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    Having the formula (I); A compound effective to treat a disease associated with a Herns virus, including human cytomegalovirus, Houghs simplex virus, Epstein-Barr virus, Varicella-Zoster virus, human Herns virus-6 and 7, and Kaposi Hough virus : Formula I Wherein R 1 -R 5 is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms , from 3 to 10 carbon atoms, cycloalkyl of 3 to 10 membered heterocycloalkyl of carbon members, aryl, heteroaryl, halogen, -CN, -NO 2, -CO 2 R 6, -COR 6, -OR 6, -SR 6 , -SOR 6 , -SO 2 R 6 , -CONR 7 R 8 , -NR 6 N (R 7 R 8 ), -N (R 7 R 8 ) or WY- (CH 2 ) n -Z At least one of R < 1 > -R < 5 > is not hydrogen; R 2 and R 3 or R 3 and R 4 together form a 3- to 7-membered heterocycloalkyl or a 3- to 7-membered heteroaryl; R 6 and R 7 are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl; R 8 is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, 3 to 10 membered heterocycloalkyl, aryl or heteroaryl , R 7 and R 8 can form a heterocycloalkyl of 3 to 7 members together, and; W is O, NR < 6 > or absent; Y is - (CO) - or - (CO 2 ), or is absent; Z is alkyl of 1 to 4 carbon atoms, -CN, -CO 2 R 6, COR 6, -CONR 7 R 8, -OCOR 6, -NR 6 COR 7, -OCONR 6, -OR 6, -SR 6 , -SOR 6 , -SO 2 R 6 , SR 6 N (R 7 R 8 ), -N (R 7 R 8 ) or phenyl; G is aryl or fused bicyclic heteroaryl; X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J; J is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl; n is an integer of 1 to 6;
    公开号:KR20010089551A
    申请号:KR1020017007053
    申请日:1999-12-06
    公开日:2001-10-06
    发明作者:블룸조너선데이빗；큐란케빈죠셉；디그랜디마틴죠셉；더쉰러셀조지；랭스탠리앨버트；노르톤에밀리부처；로쓰애드마안토니아；오하라브라이언마크
    申请人:이곤 이 버그；아메리칸 홈 푸로닥츠 코포레이션；
    IPC主号:
    专利说明:

    ALPHA-METHYLBENZYL-CONTAINING THIOREA INHIBITORS OF HERPES VIRUSES CONTAINING A PHENYLENEDIAMINE GROUP OF HERPES VIRUS COMPRISING Phenylenediamine Group}
    [1] Eight kinds of viruses that are members of the Houghs virus class have been identified (Roizman, B. 1996. Herpesviridae, 2221-2230. In BN Fields, DM Knipe, and PM Howley (ed.), Fields Virology, 3rd ed. Lippincott-Raven Publishers, Philadelphia, Pa.). Each member of this class is characterized by a transmembrane virus containing a proteinaceous envelope and a nucleocapsid, the latter containing a relatively large double-stranded DNA genome of the virus (i.e., approximately 80-250 kb). Members of the human alpha Huffs virus subclass are neurotropic and include Huffs simplex virus type 1 (HSV-1) and type 2 (HSV-2), and Varicella-Zoster virus (VZV). Human Beta Herns viruses are cytomegalovirus (HCMV), human HERPES virus 6 (HHV-6) and human HERP virus 7 (HHV-7). Gamma Herns virus is lymph-friendly and includes Epstein-Barr virus (EBV) and Kaposi's Huffs virus (HHV-8). Each of these Herns viruses was transformed with HSPs and HSV-2 (Whitley, RJ 1996. Herpes Simplex Viruses, p. 2297-2342, In BNFields, DM Knipe, and PM Howley Ed.), Fields Virology, 3rd Ed., Lippincott-Raven Publishers, Philadelphia, Pa.); (VZV [Arvin, A. 1996. Varicella-Zoster Virus, p. 2547-2585. In BN Fields, DM Knipe, and PM Hawley (eds.), Fields Virology, 3rd ed., Lippincott- Raven Publishers, Philadelphia, Pa.); Epstein-Barr Virus, pp. 2397-2446. In BN Fields, DM Knipe, and PM Howley (ed.), Fields Virology, 3rd ed., Lippincott -Raven Publishers, Philadelphia, Pa.); Pneumonia and retinitis (HCMV [(Britt, WJ, and Alford, CA 1996. Cytomegalovirus, p. 2493-2523. In BN Fields, DM Knipe, and PM Howley (ed.), Fields Virology, 3rd ed., Lippincott-Raven Publishers , Philadelphia, Pa.); HHV-6 (Pellet, PE, and Black, JB 1996. Human Herpesvirus 6, p. 2587-2608. In BN Fields, DM Knipe, and PM Howley (ed. ), Fields Virology, 3rd ed. Lippincott-Raven Publishers, Philadelphia, PA] and HHV-7 [Frenkel, N., and Roffman, E. 1996. Human Herpesvirus 7, p.2609-2622. In BN Fields, DMKnipe Philadelphia, Pa.); and Kaposi's sarcoma (HHV-8 [Neipel, F., Albrecht, JC, and Fleckenstein, B., 1997, and PM Howley (eds.), Fields Virology, 3rd ed., Lippincott-Raven Publishers, Cell-homologous genes in the Kaposi's sarcoma-associated rhadinovirus human herpesvirus 8: determinants of its pathogenicity. J. Virol. 71: 4187-92, 1997. HCMV is considered in more detail below Primary sensation After the infection, the Huff's virus enters the incubation period within the infected individual and exists for the rest of his / her lifetime. The periodic recurrence of the potential virus is clinically relevant: in the case of HSV, May be transferred to the infant, causing skin or eye infections, central nervous system infections, or metastatic infections (ie, multiple organs or systems). Shingles is a clinical sign of resumption of VZV activity. Treatment of HSV and VZV is generally performed using antiviral drugs such as acroclover (Glaxo Wellcome), moxibustion clover (Roche) and Asta, and targets virus-encoded DNA polymerases.
    [2] HCMV is an opportunistic pathogen present everywhere that infects 50-90% of adult populations (Britt, WJ, and Alford, CA 1996. Cytomegalovirus, p. 2493-2523. In BN Fields, DM Knipe, and PM Howley , Fields Virology, 3rd ed., Lippincott-Raven Publishers, Philadelphia, Pa.). Primary infection of HCMV usually has no subjective symptoms, but heterozygous negative mononucleosis is observed. The virus is transferred horizontally by sexual contact, breast milk, and saliva. Uterine transmission of HCMV from pregnant women to the fetus occurs and is often the cause of serious clinical illness. HCMV survives in a latent state for the remainder of his / her lifetime in the infected human. Cell-mediated immunity plays an important role in regulating activity resumption from latency. Damaged cellular immunity resumes the activity of latent HCMV in positive sera.
    [3] HCMV disease is associated with defective or immature cell immunity. There are mainly three classes of people with HCMV disease (see Britt and Alford, 1996). (1) In immunocompromised (AIDS) patients, HCMV is one of the two most common pathogens causing clinical disease (the remainder being Pneumocystis ). Infection of the adrenal glands, lungs, GI tract, and other organs, including the central nervous system, is often reported, but the most common manifestation of HCMV in AIDS is retinitis. 90% of AIDS patients have active HCMV infection; 25-40% (approximately 85,000 patients in the US) have life-or-sight-threatening HCMV disease. HCMV is the cause of death of 10% of humans with AIDS. (2). HCMV activity resumption or reinfection is common in patients with renal, hepatic, cardiac, and genetically different allogeneic bone marrow transplants due to immune system inhibition to reduce the risk of graft rejection. Pneumonia is the most common HCMV disease in these patients and occurs in 70% of these transplant patients. (3) Congenital infection due to HCMV occurs in 1% of all newborns, about 40 K per year. Twenty-five percent of these infants show signs of HCMV disease between the ages of 0-3. HCMV disease is a progressive disease that causes mental retardation and neurodegeneration in childhood. Recent studies suggest that treatment with anti-HCMV drugs may reduce the mortality of these children.
    [4] Many antiviral drugs are currently on the market (Bron, D., R. Snoeck, and L. Lagneaux, 1996. New insights into the pathogenesis and treatment of cytomegalovirus. Exp. Opin. Invest. Drugs 5: 337-344; Crumpacker , 1996. Ganciclovir. New Eng. J. Med. 335: 721-729; Sachs, S., and F. Alrabiah. 1996. Novel herpes treatments: a review Exp. Opin. Invest. Drugs 5: 169-183 ). These include moxibustion clovers (Roche), nucleoside analogs with hematopoietic cytotoxicity; Astra, a pyrophosphate analog with renal toxicity; And try a forer (Gilead), nucleoside phosphonates with acute renal toxicity. Each of these drugs targets a virus-encoded DNA polymerase and is typically administered intravenously due to its low bioavailability, and as noted above, is a significant source of toxicity. Clinically occurring ganoderma clover-resistant mutants are often try-forvers and cross-resistant. Thus, it is safer (i. E., Less toxic) that oral bioavailability antiviral drugs are needed for new viral targets.
    [5] It is known that phenylthiourea has been utilized in various pharmaceutical fields. WO 97/40028 to Armistead et al. Teaches phenylurea and thiourea as inosine monophosphate dehydrogenase (IMPDH) enzyme inhibitors taught to play an important role in viral replication disorders such as Houghs.
    [6] WO 96/25157 to Widdowson et al. Teaches phenylurea and thiourea compounds of the following formula to treat diseases mediated by chemokines, interleukin-8.
    [7]
    [8] U.S. Patent No. 5,593,993 to Morin, Jr., et al. Teaches certain phenylthiourea compounds to inhibit AIDS treatment and replication of HIV-related viruses.
    [9] Accordingly, the object of the present invention is to provide a method for the treatment of hepatitis B virus, including human cytomegalovirus, Huffs simplex virus, Epstein-Barr virus, Varicella-Zoster virus, human Herns virus- Or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment and /
    [10] In accordance with the present invention there is provided a compound of the formula: [image] or a pharmaceutically acceptable salt thereof, wherein:
    [11]
    [12] In this formula,
    [13] R 1 -R 5 is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, 10 carbon atoms, cycloalkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, halogen, -CN, -NO 2, -CO 2 R 6, -COR 6, -OR 6, -SR 6 , -SOR 6, -SO 2 R 6 , -CONR 7 R 8, -NR 6 n (R 7 R 8), -N (R 7 R 8) or WY- (CH 2) n -Z ( R 1 - And at least one of R < 5 > is not hydrogen; R 2 and R 3 or R 3 and R 4 together form a 3- to 7-membered heterocycloalkyl or a 3- to 7-membered heteroaryl;
    [14] R 6 and R 7 are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl;
    [15] R 8 is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, 3 to 10 membered heterocycloalkyl, aryl or heteroaryl ,
    [16] R 7 and R 8 taken together may form a 3- to 7-membered heterocycloalkyl;
    [17] W is O, NR < 6 > or absent;
    [18] Y is - (CO) - or - (CO 2 ), or is absent;
    [19] Z is alkyl of 1 to 4 carbon atoms, -CN, -CO 2 R 6, CO 6, -CONR 7 R 8, -OCOR 6, -NR 6 COR 7, -OCONR 6, -OR 6, -SR 6 , -SOR 6 , -SO 2 R 6 , SR 6 N (R 7 R 8 ), -N (R 7 R 8 ) or phenyl;
    [20] G is alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, halogen, -CN, -NO 2, -CO 2 R 6, -COR 6, -OR 6, -SR 6, -SOR 6, - SO 2 R 6, -CONR 7 R 8, -NR 6 n (R 7 R 8), -N (R 7 R 8) or WY- (CH 2) n aryl optionally substituted with one or more body refinancing selected from -Z Or
    [21] G is fused bicyclic heteroaryl;
    [22] X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J;
    [23] J is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl;
    [24] n is an integer of 1 to 6;
    [25] In some preferred embodiments of the invention, R 1 -R 5 are independently alkyl of 1 to 6 carbon atoms, halogen, perhaloalkyl of 1 to 6 carbon atoms, OR 6 or N (R 7 R 8 ). Preferably, R 1 -R 5 1 to 3 of is not hydrogen. In a more preferred embodiment of the invention R < 4 > is halogen, cyano or trifluoromethyl.
    [26] In some aspects of the invention, G is substituted. In a preferred embodiment of the invention G is 2-fluorophenyl. In another preferred embodiment of the invention G is benzofuran, isoquinoline or quinoline.
    [27] In some embodiments of the present invention, X is a bond, C 1 -C 4 alkyl or CH (J), wherein J is C 1 -C 6 alkyl. Preferably, if X is C 1 -C 4 alkyl, then alkyl is straight chain alkyl. When X is CH (J), J is preferably methyl.
    [28] Preferred compounds of the present invention are the following compounds and their pharmaceutical salts.
    [29] - {4- [3- (1-benzofuran-2-yl-ethyl) -thioureido] -phenyl} -2- trifluoromethylbenzamide,
    [30] 4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -benzamide,
    [31] (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [32] 1-carboxylic acid {4- [3- (1-benzofuran-2-yl-ethyl) -thioureido] -phenyl}
    [33] (4- {3- [1- (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [34] (4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [35] 2-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [36] 2-carboxylic acid (4- {3- [1- (1-benzofuran-2-yl-ethyl) -thioureido] -phenyl}
    [37] 2-carboxylic acid (4- {3- [1- (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [38] 2-carboxylic acid (4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [39] (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [40] (4- {3- [1- (1-benzofuran-2-yl-ethyl) -thioureido] -phenyl} -amide,
    [41] 3-carboxylic acid (4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [42] (4- {3- [1- (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [43] (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [44] 4-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [45] 6-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [46] 8-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [47] - (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -2-trifluoromethyl-
    [48] 2-Cyano-N- (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -benzamide,
    [49] - (3-chloro-4-isobutoxy-phenyl) -thioureido] -phenyl} -2-fluoro-benzamide,
    [50] 2-fluoro-N- {4- [3- (3-fluoro-4-methoxy-phenyl) -thioureido] -phenyl}
    [51] - (3-chloro-4- (2-methoxy-ethoxy) -phenyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    [52] 2-fluoro-N- {4- [3- (3-fluoro-4-methyl-phenyl) -thioureido] -phenyl}
    [53] 2-fluoro-N- {4- [3- (4-methoxy-3-trifluoromethyl-phenyl) -thioureido] -phenyl} -benzamide,
    [54] -Thioureido] -phenyl} -2-fluoro-benzamide, < / RTI >
    [55] - (3-chloro-4-methoxy-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    [56] - {4- [3- (5-chloro-2-hydroxy-phenyl) -thioureido] -phenyl} -2-fluoro-benzamide,
    [57] Yl} -thioureido] -phenyl} -2-fluoro-benzamide, < RTI ID = 0.0 &
    [58] 2-Fluoro-N- {4- [3- (4-methyl-3-trifluoromethyl-phenyl) -thioureido] -phenyl} -benzamide,
    [59] (S) -N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    [60] - (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    [61] 2-fluoro-ethoxy) -phenyl] -thioureido} -phenyl) -benzamide < / RTI > ,
    [62] Phenyl} -thioureido] -phenyl} -2-fluoro-benzamide, N- {4- [3-
    [63] (4- {3- [1- (4-Dimethylsulfamoyl-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    [64] Phenyl] -ethyl} -thioureido) -phenyl] -benzamide, < / RTI > < RTI ID = 0.0 &
    [65] - (2, 2-trifluoro-ethoxy) -phenyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    [66] 2-fluoro-N- {4- [3 - ((1S) -1-p-tolyl-ethyl) -thioureido] -phenyl}
    [67] 2-fluoro-N- {4- [3 - ((1 R) -1-p-tolyl-ethyl) -thioureido] -phenyl}
    [68] 2-Fluoro-N- {4- [3 - ((1S) -1-phenyl- ethyl) -thioureido] -phenyl} -benzamide,
    [69] (4-chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    [70] - (4-chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    [71] 2-fluoro-N- {4- [3 - ((1 R) -1-phenyl- ethyl) -thioureido] -phenyl}
    [72] (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -phenyl) -2-methoxy-
    [73] Yl} -thioureido] -phenyl} -2-methoxy-benzamide, < RTI ID = 0.0 &
    [74] N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-methoxy-
    [75] - (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -benzamide,
    [76] - (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -4-trifluoromethyl-benzamide,
    [77] (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -benzamide,
    [78] (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    [79] - (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -4-fluoro-benzamide,
    [80] Phenyl) -ethyl] -thioureido} -phenyl) -2-methoxy-benzamide, < RTI ID = 0.0 &
    [81] - (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-methoxy-benzamide,
    [82] (Trifluoromethyl) phenyl] ethyl} amino) carbothioyl] amino} phenyl) benzamide, 2-fluoro-N-
    [83] (4- {3 - [(1S) -1- (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [84] (4- {3 - [(1S) -1- (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [85] (4- {3 - [(1S) -1- (4-chloro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    [86] (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide, and
    [87] Amino] phenyl} -1-naphthyl) ethyl] amino} carbothioyl) amino] -1H- Phenyl} -1-isoquinolinecarboxamide,
    [88] And pharmaceutical salts thereof.
