.61 mmol) of the compound of Preparation C in 25 ml of anhydrous dimethylformamide were introduced into a 50 ml one-necked flask protected from moisture. 0.244 g (0.201 ml, 1.61 mmol) of piperonylamine and 0.531 g (1.61 mmol) of TOTU were added to the solution. The solution was cooled to 0 ° C. in a cold bath. Then 0.415 g (0.564 ml, 3.22 mmol) of N, N-diisopropylethylamine were added. The mixture was warmed to rt and stirred overnight. [728] After monitoring by TLC (90/10 CH 2 Cl 2 / MeOH), DMF was removed in vacuo. The obtained crystalline residue was dissolved in dichloromethane. The organic phase is 1N HCl, H 2 O, saturated NaHCO 3, and finally by using the H 2 0 and washed successively. The organic phase was dried over Na 2 SO 4 and the solution was removed in vacuo. Recrystallization from 30 ml of acetonitrile gave 0.540 g of the product as follows. [729] Weight: 0.390 g; Yield = 54.6% [730] [731] Example 10 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid benzylamide [732] The product was obtained in 56.8% (0.110 g) yield by crystallization from acetonitrile and following the procedure of Example 9 except using benzylamine. [733] [734] Example 11 methyl 4-({[1- (3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl) methanoyl] amino} Methyl) benzoate [735] The product was obtained in a yield of 61.5% (0.135 g) according to the procedure of Example 9 except using methyl 4- (aminomethyl) benzoate hydrogen chloride and 3.5 equivalents of N, N-diisopropylethylamine. . The crude product was purified by chromatography on silica gel using a 95/5 CH 2 Cl 2 / MeOH gradient and then solidified on ether. [736] TLC: CH 2 Cl 2 / MeOH 95/5 Rf = 0.36 [737] [738] Example 12 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-hydroxy-3-methoxybenzylamide [739] The product was obtained in a yield of 42% (0.090 g) according to the procedure of Example 9, except using 4-hydroxy-3-methoxybenzylamine hydrogen chloride and 3.5 equivalents of N, N-diisopropylethylamine. Obtained. The crude product was purified by chromatography on silica gel using a 95/5 CH 2 Cl 2 / MeOH gradient and then solidified on ether. [740] [741] Example 13 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxybenzylamide [742] The product was obtained in a yield of 77.7% (0.320 g) following the procedure of Example 9 except using 4-methoxybenzylamine. The crude product was purified by chromatography on silica gel using 97/3 CH 2 Cl 2 / MeOH as eluent. The desired fractions were combined and concentrated. Solidified in the product ether and then filtered. [743] TLC: CH 2 Cl 2 / MeOH 90/10 Rf = 0.8 [744] [745] Example 14 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (4-pyridylmethyl) amide [746] The product was obtained in a yield of 67.7% (0.130 g) following the procedure of Example 9 except using 4-picolylamine. [747] The crude product was purified by chromatography on silica gel using 95/5 CH 2 Cl 2 / MeOH as eluent. The desired fractions were combined and concentrated. Solidified in the product ether and then filtered. [748] [749] Example 15 1-Methyl-2,4-dioxo-3-phenethyl-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5- Monomethyl) amide [750] [751] Step 1: Methyl 2,4-dioxo-3-phenethyl-1,2,3,4-tetrahydroquinazolin-6 carboxylate [752] 0.750 g (3.6 mmol) of the compound of Preparation A and 7.5 ml of pyridine were introduced into a round bottom flask. 0.530 g (0.5 ml; 3, 6 mmol) of phenethyl isocyanate were added. [753] The mixture was kept at 100 ° C. overnight. Since the reaction was incomplete, phenethyl isocyanate, ie 2 equivalents was added again. Precipitated with H 2 O, filtered and reslurried in hot ethanol to afford the product as follows: [754] Weight = 0.640 g; Yield = 54. 9% [755] [756] Step 2: 2,4-dioxo-3-phenethyl-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [757] The product of the preceding step was hydrolyzed with the acid according to the procedure of steps 2-4 of Preparation Example B to give 0.500 g (yield: 80%) of the desired compound. [758] [759] Step 3: 2,4-dioxo-3-phenethyl-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide [760] The product was obtained in a yield of 57.8% (0.205 g) according to the procedure of Example 1 using 250 mg (0.8 mmol) of the compound and piperonylamine obtained in the previous step 2. [761] [762] Step 4: 1-methyl-2,4-dioxo-3-phenethyl-1,2,3,4-tetrahydroquinazolin-6 carboxylic acid (benzo [1,3] dioxol-5-ylmethyl )amides [763] 0.190 g (0.46 mmol) of the product of the preceding step 1, 2 ml of dimethylformamide and 0.095 g (0.68 mmol) of K 2 CO 3 were introduced into a 25 ml round bottom flask. The mixture was stirred at rt for 15 min, then 0.325 g (0.15 ml, 2.29 mmol) iodomethane were added. Stirring was continued for 30 to 45 minutes. The solvent was removed under vacuum. The residue was dissolved in dichloromethane and washed with H 2 O. [764] The organic phase was separated by standing and then dried over Na 2 SO 4 . After concentration in vacuo, the product was chromatographed on silica gel using a 98/2 CH 2 Cl 2 / MeOH gradient and then solidified in ether to afford 0.080 g of the desired compound (yield: 76%). [765] [766] Example 16: 3- (4-methoxybenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazoline [767] 6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide [768] Step 1: Methyl 3- (4-methoxybenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazoline [769] 6-carboxylate [770] The product was obtained in a yield of 61.3% (0.750 g) following the procedure of step 1 of Example 15, except using 4-methoxybenzyl isocyanate: [771] [772] Step 2: 3- (4-methoxybenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazoline [773] 6-carboxylic acid [774] The product of the preceding step 1 was hydrolyzed with an acid according to the procedure of steps 2-4 of Preparation Example B to yield 0.680 g of the desired compound (yield: 94.8%). [775] [776] Step 3: 3- (4-methoxybenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5- Monomethyl) amide [777] The product was obtained in a yield of 79.9% (0.220 g) according to the procedure of Example 9 except for using 200 mg (0.6 mmol) of the compound obtained in the previous step 2 and piperonylamine. The crude product was solidified in dichloromethane. [778] [779] Example 17 3- (4-methoxybenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] Dioxol-5-ylmethyl) amide [780] The product obtained in Example 16 was alkylated with methyl iodide following the procedure described in step 4 of example 15. After crystallization from ether, 0.080 g of product were obtained (yield: 70. 4%). [781] [782] Example 18 3- (4-methoxybenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxybenzylamide [783] Step 1: 3- (4-methoxybenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6 carboxylic acid (4-methoxybenzyl) amide [784] The product was obtained in a yield of 82% (0.270 g) according to the procedure of Example 9 except for using 240 mg (0.74 mmol) of the compound obtained in Step 2 of Example 16 and 4-methoxybenzylamine. It was. [785] [786] Step 2: 3- (4-methoxybenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxybenzylamide [787] The compound obtained in the previous step 1 was obtained to obtain the product in the yield of 94.4% (0.260 g) according to the procedure of Example 15 step 4. [788] [789] Example 19 3- (1-naphth-1-ylethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] Dioxol5-ylmethyl) amide [790] The product was obtained following the procedure of Example 16, step 1 using 1- (1-naphthyl) ethylisocyanate of step 1. [791] [792] Example 20 2,4-dioxo-3- (pyrid-4-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol -5-ylmethyl) amide [793] Step 1: Dimethyl 4- (3-pyrid-4-ylmethylureido) isophthalate [794] Using the compound prepared in Preparation Example A and 4-pyridine methylamine, the product was obtained in a yield of 94.2% according to the procedure of Steps 1-5 of Preparation Example B. [795] [796] Step 2: Methyl 2,4-dioxo-3- (pyrid-4-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylate [797] The product was obtained following the procedure of steps 2-5 of Preparation Example B using the compound obtained in the preceding step 1. [798] [799] Step 3: 2,4-dioxo-3- (pyrid-4-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6 carboxylic acid [800] The product was obtained following the procedure of steps 2-4 of Preparation Example B using the compound obtained in the previous step 2. [801] [802] Step 4: 2,4-dioxo-3- (pyrid-4-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6 carboxylic acid (benzo [1,3] dioxol-5 -Ylmethyl) amide [803] The product was obtained in a yield of 26.7% (0.850 g) following the procedure of Example 1 using the compound and piperonylamine obtained in the preceding step 3. After insoluble matter was filtered off, dimethylformamide was removed under reduced pressure. The residue was solidified in dichloromethane. [804] [805] Example 21 2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydro-quinazolin-6 carboxylic acid benzylamide [806] Step 1: Methyl N-benzyl-6- (3-thien-2-ylmethylureido) isophthalate [807] Using the compound obtained in Preparation Example A and thiophene methylamine, the product was obtained following the procedure of Preparation Step B of Preparation Example B. [808] [809] Step 2: Methyl 2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylate [810] The product was obtained following the procedure of steps 2-5 of Preparation Example B using the compound obtained in the previous step 4. [811] [812] Step 3: 2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6 carboxylic acid [813] The product was obtained following the procedure of steps 2-4 of Preparation Example B using the compound obtained in the previous step 2. [814] [815] Step 4: 2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6 carboxylic acid benzylamide [816] The product obtained in the preceding step 3 and benzylamine were obtained in 61.9% (0.160 g) yield following the procedure of Example 1. [817] [818] Example 22 1-methyl-2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid benzylamide [819] Using the compound obtained in Example 21, the product was obtained in the yield of 87% (0.090 g) according to the procedure of Step 4 of Example 15. [820] [821] Example 23 2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol- 5-ylmethyl) amide [822] The product obtained in the yield of 59% (0.170 g) following the procedure of Example 1 using the compound and piperonylamine obtained in step 3 of example 21. [823] The crude product was solidified in dichloromethane: [824] [825] Example 24 1-methyl-2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3 ] Dioxol-5-ylmethyl) amide [826] Using the compound obtained in Example 23, the product was obtained in the yield of 79.7% (0.085 g) according to the procedure of Step 4 of Example 15. [827] TLC: CH 2 Cl 2 / MeOH 95/5 Rf = 0.8 [828] [829] Example 25 3- (4-chlorobenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5- Monomethyl) amide [830] Using the compound obtained in the first step of Preparation Example A and 4-chlorobenzyl isocyanate, the product was obtained in the yield of 67.8% (0.170 g) according to the procedure of Examples 15 Steps 1-3. [831] [832] Example 26 3- (4-chlorobenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] di Oxol-5-ylmethyl) amide [833] Using the compound obtained in Example 25, the product was obtained in the yield of 88.9% (0.085 g) according to the procedure of Step 4 of Example 15. The product was isolated by crystallization in ether. [834] [835] Example 27 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amides [836] The product was obtained according to the method of Examples 1 to 4 of Example 20, using the compound obtained in Preparation Example A in step 1 and monomethylamine, and piperonylamine for amidation in the fourth step (0.035 g). [837] [838] Example 28: 3- (benzo [1,3] dioxol-5-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [ 1,3] dioxol-5-ylmethyl) amide [839] 36% yield according to the method of steps 1 to 4 of Example 20, using piperonylamine for amidation in step 4 using the compound obtained in preparation A in step 1 and piperonylamine The product was obtained (0.040 g). [840] Step 1: Dimethyl 4- (3-benzo [1,3] dioxol-5-ylmethylureido) isophthalate [841] [842] Step 2: Methyl 3- (benzo [l, 3] dioxol-5-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [843] [844] Step 3: 3- (benzo [1,3] dioxol-5-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [845] [846] Step 4: 3- (benzo [1,3] dioxol-5-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1 , 3] dioxol-5-ylmethyl) amide [847] [848] Example 29: 3- (benzo [1,3] dioxol-5-ylmethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxyl Acid (benzo [1,3] dioxol-5-ylmethyl) amide [849] Using the compound obtained in Example 28, the product was obtained in a yield of 40.5% according to the method of Step 4 of Example 15 (0.050 g). [850] [851] Example 30 3-benzyl-1-ethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [l, 3] dioxol-5-yl Methyl) amide [852] 0.150 g (0.35 mmol) of the compound of Example 2 and then 3 ml of anhydrous DMF were placed in a stirred round bottom flask protected from moisture. 0.075 g (0.525 mmol) of K 2 CO 3 was added to the stirred solution. After the mixture was stirred for 15 minutes, 0.273 g (0.14 ml, 1.75 mmol) of iodineethane were added. Stirring was continued for about 1 hour. After removing solvent under vacuum, the residue was dissolved in 50 ml of dichloromethane and washed with 2 x 50 ml of H 2 O. After drying over Na 2 SO 4 , it was concentrated under vacuum and the product crystallized from 8 ml of acetonitrile. The product was obtained as follows. [853] Weight : 0.070 g Yield: = 43.7% [854] [855] Example 31 3-benzyl-1-cyclopropylmethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5 -Ylmethyl) amide [856] The product was obtained in 76.8% (0.130 g) yield using cyclopropylmethyl bromide according to the method of Example 30. After product solidification in diisopropyl ether was obtained. [857] [858] Example 32: 3-benzyl-1-isobutyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (benzo [1,3] dioxol-5 -Ylmethyl) amide [859] The product was obtained with yield of 35.3% (0.060 g) according to the method of Example 30 using isobutyl bromide. [860] [861] Example 33 1-Methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide [862] Step 1: Methyl 1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [863] Preparation Example C 0.870 g (2.7 mmol) of the compound obtained in Step 1 and 20 ml of benzene and 2.1 g (16.1 mmol) of AlC1 3 were maintained at 50 ° C. for 7 hours. After cooling, the medium precipitated on the water / ice mixture. Insoluble material was dissolved in dichloromethane, purified by flash chromatography and eluted with a concentration gradient of CH 2 Cl 2 / acetone. 0.510 g of the desired compound were obtained. [864] Step 2: 1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide [865] Saponification of the compound obtained in step 1 was carried out using LiOH in a dioxane / H 2 O mixture as in the above example. Amidation with piperonylamine gave 0.160 g of the desired product. [866] [867] Example 34 Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -Benzoate [868] [869] Step 1: 1-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide: [870] 1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (NMR: DMSO 1 H δ (ppm) in DMF containing TOTU and DIPEA 3.50 (s , 3H); 7.5 (d, lH); 8.20 (d, lH); 8. 50 (s, lH); 11.75 (bs, lH); 13.1 (bs, lH)) and 4-methoxy-benzylamine In the same manner as in Example 33 was used. The product was obtained as follows: [871] [872] Step 2: methyl 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoate [873] 0.8 g (2.36 mmol) of the product obtained in step 1 and 8 ml of anhydrous DMF were stirred with 1.15 g (3.54 mmol) cesium carbonate. After stirring was continued for 15 minutes, 0.81 g (3.54 mmol) of methyl-4- (bromomethyl) benzoate was added. The mixture was kept at 90 ° C. for 1 hour 15 minutes and then stirred overnight. 15 ml of water were added and then extracted with dichloromethane. The organic phase was washed with water and concentrated to dryness on a rotary evaporator. The product obtained was purified by flash chromatography eluting with a concentration gradient of CH 2 Cl 2 / MeOH to give 0.220 g of the desired product. [874] [875] Example 35: 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H] -quinazolin-3-ylmethyl] -Benzoic acid [876] 0.16 g (3.3 mmol) of the product obtained in Example 34 was hydrolyzed in a mixture of 1.2 ml dioxane and 4.2 ml water containing 28 mg of LiOH monohydrate. The mixture was kept at reflux for 10 minutes to complete the reaction. After acidification at pH 1 with concentrated HCl, the precipitate was filtered to yield 0.120 g of the desired compound. [877] [878] Example 36 1-Methyl-2,4-dioxo-3-((E) -3-phenylallyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1 , 3] dioxol-5-ylmethyl) amide [879] 0.100 g (0.28 mmol) of the compound of Example 33 and 1 ml of anhydrous DMF were stirred with 0.060 g (0.42 mmol) of K 2 CO 3 . After maintaining the mixture for 15 minutes, 0.085 g (0.42 mmol) cinnamil bromide was added. The mixture was kept at 70 ° C. for 2 hours. After concentration in vacuo, the residue was taken up in dichloromethane, washed with H 2 O and dried over Na 2 SO 4 . The solvent was removed and the product was purified by flash chromatography eluting with 95/5 gradient CH 2 Cl 2 / MeOH. Solidification in ether gave 0.070 g (yield = 51%) of the desired compound. [880] [881] mp = 174 ° C. [882] HPLC: 98.4% [883] Example 37 Benzyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [884] A mixture of 0.5 g (1.7 mmol) of compound B of Preparation Example, 0.44 g (1.7 mmol) of triphenylphosphinic acid and 0.44 ml (4.3 mmol) of benzyl alcohol was stirred in 20 ml of THF. 0.27 ml (1.7 mmol) of DEAD in 10 ml of THF was added dropwise with stirring. Stirring was continued overnight at room temperature. The precipitate formed was filtered through celite and the filtrate was concentrated under vacuum. The residue was dissolved in 50 ml of ethyl acetate and washed sequentially with H 2 O and saturated NaCl solution. After drying over MgSO 4 and concentration in vacuo, the crude product obtained was purified by flash chromatography on silica eluting with 50/50 mixture of hexanes / EtOAc. The desired fractions were combined and the solvent removed under vacuum to yield 0.190 g (yield = 29%) of the desired crystalline compound. [885] [886] Example 38 benzyl 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [887] [888] 0.084 g (0.217 mmol) of the product of Example 37 were stirred with anhydrous THF under inert atmosphere in a device protected from moisture. 0.14 ml 1.6M BuLi in hexane (0.224 mmol) was introduced. The mixture was stirred for 10 minutes, then 0.04 ml (0.642 mmol) methyl iodine were added. THF was removed under vacuum. The residue was dissolved in EtOAc and washed with H 2 O and saturated NaCl solution. After drying over MgSO 4 and concentration in vacuo, the crude product obtained is purified by flash chromatography on silica eluting with a mixture of 50/50 hexanes / EtOAc. The desired fractions were combined and the solvent removed under vacuum. The pale yellow product was solidified in ether: [889] Weight: 0.049 g yield = 56% MS: m / z 401.2 (M + H) < + > [890] [891] Example 39 4-pyridylmethyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [892] According to the method of Example 37, except using dichloromethane as a solvent, a compound was obtained. The product was obtained as follows: [893] [894] Example 40 4-pyridylmethyl 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [895] According to the method of Example 37, except using the compound of Preparation C and 4-pyridylcarbinol, a compound was obtained. [896] [897] Example 41 benzo [1,3] dioxol-5-ylmethyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [898] 0.100 g (0.337 mmol) of the compound of Preparation B and 1 ml of dry THF were placed in a round bottom flask protected from moisture. The suspension was stirred and 0.24 g (0.150 ml, 2.025 mmol) thionyl chloride were added. The mixture was refluxed for 1 hour 30 minutes. After cooling, the solution was concentrated to dryness on a rotary evaporator. 0.110 g of acid chloride obtained was used in the next step without further purification. 0.080 g (0.51 mmol) of piperonyl alcohol, 1 ml of dichloromethane and 0.051 g (0.070 ml, 0.51 mmol) of triethylamine were introduced into a round bottom flask protected from moisture. The solution was cooled to 0 ° C. [899] The acid chloride suspended in 2.5 ml of dichloromethane is added to the solution. The mixture was stirred for 48 hours at room temperature. The precipitate obtained was filtered off. 0.050 g was purified by recrystallization from acetonitrile. [900] Weight : 0.025 g yield = 17% [901] [902] Example 42: Benzo [1,3] dioxol-5-ylmethyl 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [903] A compound was obtained (0.140 g) according to the method of Example 41, except using the compound of Preparation C and piperonyl alcohol. [904] [905] [906] Example 43 Benzyl 1-benzyl-2,4-dioxo-3-pyrid-4-ylmethyl-1,2,3,4-tetrahydroquinazolin-6-carboxylate [907] 0.5 g (1.7 mmol) of the compound obtained in step 3 of Example 20 in 15 ml of dry THF was stirred, 0.2 ml (1.7 mmol) of benzyl chloride and 1.2 g. (8. 7 mmol) of K 2 CO 3 was added. The mixture was stirred at rt overnight and usually treated to give the desired compound. [908] [909] Example 44 4-pyridylmethyl 2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylate [910] 0.69 g (2.3 mmol) of the compound obtained in step 3 of Example 21 was treated according to the method of Example 37 using 4-pyridylcarbinol. The product was obtained as follows: [911] [912] Example 45 4-pyridylmethyl3- (benzo [1,3] dioxol-5-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-car Carboxylate [913] The compound was obtained according to the method of Example 37, except using the compound obtained in Step 3 of Example 28 and 4-pyridylcarbinol (0.040 g). The product was crystallized from methanol: [914] [915] Example 46 benzyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d] pyrimidine-6-carboxylate [916] [917] Step 1: 3-benzyl-6-methyl-1H-pyrido [2,3-d] pyrimidine-2,4-dione [918] 20 g (111 mmol) of ethyl 2-amino-5-methylnicotinate and 200 ml of pyridine were refluxed. 