    [89] There is no definition otherwise, and the terms used herein have the following meanings.
    [90] Alkyl, as used herein, refers to straight or branched chain lower alkyl of 1 to 6 carbon atoms. Typical alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl and hexyl.
    [91] Alkenyl as used herein refers to straight or branched chain lower alkyl of 2 to 6 carbon atoms containing at least one carbon-carbon double bond. The alkenyl includes a vinyl group.
    [92] Alkynyl as used herein refers to straight or branched chain lower alkyl of 2 to 6 carbon atoms containing at least one carbon-carbon triple bond.
    [93] The alkyl, alkenyl and alkynyl groups of the present invention may be optionally substituted.
    [94] Cycloalkyl refers to a saturated mono or bicyclic ring system of 3 to 10 carbon atoms. Typical cycloalkyl groups include cyclopentyl, cyclohexyl and cycloheptyl. The cycloalkyl group of the present invention may be substituted or unsubstituted.
    [95] Heterocycloalkyl refers to a saturated mono- or bicyclic ring system of 3 to 10 members having 1 to 3 heteroatoms selected from N, S and O, and includes aziridinyl, azetidinyl, imidazolidinyl, mor But are not limited to, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, pyrimidinyl, The heterocycloalkyl group of the present invention may be substituted or unsubstituted.
    [96] Aryl as used herein refers to an aromatic mono or bicyclic ring of 5 to 10 carbon atoms. Typical aryl groups include phenyl, naphthyl, and biphenyl. The aryl group of the present invention may be substituted or unsubstituted.
    [97] Heteroaryl as used herein refers to a 5-10 membered aromatic mono or bicyclic ring having 1 to 3 heteroatoms selected from N, S, or O, and includes thiazolyl, thiadiazolyl, oxazolyl, furyl, But are not limited to, indolyl, benzothiazolyl, benzotriazolyl, benzodioxyl, indazolyl, and benzofuryl. Preferred heteroaryls are selected from quinolyl, isoquinolyl, naphthalenyl, benzofuranyl, benzothienyl, indolyl, pyridyl, pyrazinyl, thienyl, furyl, pyrrolyl, isoxazolyl, oxazolyl, isothiazolyl , Thiazolyl, pyrazolyl, triazolyl, thiadiazolyl, and imidazolyl. The heteroaryl group of the present invention may be substituted or unsubstituted.
    [98] Perhaloalkyl refers to an alkyl group of one to six carbon atoms wherein three or more hydrogens are substituted with a halogen.
    [99] The phenyl used herein refers to a six membered aromatic ring.
    [100] Halogen used herein refers to chlorine, bromine, iodine, and fluorine.
    [101] Unless otherwise specified, the substituents may be unsubstituted and have 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms, heterocycloalkyl of 1 to 6 members, perhalo of 1 to 6 carbon atoms, Alkyl, amino, azido, hydroxy, alkylamino, dialkylamino, aryl or heteroaryl.
    [102] The carbon number refers to the number of carbon atoms in the carbon backbone and does not include carbon atoms present in substituents such as alkyl or alkoxy substituents.
    [103] Where terms are used in combination, the definitions of each individual part of the combination shall apply unless otherwise specified. For example, alkylcycloalkyl is an alkyl-cycloalkyl group, wherein the alkyl and cycloalkyl are as previously defined.
    [104] Pharmaceutically acceptable salts include those of the above formula and pharmaceutically acceptable salts such as phosphoric acid, sulfuric acid, hydrochloric acid, hydrobromic acid, citric acid, maleic acid, succinic acid, fumaric acid, acetic acid, lactic acid, nitric acid, sulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, Is an acid addition salt that may be formed from an acceptable acid.
    [105] The compounds of the present invention contain chiral centers and provide various stereoisomeric forms of compounds such as racemic mixtures and individual optical isomers. In some preferred embodiments of the present invention, the compounds of the present invention are substantially pure optical isomers. Substantially pure refers to a composition containing at least 75% of the desired isomer and may include only 25% of the undesired isomer. In a more preferred embodiment, the pure optical isomer has 90% or more of the desired isomer. In some preferred embodiments, when the target is VZV, the (S) isomer is preferred. The individual isomers may be prepared by direct preparation, by asymmetric or stereospecific synthesis, or by conventional separation of the optical isomers from the racemic mixture.
    [106] The skilled artisan can prepare the compounds of the present invention by organic synthesis by the methods described below using readily available preparations and starting materials, unless otherwise indicated. The compounds of the present invention are prepared according to the following scheme.
    [107] The novel compounds of the present invention are prepared according to the following reaction schemes.
    [108] In the case of Method 31 (2 and 3, top) and 34 (4 and 5, bottom), the reaction is carried out in a pure solvent or in a suitable solvent such as tetrahydrofuran, acetonitrile, ethyl acetate, dichloromethane, or N, N-dimethylformamide The appropriately substituted amine 2, wherein substituents R 1 -R 5 , and X are as previously described, is reacted with an appropriately substituted isothiocyanate 3, wherein substituent G is as previously described, . Likewise, by reacting an appropriately substituted isothiocyanate 4 (where substituents R < 1 > -R < 5 > and X are as hereinbefore defined) with an appropriately substituted aniline 5 wherein substituent G is as previously described The desired thiourea 1 is obtained.
    [109] Methods 31 and 34
    [110]
    [111] Alternatively, the appropriately substituted thiourea 1 is reacted with 1 mole equivalent of 1,1'-thiocarbonyldiamidazole or 1,1'-carbonyldiimidazole in a suitable solvent such as dichloromethane and tetrahydrofuran or mixtures thereof at room temperature or Di- (1,2,4) -triazole or 1,1'-carbonyl-di- (1, 2, 3, , 4) -triazole in the presence of 1 molar equivalent of anilines 2 and 5, wherein R 1 -R 5 and G are as previously described, as described in Methods 32 and 33.
    [112] Method 32, 33
    [113]
    [114] In certain cases, subsequent chemical modification of the final thiourea 1 was required. This method, Methods 35-39, is summarized below.
    [115]
    [116] Wherein at least one of R 1 -R 5 is 1-hydroxyethoxy or carboxy-methoxy, thiourea 1 in which G is as hereinbefore defined and X is as defined above is reacted at room temperature Can be prepared from the corresponding alkyl esters by alkaline hydrolysis with aqueous sodium or potassium hydroxide in a suitable solvent such as methanol, tetrahydrofuran or mixtures thereof.
    [117] Thiourea 1 in which at least one of R 1 -R 5 is 1-acyloxyethoxy or methanesulfonoxyethoxy, G is as defined above and X is a bond is prepared according to methods 37 and 38, By acylation with a suitable acylating agent such as benzoic acid chloride or methanesulfonic acid chloride in the presence of a suitable tertiary amine base such as triethylamine or diisopropylethylamine in a suitable solvent such as dichloromethane, Ethoxy < / RTI > derivatives.
    [118] Thiourea 1, wherein at least one of R 1 -R 5 is 1-aminoethoxy, G is as defined above and X is a bond, is reacted at room temperature according to Method 39 in a suitable solvent such as tetrahydrofuran and water Can be prepared from the corresponding 1-methanesulfonoxy-ethoxy derivatives by reaction with a suitable secondary amine such as dimethylamine in a mixture.
    [119] Thiourea 1 in which at least one of R 1 -R 5 is 1-aminoalkyl, G is as defined above and X is a bond is reacted with a chlorinating agent in a suitable solvent such as methanol, 1 < / RTI > tin in the presence of a base.
    [120] The intermediate isothiocyanates 3 and 4 shown in Methods 31 and 34 above are essentially prepared by the methods described in Staab, HA, and Walther, G. Justus Liebigs Ann. Chem. (Wherein R 1 -R 5 and G (in this case, R 1 -R 5 and G (2), respectively) in a suitable solvent such as dichloromethane and tetrahydrofuran or mixtures thereof, Is as hereinbefore defined and X is as hereinbefore defined, with 1 molar equivalent of 1,1'-thiocarbonyldiimidazole.
    [121] Method 41
    [122]
    [123] Intermediates 2 and 5 can be prepared according to the following protocol:
    [124] According to methods 1A-1G, amine 2, wherein R 1 -R 5 is as defined above and X is as defined above, and amine 5 are known to those skilled in the art and are described in RJ Lindsay, Comprehensive Organic Chemistry (ed. Sutherland), Volume 2, Chapter 6.3.1, Aromatic Amines, 1979]. This process
    [125] a) iron powder and a strong acid such as hydrochloric acid (Method 1A) in an alcohol solvent such as methanol or ethanol in a pure solvent or at a temperature ranging from room temperature to the reflux temperature of the solvent;
    [126] b) iron powder and glacial acetic acid (Method B) in a pure solvent or in an alcohol solvent such as methanol or ethanol, at a temperature ranging from room temperature to the reflux temperature of the solvent;
    [127] c) an iron powder and aqueous ammonium chloride (Method C) in a pure solvent or an alcoholic solvent such as methanol or ethanol, at a temperature ranging from room temperature to the reflux temperature of the solvent;
    [128] d) tin and strong inorganic acids such as hydrochloric acid (Method D) in a pure solvent or an alcoholic solvent such as methanol or ethanol, at room temperature to the reflux temperature of the solvent;
    [129] e) when R 1 -R 5 is selected from Cl, Br, i, - (OSO 2 ) -CF 3 , or - (OSO 2 ) -1- (4-methylphenyl), such as methanol, ethanol or ethyl acetate By catalytic reduction (Method E) using palladium on carbon and hydrogen under atmospheric pressure in an appropriate solvent, or;
    [130] f) when R 1 -R 5 and R 9 -R 12 are selected from Cl, Br, I, - (OSO 2 ) -CF 3 , or - (OSO 2 ) -1- (4-methylphenyl) By catalytic reduction (method E) using palladium on cyclohexene and carbon in a suitable solvent such as ethanol, at room temperature to the reflux temperature of the solvent;
    [131] g) in an alcohol solvent at a temperature ranging from room temperature to the reflux temperature of the solvent, aqueous sodium hydrosulfite (Method 1G)
    [132] To reduce nitrobenzene to form aniline.
    [133] Alternatively, according to Method 3A-3C, an amine 2, wherein R 1 -R 5 is as defined above and X is as defined above, and aniline 5 are known to those skilled in the art and described in Greene, Protective Can be prepared by cleaving an amide and an aniline nitrogen-carbon bond of a carbamate derivative of these anilines according to various procedures described in " Groups in Organic Synthesis volume 2, Chapter 7, 1991]. This process includes the following:
    [134] a) exposing the appropriately substituted arylamino-tert-butyl-carbamate to a strong acid such as trifluoroacetic acid in a pure solvent or a suitable solvent such as dichloromethane at 0 < 0 > C to room temperature (Method 3A);
    [135] b) Arylamino- (2-trimethylsilylethyl) -carbamate, suitably substituted in aqueous acetonitrile or tetrahydrofuran or mixtures thereof, at room temperature to the reflux temperature of the solvent, is reacted with a base such as tetrabutylammonium fluoride or potassium fluoride Exposure to fluoride ion (Method 3B), or;
    [136] c) exposing the arylamino-trifluoroacetamide, suitably substituted in an alcoholic solvent such as methanol or ethanol, to a strong base such as sodium or potassium hydroxide or sodium or potassium carbonate at a temperature from room temperature to the reflux temperature of the solvent (Method 3C).
    [137] Alternatively, according to Method 11, the amine 2 in which R 1 -R 5 is as defined above, X corresponds to a bond and at least one of the R 1 -R 5 substituents is defined as vinyl is prepared essentially as described in V. According to the procedure of Farina and GP Roth in Advances in Metal-Organic Chemistry, Vol. 5, 1-53, 1996), in a suitable solvent such as tetrahydrofuran or N-methylpyrrolidinone at room temperature to the reflux temperature of the solvent Palladium catalyst such as dibenzylideneacetone-bipalladium, and bromo or iodo-anilines suitably substituted with ligands such as triphenylarsine, for example 3-chloro-4-iodo-aniline and vinyl Can be prepared by palladium catalyzed coupling of trialkyltin, for example tributylvinyltin.
    [138] Alternatively, according to Method 42, amine 2, wherein R 1 -R 5 is as defined above, X is as defined above and at least one of R 2 or R 4 is defined as dialkylamino, (Dibenzylideneacetone) palladium (II) in an appropriate solvent such as tetrahydrofuran or toluene at a temperature from room temperature to 100 < 0 > C, according to the procedure of JF Hartwig and J. Louie Tetrahedron Letters 36 (21), 3609 And using a strong base such as lithium bis- (trimethylsilyl) amide, such as lithium bis- (trimethylsilyl) amide in a sealed tube, with a secondary amine For example, by palladium catalyzed amination of substituted 3- or 5-bromo- or iodo-anilines, for example 3-amino-5-bromobenzotrifluoride.
    [139] Alternatively, according to Method 43, amine 2, wherein R 1 -R 5 is as defined above and X corresponds to a bond and at least one of R 2 or R 4 is defined as alkyl, is reacted at a temperature from room temperature to the reflux temperature of the solvent with tetrahydrofuran Conditions using palladium catalysts such as [1,1'-bis (diphenylphosphino) ferrocene] palladium (II) chloride-dichloromethane complex in a suitable solvent such as tetrahydrofuran and the like and 9-borabicyclo [3.3.1] An appropriately substituted 3- or 5-bromo- or iodo-aniline, such as 3-amino-5-bromobenzotrifluoride, with an alkene, in the presence of a suitable base such as aqueous sodium hydroxide Palladium catalyzed alkylation.
    [140] Acyl and carbamoylamine derivatives used as starting materials in methods 3A-3C can be prepared according to various procedures known to those skilled in the art and described in Greene, Protective Groups in Organic Synthesis volume 2. Chapter 7, 1991 Lt; / RTI > can be prepared by derivatisation of an amine corresponding to that described in 2A-2G. This process includes the following:
    [141] a) in an appropriate solvent such as acetone, tetrahydrofuran, dimethylformamide, dichloromethane and the like in the presence or in the absence of at least one equivalent of a tertiary amine such as triethylamine or N, N-diisopropylethylamine, Reacting an appropriately substituted amine with di-tert-butyl-dicarbonate (Method 2A) to yield the corresponding arylamino-tert-butyl-carbamate;
    [142] b) in the presence of a tertiary amine such as triethylamine or diisopropylethylamine in an appropriate solvent such as dimethylformamide at room temperature, an appropriately substituted aniline is reacted with 1- [2- (trimethylsilyl) ethoxycarbonyl -Oxy] benzotriazole (Method 2B) to yield the corresponding arylamino- (2-trimethylsilylethyl) -carbamate;
    [143] c) in a suitable solvent such as a pure solvent or a suitable solvent such as tetrahydrofuran, dimethylformamide, dichloromethane, pyridine and the like, in the presence of at least one molar equivalent of a tertiary amine base such as triethylamine or N, N-diisopropylethyl- Reacting the resulting aniline with a carboxylic acid chloride or acid anhydride (Method 2C) to produce the corresponding arylaminoamide;
    [144] d) in the absence of one or more molar equivalents of a tertiary amine such as triethylamine or N, N-diisopropylethylamine in a pure solvent or a suitable solvent such as tetrahydrofuran, 1,4-dioxane and the like, Within the reflux temperature range of the solvent, the appropriately substituted nitroaniline is reacted with the carboxylic acid chloride (Method 2D) to produce the corresponding nitroarylaminoamide;
    [145] e) Synthesis of benzotriazol-1-yloxy-tris- (dimethylamino) -phosphonium hexafluorophosphate, 2- (lH-benzotriazol- l-yloxy) -1,1,3,3- In the presence of a coupling agent such as methyluronium hexafluorophosphate, dicyclohexylcarbodiimide and the like and a tertiary amine such as triethylamine or diisopropylethylamine in an appropriate solvent such as dichloromethane, dimethylformamide and the like, At room temperature, reacting an appropriately substituted aniline with a carboxylic acid (Method 2E) to produce the corresponding arylaminoamide;
    [146] in f) pyridine and a suitable solvent, such as dichloromethane, dimethylformamide, etc. in the presence of a suitable base such as, from 0 ℃ to room temperature range, arylamino -tert- butyl- appropriately protected aniline such as carbamate, etc. (where R 1 Wherein at least one of the -R 12 substituents is defined as -WY- (CH 2 ) n -Z and W, Y and Z are as defined above, with a carboxylic acid anhydride (Method 2F) to produce the corresponding carboxylic acid ester ;
    [147] g) in a suitable solvent such as acetone, tetrahydrofuran, dimethylformamide, dichloromethane and the like in the absence of one or more molar equivalents of a tertiary amine, such as triethylamine or N, N-diisopropylethylamine, Reacting an appropriately substituted aniline (wherein at least one of R 1 -R 5 is defined as hydroxyl) with di-tert-butyl-dicarbonate (Method 2G) to provide the corresponding arylamino-tert -Butyl-carbamate. ≪ / RTI >
    [148] Nitrobenzene intermediates that are eventually converted to amines 2 and 5 by the process shown in Methods 1A-1G above can be prepared according to Methods 4A, 4C, 4E-4F.
    [149] In methods 4A, 4C and 4E-4H, it is converted eventually to amine 2, R 2 and R 4 are as hereinbefore defined and R 1 , R 3 and / or R 5 is alkoxy, thioalkoxy, Sulfinyl, and dialkylamino can be prepared by reacting a nitrobenzene intermediate, such as 2-, 4-, and / or 6-fluoro-, chloro-, bromo-, iodo-, trifluoro- Or by nucleophilic substitution of (4-methylphenyl) sulfonyl-substituted nitrobenzene:
    [150] a) in a suitable solvent such as a pure solvent or a suitable solvent such as tetrahydrofuran, dioxane, acetonitrile, N, N-dimethylformamide or dimethylsulfoxide, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium hydride Halo-or sulfonate esters of nitrobenzene or benzonitrile with an appropriately substituted 2- or 4-halo- or sulfonate ester in the presence or absence of one or more equivalents of a base such as hydrochloric acid, Reaction of alcohol;
    [151] b) in a suitable solvent such as a pure solvent or tetrahydrofuran, dioxane, acetonitrile, N, N-dimethylformamide or dimethylsulfoxide at a temperature ranging from room temperature to the reflux temperature of the solvent, The reaction of preformed sodium, lithium or potassium phenoxide with a 2- or 4-halo- or sulfonate ester;
    [152] c) in a suitable solvent such as a pure solvent or tetrahydrofuran, dioxane, acetonitrile, N, N-dimethyl-formamide or dimethylsulfoxide at a temperature ranging from room temperature to the reflux temperature of the solvent, Reaction of the resulting 2- or 4-halo- or sulfonate ester with ammonia, primary or secondary amine (Method 4C, F);
    [153] d) in a suitable solvent such as tetrahydrofuran, at a temperature ranging from 0 < 0 > C to the reflux temperature of the solvent, with an appropriately substituted 2- or 4-halo- or sulfonate ester of nitrobenzene or benzonitrile, Reaction with potassium salt (Method 4G), or;
    [154] e) in a suitable solvent such as a pure solvent or tetrahydrofuran, dioxane, acetonitrile, N, N-dimethylformamide or dimethylsulfoxide at a temperature ranging from room temperature to the reflux temperature of the solvent, Following the reaction of the 2- or 4-halo- or sulfonate ester with sodium sulfide, the alkyl halide is added directly to the reaction mixture (Method 4E).
    [155] Alternatively, in the case of Processes 5C and 6, the nitrobenzene intermediate which is finally converted to the amine 2, wherein at least one of the R 1 -R 5 is defined as alkoxy, is reacted with the corresponding substituted hydride Roxy-nitrobenzene: < RTI ID = 0.0 >
    [156] a) in the presence of a base such as potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, potassium hydride or a base such as sodium hydride, in the presence of a base such as acetone, N, N-dimethylformamide, tetrahydrofuran Nitrobenzene is reacted with an alkyl halide or dialkyl sulfonate ester (Method 5C) in an appropriate solvent such as, for example, tetrahydrofuran or dimethyl sulfoxide, at a temperature ranging from room temperature to the reflux temperature of the solvent;
    [157] b) Hydroxy-nitrobenzene is reacted with an alkyl alcohols in an anhydrous aprotic solvent such as diethyl ether or tetrahydrofuran, at a temperature ranging from 0 < 0 > C to the reflux temperature of the solvent, basically according to the method described in Mitsunobu, O, Synthesis 1981, , Triphenylphosphine, and dialkyl azadicarboxylate, for example, diethyl azodicarboxylate (method 6).
    [158] Additionally, in the case of the methods 5A and 5E, the carbamoylamine derivative used as a starting material in the method 3A-3C, which is finally converted to amine 2 (wherein at least one of R 1 -R 5 is defined as alkoxy) In the presence of a suitable base such as potassium carbonate in an appropriate solvent such as acetone, toluene or N, N-dimethylformamide, at a temperature ranging from room temperature to the reflux temperature of the solvent, to the corresponding substituted hydroxyarylamino-tert-butyl- Halide, trifluoromethane-sulfonate, 4-methylbenzenesulfonate, dialkylsulfonate, ethylene carbonate, and the like.
    [159] Alternatively, in the case of the methods 7A-G, the nitrobenzene intermediate which is finally converted to the amine 2 (R 1 and / or R 3 is alkoxy and R 2 and / or R 4 is halogen and X corresponds to the bond) Can be prepared by standard halogenation reactions comprising:
    [160] a) reaction of 2- or 4-hydroxy-nitrobenzene with aqueous sodium hippuronite at room temperature (methods 7A and 7B);
    [161] b) Reaction of 2-hydroxy-4-methoxy or 2,4-dimethoxynitrobenzene with bromine in the presence or absence of trifluoroacetate in a suitable solvent such as chloroform, dichloromethane, 7C and 7D);
    [162] c) the reaction of 2,4-dimethoxynitrobenzene with benzyltrimethylammonium dichloroiodate (Method 7E) in an appropriate solvent such as glacial acetic acid in the presence of anhydrous zinc chloride at room temperature;
    [163] d) reacting 2-hydroxy-4-methoxynitrobenzene with benzyltrimethyl-ammonium dichloroiodate in a suitable solvent mixture such as dichloromethane and methanol in the presence of sodium bicarbonate at room temperature (Method 7F);
    [164] e) Reaction of 2,4-dimethoxynitrobenzene with 3,5-dichloro-1-fluoropyridine triflate in a suitable solvent such as tetrachloroethane at room temperature to the reflux temperature of the solvent (Method 7G).
    [165] In the case of Method 8, the nitrobenzene intermediate, which is finally converted to amine 2, wherein R 4 = -CF 3 -, R 1 -R 3 and R 5 -R 8 are as defined above and X corresponds to a bond, In an appropriate solvent such as N, N-dimethylformamide, in the presence of a cuprous iodide and potassium fluoride in a sealed reaction vessel, at a temperature ranging from room temperature to the reflux temperature of the solvent, - Nitrobenzene with trimethyl (trifluoromethyl) silane.
    [166] In the case of methods 19A and 19B, finally the amine 2, where R 4 = -HNCOCH 2 NR 7 R 8 or -HNCOCH 2 SR 6 , and R 1 -R 3 and R 5 are as defined above and X corresponds to a bond ) Can be converted to the corresponding substituted 4- (N-chloroacetyl) -nitroaniline in an appropriate solvent such as tetrahydrofuran and / or a mixture of water, at a temperature ranging from room temperature to the reflux temperature of the solvent, , Morpholine, or the like, or in the presence of a suitable base such as sodium or potassium carbonate in an appropriate solvent such as tetrahydrofuran, 1,4-dioxane or the like at a temperature ranging from room temperature to the reflux temperature of the solvent Can be prepared by reacting the corresponding substituted 4- (N-chloroacetyl) -nitroaniline with the appropriate thiol.
    [167] In the case of Method 25, the nitrobenzene intermediate finally converted to amine 2, wherein at least one of R 1 -R 5 is defined as triflate and X corresponds to a bond, is reacted with triethylamine or diisopropyl-ethylamine In the presence of a tertiary amine such as dichloromethane, in a suitable solvent such as dichloromethane, at a temperature ranging from 0 < 0 > C to room temperature, by reacting the corresponding phenol with trifluoromethane-sulfonic anhydride.
    [168] 9 how, in the case of 9B and 10, a method is used as a starting material in 3A-3C, cover that is finally converted into amines 2 (where at least one substituent R 1 -R 5 is defined as an alkyl phenyl alcohol or alkylsulfinyl search) Molecular amine derivatives are prepared by reacting the appropriate 4-alkylthioacylarylamino or carbamoylarylamino derivatives with an appropriate oxidizing agent such as dimethyloxirane or sodium perodate in a suitable solvent mixture such as acetone and dichloromethane or water at room temperature ≪ / RTI >
    [169] In the case of Method 12, it is used as the starting material in Methods 3A-3C and finally reacted with amine 2 where R 4 is defined as 1-hydroxyethyl, R 1 -R 3 and R 5 are as defined above, Is converted to the corresponding 4-vinylcarbamoyl aniline with sodium borohydride in the presence of mercuric acetate in a suitable solvent such as tetrahydrofuran, 1,4-dioxane and water, at room temperature, Lt; / RTI >
    [170] In the case of Method 13, it is used as the starting material in Methods 3A-3C and finally the amine 2, wherein R 4 is defined as 2-hydroxyethyl, R 1 -R 3 and R 5 are as defined above, Is converted in the presence of glacial acetic acid in an appropriate solvent such as tetrahydrofuran, 1,4-dioxane, and the like, in the range of 0 < 0 > C to room temperature, to the corresponding 4-vinylcarbamoyl aniline with sodium boron ≪ / RTI > hydride.
    [171] In the case of Method 14, the starting materials used in Methods 3A-3C and finally the amine 2 where R 4 is defined as 1- azidethyl, R 1 -R 3 and R 5 are as defined above, Carbamoylamine derivatives which are converted to the corresponding compounds of formula (I), in the presence of a dialkyl azodicarboxylate, such as diethyl azodicarboxylate and triphenylphosphine, in a suitable solvent mixture, for example tetrahydrofuran and dichloro (1-hydroxyethyl) carbamoyl aniline with hydrazoic acid in the presence of a base, e.g.
    [172] In Method 15, it is used as the starting material in Methods 3A-3C and finally the amine 2 where R 4 is defined as 3-dimethylaminoprop-1-enyl and R 1 -R 3 and R 5 are as defined above And X is as defined hereinbefore) can be reacted with bis (triphenylphosphine) palladium (II) chloride and a suitable reducing agent such as triethylamine or diisopropylethylamine in a suitable tertiary amine solvent, Iodocarbamoyl aniline with 1-dimethylamino-2-propyne in the presence of a copper iodide and at a temperature ranging from room temperature to the reflux temperature of the solvent.
    [173] In the case of Method 16, it is used as starting material in Methods 3A-3C and finally with amine 2 where R 4 is defined as 3-dimethylaminoacryloyl, R 1 -R 3 and R 5 are as defined above, and X is Bond), can be prepared by reacting the corresponding 4- (3-dimethylaminoprop-1-ynyl) carbamoyl aniline in a suitable solvent mixture, such as dichloromethane and methanol, at 0 ≪ RTI ID = 0.0 > acid. ≪ / RTI >
    [174] In the case of Processes 17 and 18, the starting materials used in Methods 3A-3C and finally the amine 2, wherein R 4 is defined as 4-isoxazol-5-yl or 4- (1H-pyrazol-3-yl) Wherein R 1 -R 3 and R 5 are as defined above and X is a bond, can be prepared by reacting the corresponding 4- ( 3-dimethylamino-acryloyl) carbamoyl aniline with hydroxylamine hydrochloride or hydrazine hydrate.
    [175] In Method 20, used as starting materials in Methods 3A-3C and finally in the presence of amine 2, where R 4 = -HNCO 2 Z, R 1 -R 3 and R 5 and Z are as defined above and X corresponds to a bond, Is reacted with a corresponding 4-aminocarbamoyl aniline in a suitable solvent mixture such as tetrahydrofuran and dichloromethane at a temperature ranging from room temperature to the reflux temperature of the solvent to 1,1-carbonyl-di- (1 , 2,4) -triazole with an appropriately substituted alcohol.
    [176] In the case of Processes 26 and 30, it is used as the starting material in Processes 3A-3C and finally converted to the amine 2, wherein at least one of the substituents R 1 -R 5 is defined as dialkylamino and X is as defined above The carbamoylamine derivative can be reacted with a suitably substituted aldehyde and 10% palladium on carbon in the presence of sodium cyanoborohydride or hydrogen gas in a suitable solvent such as water, methanol, tetrahydrofuran mixture or toluene, at room temperature ≪ / RTI >
    [177] For methods 27 and 28, amine 2, wherein at least one of R 1 -R 5 is defined as hydroxy and X is as defined above, is reacted in a suitable solvent mixture such as a methanol-water mixture, at a temperature ranging from room temperature to the reflux temperature of the solvent , Can be prepared by reacting the corresponding ester, such as acetate, with an appropriate base such as sodium bicarbonate or sodium hydroxide.
    [178] For Method 29, the amine 2, wherein at least one of R 1 -R 5 is defined as 2-hydroxybenzamido and X is as defined above, in a suitable solvent such as tetrahydrofuran, diethyl ether, , The corresponding N- (4-aminophenyl) phthalimide with lithium borohydride.
    [179] An intermediate amine 2 in which R 1 -R 5 is as defined above and X is -CH 2 - or - (CH 2 ) 2 can be prepared by the following procedure:
    [180] a) reduction of the appropriately substituted benzo-or phenylacetonitrile with a borane-dimethylsulfide complex (method 44) in an appropriate solvent such as ethylene glycol dimethyl ether, tetrahydrofuran or the like at a temperature ranging from room temperature to the reflux temperature of the solvent;
    [181] b) in an appropriate solvent such as ethylene glycol monomethyl ether, ethyl acetate, ethanol or the like in the presence of an acid such as 5% or 10% palladium on carbon and 4-methyl-benzenesulfonic acid, Reduction (Method 50);
    [182] c) reduction with lithium aluminum hydride in a suitable solvent such as tetrahydrofuran or diethyl ether at 0 < 0 > C to room temperature (Method 51).
    [183] The unsaturated nitro precursor which is used as the starting material in Method 51 and which is finally converted to the amine 2 (in which R 1 -R 5 is as defined above and X corresponds to - (CH 2 ) 2 -) is reacted with acetic acid In a suitable solvent such as dichloromethane, dichloromethane, dichloromethane, dichloromethane, dichloromethane, dichloromethane, dichloromethane, dichloromethane, dichloromethane, dichloromethane, and dichloromethane; The benzaldehyde used as starting material in Method 53 can be prepared by diisobutylaluminum hydride reduction of the appropriately substituted benzonitrile (Method 52). Substituted benzonitrile used as starting material in Method 52 is N, N < RTI ID = 0.0 > In a suitable solvent such as dimethylformamide, at a temperature ranging from room temperature to the reflux temperature of the solvent, by reacting the corresponding aryl bromide with a copper cyanide (Method 59).