13.7 ml (111 mmol) benzyl isocyanate was added. Reflux was continued overnight. After cooling, the precipitate was filtered off and washed with 2 x 100 ml of ethanol and 2 x 100 ml of ether. [919] Weight : 10 g yield 2 times = 34% [920] [921] Step 2: 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d] pyrimidine-6-carboxylic acid [922] 3.0 g (11.2 mmol) of the product of step 1, 100 ml of H 2 O, 7.1 g (44.9 mmol) KMnO 4 and 10 ml of NMP were introduced into a round bottom flask. The reaction medium was refluxed overnight. The medium was filtered when hot. The filtrate crystallized after cooling. After the new precipitate was filtered off, the filtrate was treated with 40 ml of Amberlite IR 120 (+) resin. The resin and acid mixture was filtered and the acid washed with CH 2 Cl 2 / MeOH in a mixture of 70/30. The solvent was removed under vacuum to yield 0.32 g of white solid (yield = 10%). [923] [924] Step 3: Benzyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d] pyrimidine-6-carboxylate [925] The esterification of the compound of step 2 above was carried out by the method described in Example 37 using benzyl alcohol. [926] After solidification in methanol, 0.040 g of the desired compound were obtained (yield = 31%): [927] [928] Example 47 4-pyridylmethyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d] pyrimidine-6-carboxylate [929] [930] As described in Example 37, except that the compound obtained in Step 2 of Example 46 and 4-pyridylcarbinol were used, the compound was obtained in a yield of 20% (0.050 g). [931] [932] Example 48 3-benzyl-4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amides [933] [934] Synthesis was carried out according to Synthesis Scheme 1 using benzyl isothiocyanate during cyclization to 4-oxo-2-thioxoquinozoline. After saponification and amidation with piperonylamine, the expected compound was obtained. [935] Weight: 0.100 g [936] TLC: CH 2 Cl 2 / MeOH 95/5 Rf = 0.64 [937] [938] Example 49: 4- [6- (4-hydroxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid [939] Into a stirred round bottom flask protected from moisture, 0.7 g (1.44 mmol) of Example 34 and 70 ml of anhydrous dichloromethane were introduced. The mixture was stirred and 1.4 ml (14.4 mmol) of BBr 3 in 7 ml of dichloromethane were added dropwise. After stirring for 2 hours at room temperature, the reaction was complete. After usual treatment, 0.280 g of the desired product were obtained (yield = 42%). [940] [941] Example 50: 3- (4-dimethylcarbamoyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazoline-6-carboxylic acid 4-methoxy Benzylamide [942] 0.3 g (0.64 mmol) of the compound of Example 35 were treated with 2M solution of dimethylamine in THF according to the method described in Example 1. The crude product was purified by chromatography on silica gel and condensed in ether to yield 0.160 g of the desired compound (yield: 49.9%). [943] [944] Example 51 1-methyl-3- (4-methylcarbamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-meth Oxy-benzylamide [945] The compound was obtained according to the method of Example 50, except using methylamine. [946] [947] Example 52 3-allyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [948] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 3-allyl bromide as the substrate. [949] [950] Example 53 1-methyl-2,4-dioxo-3- (2-pyrrole-1-yl-ethyl) -1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4-meth Oxy-benzylamide [951] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 1 (2-bromoethyl) pyrrole as the substrate. [952] [953] Example 54 1-Methyl-2,4-dioxo-3- (prop-2-ynyl) -1,2,3,4-tetrahydro-quinazolin-6 carboxylic acid 4-methoxy-benzyl amides [954] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and prop-2-ynyl bromide as the substrate. [955] [956] IR: 3265,1710,1667,1635,1501,1326,1249,1036,825,783,752 cm -1 [957] MP = 206 ° C [958] HPLC: 97.7% [959] Example 55 1-methyl-3- (3-methyl-but-2-enyl) -2,4-dioxo-1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4-meth Oxy-benzylamide [960] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 1-bromo-3-methyl-but-2-ene as the substrate. [961] [962] Example 56 1-Methyl-2,4-dioxo-3- (pyridin-2-ylmethyl) -1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4-methoxy-benzyl amides [963] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 2- (bromomethyl) pyridine as substrate. [964] [965] Example 57 3-carbamoylmethyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [966] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 2-chloro-acetamide as substrate. [967] [968] Example 58: 1-Methyl-2,4-dioxo-3- (pyridin-3-ylmethyl) -1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4-methoxy-benzyl amides [969] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 3- (bromomethyl) pyridine as substrate. [970] [971] Example 59; 1-methyl-3- (1-methyl-piperidin-3-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxyl Acid 4-methoxy-benzylamide [972] The compound was obtained according to the method of Step 2 of Example 34, except using the compound obtained in Step 1 of Example 34 and 3-bromomethyl-1-methyl-piperidine as the substrate. [973] [974] Example 60: 3- (4-Cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide [975] The compound was obtained according to the method of Step 2 of Example 34, except that the compound obtained in Step 1 of Example 34 and 4- (bromomethyl) benzonitrile were used as the substrate. [976] [977] Example 61 3- (3-cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide [978] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 3- (bromomethyl) -benzonitrile as the substrate. [979] TLC: CH 2 Cl 2 / MeOH 90/10 Rf = 0.80 [980] [981] HPLC: 97.1% [982] Example 62 3- (2-Methoxy-ethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin 6-carboxylic acid 4-methoxy-benzyl amides [983] The compound was obtained according to the method of Step 2 of Example 34, using the compound obtained in Step 1 of Example 34 and 1-bromo-2-methoxy-ethane as the substrate. [984] [985] Example 63: 3- (3-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide [986] The compound was obtained according to the method of Step 2 of Example 34, except using the compound obtained in Step 1 of Example 34 and 3- (bromomethyl) -1-methoxyphenyl as the substrate. [987] [988] Example 64 3-cyclopropylmethyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [989] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and bromomethylcyclopropyl as the substrate. [990] [991] Example 65 l-methyl-3- (2-morpholin-4-yl-ethyl) -2,4-dioxo-1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4- Methoxy-benzylamide [992] The compound was obtained according to the method of Step 2 of Example 34, except using the compound obtained in Step 1 of Example 34 and 4- (2-bromoethyl) morpholine as the substrate. [993] [994] Example 66 3-cyclohexylmethyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [995] The compound was obtained according to the method of Step 2 of Example 34, using the compound obtained in Step 1 of Example 34 and (bromomethyl) cyclohexane as the substrate. [996] [997] Example 67 1-Methyl-2,4-dioxo-3- (3-phenyl-propyl) -1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzyl amides [998] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 3-phenylpropyl bromide as the substrate. [999] [1000] Example 68: 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide [1001] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 4- (bromomethyl) -fluorobenzene as the substrate. [1002] [1003] Example69 3- [2- (4-diethylamino-phenyl) -2-oxo-ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazoline -6-carboxylic acid 4-methoxy-benzylamide [1004] [1005] According to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 2-chloro-1- (4-diethylamino-phenyl) -ethan-1-one as the substrate) Compound was obtained. [1006] [1007] Example 70 ethyl [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] -acetate [1008] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and ethyl-2-chloro-acetate as the substrate. [1009] [1010] Example 71: 3- (2-Hydroxy-ethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide [1011] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 2-bromoethan-1-ol as the substrate. [1012] [1013] MP = 168 ° C [1014] HPLC: 96.7% [1015] Example 72 Methyl 3- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4 dihydro-2H-quinazolin-3-yl] -pro Cypionate [1016] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and methyl 3-bromo-propanoate as the substrate. [1017] [1018] Example 73: 3- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] -propionic acid [1019] Compounds were obtained according to the method of steps 2-4 of Preparation Example B, using the compound obtained in Example 72 as the substrate. [1020] TLC: CH 2 Cl 2 / MeOH 90/10 Rf = 0.25 [1021] [1022] Example 74: ethyl 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]- Butyrate [1023] Compounds were obtained according to the method of Step 2 of Example 34, using the compound obtained in Step 1 of Example 34 and ethyl 4-bromobutyrate as substrate. [1024] [1025] Example 75 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] butyric acid [1026] Compounds were obtained according to the method of steps 2-4 of Preparation Example B, using the compound obtained in Example 74 as the substrate. [1027] [1028] Example 76 Methyl {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Phenyl} -acetate [1029] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and methyl 4- (bromomethyl) phenyl acetate as substrate. [1030] [1031] Example 77: {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -Phenyl} -acetic acid [1032] Compounds were obtained according to the method of steps 2-4 of Preparation Example B, using the compound obtained in Example 76 as the substrate. [1033] [1034] Example 78 3- (4-dimethylcarbamoylmethyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4 tetrahydro-quinazolin-6-carboxylic acid 4-meth Oxy-benzylamide [1035] Compounds were obtained from the compounds obtained in Example 77, which were transformed into acid chlorides under the action of oxarylyl chloride in situ and then treated with 2M solution of dimethylamine in THF. [1036] [1037] MP = 183 ° C [1038] HPLC: 93.2% [1039] Example 79 1-Methyl-2,4-dioxo-3-[(E) -3- (pyridin-3-yl) -allyl] -1,2,3,4-tetrahydro quinazoline-6- Carboxylic Acid 4-methoxy-Benzylamide [1040] The compound was obtained according to the method of Step 2 of Example 34, except that the compound obtained in Step 1 of Example 34 and 3-((E) -3-chloro-propylenyl) -pyridine as a substrate. [1041] [1042] Example 80 1-methyl-2,4-dioxo-3-[(E) -3- (pyridin-4-yl) -allyl] -1,2,3,4-tetrahydro quinazoline-6- Carboxylic Acid 4-methoxy-Benzylamide [1043] The compound was obtained according to the method of Step 2 of Example 34, except that the compound obtained in Step 1 of Example 34 and 4-((E) -3-chloro-propenyl) -pyridine as a substrate). . [1044] [1045] Example 81 l-Methyl-2,4-dioxo-3- (4-sulfamoyl-benzyl) -1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4-methoxy-benzyl amides [1046] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 4-bromomethyl-benzenesulfonamide as the substrate. [1047] [1048] Example 82 3- (4-methanesulfonyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy- Benzylamide [1049] 1- of Preparation B using 3- (4-methanesulfonyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid Compounds were obtained according to 5-2-5. [1050] [1051] Example 83 3- (4-dimethylsulfamoyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4-methoxy- Benzylamide [1052] Step 1: Methyl 3- (4-chlorosulfonyl-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylate [1053] Into the round bottom flask protected from moisture, 3.2 ml (47.5 mmol) of chlorosulfonic acid were introduced. The mixture was cooled in an ice bath and 2.2 g (6.80 mmol) of compound obtained in step 1 of Preparation C were added slowly. After stirring for 3 hours at room temperature, the reaction mixture was poured into a mixture of water and ice. The precipitate was filtered off and dried to yield 1.8 g of the desired product. [1054] [1055] Step 2: Methyl 3- (4-dimethylsulfamoyl-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylate [1056] To a stirred solution of 0.4 g (0.94 mmol) of the compound obtained in step 1 above in 25 ml of dichloromethane, 2 ml of 3.3 M (66 mmol) of dimethylamine in THF was added. After 1 hour, the reaction mixture was concentrated in vacuo. Chromatography on silica gel (dichloromethane / acetone: 98/2) yielded 0.370 g (yield: 91%) of the desired product. [1057] [1058] Step 3: 3- (4-dimethylsulfamoyl-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazoline-6-carboxylic acid [1059] Using the compound obtained in Step 2 as a substrate to obtain a compound according to the method of Step 2-4 of Preparation Example B. [1060] [1061] Step 4: 3- (4-dimethylsulfamoyl-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4-methoxy-benzyl amides [1062] Compounds were obtained according to the method of Example 1, except using 4-methoxybenzylamine. The desired compound was crystallized in a mixture of dichloromethane / ether. [1063] TLC: CH 2 Cl 2 / MeOH 90/10 Rf = 0.48 [1064] [1065] Example 84: 3- [4- (2-Dimethylamino-ethylsulfamoyl) -benzyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6- Carboxylic Acid 4-methoxy Benzylamide [1066] Compounds were obtained according to the method of steps 1 to 4 of Example 83 using N, N'-dimethylethylene diamine in step 2. The desired compound was crystallized in a mixture of dichloromethane / ether. [1067] [1068] Example 85 l-Methyl-3- (4-methylsulfamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro quinazoline-6-carboxylic acid 4-methoxy- Benzylamide [1069] Step 1: Methyl 1-methyl-3- (4-methylsulfamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylate [1070] Compounds were obtained following the method of steps 1-3 of Example 83 using methylamine in step 2. [1071] Step 2: 1-Methyl-3- (4-methylsulfamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4-methoxy-benzyl amides [1072] 0.2 g (0,5 mmol) of the compound obtained in step 1 was dissolved in 10 ml of dichloroethane. The solution was cooled and 2M trimethylaluminum in 3.2 ml (6.4 mmol) toluene and 0.875 g (6.4 mmol) 4-methoxy-benzylamine were added. The solution mixture was stirred overnight at room temperature and then at 60 ° C. for 24 hours. The solution was evaporated in vacuo and chromatographed on silica gel to give 0.085 g (32% yield) of the desired product (dichloromethane / ether). [1073] [1074] Example 86 methyl 3- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4 dihydro-2H-quinazolin-3-ylmethyl]- Benzoate [1075] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and methyl 3- (bromomethyl) benzoate as the substrate. [1076] [1077] Example 87 3- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid [1078] Using the compound of Example 86 as a substrate, the compound was obtained according to the method of Step 2-4 of Preparation Example B. [1079] [1080] Example 88: (E) Methyl-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3 -Day] -but-2-enoate [1081] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and methyl 3-bromocrotonate as the substrate. [1082] [1083] Example 89: 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] -but 2-enoic acid [1084] Using the compound of Example 88 as a substrate, the compound was obtained according to the method of Step 2-4 of Preparation Example B. [1085] TLC : CH 2 Cl 2 / MeOH 90/10 Rf = 0.50 [1086] [1087] Example 90 Methyl 5- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4 dihydro-2H-quinazolin-3-ylmethyl]- Furan-2-carboxylate [1088] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and methyl 5- (chloromethyl) -2-furoate as the substrate. [1089] [1090] Example 91: 5- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Furan-2-carboxylic acid [1091] The compound of Example 90 was hydrolyzed in the presence of K 2 CO 3 in a dioxane / water mixture to afford the compound. [1092] [1093] Example 92 methyl 5- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4 dihydro-2H-quinazolin-3-ylmethyl]- Thiophene-2-carboxylate [1094] The compound was obtained according to the method of Step 2 of Example 34, except that the compound obtained in Step 1 of Example 34 and methyl 5-bromomethyl-thiophene-2-carboxylate were used as the substrate. Compounds are described in J. Med. Chem., 1998, 41 (1), 74-95. [1095] [1096] Example 93: 5- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Thiophene-2-carboxylic acid [1097] The compound of Example 90 was hydrolyzed in the presence of K 2 CO 3 in a dioxane / water mixture to afford the compound. [1098] [1099] Example 94 1-Methyl-3- (4-nitro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzyl amides [1100] Compounds were obtained according to the method of step 2 of example 34, using the compound obtained in step 1 of example 34 and 4-nitrobenzyl bromide as the substrate. [1101] [1102] Example 95 3- (4-Amino-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzyl amides [1103] 1 g (2.1 mmol) of the compound of Example 94 was hydrogenated with Pd / C in an 80/20 v / v dichloromethane / methanol mixture. After stirring for 2 hours under hydrogen atmosphere, the reaction mixture was filtered. The solvent was removed under vacuum and the crude product was condensed from the mixture of dichloromethane / ether to yield 0.800 g of the desired compound (yield: 85.8%). [1104] [1105] Example 96 3- (4-dimethylamino-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide [1106] 0.220 g (0.5 mmol) of the compound of Example 95 in 5 ml of CH 3 CN, and 0.150 g (5 mmol) of powder of paraformaldehyde, 0.095 g with stirring in a round bottom flask protected from moisture. (1.5 mmol) of NaBH 3 CN and 100 μl of acetic acid were added sequentially. After 2 hours at room temperature and 1 hour 30 minutes under reflux, the reaction mixture was taken up in dichloromethane and washed with 1M NaOH. The organic phase was decanted, washed, dried and concentrated in vacuo. The product was recrystallized from acetonitrile to yield 0.130 g (yield 55%) of the desired compound. [1107] [1108] Example 97 3- (4-acetylamino-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzyl amides [1109] To the round bottom protected from moisture was added 0.190 g (0.43 mmol) of Example 95 compound in 10 ml of dichloromethane. The solution was stirred and 36 μl (40 mg, 0.51 mmol) of acetyl chloride and 72 μl triethylamine were added. After 1 hour at room temperature, 36 μl of acetyl chloride and 72 μl of triethylamine were added. After 1 hour, the organic phase was washed with 1M HCl and dried. Chromatography (dichloromethane / ether) on silica gel yielded 0.120 g of the desired compound (Yield: 57%). [1110] [1111] Example 98: 3- [4- (N, N-methylsulfonylamino) -benzyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6- Carboxylic Acid 4-methoxy-Benzylamide [1112] Compounds were obtained according to the method of Example 97 using the compound obtained in Example 95 and methanesulfonyl chloride as a substrate. [1113] [1114] Example 99 3- (benzofurazane-5-ylmethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy Benzylamide [1115] Compounds were obtained according to the method of Example 2, Example 34 using 5-bromomethyl benzofurazane and the compound obtained in Step 1 of Example 34. [1116] TLC: CH 2 Cl 2 / MeOH 90/10 Rf = 0.80 [1117] [1118] Example 100 3- [2- (4-fluorophenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazoline-6-carboxylic acid 4-methoxy-benzylamide [1119] The compound was obtained according to the method of Example 34 step 2 using the compound obtained in step 1 of example 34 and 4-fluorophenoxyethyl bromide. [1120] TLC: CH 2 Cl 2 / MeOH 90/10 Rf = 0.60 [1121] [1122] Example 101 3- (2-benzenesulfonyl-ethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy- Benzylamide [1123] Compounds were obtained according to the method of Example 34 Step 2 using the compound obtained in Step 1 of Example 34 and 2-chloroethyl phenyl sulfone. [1124] [1125] Example 102: 3- (3-Fluoro-4-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazoline-6-carboxylic acid 4 -Methoxy benzylamine [1126] The compound was obtained according to the method of Example 34 step 2 using the compound obtained in step 1 of example 34 and 4-chloromethyl-2-fluoro-1-methoxy-benzene. [1127] TLC: CH 2 Cl 2 / MeOH 90/10 Rf = 0.80 [1128] [1129] Example 103: 1-Methyl-2,4-dioxo-3- [4- (2H-tetrazol-5-yl) -benzyl] -1,2,3,4-tetrahydro quinazolin-6-carr Acid 4-methoxy-benzylamide [1130] [1131] 3 g (6.6 mmol) of the compound of Example 60, 1.3 g (19.8 mmol) of NaN 3 and 2.72 g (19.8 mmol) of triethylamine hydrochloride in 100 ml of toluene were heated at 80 ° C. under an inert atmosphere. After 5 hours, 10 ml of DMF was added and reflux was maintained overnight. After cooling, the precipitate was filtered off and washed sequentially with AcOEt, MeOH and 3N HC1. The solid obtained was treated with a mixture of AcOEt / MeOH under reflux and filtered. Chromatography on silica gel (DMF with 10% NH 4 OH) yielded 1.2 g of the desired compound (yield: 36%). [1132] [1133] Example 104 1-methyl-3- [4- (5-methyl-1,2,4-oxadiazol-3-yl) -benzyl] -2,4-dioxo-1,2,3,4 Tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [1134] Compound obtained in step 1 of Example 34 and 3- (4-chloromethyl-phenyl) -5-methyl- [1,2,4] oxadiazole (obtained from 4-hydroxymethylbenzonitrile in step 4) ) Was obtained according to the method of Example 34 Step 2. [1135] [1136] Example 105: 1-methyl-3- [4- (3-methyl-1,2,4-oxadiazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4 Tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [1137] In a round bottom containing 4 cc molecular sieve, 5 ml of DMF, 76 mg (1.02 mmol) N-hydroxy-acetamidine and 25 mg (1.02 mmol) NaH were introduced. After the mixture was stirred for 15 minutes, 0.5 g (1.02 mmol) of the compound of Example 34 were added. The reaction was heated at 65 ° C. for 4 hours and then filtered through celite. The filtrate was poured over 100 ml of water. The precipitate obtained was filtered off, washed sequentially with ethanol, water and ether and dried to give 0.210 g of the desired compound (yield: 40%). [1138] [1139] Example 106 Methyl 2-chloro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3 Ylmethyl] -benzoate [1140] The compound of Step 1 of Example 34 and methyl 2-chloro-4-chloromethyl-benzoate were obtained according to the method of Step 2 of Example 34. [1141] [1142] Example 107: 2-Chloro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo [1143] -1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid [1144] The compound of Example 106 was hydrolyzed using a solution of aqueous ethanol and K 2 CO 3 to obtain the compound. [1145] [1146] Example 108: 1-Methyl-3- [4- (1-methyl-1H-tetrazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro-quina Zoline-6-carboxylic acid 4-methoxy-benzylamide [1147] [1148] The compound of Step 1 of Example 34 and 5- (4-chloromethyl-phenyl) -1-methyl-1H-tetrazole were obtained according to the method of Step 2 of Example 34. [1149] [1150] Example 109: 1-Methyl-3- [4- (2-methyl-2H-tetrazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro-quina Zoline-6-carboxylic acid 4-methoxy-benzylamide [1151] [1152] Example 34 A compound was obtained according to the method of Example 34 step 2 using the compound obtained in step 1 and 5- (4-chloromethyl-phenyl) -2-methyl-2H-tetrazole. [1153] [1154] Example 110 Methyl 2-methoxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4 dioxo-1,4-dihydro-2H-quinazolin-3 -Ylmethyl] -benzoate [1155] Using the compound of Step 1 of Example 34 and methyl 4-bromomethyl-2-methoxy-benzoate according to the method of Step 2 of Example 34. [1156] [1157] Example 111: 2-methoxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3 -Ylmethyl] -benzoic acid [1158] The compound of Example 110 was hydrolyzed using K 2 CO 3 as a reagent in a mixture of methanol and water to obtain a compound. After acidification of the reaction mixture, the obtained precipitate was filtered to give the desired product. [1159] [1160] Example 112 Methyl 2-hydroxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4 dioxo-1,4-dihydro-2H-quinazolin-3 -Ylmethyl] -benzoate [1161] A stirred solution of 1 g (1.93 mmol) of the compound of Example 111 in 15 ml of dichloromethane is maintained at 0 ° C. and 7.7 ml (7.7 mmol) of 1 M / l BCl 3 in dichloromethane are added dropwise under inert atmosphere. It was. After stirring for 15 minutes at 0 ° C. and for 1 hour at room temperature, the reaction mixture is poured onto ice and extracted with ethyl acetate. The organic phase was dried and concentrated in vacuo. The precipitate obtained was chromatographed on silica gel (dichloromethane / methanol: 99/1) to yield 0.460 g of the desired product (yield: 47%). [1162] [1163] Example 113 2-hydroxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3 -Ylmethyl] -benzoic acid [1164] The compound of Example 112 was hydrolyzed using K 2 CO 3 as a reagent in a mixture of methanol and water to obtain a compound. After acidification of the reaction mixture, the obtained precipitate was filtered to give the desired product. [1165] [1166] Example 114 Methyl 2-methyl-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3 -Ylmethyl] -benzoate [1167] Using the compound of Step 1 of Example 34 and methyl 4-bromomethyl-2-methyl-benzoate according to the method of Step 2 of Example 34. [1168] [1169] Example 115: 2-Methyl-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3- Monomethyl] -benzoic acid [1170] The compound of Example 114 was hydrolyzed using K 2 CO 3 as a reagent in a mixture of methanol and water, and then refluxed with LiOH for 2 hours to obtain a compound. After acidification of the reaction mixture, the obtained precipitate was filtered to give the desired product. [1171] [1172] Example 116 1-methyl-2,4-dioxo-3- (pyridine-4-methyl) -1,2,3,4-tetrahydro quinazoline-carboxylic acid (benzo [1,3] dioxol -5-ylmethyl) -amide [1173] Step 1: Methyl 2,4-dioxo-1-methyl-3- (pyridin-4-ylmethyl) -1,2,3,4-tetrahydro quinazoline-6-carboxylate [1174] Compounds were obtained according to the method of step 4 of Example 15 using the compound obtained in step 2 of Example 20. [1175] Step 2: 2,4-dioxo-l-methyl-3- (pyridin-4-ylmethyl) -1,2,3,4-tetrahydro quinazoline-6-carboxylic acid [1176] Compounds were obtained according to the method of Steps 2-4 of Preparation Example B using the compound obtained in Step 1 above. [1177] Step 3: l-methyl-2,4-dioxo-3- (pyridine-4-methyl) -1,2,3,4-tetrahydro quinazoline-6-carboxylic acid (benzo [1,3] di Oxol-5-ylmethyl) -amide [1178] To 0.2 g (0.65 mmol) of the compound obtained in step 2 above in 7 ml of dichloromethane, 0.113 g (0.65 mmol) of EDCI, 0.080 g (0.65 mmol) of HOBT and 0.064 g (0.060 ml, 0.65 mmol) of 3 , 4-methylenedioxy-benzylamine was added. After stirring for 20 hours at room temperature and after conventional treatment, 0.140 g (yield: 48%) of the desired product were obtained. [1179] [1180] Example 117 1-methyl-2,4-dioxo-3- (pyridin-4-ylmethyl) -1,2,3,4-tetrahydroquinazoline-carboxylic acid 4-methoxy-benzylamide [1181] The compound was obtained according to the method of step 3 of Example 116 using the compound obtained in step 2 of Example 116 and 4-methoxy-benzylamine. After chromatography on silica gel 0.280 g (yield: 25%) of the desired product was isolated. [1182] [1183] Example 118: 1-Methyl-2,4-dioxo-3- (pyridin-4-ylmethyl) -1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4-hydroxy-benzyl amides [1184] A stirred solution of 0.280 g (0.67 mmol) of the compound of Example 117 in 20 ml of dichloromethane was maintained at 0 ° C. and 1.7 g (0.63 ml) of BBr 3 in 2 ml of dichloromethane were added dropwise under inert atmosphere. . After stirring for 20 minutes at room temperature, the reaction mixture is poured onto concentrated NaHCO 3 solution, decanted and extracted. The organic phase was dried and concentrated in vacuo to yield 0.150 g of the desired product (yield: 53.4%). [1185] [1186] Example 119: Methyl 4- [6- (3-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4 dihydro-2H-quinazolin-3-ylmethyl]- Benzoate [1187] Step 1: benzyl 3- (4-methoxycarbonyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro quinazoline-6-carboxylate [1188] Obtaining the compound according to the method of steps 1-5 to 2-5 of Preparation Example B using 4-amino-isophthalic acid 1-benzylester 3-methyl ester and methyl 4-aminomethyl benzoate in Step 1-5 It was. The desired product was purified by reflux in methanol. [1189] [1190] Step 2: benzyl 3- (4-methoxycarbonyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylate [1191] The compound was obtained according to the method of step 4 of Example 15 using the compound obtained in step 1 above. [1192] [1193] Step 3: 3- (4-methoxycarbonyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazoline-6-carboxylic acid [1194] To a stirred solution of 10.8 g (23.6 mmol) of the compound obtained in step 2 above in 120 ml of dichloromethane and 80 ml of methanol, 3.2 g of Pd / C was added at 10%. The reaction mixture was stirred for 1 h at room temperature under hydrogen atmosphere and then filtered through celite. The filtrate was concentrated in vacuo resulting in a first crystalline vesicle. The insoluble portion was extracted three times with a mixture of methanol / water / saturated NaHCO 3. The organic phase was collected and acidified to pH 1 with concentrated hydrochloric acid solution to give the desired product a corresponding second vesicle. Both vesicles were pooled together and dried under vacuum to yield 6.9 g of the desired product (yield: 79%). [1195] [1196] Step 4: Methyl 4- [6- (3-methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoate [1197] The compound was obtained according to the method of Example 1 using the compound obtained in step 3 and 3-methoxy-benzylamine. [1198] [1199] Example 120: 4- [6- (3-methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid [1200] The compound of Example 119 was hydrolyzed using K 2 CO 3 as a reagent in a mixture of methanol and water for 8 hours under reflux to obtain a compound. After acidification of the reaction mixture, the obtained precipitate was filtered to give the desired product. [1201] [1202] Example 121 Methyl 4- [1-methyl-6- (4-methylsulfanyl-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoate [1203] Using the compound obtained in Step 3 of Example 119 and 4-methylthio-benzylamine, the compound was obtained according to the method of Example 1. [1204] [1205] Example 122: 4- [1-methyl-6- (4-methylsulfanyl-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -Benzoic acid [1206] The compound of Example 121 was hydrolyzed using K 2 CO 3 as a reagent in a mixture of methanol and water for 48 hours under reflux to obtain a compound. After acidification of the reaction mixture, the obtained precipitate was filtered to give the desired product. [1207] [1208] Example 123 Methyl 4- [1-methyl-2,4-dioxo-6- (4-trifluoromethoxy-benzylcarbamoyl) -1,4-dihydro-2H-quinazolin-3-yl Methyl] -benzoate [1209] Using the compound obtained in Step 3 of Example 119 and 4-trifluoromethoxy-benzylamine, the compound was obtained according to the method of Example 1. [1210] [1211] Example 124 Methyl 4- [6- (4-fluoro-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -Benzoate [1212] The compound was obtained according to the method of Example 1 using the compound obtained in step 3 and 4-fluorobenzylamine. [1213] [1214] Example 125: 4- [6- (4-Fluoro-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid [1215] Using the compound obtained in Example 124, a compound was obtained according to the method of Step 2-4 of Preparation Example B. [1216] [1217] Example 126 Methyl 4- {6-[(benzofurazane-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin- 3-ylmethyl} -benzoate [1218] The compound obtained in step 3 of example 119 and C-benzofurazane-5-yl-methylamine (in the first step, reacted with sodium diformylamide overnight at 70 ° C. in acetonitrile and under reflux in the second step, 2 The compound was obtained according to the method of Example 1 using a 5-bromomethyl-benzofurazane made from a solution of 5% ethanol / HCl treated for hours. [1219] [1220] Example 127: 4- {6-[(benzofurazane-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3 -Ylmethyl} -benzoic acid [1221] Using the compound obtained in Example 126, the compound was obtained according to the method of Step 2-4 of Preparation Example B. After acidification, the precipitate was filtered off. [1222] [1223] Example 128 Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate [1224] Step 1: 4-Amino-isophthalic acid 3-methyl ester [1225] The compound was obtained according to the method of step 3 of Example 119 using 4-amino-isophthalic acid 1-benzylester 3-methyl ester as a substrate. [1226] Step 2: 6-amino-N- (4-methoxy-benzyl) -isophthalamic acid methyl ester [1227] Compounds were obtained according to the method of Example 1 using the compound obtained in step 1 and 4-methoxy-benzylamine. [1228] Step 3: Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate [1229] Compounds were obtained according to the method of steps 1-5 to 2-5 of Preparation Example B using the compound obtained in step 1-5 and methyl 4-aminomethyl benzoate in step 1-5. [1230] [1231] Example 129 Methyl 4- [1-ethyl-6- (4-methoxy-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -Benzoate [1232] Using the compound obtained in Example 128 and iodomethane in DMF containing K 2 CO 3 , the compound was obtained according to the method of step 4 of Example 15. The desired compound was crystallized in a mixture of dichloromethane / ether. [1233] [1234] Example 130: 4-ethyl-6- (4-methoxy-benzylcarbamoyl) -2,4-dioxo-1,4- [1235] Dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid [1236] The compound of Example 112 was hydrolyzed using K 2 CO 3 as a reagent in a mixture of methanol and water for 3 hours under reflux to afford the compound. After acidification of the reaction mixture, the obtained precipitate was filtered to give the desired product. [1237] [1238] Example 131 3- (4-Methoxy-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (pyridin-4-yl Methyl) -amide [1239] Step 1: Methyl 3- (4-methoxybenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazoline-6-carboxylate [1240] Compounds were obtained according to the method of Example 4, Step 4 using the compound obtained in Step 1 of Example 16. [1241] Step 2: 3- (4-methoxybenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [1242] Compounds were obtained according to the method of Steps 2-4 of Preparation Example B using the compound obtained in Step 1 above. [1243] Step 3: 3- (4-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazolin-6-carboxylic acid (pyridin-4-ylmethyl )-amides [1244] Using the compound obtained in step 2 and 4- (aminomethyl) pyridine, the compound was obtained according to the method of step 3 of Example 116 (0.160 g, yield: 63%). [1245] [1246] HPLC: 97.8% [1247] Example 132 3- (4-hydroxy-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazolin-6-carboxylic acid (pyridin-4-yl Methyl) -amide [1248] To a stirred solution of 0.630 g (1.46 mmol) of the compound of Example 131 in 50 ml of dichloromethane was added 3.7 g (1.3 ml, 14.6 mmol) of BBr 3 in 5 ml of dichloromethane under inert atmosphere. . After stirring for 1 hour at room temperature, the reaction mixture was cooled and poured into 100 ml of saturated NaHCO 3 solution. The precipitate obtained was purified by chromatography on silica gel (gradient gradient of methanol in dichloromethane) and solidified in dichloromethane to give the desired compound. [1249] [1250] Example 133: 3- (4-Cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridine-4- Monomethyl) -amide [1251] Step 1: 1-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amide [1252] Compounds were obtained according to the method of Example 33 using the same substrate and 4-picolylamine in the amidation reaction step. [1253] [1254] Step 2: 3- (4-cyano-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-yl Methyl) -amide [1255] Using the compound obtained in step 1 and α-bromo-para-toluonitrile according to the method of step 2 of Example 34 to obtain a compound. [1256] [1257] Example 134 1-Methyl-2,4-dioxo-3- (3-pyridin-4-yl-allyl) -1,2,3,4-tetrahydro quinazoline-6-carboxylic acid (pyridine- 4-ylmethyl) -amide [1258] The compound was obtained according to the method of Example 34 Step 2 using the compound obtained in Step 1 of Example 133 and 4- (3-chloro-propenyl) -pyridine hydrochloride. [1259] [1260] Example 135 Methyl 4- {1-methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3- Monomethyl} -benzoate [1261] The compound was obtained according to the method of step 2 of Example 34 using the compound obtained in step 1 of example 133 and 4- (bromomethyl) -benzoate. [1262] [1263] Example 136: 4- {1-Methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3-yl Methyl} -benzoic acid [1264] Using the compound obtained in Example 135, the compound was obtained according to the method of Step 2-4 of Preparation Example B. After dissolving the compound in a hot solution of 0.1 M isopropanol / HCl, the corresponding hydrochloride was obtained. The desired compound was purified by crystallization from acetonitrile. [1265] [1266] Example 137: Methyl (4- {1-methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3 -Ylmethyl} -phenyl) -acetate [1267] The compound was obtained according to the method of step 2 of Example 34 using the compound obtained in step 1 of example 133 and methyl 4- (bromomethyl-phenyl) acetate. [1268] [1269] Example 138: (4- {1-methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3- Monomethyl} -phenyl) -acetic acid [1270] Using the compound obtained in Example 137, a compound was obtained according to the method of Step 2-4 of Preparation Example B. After dissolving the compound in a hot solution of 0.1 M isopropanol / HCl, the corresponding hydrochloride was obtained. The desired compound was purified by crystallization from acetonitrile. [1271] [1272] Example 139: Methyl 4- {1-methyl-2,4-dioxo-6-[(l-oxy-pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quina Zolin-3-ylmethyl} -benzoate [1273] To a stirred suspension of 0.500 g (1.10 mmol) of the compound of Example 135 in 20 ml of dichloromethane maintained at −20 ° C. was added 0.250 g (1.10 mmol) of meta-chloroperbenzoic acid in 5 ml of dichloromethane. . After stirring overnight at room temperature, the reaction mixture was washed sequentially with saturated Na 2 CO 3 solution and water. The organic phase was dried and concentrated in vacuo. Chromatography on silica gel (gradient gradient of methanol in dichloromethane) followed by solidification in dichloromethane / ether gave 0.300 g (yield: 57%) of the desired product. [1274] [1275] Example 140: 4- {1-Methyl-2,4-dioxo-6-[(1-oxy-pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazoline -3-ylmethyl} -benzoic acid [1276] Using the compound obtained in Example 139, a compound was obtained according to the method of Step 2-4 of Preparation Example B. [1277] [1278] Example 141 Methyl {6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -3-benzyl-2,4-dioxo-1,4-dihydro-2H-quina Sleepy-l-yl} -acetate [1279] The compound of Example 3 was alkylated using K 2 CO 3 and methylbromoacetate in DMF to obtain the compound. [1280] [1281] Example 142 {6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -3-benzyl-2,4-dioxo-3,4-dihydro-2H-quinazolin -1-yl} -acetic acid [1282] Using the compound obtained in Example 141, the compound was obtained according to the method of Step 2-4 of Preparation Example B. [1283] [1284] Example 143: Methyl 4- {6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H -Quinazolin-3-ylmethyl} -benzoate [1285] Compounds were obtained according to the method of step 2 of Example 34 using the compound obtained in Example 37 and methyl 4- (bromomethyl) -benzoate. [1286] Example 144: 4- {6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H- Quinazolin-3-ylmethyl} -benzoic acid [1287] Using the compound obtained in Example 143, the compound was obtained according to the method of Step 2-4 of Preparation Example B. [1288] [1289] Example 145 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6 carboxylic acid 4-sulfamoyl-benzylamide [1290] The compound was obtained according to the method of Example 9 using the compound obtained in Preparation Example C and 4- (aminomethyl) benzene sulfonamide. [1291] [1292] Example 146: 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid [3- (pyridin-4-ylsulfanyl)- Propyl] -amide [1293] Compounds were obtained according to the method of Example 9 using 3- (pyridin-4-ylsulfanyl) -propylamine and the compound obtained in Preparation Example C using dichloromethane as a solvent (reactant 3- (pyridine-4) -Ylsulfamil) -propylamine was obtained according to the method described in Bioorg. Med. Chem., 1996, 4, 557-562). [1294] [1295] Example 147 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6 carboxylic acid (4-morpholin-4-yl-butyl)- amides [1296] Using the compound obtained in Preparation Example C and 4-morpholin-4-yl-butylamine and using dichloromethane as a solvent, the compound was obtained according to the method of Step 3 of Example 116 (Reactant 4-Morpholine- 4-yl-butylamine was obtained according to the method described in J. Med. Chem., 1997, 40, 3915-3925). [1297] [1298] Example 148 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-benzyl-piperidin-4-yl )-amides [1299] Compounds were obtained according to the method of Example 9 using the compound obtained in Preparation Example C and 4-amino-1-benzylpiperidine and dichloromethane as a solvent. The desired compound was crystallized from a mixture of dichloromethane and ether. [1300] [1301] Example 149 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-hydroxy-benzylamide [1302] To the round bottom protected from moisture was introduced 1.9 g (4.4 mmol) of the compound of Example 13 in 200 ml of dichloromethane under inert atmosphere. To the stirred solution was added dropwise 4.2 ml (11.1 g, 44 mmol) of BBr 3 in 17 ml of dichloromethane. After 30 minutes at room temperature, the reaction mixture was poured into 500 ml of saturated solution of NaHCO 3 , extracted with dichloromethane, dried and concentrated in vacuo. Crystallization of the crude product in methanol / ether gave 1.35 g (yield: 74%) of the desired product. [1303] [1304] Example 150: Ethyl (4-{[(3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carbonyl) -amino] -methyl } -Phenoxy) -acetate [1305] [1306] To a round bottom flask protected from moisture was introduced 0.45 g (1.08 mmol) of compound in 13.5 ml of DMF under inert atmosphere. To the stirred solution, 0.3 g K 2 CO 3 (2.16 mmol) and 0.24 ml (2.016 mmol) ethyl bromoacetate were added. [1307] After 1 h at 60 ° C, the reaction mixture was concentrated in vacuo. The crude product was taken up in dichloromethane, washed with water, dried and concentrated in vacuo to yield 0.410 g (yield: 75.8%) of the desired compound. [1308] [1309] Example 151: (4-{[(3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carbonyl) -amino] -methyl} -Phenoxy) -acetic acid [1310] Compounds were obtained according to the method of steps 2-4 of Preparation Example B using the compound of Example 150. [1311] [1312] Example 152 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-dimethylcarbamoylmethoxy-benzylamide [1313] Compounds were obtained according to the method of Example 1 using the compound of Example 151 and dimethylamine in a 2 M solution in THF. [1314] [1315] Example 153: 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6carboxylic acid (3-phenyl-allyl) -amide [1316] Compounds were obtained according to the method of Example 9 using the compound of Preparation Example C and 3-phenyl-allylamine hydrochloride. [1317] [1318] Example 154 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6 carboxylic acid 4-cyano-benzylamide [1319] Compounds were obtained according to the method of Example 9 using the compound of Preparation Example C and 4-amino-benzyl benzonitrile. The desired product was solidified in a mixture of dichloromethane / ether. [1320] [1321] Example 155: 4-{[(3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carbonyl) -amino] -methyl}- Benzoic acid [1322] Compounds were obtained according to the method of steps 2-4 of Preparation Example B using the compound of Example 11. [1323] [1324] Example 156 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6 carboxylic acid 4-dimethylcarbamoyl-benzylamide [1325] Compounds were obtained according to the method of Example 1 using the compound of Example 155 and dimethylamine in a 2 M solution in THF. [1326] [1327] Example 157 3- (4-Dimethylamino-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [1328] Example 1-5 using the method of steps 1-5 to 3-5 of Preparation Example B followed by 4-dimethylamino-benzyl isocyanate in step 1-5 and then using the compound obtained in the step and 4-methoxy-benzylamine Compounds were obtained according to the method of 1. [1329] [1330] Example 158: 3- [4- (N-methylsulfonylamino) -benzyl] -1-methyl-2,4-dioxo-1,2,3,4 tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [1331] Compounds were obtained according to the method of Example 97 using the compound obtained in Example 95 and 2.5 equivalents of methanesulfonyl chloride as a substrate. [1332] [1333] Example 159: tert-butyl {5- [6- (4-methoxy-benzylcarbamoyl) -1 -methyl-2,4-dioxo [1334] -1,4-dihydro-2H-quinazolin-3-ylmethyl] -pyridin-2-yl} -carbamate [1335] The compound was obtained according to the method of Example 2, Example 34 using tert-butyl (5-bromomethylpyridin-2-yl) -carbamate and the compound obtained in Step 1 of Example 34. [1336] [1337] Example 160: 3- (6-Amino-pyridin-3-ylmethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4- Methoxy-benzylamide [1338] Compound was obtained by deprotecting the compound of Example 159 using trifluoroacetic acid in dichloromethane. [1339] [1340] HPLC : 99.5% [1341] Example 161 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6 carboxylic acid (1,3-benzo Dioxol-5-ylmethyl) -amide [1342] [1343] Step 1: 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6-carboxylic acid. [1344] Ethyl 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6-carboxylate in the presence of LiOH (Heterocycles 1998, 48 (12), 2521-2528) to obtain a compound by hydrolysis in a dioxane / water mixture. [1345] [1346] Step 2: 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6-carboxylic acid (1,3-benzo Dioxol-5-ylmethyl) -amide [1347] Compounds were obtained according to the method of Example 1 using the compound and piperonylamine obtained in step 1 above. [1348] [1349] Example 162: 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (1,3- Benzodioxol-5-ylmethyl) -amide [1350] Step 1: 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid [1351] Methyl 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylate in the presence of LiOH (Heterocycles 1994,37 (1), 563-570) was hydrolyzed in a dioxane / water mixture to obtain a mixture. [1352] [1353] Step 2: 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (1,3-benzo Dioxol-5-ylmethyl) -amide [1354] Compounds were obtained according to the method of Example 1 using the compound and piperonylamine obtained in step 1 above. [1355] [1356] Example 163: 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6-carboxylic acid (1, 3-benzodioxol-5-ylmethyl) -amide [1357] [1358] Step 1: N '-(l-benzyl-3-methyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl) -N, N-dimethyl-formamidine [1359] 0.56 g (2.5 mmol) of 6-amino-3-benzyl-lH-pyrimidine-2,4-dione (Tetrahedron Letters, 1991,32 (45), 6534-6540) in 20 ml of DMF was stirred under inert atmosphere It was. 1 ml (7.5 mmol) of N, N'-dimethylformamide dimethyl acetal was added to this solution and the mixture was heated at reflux for 20 minutes. After cooling and concentration in vacuo, the residue was taken up in dichloromethane and the organic phase was washed with water, dried over Na 2 SO 4 and concentrated in vacuo until low volume. The crude product was then precipitated by addition of ether. After filtration, 0.680 g (yield: 72.6%) of the desired compound were obtained. [1360] [1361] Step 2: N'-Cl-benzyl-5-iodine-3-methyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl) -N, N-dimethyl- Formamidine [1362] To a stirred solution of 0.68 g (2.38 mmol) of the compound obtained in step 1 above in 24 ml of anhydrous dichloromethane was added 0.64 g (2.85 mmol) of N-iodine succinimide. After 30 minutes at reflux, the reaction mixture is cooled and the organic phase is washed with water, dried over Na 2 SO 4 and concentrated in vacuo. The crude product was precipitated in ether to give 0.680 g (yield: 69.3%) of the desired compound. [1363] [1364] Step 3: 3-Benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6-carboxylic acid ethyl ester [1365] In a stirred solution of 0.68 g (1.65 mmol) of the compound obtained in step 2 above in 45 ml of anhydrous DMF, 18 mg of Pd (OAc) 2 , 8 mg of CuI, 330 mg of K 2 CO 3 , and 0.22 ml of ethyl acrylate were added sequentially. After 30 minutes at reflux, the reaction mixture was concentrated in vacuo. The residue was taken up in dichloromethane. The organic phase was filtered, washed twice with water, dried over Na 2 SO 4 and concentrated in vacuo. The crude product was purified by chromatography on silica gel (dichloromethane / methanol: 97/3) and then from ether Crystallization gave 0.320 g (yield: 57%) of the desired compound. [1366] [1367] Step 4: 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6-carboxylic acid [1368] The compound obtained in step 3 was hydrolyzed in a dioxane / water mixture in the presence of LiOH to obtain a compound. [1369] [1370] Step 5: 3-benzyl-l-methyl-2,4-dioxo-l, 2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6-carboxylic acid (1,3 -Benzodioxol-5-ylmethyl) -amide [1371] Compounds were obtained according to the method of Example 1 using the compound and piperonylamine obtained in step 4 above. [1372] [1373] Example 164: 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro 2H-pyrido [2,3-d] pyrid Midin-3-ylmethyl] -benzoic acid [1374] Step 1: 1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6 carboxylic acid [1375] 1.3 g (4.17 mmol) of the compound obtained in step 4 of Example 163 and 3.1 g (23 mmol) of AlCl 3 in 44 ml of benzene were stirred at room temperature for 2 hours. After addition of a water / ice mixture, the reaction mixture was extracted sequentially with ethyl acetate and dichloromethane. The aqueous layer was acidified at pH 1 by addition of concentrated HCl. The precipitate obtained was filtered off and washed with 10 ml of methanol and 10 ml of dichloromethane to give the desired compound (yield: 62.9%). [1376] [1377] Step 2: 1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6 carboxylic acid 4-methoxy-benzylamide [1378] Compounds were obtained according to the method of Example 1 using the compound obtained in step 2 and 4-methoxybenzylamine. [1379] [1380] Step 3: Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [2,3-d] Pyrimidin-3-ylmethyl] -benzoate [1381] Compounds were obtained according to the method of step 2 of Example 34 using the compound obtained in step 2 and methyl-4- (bromomethyl) benzoate. After cooling in ether, 0.41 g (yield: 71.1%) of the desired compound was isolated. [1382] [1383] Step 4: 4- [6- (4-methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [2,3-d] pyridine Midin-3-ylmethyl] -benzoic acid [1384] The compound was obtained according to the method of Example 35 using the compound obtained in step 3 above. [1385] [1386] Example 165: 3- (4-cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6 -Carboxylic acid 4-methoxy-benzylamide [1387] Using the compound obtained in step 2 of example 164 and 4- (bromomethyl) benzonitrile according to the method of step 2 of example 34 to obtain a compound (0.11 g; yield = 68.4%). [1388] [1389] Example 166: 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6 -Carboxylic acid 4-methoxy-benzylamide [1390] The compound was obtained according to the method of Example 2, Example 34 using 4-fluorobenzyl bromide and the compound obtained in Step 2 of Example 164. [1391] [1392] Example 167: 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (1, 3-benzodioxol-5-ylmethyl) -amide [1393] [1394] Step 1: 1-benzyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbaldehyde [1395] 9.5 g (43.9 mmol) of 3-benzyl-6-methyl-lH-pyrimidine-2,4-dione solution (Synthetic Communications 1991, 2181-2188) and 129 ml of cold acetic acid were stirred for 5 minutes, and 5.75 g of SeO 2 was added. The reaction mixture was heated to reflux for 2 hours 30 minutes, filtered and concentrated in vacuo. The residue was taken up in dichloromethane. The insoluble portion was removed and the filtrate was concentrated in vacuo. Chromatography on silica gel (dichloromethane / methanol: 95/5) yielded 4.0 g of the desired compound (yield: 39.5%). [1396] [1397] Step 2: 1-benzyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbaldehyde dimethylhydrazone [1398] To a stirred solution of 3.6 g (15.6 mmol) of the compound obtained in step 1 above in 80 ml of anhydrous DMF was added 1.2 ml (0.94 g, 15.6 mmol) of dimethylhydrazine. After stirring for 1 hour at room temperature, the solvent was removed under vacuum and the residue was dissolved in dichloromethane. The organic layer was washed, dried over Na 2 SO 4 and concentrated. Chromatography on silica gel (dichloromethane / methanol: 97/3) gave 2.5 g (yield: 59%) of the desired compound. [1399] [1400] Step 3: 1-benzyl-2,6-dioxo-3-methyl-1,2,3,6-tetrahydro-pyrimidine-4-carbaldehyde dimethylhydrazone [1401] To a stirred solution of 2.3 g (8.45 mmol) of the compound obtained in step 2 above in 58 ml of anhydrous DMF was added 2.3 ml (2.0 g, 1.69 mmol) of N, N'-dimethylformamide acetal. The reaction mixture was kept at 100 ° C. for 10 minutes and concentrated in vacuo. The residue was taken up in dichloromethane and ether was added to precipitate the product to yield 1.75 g (yield: 72.3%) of the desired compound. [1402] [1403] Step 4: Methyl l-benzyl-2,6-dioxo-3-methyl-1,2,3,6-tetrahydro-pyrimidine-4 (carbaldehyde dimethylhydrazone) -5-carboxylate [1404] To a stirred solution of 1.7 g (5.94 mmol) of the compound obtained in step 3 above in 61 ml of anhydrous acetonitrile was added 1.68 g (7.1 mmol) of Pd (OAc) 2 and 0.613 g (7.1 mmol) of methyl acrylate. It was added sequentially. After stirring for 20 minutes under reflux, the reaction mixture was filtered and concentrated in vacuo. The residue was chromatographed on silica gel (dichloromethane / methanol: 97/3) to yield 1.40 g of the desired compound (yield: 63.6%). [1405] [1406] Step 5: 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid methyl ester [1407] 1.4 g (3.78 mmol) of the solution of the compound obtained in step 4, 18 ml of chlorobenzene and 3.6 ml of acetic acid were stirred under reflux for 3 hours and concentrated in vacuo to yield 1.4 g of precipitate. The crude product in 120 ml of ethyl acetate was recrystallized to give the desired compound (0.76 g; yield: 62%). [1408] [1409] Step 6: 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid [1410] 0.76 g (2.34 mmol) of the compound obtained in step 5, 7.6 ml of methanol, 7.6 ml of water and 0.646 g (4.67 mmol) of K 2 CO 3 were stirred at room temperature overnight, and then heated to reflux for 5 minutes. It was. After cooling and water was added, the mixture was acidified to pH 1 to yield a precipitate that dissolved in a mixture of methanol / dichloromethane. The organic layer was washed with water, dried and concentrated in vacuo. The obtained residue was condensed in a mixture of dichloromethane / ether to give 0.54 g (yield: 74%) of the desired compound. [1411] [1412] Step 7: 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (1,3 -Benzodioxol-5-ylmethyl) -amide [1413] Compounds were obtained according to the method of Example 1 using the compound and piperonylamine obtained in step 6 above. [1414] [1415] Example 168 Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d ] Pyrimidin-3-ylmethyl] -benzoate [1416] Step 1: 1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid [1417] 3.3 g (10.6 mmol) of the compound obtained in step 6 of Example 167 was treated according to the method described in step 1 of Example 164 to yield 2.0 g (yield: 85.3%) of the desired compound. [1418] [1419] Step 2: 1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid 4-methoxy-benzylamide [1420] Compounds were obtained according to the method of Example 1 using the compound obtained in step 1 and 4-methoxybenzylamine (yield: 78%). [1421] [1422] Step 3: Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] Pyrimidin-3-ylmethyl] -benzoate [1423] Compounds were obtained according to the method of Example 2 of Example 34 using the compound obtained in step 2 and methyl-4- (bromomethyl) benzoate (0.2 g; yield: 78%). [1424] [1425] Example 169 tert-butyl4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4 -d] pyrimidin-3-ylmethyl] -benzoate [1426] Using the compound obtained in step 2 of example 168 and tert-butyl 4-bromomethyl-benzoate, the compound was obtained according to the method of step 2 of example 34 (yield: 80.4%). [1427] [1428] Example 170: 4- [6- (3-methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] Pyrimidin-3-ylmethyl] -benzoic acid [1429] Step 1: 1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid 3-methoxy-benzylamide [1430] Example 168 A compound was obtained according to the method of Example 1 using the compound obtained in step 1 and 3-methoxybenzylamine (yield: 62.4%). [1431] [1432] Step 2: tert-butyl 4- [6- (3-methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4- d] pyrimidin-3-ylmethyl] -benzoate [1433] Using the compound obtained in Step 1 and tert-butyl 4- (bromomethyl) benzoate, the compound was obtained according to the method of Example 34 Step 2 (yield: 80.4%). [1434] [1435] Step 3: 4- [6- (3-Methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] pyrid Midin-3-ylmethyl] -benzoic acid [1436] The compound was obtained according to the method of Example 169 step 2 using the compound obtained in step 2 above. [1437] [1438] Example 171: 3- (4-cyano-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [3,4-d] pyrimidine-6- Carboxylic Acid 4-methoxy-Benzylamide [1439] Example 168 A compound was obtained according to the method of Example 34 step 2 using the compound obtained in step 2 and (4-bromomethyl) benzonitrile. [1440] [1441] Example 172: 3-benzyl-1-methyl-6- (3-phenyl-propionyl) -1 H-quinazolin-2,4-dione [1442] Compound of Preparation C was treated with SOCl 2 in THF to produce a chloride derivative, which was treated with phenethyl magnesium bromide and CuI in the presence of THF. After conventional treatment, the desired compound was obtained. [1443] [1444] Example 173 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (E) -3-pyridin-4-yl- Allyl ester [1445] [1446] Example 174 3-benzyl-l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (E) -3-pyridin-3-yl- Allyl ester [1447] [1448] Example 175: 3-benzyl-l-methyl-6- [2- (pyridin-4-ylsulfanyl) -acetyl] -lH [1449] Quinazoline-2,4-dione [1450] [1451] Example 176: 3- (4-Aminomethyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzyl Amid [1452] Compounds were obtained by catalytic hydrogenation of the compound of Example 60 using Raney Ni and NH 3 in methanol. [1453] [1454] Example 177: 3- (2'-Cyano-biphenyl-4-ylmethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-car Acid 4-methoxy-benzylamide [1455] Compounds were obtained following the method of Example 34 Step 2 using 2- (4-bromomethylphenyl) -benzonitrile. [1456] [1457] Example 178: 1-methyl-2,4-dioxo-3- [2 '-(lH-tetrazol-5-yl) -biphenyl-4-ylmethyl] -1,2,3,4-tetra Hydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide [1458] Compounds were obtained following the method of Example 34 Step 2 using 5-[(4-bromomethyl) biphenyl] -tetrazole. [1459] [1460] Example 179: Methyl 4 '-[6- (4-methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Biphenyl-2-carboxylate [1461] Compounds were obtained following the method of Example 34 Step 2 using methyl 4- (bromomethylphenyl) benzoate. [1462] [1463] Example 180: 4 '-[6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] Biphenyl-2-carboxylic acid [1464] Compounds were obtained according to the method of Preparation Example B steps 2-4 using the compound of Example 179. [1465] [1466] Example 181: ethyl 2-fluoro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin- 3-ylmethyl] -benzoate [1467] The compound was obtained according to the method of Example 34 Step 2 using methyl 4- (bromomethyl) -2-fluoro-benzoate. [1468] [1469] Example 182: 2-Fluoro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3 -Ylmethyl] -benzoic acid [1470] Compounds were obtained according to the method of Preparation Example B steps 2-4 using the compound of Example 181. [1471] [1472] Example 183: 2-methoxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4- [1473] Dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid 2-dimethylamino-ethyl ester [1474] [1475] Example 184: 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- 2-Methyl-benzoic acid 2-dimethylamino ethyl ester [1476] [1477] Example 185: 1-Methyl-2,4-dioxo-3- [4- (5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl) -benzyl-1 , 2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy benzylamide [1478] [1479] HPLC: 100% [1480] Example 186: {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]- Phenyl} -acetic acid [1481] [1482] Example 187 1-methyl-3- (1-naphthalen-1-yl-ethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (1, 3-benzodioxol-5-ylmethyl) -amide [1483] [1484] Example 188 4- [6- (4-methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] Pyrimidin-3-ylmethyl] -benzoic acid [1485] To a stirred solution of the compound obtained in 0.5 g (0.9 mmol) of Example 169 in 50 ml of dichloromethane, 5 ml of trifluoroacetic acid was added. The mixture was stirred overnight at room temperature and 60 ml of ether was added. The product crystallized and after filtration, 0.44 g (yield: 100%) of the desired compound were obtained. [1486] [1487] Example 189 3- (3-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydrate [1488] Rho-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amide [1489] 0.5 g (1.5 mmol) in dimethylformamide (10 ml) to 0.38 g (1.9 mmol) of EDAC in the compound of Example D. HC1, 0.27 g (1.9 mmol) of HOBT was added, followed by 0.21 g (1.9 mmol) of 4-pyridylbenzylamine. Water (20 ml) was added and the mixture was stirred for 48 hours at room temperature before extraction with ethyl acetate (2 x 20 ml). The combined organic layers were washed with saturated aqueous NaCl solution (4 × 20 ml), dried over MgSO 4 and recrystallized solid product in hot ethyl acetate to yield 0.13 g (yield: 20%) of the desired compound. [1490] MS: m / z (APCI, AP +) 419.2 [M] + [1491] CHN analysis: [1492] Calculated (%): C, 66.02; H, 4.58; N, 13.39. [1493] Found (%): C, 65.73; H, 4. 47; N, 13.36. [1494] Example 190: 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro [1495] -Quinazolin-6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide [1496] According to the method of Example 189, except using 2-methoxy-4-pyridyl-benzylamine, 0.10 g (yield: 17%) of the desired compound were obtained. [1497] MS : m / z (APCI, AP +) 449.2 [M] + [1498] CHN analysis: C 24 H 2 l FN 4 0 4 · 0. 1 H 2 0 [1499] Calculated (%): C, 64.02; H, 4.75; N, 12.44. [1500] Found (%): C, 63.66; H, 5.07; N, 12.16. [1501] Example 191 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridine-3- Monomethyl) -amide [1502] According to the method of Example 189, except using 3-pyridyl-benzylamine, 0.11 g (yield: 26%) of the desired compound were obtained. [1503] MS: m / z (APCI, AP +) 419. 1 [M] + [1504] CHN analysis: C 23 H 19 FN 4 O 3 1.2 H 2 O [1505] Calculated (%): C, 62.78; H, 4. 90; N, 12.73. [1506] Found (%): C, 62.75; H, 4. 90; N, 12.73. [1507] Example 192: 3- (3-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro [1508] -Quinazolin-6-carboxylic acid 4-methoxy-benzylamide [1509] According to the method of Example 189, except using 4-methoxy-benzylamine, 0.12 g (yield: 35%) of the desired compound were obtained. [1510] MS: m / z (APCI, AP +) 448.1 [M] + [1511] CHN analysis: C 25 H 22 FN 3 O 4 · 0.1 H 2 O [1512] Calculated (%): C, 66.84; H, 4.98; N, 9.35. [1513] Found (%): C, 66.57; H, 4.83; N, 9.03. [1514] Example 193: 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro [1515] -Quinazolin-6-carboxylic acid 3-methoxy-benzylamide [1516] 0.20 g (yield: 59%) of the desired compound were obtained following the method of Example 189, except using 3-methoxy-benzylamine. [1517] MS: m / z (APCI, AP +) 448.1 [M] + [1518] CHN analysis: C 25 H 22 FN 3 0 4 [1519] Calculated (%): C, 67.11; H, 4.96; N, 9.39. [1520] Found (%): C, 66.82; H, 4.87; N, 9.11. [1521] Example 194 1-ethyl-3- (3-fluoro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro [1522] -Quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amide [1523] According to the method of Example 189, using the compound of Preparation E and 4-pyridyl-benzylamine, 0.13 g (yield: 20%) of the desired compound were obtained. [1524] MS: m / z (APCI, AP +) 433.2 [M] + [1525] CHN analysis: [1526] Calculated (%): C, 66.66; H, 4.89; N, 12.96. [1527] Found (%): C, 66.26; H, 4.71; N, 12.78. [1528] Example 195 1-ethyl-3- (3-fluoro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro [1529] -Quinazolin-6-carboxylic acid (pyridin-3-ylmethyl) -amide [1530] According to the method of Example 189, except using the compound of Preparation E and 3-pyridyl-benzylamine, 0.18 g (yield: 51%) of the desired compound were obtained. [1531] MS: m / z (APCI, AP +) 433.1 [M] + [1532] CHN analysis: [1533] Calculated (%): C, 66.66; H, 4.89; N, 12.96. [1534] Found (%): C, 66.43; H, 5.03; N, 12.84. [1535] Example 196: 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide [1536] Step 1: methyl 3- (4-bromobenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [1537] Preparation Example D According to the method of step 1, except using 4-bromobenzyl isocyanate, 4.6 g (yield: 59%) of the desired compound were obtained. [1538] MS : m / z (APCI, AP +) 388.9 [M] + [1539] CHN analysis: [1540] Calculated (%): C, 52.46; H, 3. 37; N, 7.20. [1541] Found (%): C, 52.16; H, 3. 30; N, 7.30. [1542] Step 2: Methyl 1-methyl-3- (4-bromobenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [1543] Preparation Example D According to the method of Step 2 (but using the compound obtained in Step 1), 1.49 g (yield: 71%) of the desired compound were obtained. [1544] MS: m / z (APCI, AP +) 404.9 [M] + [1545] CHN analysis: [1546] Calculated (%): C, 53.62; H, 3.75; N, 6.95. [1547] Found (%): C, 53.24; H, 3.71; N, 6.84. [1548] Step 3: 1-methyl-3- (4-bromobenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [1549] Preparation Example B According to the method of steps 2-4, except using the compound obtained in step 2, 1.3 g (yield: 87%) of the desired compound were obtained. [1550] MS : m / z (APCI, AP +) 388.9 [M] + [1551] CHN analysis: [1552] Calculated (%): C, 52.46; H, 3. 37; N, 7.20. [1553] Found (%): C, 52.12; H, 3. 30; N, 7.11. [1554] Step 4: 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzyl amides [1555] 0.24 g (yield: 76%) of the desired compound were obtained according to the method of Example 189, using the compound obtained in step 3 and 4-methoxy-benzylamine. [1556] MS: m / z (APCI, AP +) 508 [M] + [1557] CHN analysis : C 25 H 22 BrN 3 0 4 0.2 H 2 O [1558] Calculated (%): C, 58.65; H, 4.41; N, 8.21. [1559] Found (%): C, 58.32; H, 4. 32; N, 8.12. [1560] Example 197 3- (4-Bromo-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy -Pyridin-4-ylmethyl) -amide [1561] 0.22 g (yield: 33%) of the desired compound were obtained following the method of Example 189, using the compound of Step 3 and 2-methoxy-4-pyridyl-benzylamine. [1562] NMR : DMSO 1 H δ (ppm): 3.52 (3H, s); 3.79 (3 H, s); 4.43 (2H, d); 5.09 (2H, s); 6.66 (1 H, s); 6.89 (1 H, d); 7.26-7.56 (SH, m); 8.06 (1 H, d); 8.24-8.26 (1 H, m); 8.61 (1 H, m); 9.31 (1 H, t). [1563] MS: m / z (APCI, AP +) 509 [M] + [1564] Example 198 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazoline-6-carboxylic acid (pyridine- 3-ylmethyl) -amide [1565] Step 1: Methyl 3- (3,4-difluoro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [1566] Using the compound of Preparation A and 3,4-difluorobenzylamine as a substrate, the compound was obtained in a yield of 51% according to the method of Preparation Step B, Step 1-5 to Step 2-5. [1567] NMR: DMSO 1 H (ppm): 3.86 (3H, s); 5. 05 (2H, s); 6.66 (1 H, s); 7.18-7.43 (4H, m); 8.18 (lH, dd); 8.47 (lH, s). [1568] MS: m / z (APCI, AP +) 347.1 [M] + [1569] Step 2: Methyl 1-methyl-3- (3,4-difluoro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [1570] 1.5 g (yield: 72%) of the desired compound were obtained according to the method of Step 2 of Preparation Example D, using the compound obtained in Step 1, above. [1571] MS : m / z (APCI, AP +) 361.0 [M] + [1572] CHN analysis: [1573] Calculated (%): C, 60.00; H, 3.92; N, 7.77. [1574] Found (%): C, 60.05; H, 3. 85; N, 7.72. [1575] Step 3: 1-Methyl-3- (3,4-difluoro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [1576] 1.1 g (yield: 82%) of the desired compound were obtained according to the method of Step 2-4 of Preparation Example B, using the compound obtained in Step 2, above. [1577] MS: m / z (APCI, AP +) 437.0 [M] + [1578] CHN analysis: [1579] Calculated (%): C, 58.96; H, 3. 49; N, 8.09. [1580] Found (%): C, 58.67; H, 3.99; N, 7.27. [1581] Step 4: 3- (3,4-Difluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazolin-6-carboxylic acid (pyridine-3 -Ylmethyl) -amide [1582] 0.48 g (yield: 79%) of the desired compound were obtained according to the method of Example 189, using the compound obtained in step 3 and 3-pyridyl-benzylamine. [1583] MS: m / z (APCI, AP +) 437.1 [M] + [1584] CHN analysis: C 23 H 18 F 2 N 4 0 3 0.2 H 2 0 [1585] Calculated (%): C, 62.78; H, 4. 21; N, 12.73. [1586] Found (%): C, 62.50; H, 4.13; N, 12.82. [1587] Example 199 3- (3,4-Difluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazoline-6-carboxylic acid (pyridine- 4-ylmethyl) -amide [1588] 0.23 g (yield: 38%) of the desired compound were obtained according to the method of Example 189, using the compound obtained in step 3 of Example 198 and 4-pyridyl-benzylamine. [1589] MS: m / z (APCI, AP +) 437.1 [M] + [1590] CHN analysis: C 23 H l8 F 2 N 4 0 3 [1591] Calculated (%): C, 63.30; H, 4. 16; N, 12.84. [1592] Found (%): C, 63.19; H, 4.07; N, 12.81. [1593] Example 200: 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4-meth Oxy-benzylamide [1594] According to the method of Example 189, using the compound obtained in Example 189 step 3 and 4-methoxy-benzylamine, 0.11 g (yield: 39%) of the desired compound were obtained. [1595] MS: m / z (APCI, AP +) 466.2 [M] + [1596] CHN analysis : C 25 H 21 F 2 N 3 O 4 [1597] Calculated (%): C, 64.51; H, 4.55; N, 9.03. [1598] Found (%): C, 64.41; H, 4.53; N, 8.87. [1599] Example 201 3- (3-Chloro-4-fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazoline-6-carboxylic acid (pyridine -4-ylmethyl) -amide [1600] Step 1: Methyl 3- (3-chloro-4-fluoro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [1601] Using the compound of Preparation A and 3-chloro-4-fluorobenzylamine as a substrate, the compound was obtained in a yield of 18.1% according to the method of Steps 1-5 to 2-5 of Preparation Example B. [1602] MS: m / z (APCI, AP-) 361.0 [M] + [1603] Step 2: Methyl 1-methyl-3- (3-chloro-4-fluoro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate [1604] Preparation Example D 0.5 g (yield: 72%) of the desired compound were obtained according to the method of step 2, using the compound obtained in step 1 above. [1605] MS : m / z (APCI, AP +) 377.0 [M] + [1606] CHN analysis: [1607] Calculated (%): C, 57.38; H, 3.75; N, 7.44. [1608] Found (%): C, 57.34; H, 3.73; N, 7.27. [1609] Step 3: 1-methyl-3- (3-chloro-4-fluoro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid [1610] Preparation Example B 0.45 g (yield: 92%) of the desired compound were obtained according to the method of Step 2-4, using the compound obtained in Step 2 above. [1611] MS: m / z (APCI, AP +) 363.0 [M] + [1612] CHN analysis: [1613] Calculated (%): C, 56.29; H, 3.33; N, 7.72. [1614] Found (%): C, 56.24; H, 3. 21; N, 7.64. [1615] Step 4: 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (pyridine- 4-ylmethyl) -amide [1616] According to the method of Example 189, provided that the compound obtained in step 3 and 4-pyridyl-benzylamine were used, 0.17 g (yield: 69%) of the desired compound were obtained. [1617] MS: m / z (APCI, AP +) 453.1 [M] + [1618] CHN analysis: C 23 H 18 F 2 N 4 0 3 · 1.1 H 2 O [1619] Calculated (%): C, 58.44; H, 4.31; N, 11.85. [1620] Found (%): C, 58.23; H, 4. 23; N, 11.75. [1621] Example 202: 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro quinazolin-6-carboxylic acid 4- Methoxy-benzylamide [1622] 0.21 g (yield: 80%) of the desired compound were obtained according to the method of Example 189, using the compound obtained in Example 201 Step 3 and 4-methoxy-benzylamine. [1623] MS: m / z (APCI, AP +) 482.1 [M] + [1624] CHN analysis: C 25 H 21 C l FN 3 0 4 [1625] Calculated (%): C, 62.31; H, 4. 39; N, 8.72. [1626] Found (%): C, 62.12; H, 4. 37; N, 8.51. [1627] Example 203: 4- [6- (4-Methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro 2H-quinazolin-3-ylmethyl] -benzo Ethyl (2-hydroxy-ethyl) -trimethyl-ammonium [1628] To 0.5 g (1.05 mmol) of the compound of Example 34 in hot methanol was added 0.22 g (1. 03 mmol) of choline bicarbonate. The mixture was heated to reflux for 1 h. Cooled and concentrated. The resulting solid was recrystallized from ethanol to yield 0.41 g (yield: 68%) of the desired compound. [1629] CHN analysis: C 31 H 36 N 4 0 7 0 · 5 H 2 O [1630] Calculated (%): C, 63.58; H, 6. 37; N, 9.57. [1631] Found (%): C, 63.32; H, 6. 58; N, 9.57. [1632] Example 204: 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid hemicalcium salt [1633] To a suspension of 0.5 g (1.05 mmol) of the compound of Example 34 in warm tetrahydrofuran was added 1.05 ml of 1.00 N NaOH. The mixture was stirred for 0.5 h and 0.058 g (0.525 mmol) of CaCl 2 were added in one portion. The mixture was stirred for 2 hours and then concentrated. Ethanol was added and concentrated. Drying in a vacuum oven at 88 ° C. for 72 hours yielded 0.49 g (yield: 94%) of the desired compound. [1634] CHN analysis: C 52 H 44 CaN 6 O 12 · 1.0 H 2 O [1635] Calculated (%): C, 62.27; H, 4.62; N, 8. 38. [1636] Found (%): C, 61.95; H, 4. 70; N, 8. 34. [1637] Example 205: 4- [6- (4-Methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid hemi magnesium salt [1638] To a suspension of 0.5 g (1.05 mmol) of the compound of Example 34 in warm tetrahydrofuran was added 1.05 ml of 1.00 N NaOH. The mixture was stirred for 0.5 h and 0.052 g (0.525 mmol) of MgC1 2 were added in one portion. The mixture was stirred for 2 hours and then concentrated. Ethanol was added and filtered. Drying in a vacuum oven at 88 ° C. for 72 hours yielded 0.49 g (yield: 96%) of the desired compound. [1639] CHN analysis: C 52 H 44 MgN 6 0 12 · 1.0 H 2 O [1640] Calculated (%): C, 63.26; H, 4. 70; N, 8.51. [1641] Found (%): C, 63.07; H, 4.89; N, 8.50. [1642] Example 206: 3- (4-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-yl Methyl) -amide [1643] Step 1: 1-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridazin-4-ylmethyl) -amide [1644] Example 33 step 1 compound (1.00 g, 4.54 mmol), EDAC (1.13 g, 5.90 mmol), HOBT (0.675 g, 5.00 mmol) in 20 ml of DMF in 4-aminomethyl-pyridine solution (0.507 ml , 5.00 mmol) was added. The light orange suspension was stirred at rt overnight. After 24 hours, the reaction mixture was concentrated to yield an off-white solid. The solid was washed sequentially with 10 ml of ethyl acetate, saturated Na 2 CO 3 , and 10 ml of H 2 O to give 1.20 g (yield: 85.7%) of product. [1645] MP : 141-145 ℃ [1646] MS (APCI +): m / z 309.1 (M − H). [1647] Step 2: 3- (4-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl )-amides [1648] CS2CO3 (0.630 g, 1.93 mmol) was added to a suspension of the compound (0.200 g, 0.645 mmol) obtained in step 1 above in 6 ml of DMF. After stirring for 30 minutes at room temperature, a solution of 4-chlorobenzyl-bromide (0.132 g, 0.645 mmol) in 2 ml of DMF was added dropwise to the reaction mixture and stirred overnight. The white solid (cesium salt) was filtered off and the solution was concentrated. The resulting suspension was diluted with 10 ml of ethyl acetate and filtered again. The filtrate was concentrated and triturated with 10 ml of ethyl acetate to yield 0.26 g (yield: 92.9%) of white solid corresponding to the desired compound. [1649] MP : 228-230 ℃ [1650] CHN analysis : C 23 H 19 N 4 0 3 C l1 [1651] Calculated (%): C, 63.52; H, 4.40; N, 12.88. [1652] Found (%): C, 63.40; H, 4.41; N, 12.84. [1653] Example 207: 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridine-4- Monomethyl) -amide [1654] Example 206 0.2 g of the desired compound were obtained according to the method of steps 1 to 2, using 4-fluorobenzyl bromide in step 2 (yield: 74.1%). [1655] MP: 210-212 ℃ [1656] CHN analysis : C 23 H 19 N 4 0 3 F l [1657] Calculated (%): C, 66.02; H, 4.58; N, 13.39 [1658] Found (%): C, 65.74; H, 4. 60; N, 13.03. [1659] Example 208 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridine-3- Monomethyl) -amide [1660] Step 1: 1-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-3-ylmethyl) -amide [1661] Example 206 1.18 g of the desired compound were obtained according to the method of step 1, using 3-aminomethyl pyridine (yield: 83.7%). [1662] MS (APCI +): m / z 309.1 (M − H); [1663] 1 H NMR (400 MHz, DMSO-d6) δ3.43 (s, 3H, NCH3), 4.47 (d, J = 5.86 Hz, 2H, NCH2Ar), 7.31-7.34 (m, 1H, ArH), 7.48 (d, J = 8.79 Hz, 1H, ArH), 7.70 (d, J = 7.82 Hz, 1H, ArH), 8.20 (dd, J = 8.79,1.95 Hz, 1H, ArH), 8.42-8.43 (m, 1H , ArH), 8. 53 (d, J = 2.20 Hz, 2H, ArH), 9.30 (t, J = 5.62, 1H, ArH), 11.65 (s, 1H, NH) [1664] Step 2: 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-3-yl Methyl) -amide [1665] Example 206, the method of step 2 (with the use of the compound obtained in step 1 and 4-fluorobenzyl bromide) yielded 0.25 g of the desired compound (yield: 82.6%). [1666] MP: 166-168 ° C [1667] Analysis . Calcd C 23 H l9 N 4 0 3 F 1: C, 65.79; H, 4. 60; N, 13.34. Found: C, 65.40; H, 4.40; N, 13.18. [1668] Example 209 3- (4-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (pyridin-3-ylmethyl )-amides [1669] According to the method of Example 206, step 2, using the compound obtained in example 208 step 1 and 4-chlorobenzyl bromide, 0.25 g of the desired compound were obtained (yield: 89.3%). [1670] MP: 173-175 ℃ [1671] analysis. (%) Calcd C 23 H 19 N 4 0 3 C l1 : C, 62.77; H, 4. 48; N, 12.73. Found: C, 62.39; H, 4. 46; N, 12.71. [1672] Example 210: 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 3-methoxy-benzyl amides [1673] Step 1: 1-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 3-methoxy-benzylamide [1674] Example 206, step 1, except using 3-methoxybenzyl amine, afforded 1.29 g of the desired compound (yield: 83.8%). [1675] MP: 235-238 ℃ [1676] Step 2: 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 3-methoxy-benzyl amides [1677] According to the method of Example 206, step 2, using the compound obtained in step 1 and 4-fluorobenzyl bromide, 0.25 g of the desired compound were obtained (yield: 95%). [1678] MP : 176-178 ℃ [1679] analysis. (%) Calcd C 25 H 22 N 3 0 4 F 1 : C, 67.11; H, 4.96; N, 9.39. Found: C, 66.99; H, 4.99; N, 9.18. [1680] Example 211 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 3-methoxy-benzylamide [1681] According to the method of Example 206, step 2, using the compound obtained in example 210 step 1 and 4-fluorobenzyl bromide, 0.25 g of the desired compound were obtained (yield: 92%). [1682] MP: 178-180 ℃ [1683] analysis. (%) Calcd C 25 H 22 N 3 0 4 C l1 : C, 64.60; H, 4.79; N, 9.04. Found: C, 64.22; H, 4.72; N, 8. 84. [1684] Example 212 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (2-methoxy- Pyridin-4-ylmethyl) -amide [1685] Step 1: 1-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide [1686] Example 206, the method of step 1, except using (2-methoxy-pyridin-4-yl) -methylamine, afforded 1.00 g of the desired compound (yield: 76.9%). [1687] MP: 215-218 ° C [1688] MS (APCI +): m / z 339.1 (MH−). [1689] Step 2: 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (2-methoxy-pyridine -4-ylmethyl) -amide [1690] Example 206, the method of step 2, provided that the compound obtained in step 1 and 4-fluorobenzyl bromide were obtained 0.07 g of the desired compound (yield: 26.5%). [1691] MP : 174-175 ℃ [1692] analysis. (%) Calcd C 24 H 2 l N 4 0 4 F 1 : C, 64.20; H, 4.73; N, 12.48. Found: C, 63.88; H, 4.73; N, 12.08. [1693] Example 213: 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (2-methoxy-pyridine -4-ylmethyl) -amide [1694] According to the method of Example 206, step 2, using the compound obtained in example 212 step 1 and 4-chlorobenzyl bromide, 0.09 g of the desired compound was obtained (yield: 33%). [1695] MP : 169-170 ℃ [1696] analysis. (%) Calcd C 24 H 2 l N 4 0 4 C l1 : C, 62.02; H, 4.61; N, 11.98. Found: C, 62.01; H, 5.01; N, 11.70. [1697] Example 214 tert-butyl 1- {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin- 3-ylmethyl] -phenyl} -cyclopropanecarboxylate [1698] [1699] Example 206, the process of steps 1 to 2, with 4-methoxy-benzylamine in step 1, but tert-butyl 1- (4-bromomethyl-phenyl) -cyclopropanecarboxylate in step 2 0.35 g of the desired compound were obtained (yield: 67%). [1700] MP : 148-149 ℃ [1701] analysis. (%) Calcd C 33 H 35 N 3 0 6 : C, 68. 88; H, 6. 24; N, 7.30. Found: C, 68.49; H, 6. 29; N, 7.21. [1702] Example 215: 1- {4- [6- (4-methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl Methyl] -phenyl} -cyclopropanecarboxylic acid [1703] To a solution of the compound of Example 214 (0.35 g, 0.61 mmol) in 2 ml of CH 2 Cl 2 was added 2 ml of TFA. The yellow solution was stirred at rt for 4 h. The reaction mixture was concentrated and triturated with diethyl ether to yield 0.25 g of a white solid corresponding to the desired compound (yield: 79%). [1704] MP: 179-181 ℃ [1705] Analysis . (%) Calcd C 29 H 27 N 3 0 6 : C, 66.22; H, 5. 