    [184] When R 1 -R 5 is as defined above and X is an amine-2 corresponding to ether-O (CH 2 ) 2 NH 2 or -S (CH 2 ) 2 NH 2 , the requisite nitrile precursor may be reacted with a suitable May be prepared by reacting appropriately substituted phenol or thiophenol with bromoacetonitrile in an appropriate solvent such as acetone in the presence of a base at room temperature according to Method 49.
    [185] Alternatively, for amine 2 where R 1 -R 5 is as defined above and X corresponds to - (CH 2 ) 3 -, the nitrile precursor is prepared essentially as described in Wilk, B. Synthetic Comm. 23, 2481 (1993)] in an appropriate solvent such as diethyl ether or tetrahydrofuran in the presence of a suitable azodicarboxylate such as diethyl azodicarboxylate at temperatures between 0 < 0 > C and room temperature Can be prepared by reacting phenethanol with acetone cyanohydrin and triphenylphosphine (Method 54).
    [186] Alternatively, the intermediate amine 2 in which R 1 -R 5 is as defined above and X corresponds to - (CH (CH 3 )) - is reacted with a suitable acid catalyst such as 6N hydrochloric acid or an appropriate acid catalyst such as 5N sodium or potassium hydroxide Can be prepared by acid catalyzed hydrolysis of the corresponding formamide with base catalyst in a suitable solvent mixture such as water and methanol or water and ethanol at a temperature ranging from room temperature to the reflux temperature of the solvent (method 46).
    [187] The formamide precursor which is used as the starting material in Method 46 and which is finally converted to the amine 2 is treated with suitably substituted acetophenone using ammonium formate, formic acid and formamide at a temperature ranging from room temperature to the reflux temperature of the solvent according to Method 45 .
    [188] Alternatively, the amine 2 in which R 1 -R 5 is as defined above and X is - (CH (CH 3 )) - is basically described in Itsuno, S., Sakurai, Y., Ito, K. Synthesis 1988, 995, in an appropriate solvent such as tetrahydrofuran or diethyl ether in the presence of sodium borohydride and zirconium tetrachloride at room temperature, by reduction of the appropriately substituted O-methyl oxime. The required O-methyloxime can be prepared from the corresponding acetophenone by reaction with methoxylamine hydrochloride and pyridine in an appropriate solvent such as ethanol or methanol at a temperature ranging from room temperature to the reflux temperature of the solvent. (Method 47)
    [189] Amine 2 corresponding to R 1 -R 5 is as hereinbefore defined and X is -CH (J) - (J is as defined above) is reacted with an appropriately substituted Can be prepared by reduction of the ketone. Such essential ketones, which are not normally available, can be obtained by reaction of appropriately substituted benzaldehydes in an appropriate solvent such as diethyl ether or tetrahydrofuran at a temperature ranging from -78 ° C to 0 ° C with an appropriate organometallic agent such as phenyllithium, isopropylmagnesium bromide Or ethyl magnesium bromide (method 57). The resulting alcohol can be oxidized to the corresponding ketone using an appropriate oxidizing agent such as chromium trioxide at room temperature in an appropriate solvent such as aqueous sulfuric acid and acetone or pyridinium chloro chromate or pyridinium dichromate, such as dichloromethane Method 58).
    [190] The intermediate aniline 5 can be prepared according to Method 3A described above. Treatment of phenylcarbamic acid tert-butyl ester 6 (where G is as previously described) with pure trifluoroacetic acid followed by neutralization with aqueous sodium hydroxide gives the desired aniline 5 at room temperature. The required carbamic acid ester 6 (G is as previously described) is reacted with a substituted acid chloride in the presence of triethylamine in a suitable solvent such as dichloromethane, dimethylsulfoxide or dimethylformamide or mixtures thereof, 8, in which G is as hereinbefore described, and 4-aminophenylcarbamic acid tert-butyl ester 7. The carboxylic acid chloride 8 is either commercially available or prepared from the corresponding carboxylic acid by reaction with oxalyl chloride in a suitable solvent such as dichloromethane at room temperature.
    [191] Method 2C, 3A
    [192]
    [193] Alternatively, carbamic acid ester 6, where G is as previously described, is reacted with benzotriazol-1-yloxy-tris- (dimethylamino) phosphonium hexafluorophosphate, 2- (1H- Benzyltriazol-1-yloxy) -1,1,3,3-tetramethyluronium hexafluorophosphate, dicyclohexylcarbodiimide, and the like, in the presence of a suitable coupling agent such as triethylamine or diisopropylethyl In the presence of a tertiary amine base such as an amine in a suitable solvent such as dichloromethane, dimethylformamide, etc. at room temperature, the substituted carboxylic acid 8a (wherein G is as previously described) and the appropriately substituted 4-aminophenylcarbamic acid tert- Butyl ester 7 to give the corresponding aryl aminoamide.
    [194] The carboxylic acid 8a is commercially available or prepared according to literature methods. For example, if G is a substituted thiadiazole, the acid is available from the corresponding carboxylic acid ester by reacting the appropriate base with sodium or potassium hydroxide at room temperature in a suitable solvent mixture of methanol or ethanol and water.
    [195] If a carboxylic acid ester precursor which is finally converted to the acid 8 is not commercially available, it can be prepared by methods known in the literature. For example, 5-substituted-1,2,3-thiadiazole-4-carboxylic acid esters are prepared essentially according to Caron, MJ Org. Chem. 51, 4075 (1986) and Taber, D. F., Ruckle, R.E.J. Amer. Chem. Soc. 108, 7686 (1986). Thus, according to Method 21, in a suitable solvent such as acetonitrile in the presence of a tertiary amine base such as triethylamine or diisopropylethylamine, 4-methylbenzenesulfonyl azide or methanesulfonyl azide, -Ketocarboxylic acid ester is obtained, the corresponding diazo-beta-ketocarboxylic acid ester is obtained. This compound is reacted with 2,4-bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane-2, Treatment with 4-disulfide gives the desired 5-substituted-1,2,3-thiadiazole-4-carboxylic acid ester.
    [196] Alternatively, 4-substituted -1,2,3-thiadiazole-5-carboxylic acid esters can be prepared essentially according to Shafiee, A., Lalezari, I., Yazdani, S., Shahbazian. F. M., Partovi, T.J. Pharmaceutical Sci. 65, 304 (1976). Thus, according to methods 22 and 23, a beta-ketocarboxylic acid ester suitably substituted in a suitable alcohol solvent such as methanol or ethanol in the presence of a suitable base such as pyridine at room temperature to the reflux temperature of the solvent is treated with aqueous solution of semicarbazide hydrochloride To give the corresponding semicarbazone derivatives. Treatment of these compounds with pure thionyl chloride at 0 < 0 > C followed by treatment with an excess of aqueous sodium bicarbonate affords the corresponding 4-substituted-1,2,3-thiadiazole-5-carboxylic acid ester.
    [197] The 4-carboalkoxy thiazole is basically prepared according to the method of Schollkopf, U., Porsch, P., Lau, H. Liebigs Ann. Chem. 1444 (1979). Thus, according to methods 55 and 56, reacting ethylisocyanate with N, N-dimethylformamide dimethylacetal in a suitable alcohol solvent such as ethanol at room temperature gives the corresponding 3-dimethylamino-2-iso Ano-acrylic acid ethyl ester is obtained. A solution of this compound in a suitable solvent such as tetrahydrofuran is treated with gaseous hydrogen sulfide at room temperature in the presence of a suitable tertiary amine base such as triethylamine or diisopropylethylamine to give the corresponding 4-carboethoxy- Thiazole is obtained.
    [198] Additional suitably substituted thiazoles can be prepared essentially according to the procedures described in Bredenkamp, M. W., Holzafel, C. W., van Zyl, W. J. Synthetic Comm. 20, 2235 (1990). Suitable unsaturated oxazoles are essentially those described in Henneke, K. H., Schollkopf, U., Neudecker, T. Liebigs Ann. Chem. 1979 (1979)]. Substituted oxazoles are basically prepared according to the method of Galeotti, N., Montagne, C., Poncet, J., Jouin. P. Tetrahedron Lett. 33, 2807, 1 (992) and Shin, C., Okumura, K., Ito, A., Nakamura, Y. Chemistry Lett. 1305, (1994).
    [199] The following specific examples are set forth and are not to be construed as limiting the scope of the invention.
    [200] Example 1 (Method 1A)
    [201] 4-Methoxy-3-trifluoromethyl-phenylamine
    [202] A suspension of 4-methoxy-3-trifluoromethyl-nitrobenzene (2.2 g) and iron powder (1.68 g) was dissolved in ethanol (35 mL) and water (15 mL) ) ≪ / RTI > (0.42 mL) and the mixture is heated to reflux for approximately 1 hour. The mixture is cooled, filtered and concentrated under reduced pressure. The resulting oil is dissolved in ethyl acetate and extracted three times with 5% aqueous hydrochloric acid. The combined acidic extracts are cooled in an ice bath and basified with solid potassium carbonate and extracted with ethyl acetate. This organic extract is washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure and then passed through a short silica gel column (ethyl acetate is used as eluent) to give the desired compound of the amber oil.
    [203] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [204] 2,6-Dichloro-benzene-1,4-diamine
    [205] 3-Chloro-4-methylsulfanyl-phenylamine
    [206] 2,6-dibromo-benzene-1,4-diamine
    [207] 3-Chloro-4-trifluoromethyl-phenylamine
    [208] 3-Chloro-4-ethylsulfanyl-phenylamine
    [209] 4-Methoxy-3-trifluoromethyl-phenylamine
    [210] 3,5-Dichloro-4-methoxy-2-methyl-phenylamine
    [211] 5-Chloro-2-ethoxy-4-methoxy-phenylamine
    [212] 5-Chloro-4-ethoxy-2-methoxy-phenylamine
    [213] 5-Iodo-2,4-dimethoxy-phenylamine
    [214] 3,5-Diiodo-2,4-dimethoxy-phenylamine
    [215] 3,5-Dibromo-2,4-dimethoxy-phenylamine
    [216] 5-Chloro-2-methoxy-4-methyl-phenylamine
    [217] 2-Chloro-N (1), N (1) -dimethyl-benzene-
    [218] 3-Chloro-4-piperidin-l-yl-phenylamine
    [219] 3-Chloro-4-pyrrolidin-l-yl-phenylamine
    [220] N (1) -benzyl-2-chloro-benzene-1,4-diamine
    [221] Chloro-4- (4-methyl-piperazin-l-yl) -phenylamine
    [222] 2-Chloro-N (1) -methyl-N (1) - (1 -methyl-piperidin-
    [223] 2-Chloro-N (1) -methyl-N (1) - (1 -methyl-pyrrolidin-
    [224] 2-Chloro-N (1) -methyl-N (1) -phenyl-benzene-
    [225] N (1) - (1-Benzyl-pyrrolidin-3-yl) -2-chloro- N (1)
    [226] 2-Chloro-N (1) -cyclopentyl-N (1) -methyl-benzene-
    [227] 2- [(4-Amino-2-chloro-phenyl) - (2-hydroxy-ethyl) -amino]
    [228] 2-Chloro-N (1) -hexyl-N (1) -methyl-benzene-
    [229] 2-Chloro-N (1) -isobutyl-N (1) -methyl-benzene-1,4-diamine
    [230] 2 - [(4-Amino-2-chloro-phenyl) -methyl-amino]
    [231] 2-Chloro-N (1) - (3-dimethylamino-propyl) -N (1) -methyl-
    [232] 2-Chloro-N (1) - (2-dimethylamino-ethyl) -N (1) -methyl-
    [233] 2-chloro-N (1) - (2-dimethylamino-ethyl) -benzene-1,4-diamine
    [234] N (1) - (1-Benzyl-piperidin-4-yl) -2-chloro-benzene-
    [235] 2-Chloro-N (1) - (2-methoxy-ethyl) -N (1) -methyl-
    [236] 2-Chloro-N (1) - (3-dimethylamino-propyl) -benzene-1,4-diamine
    [237] N (1) - (1-Benzyl-pyrrolidin-3-yl) -2-chloro-benzene-
    [238] 3-Chloro-4- (l-methyl-piperidin-4-yloxy) -phenylamine
    [239] 3-Chloro-4- (2-dimethylamino-ethoxy) -phenylamine
    [240] 3-Chloro-4- (3-dimethylamino-propoxy) -phenylamine
    [241] 3-Chloro-4- (l-methyl-pyrrolidin-3-yloxy) -phenylamine
    [242] 3-Chloro-4-cyclohexyloxy-phenylamine
    [243] Example 2 (Method 1B)
    [244] 4-Bromo-2,4-dimethoxy-phenylamine
    [245] A suspension of 4-bromo-2,4-dimethoxy-nitrobenzene (0.48 g) and iron powder (0.42 g) in acetic acid (10 mL) and ethanol (10 mL) is heated to 120 < 0 > C for approximately 5 hours. The mixture is cooled, filtered and concentrated under reduced pressure. Water is added and the mixture is cooled in an ice bath, then neutralized with solid potassium carbonate and extracted with dichloromethane. This organic extract was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure and then chromatographed on silica gel (20% ethyl acetate in hexanes used as eluent) to give the desired compound of amber oil .
    [246] Example 3 (Method 1C)
    [247] (4-Amino-2,6-dichloro-phenoxy) -acetic acid tert-butyl ester
    [248] A solution of iron powder (0.861 g) and ammonium chloride (86 mg) was added to a solution of (4-nitro-2,6-dichloro-phenoxy) -acetic acid tert- butyl ester (1 g) in ethanol (17 mL) and water (8.6 mL) ≪ / RTI > and the mixture is heated to reflux for approximately 1 hour. The mixture is filtered and concentrated under reduced pressure. The resulting oil is partitioned between water and ethyl acetate and the organic phase is washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the desired compound as a pale yellow solid.
    [249] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [250] 4-Chloro-benzene-l, 2-diamine
    [251] N- (4-Amino-2-chloro-phenyl) -acetamide
    [252] (4-amino-2,6-dichloro-phenoxy) -acetonitrile
    [253] (4-Amino-2,6-dichloro-phenoxy) -acetic acid tert-butyl ester
    [254] (2-Amino-4-chloro-5-methoxy-phenoxy) -acetonitrile
    [255] (4-Amino-2-chloro-5-methoxy-phenoxy) -acetic acid methyl ester
    [256] (4-Amino-2-chloro-5-methoxy-phenoxy) -acetic acid tert-butyl ester
    [257] (2-Amino-4-chloro-5-methoxy-phenoxy) -acetic acid tert-butyl ester
    [258] N (1) -Benzyl-4-chloro-5-methoxy-benzene-
    [259] N- (4-Amino-2-chloro-phenyl) -2-fluoro-benzamide
    [260] N- (4-Amino-5-chloro-2-hydroxy-phenyl) -acetamide
    [261] N- (4-Amino-5-chloro-2-hydroxy-phenyl) -2-fluoro-benzamide
    [262] Furan-2-carboxylic acid (4-amino-2-chloro-phenyl)
    [263] (4-Amino-2-chloro-phenyl) -carbamic acid ethyl ester
    [264] N- (4-Amino-5-chloro-2-methyl-phenyl) -acetamide
    [265] N- (4-Amino-5-chloro-2-methyl-phenyl) -2-fluoro-benzamide
    [266] Furan-2-carboxylic acid (4-amino-5-chloro-2-methyl- phenyl)
    [267] N- (4-amino-3-chloro-phenyl) -2-fluoro-benzamide
    [268] Furan-2-carboxylic acid (4-amino-3-chloro-phenyl)
    [269] N- (4-Amino-2-chloro-phenyl) -2-dimethylamino-acetamide
    [270] N- (4-Amino-2-chloro-phenyl) -2-piperidin-
    [271] N- (4-Amino-2-chloro-phenyl) -2-morpholin-4-yl-acetamide
    [272] N- (4-Amino-2-chloro-phenyl) -methanesulfonamide
    [273] N- (4-Amino-2-chloro-phenyl) -benzamide
    [274] N- (4-Amino-2-chloro-phenyl) -2-diethylamino-acetamide
    [275] N- (4-Amino-2-chloro-phenyl) -2- pyrrolidin-1-yl-acetamide
    [276] N- (4-Amino-2-chloro-phenyl) -2-azepan-1-yl-acetamide
    [277] 2- (2-methyl-piperidin-l-yl) -acetamide <
    [278] 2- (3-methyl-piperidin-l-yl) -acetamide <
    [279] 3-Chloro-benzene-l, 2-diamine
    [280] 4-Chloro-N, N-dimethyl-benzene-l, 2-diamine
    [281] Example 4 (Method 1D)
    [282] 3,5-Dichloro-4-phenoxy-phenylamine
    [283] Dissolve concentrated hydrochloric acid (60 mL) in a slurry of 3,5-dichloro-4-phenoxy-nitrobenzene (6.1 g) and tin powder (12 g). Ethanol (60 mL) is added and the mixture is heated to reflux for approximately 1 hour. The mixture is cooled in an ice bath and basified by the addition of solid sodium hydroxide. The resulting suspension is filtered through a pad of diatomaceous earth and extracted three times with ethyl acetate. The combined organic extracts are washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to yield the desired product as a yellow solid. Recrystallization from ethyl acetate-hexane gave a pale yellow solid product.
    [284] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [285] 1-furan-2-yl-ethylamine
    [286] 3-Chloro-4-isopropoxy-phenylamine
    [287] 2-Butoxy-5-chloro-4-methoxy-phenylamine
    [288] 3,5-Dichloro-2-methoxy-4-methyl-phenylamine
    [289] 2-Benzyloxy-5-chloro-4-methoxy-phenylamine
    [290] 4-Benzyloxy-5-chloro-2-methoxy-phenylamine
    [291] 5-fluoro-2,4-dimethoxy-phenylamine
    [292] (4-amino-2,6-dichloro-phenoxy) -acetic acid ethyl ester
    [293] 3,5-Dichloro-4-phenoxy-phenylamine
    [294] 2- (4-Amino-2-chloro-5-methoxy-phenoxy) -acetamide
    [295] (4-Amino-2-chloro-5-methoxy-phenoxy) -acetonitrile
    [296] 2- (2-Amino-4-chloro-5-methoxy-phenoxy) -ethanol
    [297] 2- (4-Amino-2-chloro-5-methoxy-phenoxy) -ethanol
    [298] 4- (4-Amino-2-chloro-5-methoxy-phenoxy) -butyronitrile
    [299] 4-Amino-2-chloro-5-methoxy-phenol
    [300] 2-Amino-4-chloro-5-methoxy-phenol
    [301] 5-Chloro-4-methoxy-2-morpholin-4-yl-phenylamine
    [302] 4-chloro-5-methoxy-N (1), N (1) -dimethyl-
    [303] 5-Chloro-4-methoxy-2-piperidin-l-yl-phenylamine
    [304] 5-Chloro-4-methoxy-2-pyrrolidin-l-yl-phenylamine
    [305] 2-Chloro-N (1) -cyclohexyl-N (1) -methyl-benzene-
    [306] N (2) -benzyl-4-methoxy-benzene-l, 2-diamine
    [307] 2- (4-Amino-2-chloro-phenoxy) -ethanol
    [308] 2-Chloro-N (1) -cyclohexyl-N (1) -ethyl-benzene-1,4-diamine
    [309] 4-Butoxy-3-chloro-phenylamine
    [310] (4-Amino-2-chloro-phenoxy) -acetonitrile
    [311] 2-Chloro-N (1) -cyclohexyl-benzene-1,4-diamine
    [312] 2-chloro-N (1), N (1) -dipropyl-benzene-1,4-diamine
    [313] 3-Chloro-4- (2,2,2-trifluoro-ethoxy) -phenylamine
    [314] 3-Chloro-4- (octahydro-quinolin-l-yl) -phenylamine
    [315] N (1) -allyl-2-chloro-N (1) -cyclohexyl-benzene-1,4-diamine
    [316] N- (4-Amino-2-methoxy-5-methyl-phenyl) -2-fluoro-
    [317] Furan-2-carboxylic acid (4-amino-2-methoxy-5-methyl- phenyl)
    [318] N- (4-amino-naphthalen-1-yl) -2-fluoro-benzamide
    [319] 3-Chloro-N, N-dimethyl-benzene-l, 2-diamine
    [320] 3-Chloro-4-propoxy-phenylamine
    [321] 3-Iodo-4-methoxy-phenylamine
    [322] 3-Chloro-2,4-dimethoxy-aniline
    [323] 3-Bromo-4-methoxy-phenylamine
    [324] 3-Chloro-4-ethoxy-phenylamine
    [325] Example 5 (Method 1E)
    [326] (4-amino-phenyl) -carbamic acid isobutyl ester
    [327] To a solution of N- (4-nitro-phenyl) -isobutylamide (2.0 g) in 100 mL ethylene glycol monomethyl ether (100 mL) was added 10% palladium on carbon (275 mg). The mixture is hydrogenated at 30 psi hydrogen in a Parr hydrogenation apparatus at room temperature for 2 hours. The catalyst is removed by filtration through diatomaceous earth and the filtrate is azeotropically mixed with heptane three times and evaporated to dryness under reduced pressure. Trituration of the residue with heptane gives the desired product of a white solid.
    [328] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [329] 2-methyl-3H-benzoimidazol-5-ylamine
    [330] N- (4-amino-phenyl) -formamide
    [331] 1H-benzoimidazol-5-ylamine
    [332] (4-amino-phenyl) -carbamic acid isobutyl ester
    [333] N- (4-amino-phenyl) -isobutyramide
    [334] N- (5-amino-pyridin-2-yl) -2-methyl-benzamide
    [335] Furan-2-carboxylic acid (5-amino-pyridin-2-yl)
    [336] N- (5-Amino-pyridin-2-yl) -2-fluoro-benzamide
    [337] [6- (2,2,2-Trifluoro-acetylamino) -pyridin-3-yl] -carbamic acid tert-butyl ester
    [338] N- (5-amino-pyridin-2-yl) -2,2,2-trifluoro-acetamide
    [339] (4-Amino-benzyl) -carbamic acid tert-butyl ester
    [340] 2- (3,5-Bis-trifluoromethyl-phenyl) -ethylamine
    [341] 1-tert-butyl-1H-imidazol-2-ylamine
    [342] 3- (3-Dimethylamino-propyl) -5-trifluoromethyl-phenylamine
    [343] Example 6 (Method 1F)
    [344] N- (4-amino-2-methylphenyl) -2-fluorobenzamide
    [345] (30 mL), ethanol (70 mL), water (30 mL) and 10% palladium on charcoal (3 g, ) Is heated at reflux for 30 minutes. The mixture is filtered through diatomaceous earth and concentrated under reduced pressure. The resulting oil is dissolved in 50 mL of ethyl acetate and cooled at 4 [deg.] C for 12 hours. Filtration yields the product of a tan solid.
    [346] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [347] N- (4-Amino-2-methyl-phenyl) -acetamide
    [348] 2-methyl-benzooxazol-6-ylamine
    [349] N- (4-amino-3-methoxy-phenyl) -acetamide
    [350] 2-Acetylamino-5-amino-benzoic acid
    [351] N- (4-amino-phenyl) -acetamide
    [352] [4- (3-Amino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [353] [4- (2-Amino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [354] N- (4-Amino-2-cyano-phenyl) -acetamide
    [355] N- (4-amino-2,5-dimethoxy-phenyl) -2-fluoro-benzamide
    [356] Furan-2-carboxylic acid (4-amino-2,5-dimethoxy-phenyl) -amide
    [357] N- (4-Amino-2-cyano-phenyl) -2-fluoro-benzamide
    [358] Furan-2-carboxylic acid (4-amino-2-methoxy-phenyl)
    [359] N- (4-Amino-2-methoxy-phenyl) -2-fluoro-benzamide
    [360] N- (4-Amino-2-methoxy-5-methyl-phenyl) -acetamide
    [361] N- (4-Amino-2-benzoyl-phenyl) -acetamide
    [362] N- (4-Amino-2-benzoyl-phenyl) -2-fluoro-benzamide
    [363] Furan-2-carboxylic acid (4-amino-2-benzoyl-phenyl)
    [364] N- (4-amino-3-methyl-phenyl) -acetamide
    [365] N- (4-Amino-3-methyl-phenyl) -2-fluoro-benzamide
    [366] Furan-2-carboxylic acid (4-amino-3-methyl-phenyl)
    [367] 5-Amino-2 - [(2-fluorobenzoyl) amino] -N-phenylbenzamide
    [368] Furan-2-carboxylic acid (4-amino-2-phenylcarbamoyl-phenyl) amide
    [369] N- (4-Amino-naphthalen-1-yl) -acetamide
    [370] Furan-2-carboxylic acid (4-amino-naphthalen-l-yl) -amide
    [371] N- (4-Amino-2-trifluoromethyl-phenyl) -acetamide
    [372] Furan-2-carboxylic acid (4-amino-2-cyano-phenyl)
    [373] Furan-2-carboxylic acid (4-amino-2-trifluoromethyl-phenyl) -amide
    [374] N- (4-Amino-2-methyl-phenyl) -2-fluoro-benzamide
    [375] Furan-2-carboxylic acid (4-amino-2-methyl-phenyl)
    [376] 5-Amino-2- (2-fluoro-benzoylamino) -benzoic acid
    [377] 5-Amino-2 - [(furan-2-carbonyl) -amino] -benzoic acid
    [378] N- (4-Amino-2-cyano-phenyl) -2,2,2-trifluoro-acetamide
    [379] N- (4-Amino-3-methyl-phenyl) -2,6-difluoro-benzamide
    [380] N- (4-Amino-3-trifluoromethyl-phenyl) -acetamide
    [381] N- (4-Amino-3-trifluoromethyl-phenyl) -2-fluoro-benzamide
    [382] N- (4-Amino-2-trifluoromethyl-phenyl) -2,2,2-trifluoro-acetamide
    [383] N- (4-Amino-2-methoxy-phenyl) -2,2,2-trifluoro-acetamide
    [384] N- (4-Amino-2-trifluoromethyl-phenyl) -2-fluoro-N- (2- fluoro-benzoyl)
    [385] N- (4-Amino-2-trifluoromethyl-phenyl) -2-fluoro-benzamide
    [386] Implementation 7 (Method 1G)
    [387] N- (4-amino-2-chlorophenyl) -2-thiomorpholino-4-yl-acetamide
    [388] A solution of N- (2-chloro-4-nitrophenyl) -2-thiomorpholino-4-yl-acetamide (3.02 g) in ethanol (200 mL) ). The mixture is heated at reflux for 12 hours, cooled and then poured into water. The mixture is extracted with ethyl acetate. The ethyl acetate solution is washed twice with saturated aqueous sodium chloride, dried over anhydrous potassium carbonate, filtered through a pad of diatomaceous earth and then concentrated under reduced pressure to give an oil. Addition of toluene and cooling of the solution gives the desired product of a bright orange crystalline solid.
    [389] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [390] N- (4-Amino-2-chloro-phenyl) -2-thiomorpholin-
    [391] N- (4-Amino-2-chloro-phenyl) -2-dipropylamino-acetamide
    [392] Example 8 (Method 2A)
    [393] (3-Chloro-4-iodo-phenyl) -carbamic acid tert-butyl ester
    [394] Di-tert-butyl-dicarbonate (8.6 g) was added to a solution of 3-chloro-4-iodo-aniline (10 g) in tetrahydrofuran (40 mL) containing diisopropylethylamine (6.9 mL) And the mixture is heated to reflux. After approximately 15 hours, an additional portion of diisopropylethylamine (6.9 mL) and di-tert-butyl-dicarbonate (21 g) are added and heated continuously for approximately 24 hours. The solution was cooled, concentrated under reduced pressure, then diluted with ethyl acetate and washed three times with 5% aqueous hydrochloric acid and once with saturated aqueous sodium chloride. The solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the desired crude product of the brown oil. Hexane is added to crystallize and the collected solid is recrystallized from hexane to give the desired product of a white solid.
    [395] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [396] N '- (4-nitro-benzoyl) -hydrazinecarboxylic acid tert-butyl ester
    [397] (3-Chloro-4-iodo-phenyl) -carbamic acid tert-butyl ester
    [398] (4-Bromo-3-chloro-phenyl) -carbamic acid tert-butyl ester
    [399] (3-Chloro-4-vinyl-phenyl) -carbamic acid tert-butyl ester
    [400] (3-Chloro-4-methylsulfanyl-phenyl) -carbamic acid tert-butyl ester
    [401] (4-Amino-3-chloro-phenyl) -carbamic acid tert-butyl ester
    [402] (4-chloro-2-nitro-phenyl) -carbamic acid tert-butyl ester
    [403] (3-tert-Butoxycarbonylamino-5-chloro-phenyl) -carbamic acid tert-butyl ester
    [404] (4-nitro-benzyl) -carbamic acid tert-butyl ester
    [405] (3-Bromo-5-trifluoromethyl-phenyl) -carbamic acid tert-butyl ester
    [406] (2-Amino-3-chloro-5-trifluoromethyl-phenyl) -carbamic acid tert-butyl ester
    [407] Example 9 (Method 2B)
    [408] (3-Chloro-4-vinyl-phenyl) -carbamic acid-2-trimethylsilanyl-ethyl ester
    [409] To a solution of 3-chloro-4-vinyl-phenylamine (3.4 g) in N, N-dimethylformamide (44 mL) containing diisopropylethylamine (5.8 mL) was added 1- [2- (trimethylsilyl) Oxycarbonyl-oxy] benzotriazole (7.1 g) was added and the mixture was stirred at room temperature under an argon atmosphere for 3 days. The solution is diluted with water and extracted three times with diethyl ether. The combined organic extracts are washed successively with water, saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Chromatography of the resulting residue on silica gel (using 10% ethyl acetate in hexanes as eluent) gave the desired product of the yellow oil.
    [410] Example 10 (Method 2C)
    [411] [4- (2-Fluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [412] To a solution of mono-N- (t-butoxycarbonyl) -1,4-phenylenediamine (1.58 g) and triethylamine (1.50 mL) in 25 mL of dichloromethane was added o-fluorobenzoyl chloride (1.20 g) . A solid is formed immediately, which is filtered and washed with fresh solvent to give 1.90 g of a white solid.