35; N, 7.77. Found: C, 66.61; H, 5.40; N, 8.04. [1706] Example 216 3-benzyl-6-benzylsulfanyl-1-methyl-lH-quinazolin-2,4-dione [1707] [1708] Step 1: 5-iodine-2-methylamino-benzoic acid [1709] To 30 ml of a solution of N-methylanthranilic acid in acetic acid (5.00 g, 3.31 mmol) was added 60 ml of H 2 0 and I 2 (8.39 g, 3.31 mmol) in portions over 5 minutes. The reaction mixture was stirred at rt for 2 days. After 48 hours, the product was filtered and washed with 30 ml of H 2 0. The mother liquor was concentrated to produce additional product. [1710] Weight: 7.3 g; Yield = 80% [1711] MP: 170-172 ℃ [1712] MS (APCI +): m / z 276.0 (M − H). [1713] Step 2: 3-benzyl-6-iodine-1-methyl-lH-quinazolin-2,4-dione [1714] Et 3 N was slowly added to a mixture of compound (0.50 g, 1.9 mmol), isocyanate (0.236 g, 1.58 mmol), and CF 3 CO 2 Ag (0.838 g, 3.80 mmol) obtained in step 1 above. The reaction mixture was heated at reflux for 1.5 h. After cooling to room temperature, the silver sulfide was filtered and the filtrate was concentrated to give a brown oil. The product was chromatographed on silica gel (ethyl acetate / hexane: 20/80) to yield 0.300 g (48.0%) of a white solid. [1715] MP: 149-150 ℃ [1716] MS (APCI +): m / z 391.0 (M − H). [1717] Step 3: 3-benzyl-6-benzylsulfanyl-1-methyl-1H-quinazolin-2,4-dione [1718] After 5 min washing with N 2 , KHC0 3 (0.009 g, 0.089 mmol), PPh 3 (0.007 g, 0.027 mmol), n-Bu 4 NI (0.033 g, 0.089 mmol), Pd (OAc ) In a mixture of 2 (0.002 g, 0.009 mmol) in 5 ml of dioxane (0.035 g, 0.089 mmol) and butyl-thiocarbamic acid S-benzyl ester (0.020 g, 0.089 mmol) in room temperature Was added. The brown oil was heated at 100 ° C overnight. After 24 hours, the reaction mixture was cooled to room temperature, diluted with 20 ml of ethyl acetate, filtered through a celite sheet, washed with H 2 0 (2 × 5 ml) and concentrated to yield a yellow oil. Polishing with diethyl gave 0.025 g (yield: 72%) of yellow solid corresponding to the desired compound. [1719] MP : 117-118 ℃ [1720] analysis. (%) Calcd C 23 H 20 N 2 0 2 S 1 : C, 69.66; H, 5. 31; N, 7.06. Found: C, 69.26; H, 5.04; N, 6.93. [1721] Example 217 3-benzyl-1-methyl-6-phenylmethanesulfinyl-lH-quinazolin-2,4-dione [1722] [1723] To 9 ml of anhydrous CH 2 Cl 2 compound solution of Example 216 (0.050 g, 0.129 mmol) was added m-chloro-perbenzoic acid (0.029 g, 0.127 mmol) at −5 ° C. After stirring at −5 ° C. for 3 hours, the reaction mixture was quenched with 20 ml of NaHC0 3 in an ice bath. The organic layer was separated and the aqueous layer was extracted with CH 2 Cl 2 (2 × 20 ml). The combined organic layers were concentrated to yield a yellow oil. The product was purified by chromatography on silica gel (ethyl acetate / hexane: 30/70) to yield 0.070 g (yield: 33.7%) of white solid corresponding to the desired compound. [1724] MP : 182-183 ℃ [1725] analysis. (%) Calcd C 23 H 20 N 2 0 3 S 1 : C, 67.84; H, 5.03; N, 6.88. Found: C, 68.13; H, 4.86; N, 6.48. [1726] Example 218: 3-benzyl-1-methyl-6-phenylmethanesulfonyl-1H-quinazolin-2,4-dione [1727] To 25 ml of an aqueous solution of the compound of Example 216 (0.133 g, 0.342 mmol) of CH 2 Cl 2 was added m-chloro-perbenzoic acid (0.153 g, 0.685 mmol) at −5 ° C. After 5 min stirring at -5 ° C, the ice bath was removed and the reaction mixture was stirred at room temperature for 3 h. The reaction was complete and quenched with 5 ml of saturated NaHC0 3 . The organic layer was separated and the aqueous layer was extracted with CH 2 Cl 2 (2 × 20 ml). The combined organic layers were concentrated to yield a yellow oil. Polishing with ethyl acetate gave 0.80 g (yield 56%) of a light yellow solid corresponding to the desired compound. [1728] MP: 173-175 ℃ [1729] analysis. (%) Calcd C 23 H 20 N 2 0 4 S l : C, 64.73; H, 4.89; N, 6.56. Found: C, 64.34; H, 4.72; N, 6.18. [1730] Example 219: 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid tert-butoxycarbonylmethyl ester [1731] [1732] To 0.40 g (0.84 mmol) of the compound of Example 35 in dimethylformamide (10 ml) was added 0.13 g (l.Ommol) of di-isopropylethylamine, followed by 0.18 g (1.18 mmol) of tert-butyl Acetyl chloride was added. The mixture was stirred at rt overnight before concentration in vacuo and then diluted with ethyl acetate (20 ml). The organic layer was washed with saturated aqueous NaCl solution (2 × 20 ml), dried over MgSO 4 and purified by flash chromatography (EtOAC / hexane eluent) to yield 0.11 g (yield: 23%) of the desired compound. [1733] MS : m / z (APCI, AP +) 588.4 [M] + [1734] CHN analysis (%) : C 32 H 33 N 3 0 8 1.8 H 2 0 calcd: C, 61.97; H, 5.61; N, 6.70. Found: C, 61. 58; H, 5.61; N, 6.70. [1735] Example 220: 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid dimethylamino-dimethyl-propyl ester [1736] [1737] To 0.30 g (1.6 mmol) of the compound of Example 35 in dimethylformamide (20 ml) was added 0.39 g (2.1 mmol) of EDAC HCl, 0.28 g (2.1 mmol) of HOBT, followed by 0.27 g (2.1 mmol). Dimethylaminodimethyl-propan-1-ol was added. Water (20 ml) was added and the mixture was stirred at rt overnight before extraction with ethyl acetate (2 × 20 ml). The combined organic layers were washed with saturated aqueous NaCl solution (4 × 20 ml) and dried over MgSO 4 . The crude product was dissolved in EtOAc / MeOH and saturated etheric HCl was added. After concentration and solidification in EtOAc, 0.49 g (yield 43%) of the desired compound were obtained. [1738] MS: m / z (APCI, AP +) 587.0 [M] + [1739] CHN analysis (%): C 33 H 38 N 4 0 6 1.0 HC1 1.2 H 2 0 calcd: C, 61.40; H, 6. 48; N, 8.68. Found: C, 61.01; H, 6. 31; N, 8.99. [1740] Example 221: 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid dimethylamino-methyl-propyl ester [1741] [1742] To 0.20 g (1.6 mmol) of the compound of Example 35 in dimethylformamide (20 ml) was added 0.39 g (2.1 mmol) of EDAC HCl, 0.28 g (2.1 mmol) of HOBT, followed by 0.24 g (2.1 mmol). Dimethylaminodimethyl-propan-1-ol was added. Water (20 ml) was added and the mixture was stirred at rt overnight before extraction with ethyl acetate (2 × 20 ml). The combined organic layers were washed with saturated aqueous NaCl solution (4 × 20 ml) and dried over MgSO 4 . The crude product was dissolved in EtOAc / MeOH and saturated etheric HCl was added. After concentration and solidification in EtOAc, 0.21 g (yield 21%) of the desired compound were obtained. [1743] MS: m / z (APCI, AP +) 573.2 [M] + [1744] CHN analysis (%) : C 32 H 36 N 4 0 6 1.1 HCl 0. 48 H 2 0 calcd: C, 62.22; H, 6. 19; N, 9.07. Found: C, 61.82; H, 6.00; N, 9.16. [1745] Example 222 4- [6- (4-methoxy-benzylcarbamoyl) -l-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid 2-dimethylamino-ethyl ester [1746] [1747] To 0.13 g (1.5 mmol) of the compound of Example 35 in dimethylformamide (10 ml) were added 0.18 g (2.0 mmol) of EDAC HCl, 0.27 g (2.0 mmol) of HOBT, followed by 0.18 g (2.0 mmol). Dimethylaminodimethyl-propan-1-ol was added. Water (20 ml) was added and the mixture was stirred at rt overnight before extraction with ethyl acetate (2 × 20 ml). The combined organic layers were washed with saturated aqueous NaCl solution (2 × 20 ml) and dried over MgSO 4 . The crude product was solidified in EtOAc / MeOH to afford 0.49 g (yield: 60%) of the desired compound. [1748] MS : m / z (APCI, AP +) 545.3 [M] + [1749] CHN analysis (%): C 30 H 32 N 4 0 6 0.25 H 2 0 calc .: C, 65.62; H, 5.97; N, 10.20. Found: C, 65.62; H, 5.92; N, 10.23. [1750] Example 223 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid chloromethyl ester [1751] [1752] To 1.0 g (2.1 mmol) of the compound of Example 35 in dimethylformamide (15 ml) was added 0.47 g (3.6 mmol) of diisopropylethylamine, followed by 1.86 g (10.5 mmol) of chloro-iomethane. Added. The mixture was stirred overnight at room temperature before dilution with ethyl acetate (20 ml). The organic layer was washed with water (1 × 10 ml), saturated aqueous NaCl solution (2 × 10 ml) and dried over MgSO 4 . After solidification in ether, 0.29 g (yield 26%) of the desired compound were obtained. [1753] MS: m / z (APCI, AP +) 522.2 [M] + [1754] CHN Analysis (%): C 27 H 24 C l N 3 O 6 Calculated: C, 62.13; H, 4.63; N, 8.05. Found: C, 62.08; H, 4.61; N, 7.95. [1755] Example 224: 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid 2-tert-butoxycarbonylamino-3-methyl-1-butanoyloxymethyl ester ester [1756] [1757] To 0.29 g (0.96 mmol) of t-butoxy after adding 0.12 g (0.96 mmol) of di-isopropylethylamine to 0.39 g (0.75 mmol) of the compound of Example 223 in dimethylformamide (10 ml) Carbonyl-Leucine was added. The mixture was stirred overnight at 60-70 ° C. for 12 hours, cooled and diluted with ethyl acetate (20 ml). The organic layer was washed with water (1 × 10 ml), 5% aqueous NaHC0 3 solution (1 × 10 ml), saturated aqueous NaCl solution (1 × 10 ml), dried over MgS0 4 and flash chromatography (EtOAC / hexane eluent). Purification with yield yielded 0.14 g (yield: 25%) of the desired compound. [1758] MS : m / z (APCI, AP +) 701.3 [M-Boc] - [1759] CHN analysis (%) : C 37 H 42 N 4 0 10 Calcd: C, 61.97; H, 5.61; N, 6.70. Found: C, 61.58; H, 5.61; N, 6.70. [1760] Example 225: 4- [6- (4-methoxy-benzylcarbanoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid 2-amino-3-methyl-butanoyloxymethyl ester hydrochloride [1761] [1762] To 0.14 g (0.19 mmol) of the compound of Example 224 in dioxane (10 ml) was added 1.0 M HC1 in ether (10 ml). After HCl gas was bubbled off for 2 minutes, the mixture was stirred at room temperature for 90 minutes. After concentration and trituration in EtOAc, 0.039 g (yield: 30%) of the desired compound were obtained. [1763] MS: m / z (APCI, AP +) 603.2 [M] + [1764] CHN analysis (%): C 37 H 42 N 4 0 10 Cal .: C, 61.97; H, 5.61; N, 6.70. Found: C, 61.58; H, 5.61; N, 6.70. [1765] Example 226: 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid 2- (2-tert-butoxycarbonylamino-3-methylbutanoylamino) -3-methyl-butanoyloxymethyl ester [1766] [1767] Step 1: 2- (2-tert-butoxycarbonylamino-3-methyl-butanoylamino) -3-methyl-butyric acid methyl ester [1768] To 1.3 g (5.9 mmol) of t-butoxycarbonyl-leucine in dimethylformamide (15 ml) was added 1.4 g (7.1 mmol) of EDAC HCl, 0.95 g (7.12 mmol) of HOBT, followed by 1.0 g ( 5.9 mmol) NH 2 -Leu-OMe was added. Water (20 ml) was added and the mixture was stirred at rt overnight before extraction with ethyl acetate (2 × 20 ml). The combined organic layers were washed with 10% aqueous Na 2 CO 3 solution (1 × 10 ml), saturated aqueous NaCl solution (2 × 20 ml) and dried over MgSO 4 . Solidification in ether afforded 1.05 g (yield 53%) of the desired compound. [1769] MS: m / z (APCI, AP +) 331.2 [M] + [1770] CHN analysis (%) : C 16 H 30 N 2 0 5 calc .: C, 58.16; H, 9. 15; N, 8.48. Found: C, 58. 32; H, 9.24; N, 8. 51. [1771] Step 2: 2- (2-tert-butoxycarbonylamino-3-methyl-butanoylamino) -3-methyl-butyric acid [1772] To the compound obtained in step 1 above 0.4 g (1.2 mmol) in 3: 1: 1 methanol / water / THF (10 ml) was added 0.06 g (1.44 mmol) of LiOH H 2 O. The mixture was stirred at rt overnight. Partitioned between water (20 ml) and ethyl acetate (30 ml). The layers were separated and the aqueous layer was made acidic with 2 M HCl. The product was extracted with EtOAc (2 × 20 ml), washed with saturated aqueous NaCl solution (1 × 20 ml) and dried over MgSO 4 . Solidification in ether gave 0.22 g (yield: 58%) of the desired compound. [1773] MS : m / z (APCI, AP +) 317.2 [M] + [1774] CHN analysis (%) : C 15 H 28 N 2 0 5 calc: C, 56.94; H, 8.92; N, 8.85. Found: C, 56.72; H, 8.89; N; 8. 64 [1775] Step 3: 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid 2- (2-tert-butoxycarbonylamino-3-methyl-butanoylamino) -3-methyl-butanoyloxymethyl ester [1776] To 0.29 g (0.56 mmol) of the compound obtained in Example 223 in dimethylformamide (10 ml) was added 0.092 g (0.72 mmol) of di-isopropylethylamine, followed by 0.23 g (0.72 mmol) of the above step. After addition of the compound obtained in 2, NaI (catalyst) was added. The mixture was stirred overnight at 50 ° C for 18 h. Cool, dilute with water and extract with ethyl acetate (2 x 20 ml). The combined organic layers were washed with saturated aqueous NaHCO 3 solution (1 × 10 ml), saturated aqueous NaCl solution (3 × 10 ml), dried over MgSO 4 and solidified in a mixture of EtOAc / hexanes to yield 0.27 g (yield: 63%). The desired compound was produced. [1777] MS : m / z (APCI, AP +) 800.4 [M-Boc] - [1778] CHN analysis (%): C 37 H 42 N 4 O l 0 calculated: C, 62.91; H, 6. 41; N, 8.73. Found: C, 62.59; H, 6. 44; N, 8. 39. [1779] Example 227: 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoic acid 2- (2-amino-3-methyl-butanoylamino) -3-methyl-butanoyloxymethyl ester [1780] [1781] To 0.25 g (0.31 mmol) of the compound of Example 226 in dioxane (10 ml) was added 1.0 M HC1 in ether (10 ml). After allowing HCl gas to evolve for 2 minutes, the mixture was stirred at room temperature for 90 minutes. After concentration and trituration in EtOAc, 0.12 g (yield: 55%) of the desired compound were obtained. [1782] MS : m / z (APCI, AP +) 700.0 [M] + [1783] CHN analysis (%) : C 37 H 43 N 5 0 9 calcd: C, 63.33; H, 6. 18; N, 9.98. Found: C, 62.99; H, 6.06; N; 9.72. [1784] Examples 228-345: [1785] The following compounds were obtained following the method described in Example 168 and following the method of Example 169. [1786] 3- [2- (4-Bromo-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide, [1787] 3- [2- (4-fluoro-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide, [1788] 3- [2- (4-Chloro-phenoxy) -ethyl] -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine -6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide, [1789] 3- (4-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 2-methoxy-pyridin-4-ylmethyl) -amide, [1790] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide, [1791] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide, [1792] 3- (3-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 2-methoxy-pyridin-4-ylmethyl) -amide, [1793] 3- (3-Bromo-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide, [1794] 3- (3-Fluoro-benzyl) -l-methyl-2,4-dioxo-l, 2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide, [1795] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6- Carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide, [1796] 3- (3-chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6 -Carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide, [1797] 3- (3-Methoxy-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide, [1798] 3- (4-Methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl) -amide, [1799] 3- [2- (4-Bromo-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (2-ethoxy-pyridin-4-ylmethyl) -amide, [1800] 3- [2- (4-Fluoro-phenoxy) -ethyl] -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (2-ethoxy-pyridin-4-ylmethyl) -amide, [1801] 3- [2- (4-chloro-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine -6-carboxylic acid (2-ethoxy-pyridin-4-ylmethyl) -amide, [1802] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-ethoxy-pyridin-4-ylmethyl) -amide, [1803] 3- (4-Fluoro-benzyl) -l-methyl-2,4-dioxo-l, 2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-ethoxy-pyridin-4-ylmethyl) -amide, [1804] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 2-ethoxy-pyridin-4-ylmethyl) -amide, [1805] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-ethoxy-pyridin-4-ylmethyl) -amide, [1806] 3- (3-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-ethoxy-pyridin-4-ylmethyl) -amide, [1807] 3- (3,4-Difluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6- Carboxylic acid (2-ethoxy-pyridin-4-ylmethyl) -amide, [1808] 3- (3-chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6 -Carboxylic acid (2-ethoxy-pyridin-4-ylmethyl) -amide, [1809] 3- (3-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-ethoxy-pyridin-4-ylmethyl) -amide, [1810] 3- (4-Methoxy-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-ethoxy-pyridin-4-ylmethyl) -amide, [1811] 3- [2- (4-Bromo-phenoxy) -ethyl] -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (pyridin-4-ylmethyl) -amide, [1812] 3- [2- (4-fluoro-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (pyridin-4-ylmethyl) -amide, [1813] 3- [2- (4-chloro-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine -6-carboxylic acid (pyridin-4-ylmethyl) -amide, [1814] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( Pyridin-4-ylmethyl) -amide, [1815] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-4-ylmethyl) -amide, [1816] 3- (4-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-4-ylmethyl) -amide, [1817] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( Pyridin-4-ylmethyl) -amide, [1818] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-4-ylmethyl) -amide, [1819] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-4-ylmethyl) -amide, [1820] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6- Carboxylic acid (pyridin-4-ylmethyl) -amide, [1821] 3- (3-chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6 -Carboxylic acid (pyridin-4-ylmethyl) -amide, [1822] 3- (3-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-4-ylmethyl) -amide, [1823] 3- (4-Methoxy-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-4-ylmethyl) -amide, [1824] 3- [2- (4-Bromo-phenoxy) -ethyl] -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (2-amino-pyridin-4-ylmethyl) -amide, [1825] 3- [2- (4-Fluoro-phenoxy) -ethyl] -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (2-amino-pyridin-4-ylmethyl) -amide, [1826] 3- [2- (4-Chloro-phenoxy) -ethyl] -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine -6-carboxylic acid (2-amino-pyridin-4-ylmethyl) -amide, [1827] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 2-amino-pyridin-4-ylmethyl) -amide, [1828] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-amino-pyridin-4-ylmethyl) -amide, [1829] 3- (4-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-amino-pyridin-4-ylmethyl) -amide, [1830] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 2-amino-pyridin-4-ylmethyl) -amide, [1831] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-amino-pyridin-4-ylmethyl) -amide, [1832] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-amino-pyridin-4-ylmethyl) -amide, [1833] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6- Carboxylic acid (2-amino-pyridin-4-ylmethyl) -amide, [1834] 3- (3-chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6 -Carboxylic acid (2-amino-pyridin-4-ylmethyl) -amide, [1835] 3- (3-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-amino-pyridin-4-ylmethyl) -amide, [1836] 3- (4-Methoxy-benzyl) -l-methyl-2,4-dioxo-l, 2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-amino-pyridin-4-ylmethyl) -amide, [1837] 3- [2- (4-Bromo-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (6-methoxy-pyridin-3-ylmethyl) -amide, [1838] 3- [2- (4-fluoro-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (6-methoxy-pyridin-3-ylmethyl) -amide, [1839] 3- [2- (4-Chloro-phenoxy) -ethyl] -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine -6-carboxylic acid (6-methoxy-pyridin-3-ylmethyl) -amide, [1840] 3- (4-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 6-methoxy-pyridin-3-ylmethyl) -amide, [1841] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-methoxy-pyridin-3-ylmethyl) -amide, [1842] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-methoxy-pyridin-3-ylmethyl) -amide, [1843] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 6-methoxy-pyridin-3-ylmethyl) -amide, [1844] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-methoxy-pyridin-3-ylmethyl) -amide, [1845] 3- (3-Fluoro-benzyl) -l-methyl-2,4-dioxo-l, 2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-methoxy-pyridin-3-ylmethyl) -amide, [1846] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6- Carboxylic acid (6-methoxy-pyridin-3-ylmethyl) -amide, [1847] 3- (3-chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6 -Carboxylic acid (6-methoxy-pyridin-3-ylmethyl) -amide, [1848] 3- (3-Methoxy-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-methoxy-pyridin-3-ylmethyl) -amide, [1849] 3- (4-Methoxy-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-methoxy-pyridin-3-ylmethyl) -amide, [1850] 3- [2- (4-Bromo-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (6-ethoxy-pyridin-3-ylmethyl) -amide, [1851] 3- [2- (4-fluoro-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (6-ethoxy-pyridin-3-ylmethyl) -amide, [1852] 3- [2- (4-chloro-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine -6-carboxylic acid (6-ethoxy-pyridin-3-ylmethyl) -amide, [1853] 3- (4-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 6-ethoxy-pyridin-3-ylmethyl) -amide, [1854] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-ethoxy-pyridin-3-ylmethyl) -amide, [1855] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-ethoxy-pyridin-3-ylmethyl) -amide, [1856] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 6-ethoxy-pyridin-3-ylmethyl) -amide, [1857] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-ethoxy-pyridin-3-ylmethyl) -amide, [1858] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-ethoxy-pyridin-3-ylmethyl) -amide, [1859] 3- (3,4-Difluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6- Carboxylic acid (6-ethoxy-pyridin-3-ylmethyl) -amide, [1860] 3- (3-chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6 -Carboxylic acid (6-ethoxy-pyridin-3-ylmethyl) -amide, [1861] 3- (3-Methoxy-benzyl) -l-methyl-2,4-dioxo-l, 2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-ethoxy-pyridin-3-ylmethyl) -amide, [1862] 3- (4-Methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-ethoxy-pyridin-3-ylmethyl) -amide, [1863] 3- [2- (4-Bromo-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (pyridin-3-ylmethyl) -amide, [1864] 3- [2- (4-fluoro-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (pyridin-3-ylmethyl) -amide, [1865] 3- [2- (4-Chloro-phenoxy) -ethyl] -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine -6-carboxylic acid (pyridin-3-ylmethyl) -amide, [1866] 3- (4-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( Pyridin-3-ylmethyl) -amide, [1867] 3- (4-Bromo-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-3-ylmethyl) -amide, [1868] 3- (4-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-3-ylmethyl) -amide, [1869] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( Pyridin-3-ylmethyl) -amide, [1870] 3- (3-Bromo-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-3-ylmethyl) -amide, [1871] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-3-ylmethyl) -amide, [1872] 3- (3,4-Difluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6- Carboxylic acid (pyridin-3-ylmethyl) -amide, [1873] 3- (3-chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6 -Carboxylic acid (pyridin-3-ylmethyl) -amide, [1874] 3- (3-Methoxy-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-3-ylmethyl) -amide, [1875] 3- (4-Methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (Pyridin-3-ylmethyl) -amide, [1876] 3- [2- (4-Bromo-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (6-amino-pyridin-3-ylmethyl) -amide, [1877] 3- [2- (4-fluoro-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (6-amino-pyridin-3-ylmethyl) -amide, [1878] 3- [2- (4-Chloro-phenoxy) -ethyl] -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine -6-carboxylic acid (6-amino-pyridin-3-ylmethyl) -amide, [1879] 3- (4-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 6-amino-pyridin-3-ylmethyl) -amide, [1880] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-amino-pyridin-3-ylmethyl) -amide, [1881] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-amino-pyridin-3-ylmethyl) -amide, [1882] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 6-amino-pyridin-3-ylmethyl) -amide, [1883] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-amino-pyridin-3-ylmethyl) -amide, [1884] 3- (3-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-amino-pyridin-3-ylmethyl) -amide, [1885] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6- Carboxylic acid (6-amino-pyridin-3-ylmethyl) -amide, [1886] 3- (3-chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6 -Carboxylic acid (6-amino-pyridin-3-ylmethyl) -amide, [1887] 3- (3-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-amino-pyridin-3-ylmethyl) -amide, [1888] 3- (4-Methoxy-benzyl) -l-methyl-2,4-dioxo-l, 2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (6-amino-pyridin-3-ylmethyl) -amide, [1889] 3- [2- (4-Bromo-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (2-methylamino-pyridin-4-ylmethyl) -amide, [1890] 3- [2- (4-Bromo-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyri Midine-6-carboxylic acid (2-methylamino-pyridin-4-ylmethyl) -amide, [1891] 3- [2- (4-chloro-phenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine -6-carboxylic acid (2-methylamino-pyridin-4-ylmethyl) -amide, [1892] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 2-methylamino-pyridin-4-ylmethyl) -amide, [1893] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methylamino-pyridin-4-ylmethyl) -amide, [1894] 3- (4-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methylamino-pyridin-4-ylmethyl) -amide, [1895] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid ( 2-methylamino-pyridin-4-ylmethyl) -amide, [1896] 3- (3-Bromo-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methylamino-pyridin-4-ylmethyl) -amide, [1897] 3- (3-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methylamino-pyridin-4-ylmethyl) -amide, [1898] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6- Carboxylic acid (2-methylamino-pyridin-4-ylmethyl) -amide, [1899] 3- (3-chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6 -Carboxylic acid (2-methylamino-pyridin-4-ylmethyl) -amide, [1900] 3- (3-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methylamino-pyridin-4-ylmethyl) -amide, and [1901] 3- (4-Methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (2-methylamino-pyridin-4-ylmethyl) -amide. [1902] Examples 345 to 461: [1903] The following compounds were obtained according to the method described in Example 131: [1904] 3- (3,4-Dichloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides, [1905] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amide , [1906] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl)- amides, [1907] 3- (3-Iodine-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amide , [1908] 3- (3,4-Dichloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy-pyridine- 4-ylmethyl) -amide, [1909] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy- Pyridin-4-ylmethyl) -amide, [1910] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy -Pyridin-4-ylmethyl) -amide, [1911] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy -Pyridin-4-ylmethyl) -amide, [1912] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy-pyridine-4 -Ylmethyl) -amide, [1913] 3- (3-Iodine-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy-pyridine-4- Monomethyl) -amide, [1914] 3- (4-Iodine-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy-pyridine-4- Monomethyl) -amide, [1915] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-hydroxy- Pyridazin-4-ylmethyl) -amide, [1916] 