    [413] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [414] N- (3-Methoxy-4-nitro-phenyl) -acetamide
    [415] N- (4-amino-phenyl) -isobutylamide
    [416] 2,2,2-Trifluoro-N- (2-methoxy-4-nitro-phenyl) -acetamide
    [417] [4- (2-methyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [418] Acetic acid 2- (4-tert-butoxycarbonylamino-phenylcarbamoyl) -phenyl ester
    [419] [4- (4-Fluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [420] [4- (3-Fluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [421] [4- (2-Fluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [422] [4- (2-Methoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [423] [4- (3-Methoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [424] [4- (4-Methoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [425] [4- (2,2-Dimethyl-propionylamino) -phenyl] -carbamic acid tert-butyl ester
    [426] [4- (2-Bromo-acetylamino) -phenyl] -carbamic acid tert-butyl ester
    [427] [4- (2,2,2-Trifluoro-acetylamino) -phenyl] -carbamic acid tert-butyl ester
    [428] (4-Benzoylamino-phenyl) -carbamic acid tert-butyl ester
    [429] (4-methanesulfonylamino-phenyl) -carbamic acid tert-butyl ester
    [430] (4-phenylacetylamino-phenyl) -carbamic acid tert-butyl ester
    [431] {4 - [(Thiophene-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [432] [4- (3-nitro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [433] [4- (3-Acetylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [434] [4- (3-Methanesulfonylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [435] Ethyl [3 - [[4 - [[(1,1-dimethylethoxy) carbonyl] amino] phenyl] amino] carbonyl] phenyl] carbamate
    [436] [4- (2-Trifluoromethyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [437] [4- (2,6-Difluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [438] [4- (2-Chloro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [439] [4- (2-Bromo-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [440] [4- (2-nitro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [441] {4 - [(benzo [b] thiophene-2-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester
    [442] {4 - [(pyridine-4-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester
    [443] {4 - [(Naphthalene-2-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester
    [444] {4 - [(Naphthalene-1-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester
    [445] {4 - [(3-Bromo-thiophene-2-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester
    [446] {4 - [(biphenyl-2-carbonyl) -amino] phenyl} carbamic acid tert-butyl ester
    [447] N- (4-tert-Butoxycarbonylamino-phenyl) -phthalamic acid
    [448] [4- (2,3-Difluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [449] [4- (2,5-Difluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [450] [4- (2,4-Difluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [451] [4- (2-Acetylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [452] [4- (2-Methanesulfonylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [453] [4- (2,3,4-Trifluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [454] [4- (2,3,4,5,6-pentafluoro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [455] N- (4-tert-Butoxycarbonylamino-phenyl) -isophthalamic acid methyl ester
    [456] 2-Methylsulfanyl-N- [4- (2,2,2-trifluoro-acetylamino) -phenyl] -benzamide
    [457] [4- (3-Benzyloxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [458] [4- (3-Butoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [459] {4 - [(5-Difluoromethyl-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [460] {4 - [(Thiophene-3-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [461] {4- [(5-methyl-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [462] {4 - [(5-Bromo-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [463] (4-hexanoylamino-phenyl) -carbamic acid tert-butyl ester
    [464] [4- (2-Thiophen-2-yl-acetylamino) -phenyl] -carbamic acid tert-butyl ester
    [465] {4 - [(Pyridine-3-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [466] {4 - [(4-Bromo-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [467] {4 - [(furan-3-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [468] (4-phenoxycarbonylamino-phenyl) -carbamic acid tert-butyl ester
    [469] {4 - [(Benzo [1.3] dioxol-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [470] [4- (3-Trifluoromethoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [471] N- (2,5-dimethoxy-4-nitro-phenyl) -2-fluoro-benzamide
    [472] {4 - [(furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [473] [4- (2-phenoxy-acetylamino) -phenyl] -carbamic acid tert-butyl ester
    [474] {4 - [(5-Nitro-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [475] {4 - [(5-Chloro-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [476] {4 - [(3-Methyl-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [477] [4- (2-Methoxy-acetylamino) -phenyl] -carbamic acid tert-butyl ester
    [478] {4 - [(4-Furan-3-yl- [1.2.3] thiadiazole-5-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [479] {4- [(5-tert-Butyl-furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [480] N- [3-cyano-4- (2,2,2-trifluoro-acetylamino) -phenyl] -2-fluoro-benzamide
    [481] Furan-2-carboxylic acid [3-cyano-4- (2,2,2-trifluoro-acetylamino) -phenyl]
    [482] N- (4-Acetylamino-2-cyano-phenyl) -2,2,2-trifluoro-acetamide
    [483] 2,2,2-Trifluoro-N- (4-nitro-2-trifluoromethyl-phenyl) -acetamide
    [484] N- (4-acetylamino-2-trifluoromethyl-phenyl) -2,2,2-trifluoro-acetamide
    [485] 2-fluoro-N- [4- (2,2,2-trifluoro-acetylamino) -3-trifluoromethyl-phenyl]
    [486] Furan-2-carboxylic acid [4- (2,2,2-trifluoro-acetylamino) -3-trifluoromethylphenyl] amide
    [487] 2-Fluoro-N- (2-methyl-benzooxazol-6-yl) -benzamide
    [488] 4- (2-Fluoro-benzoylamino) -2-hydroxy-benzoic acid phenyl ester
    [489] {4 - [(isoxazole-5-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [490] N- (4-acetylamino-2-methoxy-phenyl) -2,2,2-trifluoro-acetamide
    [491] 2-fluoro-N- [3-methoxy-4- (2,2,2-trifluoro-acetylamino) -phenyl]
    [492] Fluoro-N- (2-fluoro-benzoyl) -N- (4-nitro-2- trifluoromethyl- phenyl)
    [493] {4 - [(lH-pyrazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [494] {4 - [(lH-imidazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [495] {4 - [(5-methyl- [1,2,3] thiadiazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [496] 4 - [(5-Furan-3-yl- [1,2,3] thiadiazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [497] 2,2,2-Trifluoro-N- (5-nitro-pyridin-2-yl) -acetamide
    [498] {4 - [(1 -methyl-1 H-pyrazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [499] 4- (2-Fluoro-benzoylamino) -2-hydroxy-benzoic acid methyl ester
    [500] N- (5-Chloro-2,4-dimethoxy-phenyl) -oxalamic acid
    [501] 5-carboxylic acid (4-amino-phenyl) -amide
    [502] 2-Fluoro-N- (4-nitro-benzyl) -benzamide
    [503] Furan-2-carboxylic acid 4-nitro-benzylamide
    [504] N- [3-chloro-5- (2,2,2-trifluoro-acetylamino) -phenyl] -2,2,2-trifluoro-acetamide
    [505] N- (3-Amido-5-chloro-phenyl) -2,2,2-trifluoro-acetamide
    [506] [4- (2-Fluoro-benzoylamino) -benzyl] -carbamic acid tert-butyl ester
    [507] [4- (2,6-Difluoro-benzoylamino) -benzyl] -carbamic acid tert-butyl ester
    [508] 2,6-Difluoro-N- (4-nitro-benzyl) -benzamide
    [509] {4 - [(furan-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [510] N- (3-Amino-5-chloro-phenyl) -acetamide
    [511] [4- (3-Chloro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [512] [4- (4-Chloro-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [513] [4- (4-Dimethylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [514] (4-Benzenesulfonylamino-phenyl) -carbamic acid tert-butyl ester
    [515] [4- (3-Trifluoromethyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [516] 2,2,2-Trifluoro-N- (5-nitro-pyrimidin-2-yl) -acetamide
    [517] Example 11 (Method 2D)
    [518] 2-Chloro-N- (2-chloro-4-nitrophenyl) acetamide
    [519] A solution of 2-chloro-4-nitroaniline (19.0 g) and chloroacetyl chloride (30 mL) in tetrahydrofuran (150 mL) is heated at reflux for 1 hour. The solution is cooled and concentrated under reduced pressure to yield a wet yellow solid. Ether (250 mL) is added and the yellow solid is collected.
    [520] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [521] N- (4-nitro-3-trifluoromethyl-phenyl) -acetamide
    [522] (2-Chloro-4-nitro-phenyl) -carbamic acid ethyl ester
    [523] 2-Acetylamino-5-nitro-benzoic acid
    [524] Furan-2-carboxylic acid (5-chloro-2-hydroxy-4-nitro-phenyl)
    [525] Furan-2-carboxylic acid (2-methyl-4-nitro-phenyl) -amide
    [526] Furan-2-carboxylic acid (2-methoxy-4-nitro-phenyl) -amide
    [527] N- (2-Chloro-4-nitro-phenyl) -benzamide
    [528] 2-Methoxy-N- (4-nitro-phenyl) -acetamide
    [529] N- (4-nitro-phenyl) -acrylamide
    [530] N- (4-nitro-phenyl) -isobutylamide
    [531] [(4-acryloylamino) -phenyl] -carbamic acid tert-butyl ester
    [532] (4-nitro-phenyl) -carbamic acid isobutyl ester
    [533] [1,2,3] thiadiazole-4-carboxylic acid (5-nitro-pyridin-2-yl)
    [534] Furan-2-carboxylic acid (5-nitro-pyridin-2-yl)
    [535] 2-Fluoro-N- (5-nitro-pyridin-2-yl) -benzamide
    [536] N- (2-Chloro-4-nitro-phenyl) -2-fluoro-benzamide
    [537] Furan-2-carboxylic acid (2,5-dimethoxy-4-nitro-phenyl) -amide
    [538] N- (2-cyano-4-nitro-phenyl) -2-fluoro-benzamide
    [539] 2-Fluoro-N- (2-methoxy-4-nitro-phenyl) -benzamide
    [540] Methyl-N- (5-nitro-pyridin-2-yl) -benzamide
    [541] Furan-2-carboxylic acid (2-methoxy-5-methyl-4-nitro-phenyl)
    [542] 2-Fluoro-N- (2-methoxy-5-methyl-4-nitro-phenyl)
    [543] N- (2-Benzoyl-4-nitro-phenyl) -acetamide
    [544] N- (2-Benzoyl-4-nitro-phenyl) -2-fluoro-benzamide
    [545] Furan-2-carboxylic acid (2-benzoyl-4-nitro-phenyl) -amide
    [546] N- (3-methyl-4-nitro-phenyl) -acetamide
    [547] 2-Fluoro-N- (3-methyl-4-nitro-phenyl) -benzamide
    [548] Furan-2-carboxylic acid (3-methyl-4-nitro-phenyl) -amide
    [549] 2-acetylamino-5-nitro-N-phenyl-benzamide
    [550] 2 - [(2-fluorobenzoyl) amino] -5-nitro-N-phenylbenzamide
    [551] Furan-2-carboxylic acid (4-nitro-2-phenylcarbamoyl-phenyl) -amide
    [552] 2-Fluoro-N- (4-nitro-naphthalen-l-yl) -benzamide
    [553] Furan-2-carboxylic acid (4-nitro-naphthalen-l-yl) -amide
    [554] N- (5-chloro-2-hydroxy-4-nitro-phenyl)
    [555] N- (5-chloro-2-hydroxy-4-nitro-phenyl) -2-fluoro-benzamide
    [556] Furan-2-carboxylic acid (2-chloro-4-nitro-phenyl) -amide
    [557] N- (4-nitro-2-trifluoromethyl-phenyl) -acetamide
    [558] Furan-2-carboxylic acid (2-cyano-4-nitro-phenyl)
    [559] 2-Fluoro-N- (4-nitro-2-trifluoromethyl-phenyl) -benzamide
    [560] Furan-2-carboxylic acid (4-nitro-2-trifluoromethyl-phenyl) -amide
    [561] 2-Fluoro-N- (2-methyl-4-nitro-phenyl) -benzamide
    [562] N- (5-Chloro-2-methyl-4-nitro-phenyl) -2-fluoro-benzamide
    [563] Furan-2-carboxylic acid (5-chloro-2-methyl-4-nitro-phenyl)
    [564] 2- (2-Fluoro-benzoylamino) -5-nitro-benzoic acid
    [565] 2 - [(furan-2-carbonyl) -amino] -5-nitro-benzoic acid
    [566] N- (3-chloro-4-nitro-phenyl) -2-fluoro-benzamide
    [567] Furan-2-carboxylic acid (3-chloro-4-nitro-phenyl) -amide
    [568] 2,6-difluoro-N- (3-methyl-4-nitro-phenyl) -benzamide
    [569] 2-Fluoro-N- (4-nitro-3-trifluoromethyl-phenyl) -benzamide
    [570] Furan-2-carboxylic acid (4-nitro-3-trifluoromethyl-phenyl) -amide
    [571] 2-Chloro-N- (2-chloro-4-nitro-phenyl) -acetamide
    [572] N- (2-chloro-4-nitrophenyl) methanesulfonamide
    [573] Furan-2-carboxylic acid [3-methoxy-4- (2,2,2-trifluoro-acetylamino) -phenyl]
    [574] N- (2-Chloro-4-nitro-phenyl) -2,2,2-trifluoro-acetamide
    [575] Example 12
    [576] {4 - [(4-Phenyl- [1,2,3] thiadiazole-5-carbonyl) -amino] -phenyl} carbamic acid tert-butyl
    [577] To a solution of l- (N-tert-butoxycarbonyl) -1,4-phenylenediamine (0.8 g) and 4-phenyl [l, 2,3] thiadiazole-5-carboxylic acid (1 g) in dichloromethane 1.7 g) is treated with triethylamine (1.3 mL) and benzotriazole-1-yloxy-tris (dimethylamino) phosphonium hexa-fluorophosphate (1.6 g). After stirring at room temperature, the reaction is diluted with water and extracted with dichloromethane. The organic layer is washed with 0.5 N hydrochloric acid, saturated sodium bicarbonate and water, then dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain the desired product.
    [578] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [579] {4 - [(lH-pyrrole-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [580] {4 - [(pyrazine-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [581] {4- [(5-methyl-thiophene-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [582] {4 - [(l-methyl-lH-pyrrole-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [583] {4 - [(Quinoline-8-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [584] {4 - [(Benzofuran-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [585] {4 - [(isoquinoline-1-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [586] {4 - [(Quinoline-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [587] {4 - [(pyridine-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [588] {4 - [(isoquinoline-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [589] {4 - [([1,2,3] thiadiazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [590] {4 - [(1H- [1.2.3] thiazole-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [591] [4- (2-Methylsulfanyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [592] {4 - [(Quinoline-4-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [593] {4 - [(4-methyl- [1,2,3] thiadiazole-5-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [594] {4 - [(4-Phenyl- [1,2,3] thiadiazole-5-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [595] {4 - [(lH-indole-2-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [596] [1,2,3] thiadiazole-4-carboxylic acid 4-nitro-benzylamide
    [597] {4 - [([1,2,3] thiadiazole-4-carbonyl) -amino] -benzyl} -carbamic acid tert-butyl ester
    [598] Acetic acid 4- (4-tert-butoxycarbonylamino-phenylcarbamoyl) -phenyl ester
    [599] {4 - [(Quinoline-6-carbonyl) -amino] -phenyl} -carbamic acid tert-butyl ester
    [600] Example 13 (Method 2F)
    [601] Acetic acid 2- (4-tert-Butoxycarbonylamino-2,6-dichloro-phenoxy) -ethyl ester
    [602] A solution of [3,5-Dichloro-4- (2-hydroxy-ethoxy) -phenyl] -carbamic acid tert-butyl ester (0.85 g) in pyridine (14 mL) was treated with acetic anhydride (1.24 mL) Is stirred at room temperature for 15 hours. The solvent is removed under reduced pressure and the residue is dissolved in ethyl acetate. This solution is washed twice with 5% aqueous hydrochloric acid and once with saturated aqueous sodium bicarbonate followed by saturated aqueous sodium chloride. The solution is dried over anhydrous magnesium sulfate and the solvent is removed under reduced pressure to give the desired product of a colorless oil.
    [603] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [604] Phenylsulfanyl-acetonitrile
    [605] Acetic acid 2- (4-tert-Butoxycarbonylamino-2,6-dichloro-phenoxy) -ethyl ester
    [606] Example 14 (Method 2G)
    [607] (3,5-Dichloro-4-hydroxy-phenyl) -carbamic acid tert-butyl ester
    [608] A solution of 2,6-dichloro-4-aminophenol (9.5 g) in tetrahydrofuran (130 mL) was added ed-tert-butyl-dicarbonate (11.7 g) and the mixture was heated to reflux for approximately 15 hours. The solution is cooled, concentrated under reduced pressure, diluted with ethyl acetate and washed three times with 5% aqueous hydrochloric acid and once with saturated aqueous sodium chloride. The solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the desired crude product. When this material is triturated with cold dichloromethane, a white solid product is obtained.
    [609] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [610] (3-Amino-5-chloro-phenyl) -carbamic acid tert-butyl ester
    [611] Example 15 (Method 3A)
    [612] 3,5-Dichloro-4-ethoxy-phenylamine
    [613] Trifluoroacetic acid (5 mL) is added to solid (3,5-dichloro-4-ethoxy-phenyl) carbamic acid tert-butyl ester (0.97 g) and the mixture is stirred at room temperature for approximately 45 minutes. Water is added and the mixture is cooled in an ice bath and then basified with solid potassium carbonate. The solution is extracted three times with ethyl acetate and the combined organic phases are washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. Concentration under reduced pressure and recrystallization from hexane gives the desired product of a pale yellow crystalline solid.