3- (3,4-Dichloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-hydroxy-pyridazine -4-ylmethyl) -amide, [1917] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-hydroxy -Pyridazin-4-ylmethyl) -amide, [1918] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-hydroxy-pyridazine- 4-ylmethyl) -amide, [1919] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-hydroxy-pyridazine-4 -Ylmethyl) -amide, [1920] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-hydroxy-pyridazine- 4-ylmethyl) -amide, [1921] 3- (4-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-hydroxy-pyridazine- 4-ylmethyl) -amide, [1922] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-hydroxy-pyridazine-4 -Ylmethyl) -amide, [1923] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-hydroxy-pyridazine- 4-ylmethyl) -amide, [1924] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methylamino- Pyridazin-4-ylmethyl) -amide, [1925] 3- (3,4-Dichloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methylamino-pyridazine -4-ylmethyl) -amide, [1926] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-methylamino -Pyridazin-4-ylmethyl) -amide, [1927] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methylamino-pyridazine- 4-ylmethyl) -amide, [1928] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methylamino-pyridazine-4 -Ylmethyl) -amide, [1929] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methylamino-pyridazine- 4-ylmethyl) -amide, [1930] 3- (4-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methylamino-pyridazine- 4-ylmethyl) -amide, [1931] 3- (4-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methylamino-pyridazine-4 -Ylmethyl) -amide, [1932] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methylamino-pyridazine- 4-ylmethyl) -amide, [1933] 3- (3,4-Difluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methoxy- Pyridazin-4-ylmethyl) -amide, [1934] 3- (3,4-Dichloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-methoxy-pyridazine -4-ylmethyl) -amide, [1935] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-methoxy -Pyridazin-4-ylmethyl) -amide, [1936] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methoxy-pyridazine- 4-ylmethyl) -amide, [1937] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methoxy-pyridazine-4 -Ylmethyl) -amide, [1938] 3- (3-Bromo-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methoxy-pyridazine- 4-ylmethyl) -amide, [1939] 3- (3-Iodine-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methoxy-pyridazine-4 -Ylmethyl) -amide, [1940] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methoxy-pyridazine- 4-ylmethyl) -amide, [1941] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methoxy-pyridazine-4 -Ylmethyl) -amide, [1942] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-methoxy-pyridazine- 4-ylmethyl) -amide, [1943] 3- (4-Iodine-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methoxy-pyridazine-4 -Ylmethyl) -amide, [1944] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-hydroxy- Pyridazin-4-ylmethyl) -amide, [1945] 3- (3,4-Dichloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-hydroxy-pyridazine -4-ylmethyl) -amide, [1946] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-hydroxy -Pyridazin-4-ylmethyl) -amide, [1947] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-hydroxy-pyridazine- 4-ylmethyl) -amide, [1948] 3- (3-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-hydroxy-pyridazine-4 -Ylmethyl) -amide, [1949] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-hydroxy-pyridazine- 4-ylmethyl) -amide, [1950] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-hydroxy-pyridazine- 4-ylmethyl) -amide, [1951] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-hydroxy-pyridazine-4 -Ylmethyl) -amide, [1952] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-hydroxy-pyridazine- 4-ylmethyl) -amide, [1953] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-amino-pyri Dazin-4-ylmethyl) -amide, [1954] 3- (3,4-Dichloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-amino-pyridazine- 4-ylmethyl) -amide, [1955] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-amino- Pyridazin-4-ylmethyl) -amide, [1956] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-amino-pyridazine-4 -Ylmethyl) -amide, [1957] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-amino-pyridazine-4- Monomethyl) -amide, [1958] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-amino-pyridazine-4 -Ylmethyl) -amide, [1959] 3- (4-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-amino-pyridazine-4 -Ylmethyl) -amide, [1960] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-amino-pyridazine-4- Monomethyl) -amide, [1961] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-amino-pyridazine-4 -Ylmethyl) -amide, [1962] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-ethoxy- Pyridazin-4-ylmethyl) -amide, [1963] 3- (3,4-Dichloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-ethoxy-pyridazine -4-ylmethyl) -amide, [1964] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-ethoxy -Pyridazin-4-ylmethyl) -amide, [1965] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-ethoxy-pyridazine- 4-ylmethyl) -amide, [1966] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-ethoxy-pyridazine-4 -Ylmethyl) -amide, [1967] 3- (3-Bromo-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-ethoxy-pyridazine- 4-ylmethyl) -amide, [1968] 3- (3-Iodine-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-ethoxy-pyridazine-4 -Ylmethyl) -amide, [1969] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-ethoxy-pyridazine- 4-ylmethyl) -amide, [1970] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-ethoxy-pyridazine-4 -Ylmethyl) -amide, [1971] 3- (4-Bromo-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-ethoxy-pyridazine- 4-ylmethyl) -amide, [1972] 3- (4-Iodine-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-ethoxy-pyridazine-4 -Ylmethyl) -amide, [1973] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methylamino- Pyridazin-4-ylmethyl) -amide, [1974] 3- (3,4-Dichloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methylamino-pyridazine -4-ylmethyl) -amide, [1975] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methylamino-pyridazine- 4-ylmethyl) -amide, [1976] 3- (3-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methylamino-pyridazine-4 -Ylmethyl) -amide, [1977] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methylamino-pyridazine- 4-ylmethyl) -amide, [1978] 3- (4-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methylamino-pyridazine- 4-ylmethyl) -amide, [1979] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methylamino-pyridazine-4 -Ylmethyl) -amide, [1980] 3- (4-Bromo-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methylamino-pyridazine- 4-ylmethyl) -amide, [1981] 3- (3,4-Difluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methyl-pyri Dazin-4-ylmethyl) -amide, [1982] 3- (3,4-Dichloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-amino-pyridazine- 4-ylmethyl) -amide, [1983] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methyl- Pyridazin-4-ylmethyl) -amide, [1984] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methyl-pyridazine-4 -Ylmethyl) -amide, [1985] 3- (3-Chloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methyl-pyridazine-4- Monomethyl) -amide, [1986] 3- (3-Bromo-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (l-methyl-pyridazine-4 -Ylmethyl) -amide, [1987] 3- (4-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methyl-pyridazine-4 -Ylmethyl) -amide, [1988] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methyl-pyridazine-4- Monomethyl) -amide, [1989] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-methyl-pyridazine-4 -Ylmethyl) -amide, [1990] 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-ethoxy- Pyridazin-4-ylmethyl) -amide, [1991] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-ethoxy -Pyridazin-4-ylmethyl) -amide, [1992] 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-ethoxy-pyridazine- 4-ylmethyl) -amide, [1993] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-ethoxy-pyridazine-4 -Ylmethyl) -amide, [1994] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-ethoxy-pyridazine- 4-ylmethyl) -amide, [1995] 3- (3-Iodine-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-ethoxy-pyridazine-4 -Ylmethyl) -amide, [1996] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-ethoxy-pyridazine- 4-ylmethyl) -amide, [1997] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-ethoxy-pyridazine-4 -Ylmethyl) -amide, [1998] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-ethoxy-pyridazine- 4-ylmethyl) -amide, [1999] 3- (4-Iodine-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-ethoxy-pyridazine-4 -Ylmethyl) -amide, [2000] 3- (3,4-Difluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-amino-pyri Dazin-4-ylmethyl) -amide, [2001] 3- (3,4-Dichloro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (2-amino-pyridazine-4 -Ylmethyl) -amide, [2002] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-amino- Pyridazin-4-ylmethyl) -amide, [2003] 3- (3-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-amino-pyridazine-4 -Ylmethyl) -amide, [2004] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-amino-pyridazine-4- Monomethyl) -amide, [2005] 3- (3-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-amino-pyridazine-4 -Ylmethyl) -amide, [2006] 3- (4-Fluoro-benzyl) -l-methyl-2,4-dioxo-l, 2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-amino-pyridazine-4 -Ylmethyl) -amide, [2007] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-amino-pyridazine-4- Monomethyl) -amide, [2008] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-amino-pyridazine-4 -Ylmethyl) -amide, [2009] 3- (3,4-Difluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methyl-pyri Dazin-4-ylmethyl) -amide, [2010] 3- (3,4-Dichloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methyl-pyridazine- 4-ylmethyl) -amide, [2011] 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methyl- Pyridazin-4-ylmethyl) -amide, [2012] 3- (3-Fluoro-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methyl-pyridazine-4 -Ylmethyl) -amide, [2013] 3- (3-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methyl-pyridazine-4- Monomethyl) -amide, [2014] 3- (3-Bromo-benzyl) -l-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methyl-pyridazine-4 -Ylmethyl) -amide, [2015] 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methyl-pyridazine-4 -Ylmethyl) -amide, [2016] 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methyl-pyridazine-4- Monomethyl) -amide, and [2017] 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methyl-pyridazine-4 -Ylmethyl) -amide. [2018] Example 462 [2019] Evaluation of In Vitro Activity of Compounds of Formula (I) According to the Invention [2020] The activity of the compounds of formula (I) of the invention which inhibit matrix metalloprotease 13 was evaluated by measuring their IC50 values (concentrations necessary to inhibit 50% of enzyme activity) according to the protocol described below. [2021] MMP13CD Thiopeptolide Assay : Proteolysis of the thiopeptide substrate Ac-Pro-Leu-Gly-thioester-Leu-Leu-Gly-OEt was used as the primary screen for measuring IC 50 for MMP13 inhibitors. 100 μl of reaction was 50 mM HEPES, 100 mM CaCl 2 , pH 7.0 (RT), 1 mM 5,5′-dithiobis (2-nitrobenzoic acid) (DTNB), 100 μM substrate, inhibitor in 2.0% DMSO and 2.5 nM of human collagenase-3 catalytic domain enzyme. Inhibitors were screened from 100 μM to 0.5 nM. Absorbance change at 405 nm was monitored continuously for 10-15 minutes on a microplate reader at room temperature. IC 50 values were calculated by plotting the percentage of control velocity in the inhibited treatment against the inhibitor concentration. [2022] Example IC 50 (μM) Example IC 50 (μM) One 0.193 26 0.009 2 0.183 27 1.7 3 0.021 28 0.017 4 1.87 29 0.003 5 0.366 30 0.026 6 0.049 31 0.157 7 0.167 32 0.6 8 1.32 33 0.75 9 0.005 34 0.004 10 0.057 35 0.001 11 2.25 36 0.028 12 0.042 37 0.029 13 0.012 38 0.031 14 0.051 39 0.011 15 0.7 40 0.004 16 0.015 41 0.007 17 0.009 42 0.0025 18 0.01 43 1.21 20 0.051 44 0.016 21 0.3 45 0.007 22 0.096 46 0.096 23 0.029 47 0.062 24 0.009 48 0.014 25 0.028 [2023] [2024] Studies of the results in Table 1 show that the products of the invention tested in the assay effectively inhibit matrix metalloprotease 13. [2025] The protocol described above was also used to measure the activity of the compounds of the invention on MMP1, MMP2, MMP3, MMP7, MMP9, MMP12 and MMP14. IC 50 values obtained in these MMPs often exceeded 100 μM. These results indicate that the compounds of the present invention are selective as MMP13 inhibitors. [2026] Bibliographic References [2027] # MONTANA J. and BAXTER A., Current opinion in drug discovery and development, 2000, 3 (4), 353-361. [2028] # CLARK IM et al., Current opinion in anti-inflammatory and immunomodulatory investigational drugs, 2000, 2 (1), 16-25.
权利要求:
Claims (39) [1" claim-type="Currently amended] Compounds of formula (I), optionally racemic forms thereof, isomers thereof, N-oxides thereof, or pharmaceutically acceptable salts thereof: <Formula I> Where: R 1 is hydrogen, amino, or (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, mono (C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, di ( C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, aryl, aryl (C 1 -C 6 ) alkyl, heterocycle, and 3- to 6-membered cycloalkyl (C 1 -C 6 ) alkyl, wherein The groups may be unsubstituted or substituted with amino, (C 1 -C 6 ) alkyl, cyano, halo (C 1 -C 6 ) alkyl, C (═O) OR 4 , OR 4 and SR 4, where R 4 is hydrogen or (C 1 -C 6 ) alkyl; substituted with one or more groups which may be the same or different). W represents an oxygen atom, a sulfur atom, or a = NR 'group where R' represents (C 1 -C 6 ) alkyl, hydroxyl, or cyano, X 1 , X 2 and X 3 are independently of each other a nitrogen atom or a —CR 6 group wherein R 6 is hydrogen, (C 1 -C 6 ) alkyl, amino, mono (C 1 -C 6 ) alkylamino, di (C 1 -C 6 ) alkylamino, hydroxyl, (C 1 -C 6 ) alkoxy and halogen), provided that no more than two of X 1 , X 2 and X 3 simultaneously represent nitrogen atoms. Indicates, Y represents a group selected from an oxygen atom, a sulfur atom, -NH, and -N (C 1 -C 6 ) alkyl, Z represents an oxygen atom, a sulfur atom -NR 7 group, where R 7 represents a group selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl, and heteroaryl), or When Y is an oxygen atom, a sulfur atom, or a -N (C 1 -C 6 ) alkyl group, Z is unsubstituted or (C 1 -C 6 ) alkyl, aryl, aryl (C 1 -C 6 ) alkyl, aromatic Or optionally represents a carbon atom substituted with a non-aromatic heterocycle or cycloalkyl, n is an integer from 1 to 8, Z 1 is -CR 8 R 9 , wherein R 8 and R 9 are independently of each other hydrogen, (C 1 -C 6 ) alkyl, halo (C 1 -C 6 ) alkyl, halogen, amino, OR 4 , SR 4 or C (= O) OR 4, where R 4 represents hydrogen or (C 1 -C 6 ) alkyl] when n is 2 or more, the hydrocarbon chain Z 1 optionally contains one or more multiple bonds and / or a sulfur atom in which one of the carbon atoms in the hydrocarbon chain Z 1 is an oxygen atom, unsubstituted or substituted with one or two oxygen atoms, Or a nitrogen atom unsubstituted or substituted with (C 1 -C 6 ) alkyl, When one of the carbon atoms in the hydrocarbon chain Z 1 is unsubstituted or substituted with a sulfur atom substituted with one or two oxygen atoms, the -C (= Y) -Z- group may be optionally absent in general formula (I), A is a 5 or 6 membered monocycle comprising 1 to 4 heteroatoms selected from aromatic or non-aromatic, nitrogen, oxygen and sulfur, and Represents a group selected from the group consisting of two aromatic or non-aromatic bicycles which may be the same or different and comprise 0-4 heteroatoms selected from nitrogen, oxygen and sulfur, m is an integer from 0 to 7, R 2 groups may be the same or different and may be (C 1 -C 6 ) alkyl, halogen, —CN, N0 2 , SCF 3 , -CF 3 , -OCF 3 , -NR 10 R 11 , -OR 10 ,- SR 10 , -SOR 10 , -SO 2 R 10 ,-(CH 2 ) k SO 2 NR 1O R 11 , -X 5 (CH 2 ) k C (= O) OR 10 ,-(CH 2 ) k C ( = O) OR 10 , -X 5 (CH 2 ) k C (= 0) NR 1O R 11 ,-(CH 2 ) k C (= 0) NR 1O R 11 , and -X 4 -R 12 . , Wherein X 5 represents a group selected from oxygen, sulfur optionally substituted with one or two oxygen atoms, and nitrogen substituted with hydrogen or (C 1 -C 6 ) alkyl, k is an integer from 0 to 3, R 10 and R 11 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, X 4 represents a group selected from a single bond, —CH 2 —, an oxygen atom, a sulfur atom optionally substituted with one or two oxygen atoms, and a nitrogen atom substituted with hydrogen or (C 1 -C 6 ) alkyl, R 12 is substituted with one or more groups, which may be aromatic or nonaromatic, heterocyclic or non-heterocyclic, unsubstituted or the same or different groups selected from (C 1 -C 6 ) alkyl, halogen, hydroxyl and amino A 5- or 6-membered ring, and when the ring is heterocyclic, it contains 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur; R 3 is hydrogen, (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, wherein the group is unsubstituted or amino, cyano, halo (C 1 -C 6 ) alkyl , Cycloalkyl, -C (= 0) NR 10 R 11 , -C (= 0) OR 10 , OR 10 , and SR 10 , wherein R 10 and R 11 can be the same or different and are hydrogen or (C 1 -C 6 ) alkyl which is substituted with one or more groups which may be the same or different), or Is a group of the formula Where p is an integer from 0 to 8, Z 2 is —CR 13 R 14 wherein R 13 and R 14 are independently of each other hydrogen, (C 1 -C 6 ) alkyl, phenyl, halo (C 1 -C 6 ) alkyl, halogen, amino, OR 4 , SR 4 and —C (═O) OR 4, wherein R 4 represents hydrogen or (C 1 -C 6 ) alkyl, and when p is 2 or more, the hydrocarbon chain Z 2 optionally contains one or more multiple bonds Or one of the carbon atoms in the hydrocarbon chain Z 2 is replaced by an oxygen atom, a sulfur atom unsubstituted or substituted with one or two oxygen atoms, or a nitrogen atom unsubstituted or substituted with (C 1 -C 6 ) alkyl Can be, B is an aromatic or non-aromatic five or six membered monocycle comprising 0 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and Represents a group selected from a bicycle consisting of two aromatic or non-aromatic, five or six membered rings, which may be the same or different and include 0 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, q is an integer from 0 to 7, R 5 groups may be the same or different and may be selected from (C 1 -C 6 ) alkyl, halogen, —CN, NO 2 , —CF 3 , —OCF 3 , — (CH 2 ) k NR 15 R 16 , —N ( R 15 ) C (= O) R 16 , -N (R 15 ) C (= O) OR 16 , -N (R 15 ) SO 2 R 16 , -N (SO 2 R 15 ) 2 , -OR 15 , -S (O) k1 R 15 , -SO 2 -N (R 15 )-(CH 2 ) k2 -NR 16 R 17 ,-(CH 2 ) k SO 2 NR 15 R 16 , -X 7 (CH 2 ) k C (= 0) OR 15 ,-(CH 2 ) k C (= 0) OR 15 , -C (= 0) O- (CH 2 ) k2 -NR 15 R 16 , -C (= 0) O- (CH 2 ) k 2 -C (= 0) OR 18 , -X 7 (CH 2 ) k C (= 0) NR 15 R 16 ,-(CH 2 ) k C (= 0) NR 15 R 16 , -R 19 -C (= 0) OR 15 , -X 6 -R 20 , and -C (= 0) -R 21 -NR 15 R 16 , wherein X 7 represents a group selected from an oxygen atom, sulfur optionally substituted with one or two oxygen atoms, and nitrogen substituted with hydrogen or (C 1 -C 6 ) alkyl, k is an integer from 0 to 3, k 1 is an integer from 0 to 2, k 2 is an integer from 1 to 4, R 15 , R 16 and R 17 , which may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, R 18 is (C 1 -C 6) alkyl, -R 21 -NR 15 R 16, - R 21 -NR 15 -C (= O) -R 21 -NR 16 R 17, and -C (= O) OR A group selected from 21 -NR 15 R 16 , wherein R 21 represents a linear or branched (C 1 -C 6 ) alkylene group, and R 15 , R 16 and R 17 are as defined above, R 19 represents a (C 3 -C 6 ) cycloalkyl group, X 6 represents a group selected from a single bond, —CH 2 —, an oxygen atom, sulfur optionally substituted with one or two oxygen atoms, and a nitrogen atom substituted with a hydrogen atom or a (C 1 -C 6 ) alkyl group, R 20 is unsubstituted or (C 1 -C 6 ) alkyl, halogen, hydroxyl, oxo, cyano, tetrazole, amino, and —C (═O) OR 4 , wherein R 4 is hydrogen or (C Aromatic or non-aromatic, heterocyclic or non-heterocyclic, 5- or 6-membered ring, which is substituted with one or more groups which may be the same or different, selected from 1 -C 6 ) alkyl) Heterocyclic, it contains from 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, However, in the case where X 1 represents a nitrogen atom, X 2 can not represent a carbon atom substituted with a methyl group or an NH-CH 3. [2" claim-type="Currently amended] The method of claim 1, R 1 represents hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl or 3- to 6-membered cycloalkyl (C 1 -C 6 ) alkyl, W represents an oxygen atom or a sulfur atom, X 1 represents a nitrogen atom or -CR 6 , where R 6 represents a hydrogen atom, X 2 and X 3 each represent —CR 6 (where R 6 represents a hydrogen atom), Y represents an oxygen atom, A compound of formula (I) wherein Z represents an oxygen atom or -NR 7 , wherein R 7 represents a hydrogen atom, optionally a racemic form thereof, an isomer thereof, an N-oxide thereof, or a pharmaceutically acceptable salt thereof . [3" claim-type="Currently amended] The method of claim 1, n is an integer from 1 to 6, Z 1 represents -CR 8 R 9 (wherein R 8 represents a hydrogen atom and R 9 represents a hydrogen atom or a methyl group), when n is 2 or more, the hydrocarbon chain Z 1 optionally comprises a double bond, or One of the carbon atoms in the hydrocarbon chain Z 1 may be replaced with an oxygen atom or a sulfur atom which is unsubstituted or substituted with one or two oxygens, A is phenyl, pyridyl, thienyl, imidazolyl, furyl, piperidyl, 1,3-benzodioxyl, benzodioxyyl, benzothienyl, benzofuryl, benzofurazanyl, 2,1,3- Group selected from benzothiadiazolyl, and indolyl, m is an integer from 0 to 7, R 2 groups may be the same or different and may be (C 1 -C 6 ) alkyl, halogen, -CN, -CF 3 , -OCF 3 , -NR 10 R 11 , -OR 10 , -SR 10 , -SO 2 R 10, - (CH 2) k SO 2 NR 1O R 11, -X 5 (CH 2) k C (= O) OR 10, - (CH 2) k C (= O) OR 10, -X 5 ( CH 2 ) k C (= 0) NR 10 R 11 ,-(CH 2 ) k C (= 0) NR 10 R 11 , and -X 4 -R 12 , wherein Wherein X 5 represents O, S or NH, k is an integer from 0 to 3, R 10 and R 11 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, X 4 Represents a single bond, —CH 2 —, or an oxygen atom, and R 12 is unsubstituted or substituted with one or more groups which may be the same or different, selected from (C 1 -C 6 ) alkyl, halogen, hydroxyl and amino Indicating A compound of formula (I), optionally a racemic form thereof, an isomer thereof, an N-oxide thereof, or a pharmaceutically acceptable salt thereof. [4" claim-type="Currently amended] The method of claim 1, R 3 is hydrogen, (C 1 -C 6 ) alkyl or a group of formula wherein p is an integer from 0 to 3, Z 2 represents —CR 13 R 14 , wherein R 13 and R 14 independently of one another represent a group selected from hydrogen, methyl, or phenyl, when p is 2 or more, the hydrocarbon chain Z 2 optionally contains one double bond, or One of the carbon atoms in the hydrocarbon chain Z 2 is replaced with an oxygen atom, a sulfur atom unsubstituted or substituted with one or two oxygen atoms, a nitrogen atom unsubstituted or substituted with a (C 1 -C 6 ) alkyl, or carbonyl group, B is phenyl, pyridyl, thienyl, imidazolyl, furyl, 1,3-benzodioxyl, benzodioxyyl, benzothienyl, benzofuryl, 2,1,3-benzothiadiazolyl, benzofurazanyl , A group selected from naphthyl and indolyl, q is an integer from 0 to 3, R 5 groups may be the same or different and may be selected from (C 1 -C 6 ) alkyl, halogen, —CN, NO 2 , —CF 3 , —OCF 3 , — (CH 2 ) k NR 15 R 16 , —N ( R 15 ) C (= O) R 16 , -N (R 15 ) COR 16 , -N (R 15 ) SO 2 R 16 , -N (SO 2 R 15 ) 2 , -OR 15 , -S (O) k1 R 15 , -SO 2 -N (R 15 )-(CH 2 ) k2 -NR 16 R 17 ,-(CH 2 ) k SO 2 NR 15 R 16 , -X 7 (CH 2 ) k C (= O ) OR 15 ,-(CH 2 ) k C (= O) OR 15 , -C (= O) O- (CH 2 ) k2 -NR 15 R 16 , -X 7 (CH 2 ) k C (= O) NR 15 R 16 , and — (CH 2 ) k C (═O) NR 15 R 16 , wherein X 7 is S, O or NH, k is an integer from 0 to 3, k 1 is an integer from 0 to 2, k 2 is an integer from 1 to 4, R 15 , R 16 and R 17 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, optionally the racemic form thereof, isomer thereof, N-oxide thereof , Or pharmaceutically acceptable salts thereof. [5" claim-type="Currently amended] R 1 is hydrogen, amino, (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, mono (C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, di ( C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, aryl, aryl (C 1 -C 6 ) alkyl, heterocycle, and 3- to 6-membered cycloalkyl (C 1 -C 6 ) alkyl ( Wherein the group is unsubstituted or amino, (C 1 -C 6 ) alkyl, cyano, halo (C 1 -C 6 ) alkyl, C (═O) OR 4 , OR 4 and SR 4, where R 4 is hydrogen Or (C 1 -C 6 ) alkyl] is substituted with one or more groups which may be the same or different, and W represents an oxygen atom, a sulfur atom, or a = NR 'group where R' is (C 1 -C 6 ) alkyl, hydroxyl, or cyano), X 1 represents a nitrogen atom or a -CR 6 group, wherein R 6 represents a hydrogen atom, X 2 and X 3 independently of one another represent a —CR 6 group wherein R 6 represents a group selected from hydrogen, (C 1 -C 6 ) alkyl, amino, hydroxyl and halogen), Y represents an oxygen atom, Z represents an oxygen atom or a -NR 7 group wherein R 7 represents a group selected from hydrogen and (C 1 -C 6 ) alkyl n is an integer from 1 to 6, Z 1 represents —CR 8 R 9 , wherein R 8 and R 9 are, independently of each other, a group selected from hydrogen, (C 1 -C 6 ) alkyl, and hydroxyl, when n is 2 or more, the hydrocarbon chain Z 1 optionally contains one or more multiple bonds, or One of the carbon atoms in the hydrocarbon chain Z 2 may be replaced with an oxygen atom, an unsubstituted or substituted sulfur atom, or a nitrogen atom unsubstituted or substituted with (C 1 -C 6 ) alkyl, A is phenyl, pyridyl, thienyl, imidazolyl, furyl, 1,3-benzodioxyl, benzodioxyyl, benzothienyl, benzofuryl, benzofurazanyl, 2,1,3-benzothiadiazolyl A group selected from, and indolyl, m is an integer from 0 to 3, R 2 groups may be the same or different and may be (C 1 -C 6 ) alkyl, halogen, -CN, -CF 3 , -OCF 3 , -NR 10 R 11 , -OR 10 , -SR 10 , -SO 2 R 10, - (CH 2) k SO 2 NR 1O R 11, -X 5 (CH 2) k C (= O) OR 10, - (CH 2) k C (= O) OR 10, -X 5 ( CH 2 ) k C (= 0) NR 10 R 11 ,-(CH 2 ) k C (= 0) NR 10 R 11 , and -X 4 -R 12 , wherein X 5 here represents O, S or NH, k is an integer from 0 to 3, R 