    [614] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [615] 5-Bromo-pyridin-3-ylamine
    [616] 3-Chloro-4-methanesulfonyl-phenylamine
    [617] N- (4-Amino-phenyl) -2-methyl-benzamide
    [618] Acetic acid 2- (4-amino-phenylcarbamoyl) -phenyl ester
    [619] N- (4-amino-phenyl) -4-fluoro-benzamide
    [620] N- (4-Amino-phenyl) -3-fluoro-benzamide
    [621] N- (4-amino-phenyl) -2-fluoro-benzamide
    [622] N- (4-amino-phenyl) -2-methoxy-benzamide
    [623] N- (4-amino-phenyl) -3-methoxy-benzamide
    [624] N- (4-amino-phenyl) -4-methoxy-benzamide
    [625] N- (4-amino-phenyl) -2-phenyl-acetamide
    [626] N- (4-Amino-phenyl) -2,2-dimethyl-propionamide
    [627] N- (4-amino-phenyl) -2,2,2-trifluoro-acetamide
    [628] Thiophene-2-carboxylic acid (4-amino-phenyl) -amide
    [629] Pyrrole-2-carboxylic acid (4-amino-phenyl) -amide
    [630] N- (4-amino-phenyl) -3-nitro-benzamide
    [631] 3-Acetylamino-N- (4-amino-phenyl) -benzamide
    [632] N- (4-amino-phenyl) -3-dimethylamino-benzamide
    [633] N- (4-amino-phenyl) -3-methanesulfonylamino-benzamide
    [634] N- (4-Amino-phenyl) -2-trifluoromethyl-benzamide
    [635] N- (4-amino-phenyl) -2,6-difluoro-benzamide
    [636] N- (4-amino-phenyl) -2-chloro-benzamide
    [637] N- (4-amino-phenyl) -2-bromo-benzamide
    [638] N- (4-amino-phenyl) -2-nitro-benzamide
    [639] Pyrazine-2-carboxylic acid (4-amino-phenyl) -amide
    [640] 5-methyl-thiophene-2-carboxylic acid (4-amino-phenyl) -amine
    [641] Quinoline-8-carboxylic acid (4-amino-phenyl) -amide
    [642] Methyl-lH-pyrrole-2-carboxylic acid (4-amino-phenyl) -amide
    [643] Benzo [b] thiophene-2-carboxylic acid (4-amino-phenyl) -amide
    [644] Benzofuran-2-carboxylic acid (4-amino-phenyl) -amide
    [645] N- (4-amino-phenyl) -isonicotinamide
    [646] Naphthalene-2-carboxylic acid (4-amino-phenyl) -amide
    [647] Naphthalene-1-carboxylic acid (4-amino-phenyl) -amide
    [648] Isoquinoline-1-carboxylic acid (4-amino-phenyl) -amide
    [649] Quinoline-2-carboxylic acid (4-amino-phenyl) -amide
    [650] 3,5-Dichloro-4-ethoxy-phenylamine
    [651] 4-Butoxy-3,5-dichloro-phenylamine
    [652] Isoquinoline-4-carboxylic acid (4-amino-phenyl) -amide
    [653] [1,2,3] thiadiazole-4-carboxylic acid (4-amino-phenyl) -amide
    [654] 1 H- [1,2,3] triazole-4-carboxylic acid (4-amino-phenyl)
    [655] 3-Bromo-thiophene-2-carboxylic acid (4-amino-phenyl) -amide
    [656] 4-Benzyloxy-3,5-dichloro-phenylamine
    [657] 2- (4-Amino-2,6-dichloro-phenoxy) -acetamide
    [658] (4-amino-2,6-dichloro-phenoxy) -acetic acid methyl ester
    [659] [3- (4-Amino-phenylcarbamoyl) -phenyl] -carbamic acid ethyl ester
    [660] 2-Amino-N- (4-amino-phenyl) -benzamide
    [661] Biphenyl-2-carboxylic acid (4-amino-phenyl) -amide
    [662] N- (4-amino-phenyl) -2,3-difluoro-benzamide
    [663] N- (4-Amino-phenyl) -2,5-difluoro-benzamide
    [664] N- (4-amino-phenyl) -2,4-difluoro-benzamide
    [665] 2-Acetylamino-N- (4-amino-phenyl) -benzamide
    [666] N- (4-amino-phenyl) -2-methanesulfonylamino-benzamide
    [667] N- (4-amino-phenyl) -2,3,4-trifluoro-benzamide
    [668] N- (4-amino-phenyl) -2,3,4,5,6-pentafluoro-benzamide
    [669] N- (4-amino-phenyl) -2-methylsulfanyl-benzamide
    [670] Acetic acid 2- (4-amino-2,6-dichloro-phenoxy) -ethyl ester
    [671] N- (4-amino-phenyl) -isophthalamic acid methyl ester
    [672] N- (4-amino-phenyl) -3-benzyloxy-benzamide
    [673] N- (4-amino-phenyl) -3-butoxy-benzamide
    [674] [3- (4-Amino-phenylcarbamoyl) -phenoxy] -acetic acid ethyl ester
    [675] Pyridine-2-carboxylic acid (4-amino-phenyl) -amide
    [676] Quinoline-4-carboxylic acid (4-amino-phenyl) -amide
    [677] 5-Methyl-furan-2-carboxylic acid (4-amino-phenyl) -amide
    [678] 5-difluoromethyl-furan-2-carboxylic acid (4-amino-phenyl) -amide
    [679] Indole-2-carboxylic acid (4-amino-phenyl) -amide
    [680] Methyl [l, 2,3] thiadiazole-5-carboxylic acid (4-amino-phenyl) -amide
    [681] Thiophene-3-carboxylic acid (4-amino-phenyl) -amide
    [682] 5-Chloro-furan-2-carboxylic acid (4-amino-phenyl) -amide
    [683] 5-Nitro-furan-2-carboxylic acid (4-amino-phenyl) -amide
    [684] N- (4-amino-phenyl) -2-thiophen-2-yl-acetamide
    [685] 3-Methyl-furan-2-carboxylic acid (4-amino-phenyl) -amide
    [686] 5-Bromo-furan-2-carboxylic acid (4-amino-phenyl) -amide
    [687] 4-Bromo-furan-2-carboxylic acid (4-amino-phenyl) -amide
    [688] N- (4-amino-phenyl) -nicotinamide
    [689] N- (4-aminophenyl) -3-furancarboxamide
    [690] 4-phenyl- [l, 2,3] thiadiazole-5-carboxylic acid (4-amino- phenyl)
    [691] Acetic acid 3- (4-amino-phenylcarbamoyl) -phenyl ester
    [692] Benzo [l, 3] dioxole-4-carboxylic acid (4-amino-phenyl)
    [693] N- (4-amino-phenyl) -3- (2-dimethylamino-ethoxy) -benzamide
    [694] N- (4-amino-phenyl) -3-trifluoromethoxy-benzamide
    [695] N- (4-amino-phenyl) -3- (2-morpholin-4-yl-ethoxy)
    [696] (4-Amino-phenyl) -carbamic acid hexyl ester
    [697] Furan-2-carboxylic acid (4-amino-phenyl) -amide
    [698] (4-amino-phenyl) -carbamic acid phenyl ester
    [699] Hexanoic acid (4-amino-phenyl) -amide
    [700] N- (4-amino-phenyl) -acrylamide
    [701] N- (4-Amino-phenyl) -2-methoxy-acetamide
    [702] 4-furan-3-yl [1,2,3] thiadiazole-5-carboxylic acid (4-amino- phenyl)
    [703] 5-tert-Butyl-furan-2-carboxylic acid (4-amino-phenyl)
    [704] 3-Chloro-4-methanesulfinyl-phenylamine
    [705] 5-Methyl- [l, 2,3] thiadiazole-4-carboxylic acid (4-amino-phenyl)
    [706] 2- (4-Amino-2-chloro-phenyl) -ethanol
    [707] (4-Amino-2-chloro-phenyl) -carbamic acid 2-piperidin-1-yl-ethyl ester
    [708] 5-Chloro-N, N-dimethyl-benzene-1,3-diamine
    [709] 3- (2-Methyl-butyl) -5-trifluoromethyl-phenylamine
    [710] 3-isobutyl-5-trifluoromethyl-phenylamine
    [711] Furan-2-carboxylic acid (4-aminomethyl-phenyl) -amide
    [712] N- (4-Aminomethyl-phenyl) -2-fluoro-benzamide
    [713] [1,2,3] thiadiazole-4-carboxylic acid (4-aminomethyl-phenyl) -amide
    [714] N- (4-Aminomethyl-phenyl) -2,6-difluoro-benzamide
    [715] Oxazole-4-carboxylic acid (4-amino-phenyl) -amide
    [716] N- (4-amino-phenyl) -3-chloro-benzamide
    [717] N- (4-amino-phenyl) -4-chloro-benzamide
    [718] Acetic acid 4- (4-amino-phenylcarbamoyl) -phenyl ester
    [719] N- (4-amino-phenyl) -4-dimethylamino-benzamide
    [720] L- (4-Amino-phenyl) -3- (3,5-bis-trifluoromethyl-phenyl) -thiourea
    [721] N- (4-Amino-phenyl) -2-iodo-benzamide
    [722] N- (4-amino-phenyl) -3-trifluoromethyl-benzamide
    [723] Example 16 (Method 3B)
    [724] L- (4-Amino-2-chloro-phenyl) -ethanol
    [725] A 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (5.7 mL) was added to a solution of [3-chloro-4- (1-hydroxy-ethyl) -phenyl] carbamic acid 2-trimethylsilanyl- And the mixture is stirred at room temperature for approximately 3.5 hours. The solution is concentrated under reduced pressure, dissolved in a 1: 1 mixture of ethyl acetate and hexane, successively washed with water and then saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. Removal of the solvent under reduced pressure followed by chromatography on silica gel (40% ethyl acetate in hexanes was used as eluent) gave the product of the amber oil.
    [726] Example 17 (Method 3C)
    [727] N- (4-amino-3-cyanophenyl) -2-fluoro-benzamide
    [728] (5.0 g) was added to a solution of N- [3-cyano-4- (2,2,2-trifluoroacetyl-amino) -phenyl] -2-fluoro Benzamide (2.5 g) and the mixture is refluxed overnight. After the solvent is removed under reduced pressure, the residue is suspended in water and extracted with dichloromethane. The organic extracts are collected, washed with water followed by saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to yield the desired compound as a white solid.
    [729] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [730] N- (4-amino-phenyl) -2-methanesulfinyl-benzamide
    [731] N- (4-Amino-3-cyano-phenyl) -2-fluoro-benzamide
    [732] Furan-2-carboxylic acid (4-amino-3-cyano-phenyl)
    [733] N- (4-amino-3-cyano-phenyl) -acetamide
    [734] Furan-2-carboxylic acid (4-amino-3-trifluoromethyl-phenyl) -amide
    [735] N- (4-amino-3-methoxy-phenyl) -acetamide
    [736] N- (4-Amino-3-methoxy-phenyl) -2-fluoro-benzamide
    [737] Furan-2-carboxylic acid (4-amino-3-methoxy-phenyl)
    [738] Example 17 (Method 4A)
    [739] 2-Chloro-1-cyclohexyl-4-nitro-benzene
    [740] Cyclohexanol (2.9 g) in dimethyl sulfoxide (20 mL) is slowly added to a flask containing potassium hydride (0.90 g, prewashed with hexane 3 times) under an argon atmosphere and the solution is stirred at room temperature for about 1 hour. A solution of 3-chloro-4-fluoro-nitrobenzene (1 g) in dimethyl sulfoxide (10 mL) is added and the resulting dark red solution is heated to approximately 100 ° C for 3 hours. The reaction mixture is cooled, diluted with diethyl ether (300 mL) and then washed successively with saturated aqueous ammonium chloride, then with water, then with saturated aqueous sodium chloride. The organic layer is dried over anhydrous magnesium sulfate, the solvent is removed under reduced pressure and the resulting oil is chromatographed on silica gel (eluting with 5% ethyl acetate in hexanes) to give the desired product as an orange solid.
    [741] Example 18 (Method 4C)
    [742] (2-chloro-4-nitro-phenyl) -methyl- (1-methyl-pyrrolidin-
    [743] 3-Chloro-4-fluoronitrobenzene (1.0 g) and N, N'-dimethyl-3-aminopyrrolidine (1.72 g) were collected and stirred for about 24 hours. The mixture is diluted with ethyl acetate, washed twice with water, once with saturated sodium chloride, and dried over anhydrous sodium sulfate. After removal of the solvent under reduced pressure, the residue is chromatographed on silica gel (using pure ethyl acetate followed by pure methanol as eluent) to give the desired product of a yellow oil.
    [744] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [745] (2-Chloro-4-nitro-phenyl) -dipropyl-amine
    [746] L- (2-Chloro-4-nitro-phenyl) -piperidine
    [747] L- (2-Chloro-4-nitro-phenyl) -pyrrolidine
    [748] (2-Chloro-4-nitro-phenyl) -cyclohexyl-methyl-amine
    [749] Benzyl- (2-chloro-4-nitro-phenyl) -amine
    [750] (2-chloro-4-nitro-phenyl) -methyl- (1-methyl-piperidin-
    [751] (2-Chloro-4-nitro-phenyl) -cyclohexyl-ethyl-amine
    [752] (2-Chloro-4-nitro-phenyl) -cyclohexyl-amine
    [753] (2-chloro-4-nitro-phenyl) -methyl- (1-methyl-pyrrolidin-
    [754] (L-Benzyl-pyrrolidin-3-yl) - (2-chloro-4-nitro- phenyl)
    [755] (2-Chloro-4-nitro-phenyl) -cyclopentyl-methyl-amine
    [756] L- (2-Chloro-4-nitro-phenyl) -decahydro-quinoline
    [757] Allyl- (2-chloro-4-nitro-phenyl) -cyclohexyl-amine
    [758] 2 - [(2-Chloro-4-nitro-phenyl) - (2- hydroxy- ethyl) -amino]
    [759] (2-Chloro-4-nitro-phenyl) -isobutyl-methyl-amine
    [760] (2-Chloro-4-nitro-phenyl) -hexyl-methyl-amine
    [761] 2 - [(2-Chloro-4-nitro-phenyl) -methyl- amino] -ethanol
    [762] N- (2-chloro-4-nitro-phenyl) -N, N ', N'-trimethyl-
    [763] N- (2-chloro-4-nitro-phenyl) -N, N ', N'-trimethyl-
    [764] (L-Benzyl-piperidin-4-yl) - (2-chloro-4-nitro- phenyl)
    [765] N- (2-Chloro-4-nitro-phenyl) -N ', N'-dimethyl-
    [766] N- (2-chloro-4-nitro-phenyl) -N ', N'-dimethyl-
    [767] (2-chloro-4-nitro-phenyl) - (2-methoxy-ethyl)
    [768] (L-Benzyl-pyrrolidin-3-yl) - (2-chloro-4-nitro- phenyl)
    [769] 4-Piperidin-1-yl-3-trifluoromethyl-benzonitrile
    [770] 4-Dimethylamino-3-trifluoromethyl-benzonitrile
    [771] 4- (4-Methyl-piperazin-1-yl) -3-trifluoromethyl-benzonitrile
    [772] Example 19 (Method 4E)
    [773] Butyl- (2-chloro-4-nitro-phenyl) thioether
    [774] A solution of 3-chloro-4-fluoro-nitrobenzene (5.0 g) and sodium sulfide (2.5 g) in N, N-dimethylformamide (30 mL) was stirred at room temperature for 1 hour and then 1-iodobutane 12.6 g). The solvent is removed under reduced pressure and the resulting residue is treated with ethyl acetate and hexane to precipitate inorganic salts. The solids are removed by filtration and the filtrate is reduced under reduced pressure. The residue produced using dichloromethane as an eluent is passed through a hydrous magnesium silicate to give the desired compound in the form of a yellow solid.