10 and R 11 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, X 4 represents —CH 2 — or an oxygen atom, R 12 represents phenyl which is unsubstituted or substituted with one or more groups which may be the same or different selected from (C 1 -C 6 ) alkyl, halogen and hydroxyl, R 3 is hydrogen, (C 1 -C 6 ) alkyl, and Is a group of the formula Where p is an integer from 0 to 6, Z 2 represents —CR 13 R 14 , wherein R 13 and R 14 independently of one another represent hydrogen, (C 1 -C 6 ) alkyl and hydroxy, When p is 2 or more, the hydrocarbon chain Z 2 optionally contains one or more multiple bonds, or a sulfur atom in which one of the carbon atoms in the hydrocarbon chain Z 2 is an oxygen atom, unsubstituted or substituted with one or two oxygen atoms, or unsubstituted Or a nitrogen atom substituted with (C 1 -C 6 ) alkyl, B is phenyl, pyridyl, thienyl, imidazolyl, furyl, 1,3-benzodioxyl, benzodioxyyl, benzothienyl, benzofuryl, 2,1,3-benzothiadiazolyl, benzofurazanyl , A group selected from naphthyl and indolyl, q is an integer from 0 to 3, R 5 groups may be the same or different and may be selected from (C 1 -C 6 ) alkyl, halogen, —CN, NO 2 , —CF 3 , —OCF 3 , — (CH 2 ) k NR 15 R 16 , —N ( R 15 ) C (= O) R 16 , -N (R 15 ) COR 16 , -N (R 15 ) SO 2 R 16 , -N (SO 2 R 15 ) 2 , -OR 15 , -S (O) k1 R 15 , -SO 2 -N (R 15 )-(CH 2 ) k2 -NR 16 R 17 ,-(CH 2 ) k SO 2 NR 15 R 16 , -X 7 (CH 2 ) k C (= O ) OR 15 ,-(CH 2 ) k C (= O) OR 15 , -C (= O) O- (CH 2 ) k2 -NR 15 R 16 , -X 7 (CH 2 ) k C (= O) NR 15 R 16 ,-(CH 2 ) k C (= 0) NR 15 R 16 , and -X 6 -R 20 , wherein X 7 is S, O or NH, k is an integer from 0 to 3, k 1 is an integer from 0 to 2, k 2 is an integer from 1 to 4, R 15 , R 16 and R 17 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, X 6 represents a single bond, -CH 2- , an oxygen atom, or a sulfur atom unsubstituted or substituted with one or two oxygen atoms, R 20 is aromatic or non-aromatic, heterocyclic or non-heterocyclic, unsubstituted or substituted with one or more groups which may be the same or different, selected from (C 1 -C 6 ) alkyl, halogen, hydroxyl and amino. , A compound of formula (I) representing a 5- or 6-membered ring, when the ring is heterocyclic, comprising 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur, optionally racemic forms thereof , Isomers thereof, N-oxides thereof, or pharmaceutically acceptable salts thereof. [6" claim-type="Currently amended] The method of claim 1, R 1 is hydrogen, mono (C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, di (C 1 -C 6 ) alkylamino (C 1 -C 6 ) alkyl, (C 1 -C 6 ) Alkyl, (C 3 -C 6 ) alkenyl, (C 3 -C 6 ) alkynyl, aryl, aryl (C 1 -C 6 ) alkyl, and 3- to 6-membered cycloalkyl (C 1 -C 6 ) alkyl Represents a group selected from W represents an oxygen atom or a sulfur atom, X 1 represents a nitrogen atom or a —CH group, X 2 and X 3 represent a -CH group, Y represents a group selected from an oxygen atom, a sulfur atom, -NH, and -N (C 1 -C 6 ) alkyl, Z represents an oxygen atom or an -NH group, n is an integer from 1 to 3, Z 1 represents —CR 8 R 9 , wherein R 8 and R 9 independently of one another represent a group selected from hydrogen, (C 1 -C 6 ) alkyl and hydroxy, When n is 2 or more, the hydrocarbon chain Z 1 optionally contains one double bond, or one of the carbon atoms in the hydrocarbon chain Z 1 is an oxygen atom, an unsubstituted or substituted with one or two oxygen atoms, or —NH Can be replaced with A is phenyl, pyridyl, thienyl, imidazolyl, furyl, 1,3-benzodioxolyl, benzodioxyyl, benzothienyl, benzofuryl, 2,1,3-benzothiadiazolyl, benzofurazanyl , A group selected from naphthyl and indolyl, m is an integer from 0 to 3, R 2 groups may be the same or different and may be (C 1 -C 6 ) alkyl, halogen, -CN, -CF 3 , -OCF 3 , -NR 10 R 11 , -OR 10 , -SR 10 , -SO 2 R 10, - (CH 2) k SO 2 NR 1O R 11, -X 5 (CH 2) k C (= O) OR 10, - (CH 2) k C (= O) OR 10, -X 5 ( CH 2 ) k C (= 0) NR 10 R 11 ,-(CH 2 ) k C (= 0) NR 10 R 11 , and -X 4 -R 12 , wherein X 5 here represents O, S or NH, k is an integer from 0 to 3, R 10 and R 11 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, X 4 represents —CH 2 — or an oxygen atom, R 12 represents a phenyl group which is unsubstituted or substituted with one or more groups which may be the same or different selected from (C 1 -C 6 ) alkyl, halogen and hydroxyl, R 12 represents phenyl which is unsubstituted or substituted with one or more groups which may be the same or different selected from (C 1 -C 6 ) alkyl, halogen and hydroxyl, R 3 is a group of the formula Where p is an integer from 0 to 3, Z 2 represents —CR 13 R 14 , wherein R 13 and R 14 independently of one another represent hydrogen, (C 1 -C 6 ) alkyl and hydroxy, When p is 2 or more, the hydrocarbon chain Z 2 optionally contains one double bond, or a sulfur atom in which one of the carbon atoms in the hydrocarbon chain Z 2 is an oxygen atom, unsubstituted or substituted with one or two oxygen atoms, or unsubstituted Or a nitrogen atom substituted with (C 1 -C 6 ) alkyl, B is phenyl, pyridyl, thienyl, imidazolyl, furyl, 1,3-benzodioxolyl, benzodioxyyl, benzothienyl, benzofuryl, 2,1,3-benzothiadiazolyl, benzofurazanyl , A group selected from naphthyl and indolyl, q is an integer from 0 to 3, R 5 groups may be the same or different and may be selected from (C 1 -C 6 ) alkyl, halogen, —CN, NO 2 , —CF 3 , —OCF 3 , — (CH 2 ) k NR 15 R 16 , —N ( R 15 ) C (= O) R 16 , -N (R 15 ) C (= O) OR 16 , -N (R 15 ) SO 2 R 16 , -N (SO 2 R 15 ) 2 , -OR 15 , -S (O) k1 R 15 , -SO 2 -N (R 15 )-(CH 2 ) k2 -NR 16 R 17 ,-(CH 2 ) k SO 2 NR 15 R 16 , -X 7 (CH 2 ) k C (= 0) OR 15 ,-(CH 2 ) k C (= 0) OR 15 , -C (= 0) O- (CH 2 ) k 2 -NR 15 R 16 ,-(CH 2 ) k C ( = O) NR 15 R 16 , and -X 6 -R 20 , wherein X 7 is S, O or NH, k is an integer from 0 to 3, k 1 is an integer from 0 to 2, k 2 is an integer from 1 to 4, R 15 , R 16 and R 17 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, X 6 represents a single bond, -CH 2- , an oxygen atom, or a sulfur atom unsubstituted or substituted with one or two oxygen atoms, R 20 is aromatic or non-aromatic, heterocyclic or non-heterocyclic, unsubstituted or substituted with one or more groups which may be the same or different, selected from (C 1 -C 6 ) alkyl, halogen, hydroxyl and amino. , A compound of formula (I), optionally a racemic thereof, which represents a five or six membered ring, when the ring is heterocyclic, comprising 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur Forms, isomers thereof, N-oxides thereof, or pharmaceutically acceptable salts thereof. [7" claim-type="Currently amended] The method of claim 1, R 1 represents hydrogen, (C 1 -C 6 ) alkyl, (C 3 -C 6 ) alkenyl, aryl (C 1 -C 6 ) alkyl, 3- to 6-membered cycloalkyl (C 1 -C 6 ) alkyl Indicate, W represents an oxygen atom, X 1 represents a -CH group or a nitrogen atom, X 2 and X 3 each represent a -CH group, Y represents an oxygen atom, Z represents an oxygen atom or an -NH group, n is an integer from 1 to 3, Z 1 represents —CR 8 R 9 , wherein R 8 and R 9 independently of one another represent a group selected from hydrogen and methyl, when n is 2 or more, the hydrocarbon chain Z 1 optionally contains one double bond, or one of the carbon atoms in the hydrocarbon chain Z 1 is an oxygen atom, an unsubstituted or substituted one or two oxygen atoms, or —NH Can be replaced with A represents a group selected from phenyl, pyridyl, thienyl, imidazolyl, furyl, and 1,3-benzodioxolyl, m is an integer from 0 to 3, R 2 groups may be the same or different and may be (C 1 -C 6 ) alkyl, halogen, -CN, -CF 3 , -OCF 3 , -NR 10 R 11 , -OR 10 , -SR 10 , -SO 2 R 10, - (CH 2) k SO 2 NR 1O R 11, -X 5 (CH 2) k C (= O) OR 10, - (CH 2) k C (= O) OR 10, -X 5 ( CH 2 ) k C (= 0) NR 10 R 11 and- (CH 2 ) k C (= 0) NR 10 R 11 , X 5 here represents O, S or NH, k is an integer from 0 to 3, R 10 and R 11 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, R 3 is a group of the formula Where p is an integer from 0 to 3, Z 2 represents —CR 13 R 14 , wherein R 13 and R 14 represent, independently of each other, a group selected from hydrogen and methyl, When p is 2 or more, the hydrocarbon chain Z 2 optionally contains one double bond, or a sulfur atom in which one of the carbon atoms in the hydrocarbon chain Z 2 is an oxygen atom, unsubstituted or substituted with one or two oxygen atoms, or unsubstituted Or a nitrogen atom substituted with (C 1 -C 6 ) alkyl, B represents a group selected from phenyl, pyridyl, thienyl, imidazole, furyl and 1,3-benzodioxolyl, q is an integer from 0 to 3, R 5 groups may be the same or different and may be selected from (C 1 -C 6 ) alkyl, halogen, —CN, NO 2 , —CF 3 , —OCF 3 , — (CH 2 ) k NR 15 R 16 , —N ( R 15 ) C (= O) R 16 , -N (R 15 ) C (= O) OR 16 , -N (R 15 ) SO 2 R 16 , -N (SO 2 R 15 ) 2 , -OR 15 , -S (O) k1 R 15 , -SO 2 -N (R 15 )-(CH 2 ) k2 -NR 16 R 17 ,-(CH 2 ) k SO 2 NR 15 R 16 , -X 7 (CH 2 ) k C (= 0) OR 15 ,-(CH 2 ) k C (= 0) OR 15 , -C (= 0) O- (CH 2 ) k2 -NR 15 R 16 , -X 7 (CH 2 ) k C (= 0) NR 15 R 16 , and-(CH 2 ) k C (= 0) NR 15 R 16 , wherein X 7 is S, O or NH, k is an integer from 0 to 3, k 1 is an integer from 0 to 2, k 2 is an integer from 1 to 4, R 15 , R 16 and R 17 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, optionally the racemic form thereof, isomer thereof, N-oxide thereof , Or pharmaceutically acceptable salts thereof. [8" claim-type="Currently amended] The method of claim 1, A compound of formula (I) wherein R 1 represents a hydrogen atom or a (C 1 -C 6 ) alkyl group, optionally a racemic form thereof, an isomer thereof, an N-oxide thereof, or a pharmaceutically acceptable salt thereof. [9" claim-type="Currently amended] The method of claim 1 W represents an oxygen atom, Y represents an oxygen atom, Z represents an NH group, Z 1 represents a methylene group, A compound of formula (I) wherein n is equal to 0, optionally a racemic form thereof, an isomer thereof, an N-oxide thereof, or a pharmaceutically acceptable salt thereof. [10" claim-type="Currently amended] The method of claim 1, X 1 represents a -CH group or a nitrogen atom, A compound of formula (I), wherein X 2 and X 3 represent a —CH group, optionally a racemic form thereof, an isomer thereof, an N-oxide thereof, or a pharmaceutically acceptable salt thereof. [11" claim-type="Currently amended] The method of claim 1, A compound of formula (I) wherein X 1 and X 3 each represent a -CH group and X 2 represents a -CH group or a nitrogen atom, optionally, its racemic form, an isomer thereof, an N-oxide thereof, or a pharmaceutically thereof Acceptable salts. [12" claim-type="Currently amended] The method of claim 1, X 1 and X 3 each represent a —CH group, A compound of formula (I), wherein X 2 represents a nitrogen atom, optionally a racemic form thereof, an isomer thereof, an N-oxide thereof, or a pharmaceutically acceptable salt thereof. [13" claim-type="Currently amended] The method of claim 1, A is a group selected from phenyl, pyridyl, 1,3-benzodioxolyl and benzofurazanyl, m is 0 or 1, A compound of formula (I) wherein R 2 represents a group selected from (C 1 -C 6 ) alkoxy, hydroxy, halogen, and (C 1 -C 6 ) thioalkoxy, optionally, racemic form thereof, isomer thereof, N Oxides, or pharmaceutically acceptable salts thereof. [14" claim-type="Currently amended] The method of claim 1, R 3 is a group of the formula Where p is 1, Z 2 is a methylene group, B represents a group selected from phenyl, pyridyl, 1,3-benzodioxolyl and benzofurazanyl, q is an integer from 0 to 2, R 5 is -CN,-(CH 2 ) k NR 15 R 16 , -S (O) k1 R 15 ,-(CH 2 ) k SO 2 NR 15 R 16 ,-(CH 2 ) k C (= O) OR 15 ,-(CH 2 ) k C (= 0) NR 15 R 16 and -X 6 -R 20 , wherein k is an integer from 0 to 1, k 1 is an integer from 0 to 2, R 15 and R 16 may be the same or different and are selected from hydrogen and (C 1 -C 6 ) alkyl, X 6 represents a bond, A compound of formula (I), optionally in its racemic form, wherein R 20 represents a 5-membered heterocyclic ring which contains 3 to 4 heteroatoms selected from oxygen and nitrogen and a methyl group and is optionally substituted with a methyl or oxo group Isomers, N-oxides thereof, or pharmaceutically acceptable salts thereof. [15" claim-type="Currently amended] The compound of formula (I) according to claim 1, wherein 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid benzylamide, 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (4-pyridylmethyl) amide, 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide, 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (2-thienylmethyl) amide, 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (3-pyridylmethyl) amide, 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxybenzylamide, 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-chlorobenzylamide, 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methylbenzylamide, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide , 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid benzylamide, -Methyl 4-({[1- (3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl) metanoyl] amino} methyl) benzo Eight, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-hydroxy-3-methoxybenzylamide, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy benzylamide, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (4-pyridylmethyl) amide, 1-methyl-2,4-dioxo-3-phenethyl-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amides, 3- (4-methoxybenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl )amides, 3- (4-methoxybenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol- 5-ylmethyl) amide, 3- (4-methoxybenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxybenzylamide, 3- (1-naphth-1-ylethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol- 5-ylmethyl) amide, 2,4-dioxo-3- (pyrid-4-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5- Monomethyl) amide, 2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid benzylamide, -1-methyl-2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid benzylamide, 2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-yl Methyl) amide, 1-methyl-2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol -5-ylmethyl) amide, 3- (4-chlorobenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amides, 3- (4-chlorobenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5 -Ylmethyl) amide, 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid benzo [1,3] dioxol-5-ylmethyl) amide, -3- (benzo [1,3] dioxol-5-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3 ] Dioxol-5-ylmethyl) amide, -3- (benzo [l, 3] dioxol-5-ylmethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide, 3-benzyl-1-ethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide , 3-benzyl-1-cyclopropylmethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl )amides, 3-Benzyl-1-isobutyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amides, 1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide, Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate , 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H] -quinazolin-3-ylmethyl] -benzoic acid, 1-methyl-2,4-dioxo-3-((E) -3-phenylallyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] Dioxol-5-ylmethyl) amide, Benzyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate, Benzyl 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate, 4-pyridylmethyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate, 4-pyridylmethyl 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6carboxylate, Benzo [1,3] dioxol-5-ylmethyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6carboxylate, Benzo [1,3] dioxol-5-ylmethyl 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate, Benzyl 1-benzyl-2,4-dioxo-3-pyrid-4-ylmethyl-1,2,3,4-tetrahydro-quinazolin-6-carboxylate, 4-pyridylmethyl 2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6carboxylate, 4-pyridylmethyl 3- (benzo [1,3] dioxol-5-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate, Benzyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d] pyrimidine-6-carboxylate 4-pyridylmethyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d] pyrimidine-6carboxylate, 3-benzyl-4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide, 4- [6- (4-hydroxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid, 3- (4-dimethylcarbamoyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzylamide , 1-methyl-3- (4-methylcarbamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzyl amides, 3-allyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4methoxy-benzylamide, 1-methyl-2,4-dioxo-3- (2-pyrrole-1-ylethyl) -1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzyl amides, 1-methyl-2,4-dioxo-3-prop-2-ynyl-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 1-methyl-3- (3-methyl-but-2-enyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide, 1-methyl-2,4-dioxo-3-pyridin-2-ylmethyl-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3-carbamoylmethyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 1-methyl-2,4-dioxo-3-pyridin-3-ylmethyl-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, -1-Methyl-3- (1-methyl-piperidin-3-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-meth Oxy-benzylamide, 3- (4-cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- (3-cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- (2-methoxy-ethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- (3-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3-cyclopropylmethyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 1-Methyl-3- (2-morpholin-4-ylethyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide, 3-cyclohexylmethyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 1-methyl-2,4-dioxo-3- (3-phenyl-propyl) -1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- [2- (4-diethylamino-phenyl) -2-oxo-ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carr Acid 4-methoxy-benzylamide, Ethyl [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] -acetate, 3- (2-hydroxy-ethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzylamide, Methyl 3- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] -propionate , 3- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] -propionic acid, Ethyl 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] -butyrate, 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] -butyric acid, Methyl {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -phenyl }-acetate, -{4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -phenyl} Acetic acid, -3- (4-dimethylcarbamoylmethyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide, -1-Methyl-2,4-dioxo-3-[(E) -3- (pyridin-3-yl) -allyl] -1,2,3,4-tetrahydro-quinazolin-6-carboxyl Acid 4-methoxy-benzylamide, 1-methyl-2,4-dioxo-3-[(E) -3- (pyridin-4-yl) -allyl] -1,2,3,4-tetrahydro-quinazolin-6 carboxylic acid 4-methoxy-benzylamide, 1-methyl-2,4-dioxo-3- (4-sulfamoyl-benzyl) -1,2,3,4-tetrahydroquinazolin-6 carboxylic acid 4-methoxy-benzylamide, 3- (4-Methanesulfonyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide , 3- (4-dimethylsulfamoyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide , 3- [4- (2-dimethylamino-ethylsulfamoyl) -benzyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 1-methyl-3- (4-methylsulfamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide , Methyl 3- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate , 3- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid, -(E) methyl-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] -But-2-enoate, 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] -but-2- Enonic Acid, -Methyl 5- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -furan- 2-carboxylate, 5- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -furan-2 Carboxylic acid, Methyl 5- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -thiophene -2-carboxylate, 5- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -thiophene- 2-carboxylic acid, 1-methyl-3- (4-nitro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- (4-amino-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- (4-dimethylamino-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- (4-acetylamino-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6 carboxylic acid 4-methoxy-benzylamide, 3- [4- (N, N-methylsulfonylamino) -benzyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4 Methoxy-benzylamide, 3-benzofurazane-5-ylmethyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- [2- (4-fluorophenoxy) -ethyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4- Methoxy-benzylamide, 3- (2-benzenesulfonylethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- (3-Fluoro-4-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-meth Oxybenzylamine, 1-methyl-2,4-dioxo-3- [4- (2H-tetrazol-5-yl) -benzyl] -1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 1-methyl-3- [4- (5-methyl-1,2,4-oxadiazol-3-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro Quinazoline-6-carboxylic acid 4-methoxy-benzylamide, 1-methyl-3- [4- (3-methyl-1,2,4-oxadiazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro Quinazoline-6-carboxylic acid 4-methoxy-benzylamide, 2-chloro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] Benzoate, 2-chloro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] Benzoic acid, 1-methyl-3- [4- (1-methyl-1H-tetrazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6- Carboxylic acid 4-methoxy-benzylamide, 1-methyl-3- [4- (2-methyl-2H-tetrazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6- Carboxylic acid 4-methoxy-benzylamide, Methyl 2-methoxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4 dihydro-2H-quinazolin-3-ylmethyl ] -Benzoate, -2-methoxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoic acid, Methyl 2-hydroxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl Methyl] -benzoate, 2-hydroxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoic acid, Methyl 2-methyl-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoate, 2-methyl-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] Benzoic acid, -1-Methyl-2,4-dioxo-3- (pyridine-4-methyl) -1,2,3,4-tetrahydro-quinazolin-carboxylic acid (benzo [1,3] dioxol-5 -Ylmethyl) -amide, 1-methyl-2,4-dioxo-3- (pyridin-4-ylmethyl) -1,2,3,4-tetrahydro-quinazolin-carboxylic acid 4-methoxy-benzylamide, 1-methyl-2,4-dioxo-3- (pyridin-4-ylmethyl) -1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-hydroxy-benzylamide, Methyl 4- [6- (3-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate , 4- [6- (3-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid, Methyl 4- [1-methyl-6- (4-methylsulfanyl-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzo Eight, 4- [1-Methyl-6- (4-methylsulfanyl-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid, Methyl 4- [1-ethyl-2,4-dioxo-6- (4-trifluoromethoxy-benzylcarbamoyl) -1,4-dihydro-2H-quinazolin-3-ylmethyl]- Benzoate, Methyl 4- [6- (4-fluoro-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate , 4- [6- (4-Fluoro-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid, Methyl 4- {6-[(benzofurazane-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl Methyl} -benzoate, 4-6-[(benzofurazane-5-ylmeethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl} Benzoic acid, Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate, Methyl 4- [1-ethyl-6- (4-methoxy-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate , 4- [1-ethyl-6- (4-methoxy-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid, 3- (4-Methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (pyridin-4-ylmethyl)- amides, 3- (4-hydroxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides, 3- (4-cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides, 1-methyl-2,4-dioxo-3- (3-pyridin-4-yl-allyl) -1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridine-4- Monomethyl) -amide, Methyl 4- {1-methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3-ylmethyl} Benzoate, 4- {1-Methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3-ylmethyl}- Benzoic Acid, Methyl (4- {1-methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3-ylmethyl } -Phenyl) -acetate, -(4- {1-methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3-ylmethyl} -Phenyl) -acetic acid, Methyl 4- {1-methyl-2,4-dioxo-6-[(1-oxy-pyridin-4-ylmethyl) carbamoyl] -1,4-dihydro-2H-quinazolin-3- Monomethyl} -benzoate, 4- {1-Methyl-2,4-dioxo-6-[(1-oxy-pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3- Monomethyl} -benzoic acid, Methyl {6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -3-benzyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-1 Acetate-Acetate, 6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -3-benzyl-2,4-dioxo-3,4-dihydro-2H-quinazolin-1-yl } -Acetic acid, Methyl 4- {6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazoline -3-ylmethyl} -benzoate, 4- {6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin- 3-ylmethyl} -benzoic acid, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-sulfamoyl-benzylamide, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid [3- (pyridin-4-ylsulfanyl) -propyl]- amides, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (4-morpholin-4-ylbutyl) -amide, 3-Benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1-benzyl-piperidin-4-yl) -amide , 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-hydroxy-benzylamine, -Ethyl (4-{[(3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carbonyl) amino] -methyl} -phenoxy )-acetate, -(4-{[(3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carbonyl) amino] methyl} -phenoxy)- Acetic Acid, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-dimethylcarbamoylmethoxy-benzylamide, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (3-phenyl-allyl) -amide, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-cyano-benzylamide, -4-{[(3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carbonyl) -amino] -methyl} -benzoic acid, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-dimethylcarbamoyl-benzylamide, 3- (4-dimethylamino-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- [4- (N-methylsulfonylamino) -benzyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-meth Oxy-benzylamide, tert-butyl {5- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -Pyridin-2-yl} -carbamate, 3- (6-amino-pyridin-3-ylmethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy Benzylamide, 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-dupyrimidine-6-carboxylic acid (1,3-benzodioxol- 5-ylmethyl) -amide, 1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (1,3-benzodioxol -5-ylmethyl) -amide, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6-carboxylic acid (1,3-benzo Dioxo-5-ylmethyl) -amide, 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [2,3-d] pyrimidine- 3-ylmethyl] -benzoic acid, 3- (4-cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6-carboxyl Acid 4-methoxy-benzylamide, 3- (4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [2,3-d] pyrimidine-6-carboxyl Acid 4-methoxy-benzylamide, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (1,3-benzo Dioxo-5-ylmethyl) -amide, Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2Hpyrido [3,4-d] pyrimidine- 3-ylmethyl] -benzoate, 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] pyrimidine- 3-ylmethyl] -benzoic acid, 4- [6- (3-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] pyrimidine- 3-ylmethyl] -benzoic acid, 3- (4-cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxyl Acid 4-methoxy-benzylamide, 3-benzyl-1-methyl-6- (3-phenyl-propionyl) -1 H-quinazolin-2,4-dione, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (E) -3-pyridin-4-yl-allyl ester, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (E) -3-pyridin-3-yl-allyl ester, 3-benzyl-1-methyl-6- [2- (pyridin-4-ylsulfanyl) -acetyl] -1 H-quinazolin-2,4-dione, 3- (4-aminomethyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- (2'-cyano-biphenyl-4-ylmethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4- Methoxy-benzylamide, -1-Methyl-2,4-dioxo-3- [2 '-(1H-tetrazol-5-yl) -biphenyl-4-ylmethyl] -1,2,3,4-tetrahydro-quina Zoline-6-carboxylic acid 4-methoxy-benzylamide, Methyl 4 ′-[6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -ratio Phenyl-2-carboxylate, 4 '-[6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -biphenyl 2-carboxylic acid, Ethyl 2-fluoro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl Methyl] -benzoate, 2-fluoro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoic acid, 2-methoxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoic acid 2-dimethylamino-ethyl ester, 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -2-methyl -Benzoic acid 2-dimethylamino-ethyl ester, 1-methyl-2,4-dioxo-3- [4- (5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl) -benzyl] -1,2 , 3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, -{4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl] -phenyl}- Acetic Acid, -1-Methyl-3- (1-naphthalen-1-ylethyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (1,3-benzo Dioxo-5-ylmethyl) -amide, 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides, 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy-pyridine- 4-ylmethyl) -amide, 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-3-ylmethyl) -amides, 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 3-methoxy-benzylamide, 1-ethyl-3- (3-fluoro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides, 1-ethyl-3- (3-fluoro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-3-ylmethyl) -amides, 3- (4-bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide, 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy-pyridine- 4-ylmethyl) -amide, 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridine-3- Monomethyl) -amide, 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridine-4- Monomethyl) -amide, 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide, 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridine-4 -Ylmethyl) -amide, 3- (3-Chloro-4-fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy Benzylamide, 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate ( 2-hydroxy-ethyl) -trimethyl-ammonium, 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -hemicalcium benzoate , 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -hemi magnesium , 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl)- amides, 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides, 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-3-ylmethyl) -amides, 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (pyridin-3-ylmethyl) -amide , 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 3-methoxy-benzylamide, 3- (4-chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 3-methoxy-benzylamide, 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (2-methoxy-pyridine-4 -Ylmethyl) -amide, 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (2-methoxy-pyridine-4- Monomethyl) -amide, tert-butyl 1- {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl Methyll-phenyl} -cyclopropanecarboxylate, 1- {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Phenyl} -cyclopropanecarboxylic acid, 3-benzyl-6-benzylsulfanyl-1-methyl-1H-quinazolin-2,4-dione, 3-benzyl-1-methyl-6-phenylmethanesulfinyl-1H-quinazolin-2,4-dione, 3-benzyl-1-methyl-6-phenylmethanesulfonyl-1H-quinazolin-2,4-dione, 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid tert- Butoxycarbonylmethyl ester, 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid dimethylamino Dimethyl-propyl ester, 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid dimethylamino -Methyl-propyl ester, 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid 2- Dimethylamino-ethyl ester, 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid chloromethyl ester, 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid 2- tert-butoxycarbonylamino-3-methyl-1-butanoyloxymethyl ester, 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid 2- Amino-3-methyl-butanoyloxymethyl ester hydrogen chloride, 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid 2- (2-tert-butoxycarbonylamino-3-methyl-butanoylamino) -3methyl-butanoyloxymethyl ester, And 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid 2 -(2-amino-3-methyl-butanoylamino) -3-methylbutanoyloxymethyl ester. [16" claim-type="Currently amended] The compound of formula (I) according to claim 1, wherein 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] pyrimidine- 3-ylmethyl] -benzoic acid, 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxylic acid (1,3-benzo Dioxol-5-ylmethyl) amide, 4- [6- (4-Fluoro-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid, 1-methyl-2,4-dioxo-3- [4- (5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl) -benzyl] -1,2 , 3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethethyl] -hemicalcium benzoate salt Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] pyrimidine -3-ylmethyl] -benzoate 4- [6- (3-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid 1-methyl-2,4-dioxo-3- [4- (2H-tetrazol-5-yl) -benzyl] -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4 -Methoxy-benzylamide Methyl 2-hydroxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl Methyl] -benzoate 3- (4-Chloro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 3-methoxy-benzylamide 4- {6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin- 3-ylmethyl} -benzoic acid 2-hydroxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoic acid Methyl 4- [6- (3-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 3-methoxy-benzylamide 4-pyridylmethyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate Methyl 4- {6-[(1,3-benzodioxol-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazoline -3-ylmethyl} -benzoate 1-methyl-3- [4- (5-methyl-1,2,4-oxadiazol-3-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro -Quinazolin-6-carboxylic acid 4-methoxy-benzylamide 1-methyl-3- [4- (3-methyl-1,2,4-oxadiazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro -Quinazolin-6-carboxylic acid 4-methoxy-benzylamide 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1 2, 3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy-pyridine-4 -Ylmethyl) -amide 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H] quinazolin-3-ylmethyl] -benzoic acid 1- {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]- Phenyl} -cyclopropanecarboxylic acid 4-pyridylmethyl 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 3-methoxy-benzylamide 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy- Benzylamide 3- (4-Dimethylcarbamoyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzyl amides 1-methyl-3- [4- (2-methyl-2H-tetrazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6 -Carboxylic acid 4-methoxy-benzylamide 3- (4-Bromo-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (2-methoxy-pyridine- 4-ylmethyl) -amide 3- (3,4-Difluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridine-3- Monomethyl) -amide Benzo [1,3] dioxol-5-ylmethyl-3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate 3-benzyl-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide 1-methyl-3- (4-methylcarbamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzylamide 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide 4- [6- (4-Hydroxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid Methyl 4- [6- (4-fluoro-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate 3- (4-chlorobenzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amides 1-methyl-3- [4- (1-methyl-1H-tetrazol-5-yl) -benzyl] -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6 -Carboxylic acid 4-methoxy-benzylamide 3- (4-methoxybenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxybenzylamide 4-pyridylmethyl 3- (benzo [1,3] dioxol-5-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate Methyl 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoate 1-methyl-2,4-dioxo-3-pyridin-4-ylmethyl-1,2,3,4-tetrahydro-quinazolincarboxylic acid 4-methoxy-benzylamide 3- (4-Amino-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide 1-methyl-3- (4-nitro-benzyl) -2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide 2-methoxy-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoic acid 1-methyl-3- (4-methylsulfamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzylamide 1-Methyl-2,4-dioxo-3- (4-sulfamoyl-benzyl) -1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide 3- (4-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides 3- (4-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides 2-methyl-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] Benzoic acid 3- (4-cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide 4- {1-Methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3-ylmethyl}- Benzoic acid 3- (3-Fluoro-4-methoxy-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy Benzylamine 4- [1-Ethyl-6- (4-methoxy-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid 3- (benzo [1,3] dioxol-5-ylmethyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3 ] Dioxol-5-ylmethyl) amide 3- (2'-cyano-biphenyl-4-ylmethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4- Methoxy-benzylamide 4- [1-Methyl-6- (4-methylsulfanyl-benzylcarbamoyl) -2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -benzoic acid 4- {6-[(benzofurazane-5-ylmethyl) -carbamoyl] -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl } -Benzoic acid Methyl 2-methyl-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoate 3- (4-acetylamino-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid 4-methoxy-benzylamide 3- (benzo [1,3] dioxol-5-ylmethyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-ylmethyl) amide 3- (4-dimethylcarbamoylmethyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzyl amides Benzo [1,3] dioxol-5-ylmethyl 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylate {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -phenyl} Acetic acid (4- {1-methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3-ylmethyl} -Phenyl) -acetic acid 3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxybenzylamide Methyl {4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -phenyl }-acetate 3- (3-Fluoro-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-quinazolin-6-carboxylic acid (pyridin-4-ylmethyl) -amides 2,4-dioxo-3- (thien-2-ylmethyl) -1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol-5-yl Methyl) amide 1-methyl-3- (4-methylsulfamoyl-benzyl) -2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzylamide Methyl 4- {1-methyl-2,4-dioxo-6-[(pyridin-4-ylmethyl) -carbamoyl] -1,4-dihydro-2H-quinazolin-3-ylmethyl} -Benzoate 2-fluoro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl ] -Benzoic acid 3- (4-cyano-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrido [3,4-d] pyrimidine-6-carboxyl Acid 4-methoxy-benzylamide 4- [6- (3-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [3,4-d] pyrimidine- 3-ylmethyl] -benzoic acid 4- [6- (4-Methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl] -hemi magnesium salt 4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4-dihydro-2H-pyrido [2,3-d] pyrimidine- 3-ylmethyl] -benzoic acid 3- [4- (N-methylsulfonylamino) -benzyl] -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-meth Oxy-benzylamide Ethyl 2-fluoro-4- [6- (4-methoxy-benzylcarbamoyl) -1-methyl-2,4-dioxo-1,4 dihydro-2H-quinazolin-3-ylmethyl ] -Benzoate 3- (4-dimethylsulfamoyl-benzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid 4-methoxy-benzylamide 3- (4-methoxybenzyl) -1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-carboxylic acid (benzo [1,3] dioxol- 5-ylmethyl) amide. [17" claim-type="Currently amended] Intermediate Compounds of Formula (III): <Formula III> here, R 3 is as defined for the compound of formula (I). [18" claim-type="Currently amended] Intermediate Compounds of Formula (IV): <Formula IV> here, R 1 and R 3 have the same meanings as defined for the compound of formula (I). [19" claim-type="Currently amended] Reacting a compound of formula (II) with pyridine and a compound of formula (V) to obtain a compound of formula (VI), Reacting the compound of formula (VI) in the presence of Li 0 H to obtain a compound of formula (III), The compound of formula (III) obtained above is reacted with a compound of formula (VII) in the presence of an acid activator such as TOTU, so that R 1 represents hydrogen, X 1 , X 2 and X 3 are each -CH, Wherein Y is O, Z is NR 7 , W is O, and A, R 2 , Z 1 , m and n comprise obtaining a compound of formula (I) as defined above Process for the preparation of the compound of (I): <Formula I> Wherein R 2 , R 3 , Z 1 , A, n and m are as defined in claim 1, R 1 is H, X 1 , X 2 and X 3 are each -CH, Y is O, Z is -NR 7 , W is O. <Formula II> <Formula V> O = C = NR 3 Here, R 3 is as defined in claim 1. <Formula VI> Where R 3 is as defined above. <Formula III> Where R 3 is as defined above. <Formula VII> Wherein R 7 is selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, A, R 2 , Z 1 , m and n are as defined in claim 1. [20" claim-type="Currently amended] Reacting a compound of formula (VI) in the presence of a base with a compound of formula XR 1 , wherein R 1 is as defined in claim 1 and X is a leaving group such as halogen to obtain a compound of formula (IX) , Reacting a compound of formula (IX) in the presence of Li 0 H to obtain a compound of formula (IV), Preparing a compound of formula (I) comprising reacting a compound of formula (IV) with a compound of formula (VII) in the presence of an acid activator such as TOTU to obtain a compound of formula (I) Way: <Formula I> Wherein R 1 , R 2 , R 3 , A, Z 1 , m and n are as defined in claim 1 , X 1 , X 2 and X 3 are CH, W is O, Y is O, Z Is NR 7 . <Formula VI> Here, R 3 is as defined in claim 1. <Formula IX> Wherein R 1 and R 3 are as defined above. <Formula IV> R 1 and R 3 are as defined in claim 1. <Formula VII> Wherein R 7 is hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are in the summary of the invention As defined. [21" claim-type="Currently amended] R 1 is H, and R 2 , R 3 , W, Y, Z, X 1 , X 2 , X 3 , A, Z 1 , m and n are compounds of formula (I) as defined above in the presence of a base. compounds XR 1 of the formula (VIII) (where R 1 is as defined in claim 1, X is a leaving group such as halogen), a compound of formula (I), is reacted with, as the R 1 defined in claim 1 R 1 , R 2 , R 3 , W, X 1 , X 2 , X 3 , A, Z 1 , m and n, comprising the step of obtaining a compound of formula (I) as defined in claim 1 Manufacturing method. <Formula I> [22" claim-type="Currently amended] Reacting a compound of formula (XI) with AlCl 3 in a solvent such as benzene to obtain a compound of formula (XII), Obtaining a compound of formula (XII) in the presence of Li0H and dioxane / H 2 O to obtain a compound of formula (XIII), Reacting a compound of formula (XIII) with a compound of formula (VII) in the presence of an acid activator such as TOTU to obtain a compound of formula (XIV), wherein X 1 , X 2 and X 3 are CH, W is O, Y is O, Z is NR 7 , R 3 is H, and R 1 , R 2 , A, Z 1 , m and n are first As defined in the above) <Formula XI> Where R 1 is as defined above. <Formula XII> Where R 1 is as defined above. <Formula XIII> Where R 1 is as defined above. <Formula VII> Wherein R 7 is hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are As defined. <Formula XIV> Wherein X 1 , X 2 and X 3 are CH, W is O, Y is O and R 7 , A, R 2 , Z 1 , m and n are as defined above. [23" claim-type="Currently amended] Reacting a compound of formula (XIV) with a compound of formula (XV), XR 3 , wherein R 3 is as defined in claim 1 and X is a leaving group such as halogen to obtain a compound of formula (I) A process for preparing a compound of formula (I) comprising the step: <Formula XIV> Wherein X 1 , X 2 and X 3 are CH, W is O, Y is O and R 7 , A, R 2 , Z 1 , m and n are as defined above. <Formula I> Wherein X 1 , X 2 and X 3 are CH, W is O, Y is O, and R 7 , A, R 2 , R 3 , R 1 , Z 1 , m and n are as defined in claim 1 same. [24" claim-type="Currently amended] Reacting a compound of formula (III) with a compound of formula (XVI) to obtain a compound of formula (XVII), wherein X 1 , X 2 and X 3 are CH, W is O, Y is O and Z is O) <Formula III> Here, R 3 is as defined in claim 1. <Formula XVI> Here, A, R 2 , Z 1 , m and n are as defined in claim 1. <Formula XVII> Wherein A, R 2 , R 3 , Z 1 , m and n are as defined above, X 1 , X 2 and X 3 are —CH and W is O. [25" claim-type="Currently amended] In the presence of a base, a compound of formula (XVII) is reacted with a compound of formula (VIII), XR 1 , wherein R 1 is as defined in claim 1 and X is a leaving group such as halogen, A process for preparing a compound of formula (I) comprising the step of obtaining a compound: <Formula XVII> Wherein A, R 2 , R 3 , Z 1 , m and n are as defined in claim 1 , X 1 , X 2 and X 3 are each -CH and W is O. <Formula I> Wherein A, R 1 , R 2 , R 3 , Z 1 , m and n are as defined above, X 1 , X 2 and X 3 are —CH and W is O. [26" claim-type="Currently amended] Reacting a compound of formula (XIX) with a pyridine and a compound of formula (V), O = C = NR 3 , wherein R 3 is as defined in claim 1 to obtain a compound of formula (XX), Reacting a compound of formula (XX) in the presence of KMnO 4 to obtain a compound of formula (XXI), Reacting a compound of formula (XXI) in the presence of SOCl 2 and optionally a solvent to obtain a compound of formula (XXII), and Reacting a compound of formula (XXII) with a compound of formula (XVI) to yield a compound of formula (XXIV), wherein X 2 and X 3 are each -CH, X 1 is N, and Z is O Wherein Y is O, R 1 is H, W is O, and A, R 2 , R 3 , Z 1 , m and n are compounds of formula (I) as defined in claim 1: <Formula XIX> <Formula XX> Where R 3 is as defined above. <Formula XXI> Where R 3 is as defined above. <Formula XXII> Where R 3 is as defined above. <Formula XVI> Here, A, R 2 , Z 1 , n and m are as defined in claim 1. <XXIV> Wherein X 2 and X 3 are each -CH, and A, n, m, Z 1 , R 2 and R 3 are as defined above. [27" claim-type="Currently amended] The compound of formula (XXV) is reacted with N, N'-dimethylformamide dimethyl acetal under DMF reflux in the first step, and with N-iodosuccinimide in the second step to obtain the compound of formula (XXVI). step, Then reacting the compound of formula (XXVI) with ethyl acrylate in the presence of palladium diacetate, CuI and a base to obtain a compound of formula (XXVII), Then reacting the compound of formula (XXVII) in the presence of Li0H to obtain a compound of formula (XXVIII), The compound (XXVIII) is reacted with a compound of formula (VII) in the presence of an acid activator such as TOTU to give a compound of formula (XXIX), Or reacting a compound of formula (XXVIII) with AlCl 3 in the first step in the presence of benzene and in the second step with a compound of formula (VII) in the presence of an acid activator such as TOTU to give a compound of formula (XXX) And then reacting the compound of formula (XXX) with a compound of formula R 3 -X, wherein R 3 is as defined in formula (I) in the presence of a base to obtain a compound of formula (XXXI). doing A compound of formula (I), wherein X 2 and X 3 are CH, X 1 is N, Z is -NR 7 where R 7 is as defined for compound of formula (I) and W is O And Y is O) <Formula XXV> <Formula XXVI> <Formula XXXVII> <Formula XXVIII> <Formula VII> Wherein R 7 is selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are of the invention As defined in the summary. <Formula XXIX> Wherein A, R 2 , R 7 , Z 1 , m and n are as defined above and X 2 and X 3 each represent a —CH group. <Formula VII> Wherein R 7 is selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are of the invention As defined in the summary. <Formula XXX> Wherein A, R 2 , R 7 , Z 1 , m and n are as defined above and X 2 and X 3 are each a —CH group. <Formula XXXI> [28" claim-type="Currently amended] The compound of formula (XXXII) is reacted with selenium dioxide in the presence of acetic acid in the first step, with dimethylhydrazine in the second step, and with N, N'-dimethylformamide dimethylacetal under DMF reflux in the third step. Obtaining a compound of Then reacting the compound of formula (XXXIII) with methyl acrylate in the presence of palladium diacetate to obtain a compound of formula (XXXIV), Then reacting the compound of formula (XXXIV) with chlorobenzene and acetic acid to obtain a compound of formula (XXXV), Then reacting the compound of formula (XXXV) in the presence of a base to obtain a compound of formula (XXXVI), In this case, the compound of formula (XXXVI) is reacted with the compound of formula (VII) in the presence of an acid activator such as TOTU to obtain a compound of formula (XXXVII), Alternatively, the compound of formula (XXXVI) is reacted with AlCl 3 in the presence of benzene in the first step and the compound of formula (VII) in the presence of an acid activator such as TOTU in the second step to obtain the compound of formula (XXXVIII). And then reacting the compound of formula (XXXVIII) with a compound of formula R 3 -X in which R 3 is as defined for the compound of formula (I) in the presence of a base to obtain a compound of formula (XXXIX) Is a compound of formula (I) wherein X 1 and X 3 are CH, X 2 is N, Z is -NR 7 where R 7 is as defined in formula (I) and W is O And Y is O) <Formula XXXII> <Formula XXXIII> <Formula XXXIV> <Formula XXXV> <Formula XXXVI> <Formula VII> Wherein R 7 is selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are of the invention As defined in the summary. <Formula XXXVII> Wherein A, R 2 , R 7 , Z 1 , m and n are as defined above and X 1 and X 3 each represent a —CH group. <Formula VII> Wherein R 7 is selected from hydrogen, (C 1 -C 6 ) alkyl, aryl (C 1 -C 6 ) alkyl, cycloalkyl, aryl and heteroaryl, and A, R 2 , Z 1 , m and n are of the invention As defined in the summary. <Formula XXXVIII> Wherein A, R 2 , R 7 , Z 1 , m and n are as defined above and X 1 and X 3 each represent a —CH group. <Formula XXXIX> [29" claim-type="Currently amended] A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient. [30" claim-type="Currently amended] Use of a compound of any one of claims 1 to 16 for the manufacture of a medicament for the treatment of a disease or indication associated with the treatment by inhibition of type-13 substrate metalloprotease. [31" claim-type="Currently amended] The method of claim 30, The disease is arthritis, rheumatoid arthritis, osteoarthritis, osteoporosis, periodontal disease, inflammatory bowel disease, psoriasis, multiple sclerosis, heart failure, atherosclerosis, asthma, chronic obstructive pulmonary disease (COPD), age-related macular degeneration (ARMD) and cancer Characteristic uses. [32" claim-type="Currently amended] 31. The use according to claim 30, wherein said disease is arthritis. [33" claim-type="Currently amended] 31. The use according to claim 30, wherein said disease is osteoarthritis. [34" claim-type="Currently amended] 32. The use of claim 31 wherein the disease is rheumatoid arthritis. [35" claim-type="Currently amended] A method of treating a disease or indication associated with treatment with an inverse of MMP-13 comprising administering to a patient an effective amount of a compound according to any one of claims 1 to 15. [36" claim-type="Currently amended] 36. The method of claim 35 wherein The disease is arthritis, rheumatoid arthritis, osteoarthritis, osteoporosis, periodontal disease, inflammatory bowel disease, psoriasis, multiple sclerosis, heart failure, atherosclerosis, asthma, chronic obstructive pulmonary disease (COPD), age-related macular degeneration (ARMD) and cancer Characterized in the treatment method. [37" claim-type="Currently amended] 36. The method of claim 35, wherein said disease is arthritis. [38" claim-type="Currently amended] 36. The method of claim 35, wherein said disease is osteoarthritis. [39" claim-type="Currently amended] The method of claim 40, wherein said disease is rheumatoid arthritis.
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同族专利:
公开号 | 公开日 IL157109D0|2004-02-08| US20020193377A1|2002-12-19| UY27173A1|2002-09-30| ECSP034730A|2003-12-01| JP2004523546A|2004-08-05| MXPA03007248A|2005-02-14| EA200300792A1|2004-02-26| PA8539401A1|2002-10-28| CN1537105A|2004-10-13| OA12550A|2006-06-05| ZA200306008B|2005-01-26| WO2002064572A1|2002-08-22| HU0303164A2|2004-01-28| CZ20032142A3|2004-12-15| IS6886A|2003-07-24| BG108091A|2004-12-30| CA2437122A1|2002-08-22| AR032676A1|2003-11-19| NO20033593L|2003-08-13| EE200300384A|2003-12-15| BR0207268A|2005-03-15| TNSN03045A1|2005-12-23| PE20021005A1|2002-11-27| NO20033593D0|2003-08-13| SK10012003A3|2004-09-08| SV2003000876A|2003-08-19| AP200302841A0|2003-09-30| MA26994A1|2004-12-20| PL367396A1|2005-02-21| EP1368324A1|2003-12-10|
引用文献:
公开号 | 申请日 | 公开日 | 申请人 | 专利标题
法律状态:
2001-02-14|Priority to US26866101P 2001-02-14|Priority to US60/268,661 2002-02-11|Application filed by 워너-램버트 캄파니 엘엘씨 2002-02-11|Priority to PCT/EP2002/001979 2003-09-19|Publication of KR20030074827A
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