    [775] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [776] 1-Butylsulfanyl-2-chloro-4-nitro-benzene
    [777] 2-Chloro-1-cyclohexylsulfanyl-4-nitro-benzene
    [778] 2-Chloro-l-ethylsulfanyl-4-nitro-benzene
    [779] Example 20 (Method 4F)
    [780] (4-Chloro-5-methoxy-2-nitro-phenyl) -dimethyl-amine
    [781] Dimethylamine (4.0 mL of 40% aqueous solution) was added to a solution of trifluoro-methanesulfonic acid 4-chloro-5-methoxy-2-nitro-phenyl ester (1.0 g) in tetrahydrofuran (2.0 mL) Lt; / RTI > for about 15 hours. The solution is concentrated under reduced pressure and the residue is dissolved in ethyl acetate and washed with water. The aqueous layer is extracted once with ethyl acetate and the combined organic layers are washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. The solvent is removed by evaporation under reduced pressure and the residue is triturated with hexane to give the desired product as a colorless solid.
    [782] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [783] (4-Chloro-2-nitro-phenyl) -dimethyl-amine
    [784] 4- (4-Chloro-5-methoxy-2-nitro-phenyl) -morpholine
    [785] (4-Chloro-5-methoxy-2-nitro-phenyl) -dimethyl-amine
    [786] L- (4-Chloro-5-methoxy-2-nitro-phenyl) -piperidine
    [787] L- (4-Chloro-5-methoxy-2-nitro-phenyl) -pyrrolidine
    [788] Benzyl- (4-chloro-5-methoxy-2-nitro-phenyl) -amine
    [789] (2-Chloro-6-nitro-phenyl) -dimethyl-amine
    [790] Example 21 (Method 4G)
    [791] (2-Chloro-4-nitro-phenyl) -methyl-phenyl-amine
    [792] n-Butyl lithium (12.5 mL of 2.5 M solution in hexane) is added dropwise to a solution of N-methylaniline (3.0 g) in tetrahydrofuran (75 mL) at 0 ° C. The mixture is slowly warmed to room temperature and then canned again to a solution of 3-chloro-4-fluoronitrobenzene (4.9 g) in tetrahydrofuran (35 mL), re-cooled to 0 ° C and maintained at -78 ° C. After addition, the reaction mixture is warmed to room temperature over 1 hour, concentrated under reduced pressure, quenched with saturated aqueous ammonium chloride, and extracted three times with ethyl acetate. The combined organic layers are washed three times with 5% aqueous hydrochloric acid, once with water, once with saturated aqueous sodium bicarbonate, once with saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the residue is chromatographed on silica gel (eluting with 5% diethyl ether in hexanes) to give the desired product of a clear, colorless oil.
    [793] Example 22 (Method 4H)
    [794] 2,6-dichloro-4-nitrophenol
    [795] 3,4,5-Trichlorobenzene (14.86 g) is added to a solution of potassium phenoxide (8.66 g) in diethylene glycol (66 mL) and the mixture is heated to 160 DEG C for approximately 15 hours. The resulting dark brown solution is cooled to room temperature, poured onto 100 mL cold water, and extracted twice with diethyl ether. The combined organic extracts are washed with water, 10% aqueous sodium hydroxide and dried over anhydrous magnesium sulfate. After the solvent is removed under reduced pressure, the resulting oil is distilled using a Kugelrohr apparatus to obtain a yellow oil which solidifies upon standing. Recrystallization from ethanol-water gives the desired product of a pale yellow solid.
    [796] Example 23 (Method 5A)
    [797] (3,5-Dichloro-4-ethoxy-phenyl) -carbamic acid tert-butyl ester
    [798] Ethyl iodide (0.36 mL) was added to a solution of (3,5-dichloro-4-hydroxy-phenyl) -carbamic acid tert-butyl ester (1.0 g) and potassium carbonate (1.0 g) in acetone And the mixture is stirred at room temperature for approximately 15 hours. The solution is filtered, concentrated under reduced pressure, and partitioned between ethyl acetate and water. The separated aqueous layer was extracted twice more with ethyl acetate, and the combined organic extracts were washed successively with 10% aqueous sodium hydroxide, water, and dried over anhydrous sodium sulfate. Evaporation of the solvent under reduced pressure gives the desired product of a tan solid.
    [799] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [800] (3,5-Dichloro-4-ethoxy-phenyl) -carbamic acid tert-butyl ester
    [801] (4-Butoxy-3,5-dichloro-phenyl) -carbamic acid tert-butyl ester
    [802] (4-Benzyloxy-3,5-dichloro-phenyl) -carbamic acid tert-butyl ester
    [803] (4-Carbamoylmethoxy-3,5-dichloro-phenyl) -carbamic acid tert-butyl ester
    [804] [3,5-Dichloro-4- (2-nitrilo-ethoxy) -phenyl] -carbamic acid tert-butyl ester
    [805] (4-tert-Butoxycarbonylamino-2,6-dichloro-phenoxy) -acetic acid methyl ester
    [806] 3-Butoxy-benzoic acid methyl ester
    [807] 3-tert-Butoxycarbonylmethoxy-benzoic acid methyl ester
    [808] 3-Carbamoylmethoxy-benzoic acid methyl ester
    [809] [4- (3-Carbamoylmethoxy-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [810] {4- [3- (2-Chloro-ethoxy) -benzoylamino] -phenyl} -carbamic acid tert-butyl ester
    [811] Example 24 (Method 5C)
    [812] (2,6-Dichloro-4-nitro-phenoxy) -acetic acid tert-butyl ester
    [813] Tert-Butyl-bromoacetate (10 mL) was added to a solution of 2,6-dichloro-4-nitrophenol (2.5 g) and potassium carbonate (3.3 g) in dimethylformamide (50 mL) Stir for 2 days. The solution is poured into 500 mL of water, extracted three times with hexane, and the combined organic extracts are washed with saturated aqueous ammonium chloride and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the resulting oil is triturated with hexane to give the desired product of a white solid.
    [814] Using the above procedure and starting materials the following compounds were prepared:
    [815] 3-Dimethylamino-l- (4-nitro-phenyl) -propenone
    [816] 2-chloro-1-isopropoxy-4-nitro-benzene
    [817] 1,3-dichloro-2-methoxy-4-methyl-5-nitro-
    [818] 1-Chloro-4-ethoxy-2-methoxy-5-nitro-
    [819] 1-Butoxy-4-chloro-5-methoxy-2-nitro-benzene
    [820] Chloro-2-methoxy-5-nitro-4- (phenylmethoxy) benzene (CA name)
    [821] Chloro-4-methoxy-5-nitro-2- (phenylmethoxy) benzene (CA name)
    [822] (2,6-Dichloro-4-nitro-phenoxy) -acetic acid tert-butyl ester
    [823] (2,6-Dichloro-4-nitro-phenoxy) -acetonitrile
    [824] 1-Chloro-4-methoxy-2-methyl-5-nitro-
    [825] 2- (4-Chloro-5-methoxy-2-nitro-phenoxy) -acetamide
    [826] 2- (2-Chloro-5-methoxy-4-nitro-phenoxy) -acetamide
    [827] (4-Chloro-5-methoxy-2-nitro-phenoxy) -acetonitrile
    [828] (2-Chloro-5-methoxy-4-nitro-phenoxy) -acetonitrile
    [829] 4- (2-Chloro-5-methoxy-4-nitro-phenoxy) -butyronitrile
    [830] 2- (4-Chloro-5-methoxy-2-nitro-phenoxy)
    [831] 2- (2-Chloro-5-methoxy-4-nitro-phenoxy)
    [832] (2-Chloro-5-methoxy-4-nitro-phenoxy) -acetic acid tert-butyl ester
    [833] (2-Chloro-5-methoxy-4-nitro-phenoxy) -acetic acid methyl ester
    [834] (4-Chloro-5-methoxy-2-nitro-phenoxy) -acetic acid methyl ester
    [835] (4-Chloro-5-methoxy-2-nitro-phenoxy) -acetic acid tert-butyl ester
    [836] (2-Chloro-4-nitro-phenoxy) -acetonitrile
    [837] 1-Butoxy-2-chloro-4-nitro-benzene
    [838] 2-Chloro-4-nitro-1- (2,2,2-trifluoro-ethoxy)
    [839] 2-Chloro-4-nitro-1-propoxy-benzene
    [840] 2-chloro-1-ethoxy-4-nitro-benzene
    [841] 1,3-Diiodo-2,4-dimethoxy-5-nitro-benzene
    [842] 1,3-dibromo-2,4-dimethoxy-5-nitro-benzene
    [843] 3-Chloro-2,4-dimethoxy-nitrobenzene
    [844] Example 25 (Method 5E)
    [845] [3,5-Dichloro-4- (2-hydroxy-ethoxy) -phenyl] -carbamic acid tert-butyl ester
    [846] To a solution of (3,5-dichloro-4-hydroxy-phenyl) -carbamic acid tert-butyl ester (1.0 g) and potassium carbonate (0.55 g) in toluene (20 mL) was added ethylene carbonate (1.6 g) Is heated at reflux for 3 hours. To the cooled reaction mixture is added 2.5M aqueous sodium hydroxide (50 mL) and the separated organic layer is successively washed with water, saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. The solvent is removed by evaporation under reduced pressure and the resulting residue is chromatographed on silica gel (eluting with 30% ethyl acetate in hexanes) to give the desired product of the white foam.
    [847] Example 26 (Method 6)
    [848] 3- (2-Chloro-4-nitro-phenoxy) -l-methyl-pyrrolidine
    [849] To a solution of 2-chloro-4-nitrophenol (2.0 g) in tetrahydrofuran (60 mL) were added 1-methyl-3-pyrrolidinol (2.3 g), triphenylphosphine (6.0 g) and diethyl azodicarboxyl (3.6 mL) is added and the mixture is stirred at room temperature under an argon atmosphere for 1.5 hours. The solution is concentrated under reduced pressure, diluted with ethyl acetate, washed successively with 10% aqueous sodium hydroxide, water, saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate. The solvent is removed by evaporation under reduced pressure and the residue is chromatographed on silica gel (using ethyl acetate followed by 10% methanol in dichloromethane). Recrystallization of the collected product fractions with hexane gives the desired product of a yellow solid.
    [850] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [851] 4- (2-Chloro-4-nitro-phenoxy) -l-methyl-piperidine
    [852] 3- (2-Chloro-4-nitro-phenoxy) -l-methyl-pyrrolidine
    [853] [2- (2-Chloro-4-nitro-phenoxy) -ethyl] -dimethyl-amine
    [854] [3- (2-Chloro-4-nitro-phenoxy) -propyl] -dimethyl- amine
    [855] Example 27 (Method 7A)
    [856] 2-chloro-3-methoxy-6-nitro-phenol and 2,4-dichloro-3-methoxy-
    [857] To a flask containing 3-methoxy-6-nitro-phenol (0.5 g) was added aqueous sodium hypochlorite (5.25% aqueous solution, 21 mL) and the mixture was stirred at room temperature for approximately 24 hours. The mixture was cooled in an ice bath, acidified with concentrated hydrochloric acid, and extracted twice with ethyl acetate. This organic extract was dried over anhydrous magnesium sulfate, the solvent was removed by evaporation under reduced pressure, and the residue was chromatographed on silica gel (using 15% acetone in hexane as eluent) to afford mono- and di-chlorination of the yellow solid The product is obtained.
    [858] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [859] 3-Chloro-2-hydroxy-4-methoxy-nitrobenzene
    [860] 3,5-Dichloro-2-hydroxy-4-methoxy-nitrobenzene
    [861] Example 28 (Method 7B)
    [862] 2,4-dichloro-3-methyl-6-nitro-phenol
    [863] To a solution of 3-methyl-4-nitro-phenol (5.0 g) in water (150 mL) was added aqueous sodium hypochlorite (5.25% aqueous solution, 230 mL) and the mixture was stirred at room temperature for approximately 15 hours. Additional aqueous sodium hypochlorite (5.25% aqueous solution, 230 mL) is added and the mixture is stirred at room temperature for 2.5 days. The mixture is cooled in an ice bath, acidified with concentrated hydrochloric acid and extracted twice with ethyl acetate. The organic extracts are dried over anhydrous magnesium sulfate, the solvent is removed by evaporation under reduced pressure, and the residue is chromatographed on silica gel (using ethyl acetate as eluent) to give the desired product of a yellow solid. Once recrystallized with chloroform, a pure sample is obtained by analysis.
    [864] Example 29 (Method 7C)
    [865] 1-Bromo-2,4-dimethoxy-5-nitro-benzene
    [866] A solution of bromine (0.23 g) in chloroform (1 mL) was added dropwise to a solution of 2,4-dimethoxy-nitrobenzene (0.50 g) in chloroform (3 mL) and the mixture was stirred at room temperature for approximately 15 hours. Additional bromine (0.15 g) in chloroform (1 mL) is added and the reaction is stirred for an additional 4 h. The mixture is poured onto 5% aqueous sodium bisulfite and extracted with chloroform. The combined organic extracts are washed successively with 5% aqueous sodium bisulfite followed by saturated sodium chloride and dried over anhydrous sodium sulfate. Removal of the solvent under reduced pressure and recrystallization of the residue with toluene gives the desired product of a yellow solid.
    [867] Example 30 (Method 7D)
    [868] 2,4-dibromo-3-methoxy-6-nitro-phenol
    [869] A solution of bromine (1.42 g) in glacial acetic acid (3 mL) was added dropwise to a solution of 5-methoxy-2-nitro-phenol (0.25 g) and silver trifluoroacetate (0.49 g) in glacial acetic acid (3 mL) Lt; / RTI > for about 24 hours. The solution is partitioned between ethyl acetate and water and the organic layer is washed three times with 5% aqueous sodium bisulfite, three times with saturated aqueous sodium bicarbonate, and once with saturated aqueous sodium chloride. The organic layer is dried over anhydrous magnesium sulfate and the solvent is dried under reduced pressure. The residue was chromatographed on silica gel (20% ethyl acetate in hexane as eluent) and recrystallized from chloroform to give the desired bromide product of an orange solid.
    [870] Example 31 (Method 7E)
    [871] 1-Iodo-2,4-dimethoxy-5-nitro-benzene
    [872] Benzyltrimethylammonium dichloroiodate (1.90 g) and anhydrous zinc chloride (1.0 g) were added to a solution of 2,4-dimethoxy-nitrobenzene (1.0 g) in glacial acetic acid (30 mL) and the mixture was stirred do. Additional benzyltrimethylammonium dichloroiodate (0.4 g) is added after 5 h and after 24 h. Additional zinc chloride (0.5 g) and glacial acetic acid (15 mL) are added after 24 h. The mixture is stirred for 3 days at room temperature and filtered, then diluted with 5% aqueous sodium bisulfite and extracted three times with ethyl acetate. The combined organic layers are successively washed with 5% aqueous sodium bisulfite, saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the residue is triturated with hexane to give the desired product of a pale yellow solid.
    [873] Example 32 (Method 7F)
    [874] 2,4-Diiodo-3-methoxy-6-nitro-phenol
    [875] Benzyltrimethylammonium dichloroiodate (1.08 g) and sodium bicarbonate (0.85 g) were added to a solution of 5-methoxy-2-nitro-phenol (0.25 g) in dichloromethane (15 mL) and methanol The mixture is stirred at room temperature for 24 hours. The solution is filtered, the filtrate is concentrated under reduced pressure, the residue is dissolved in ethyl acetate and successively washed with 5% aqueous sodium bicarbonate, 5% aqueous sodium bisulfite and saturated aqueous sodium chloride. After drying over anhydrous magnesium sulfate, the solvent is removed by evaporation under reduced pressure, and the residue is recrystallized from toluene to give the desired product in the form of a yellow needle.
    [876] Example 33 (Method 7G)
    [877] 1-Fluoro-2,4-dimethoxy-5-nitro-benzene
    [878] 3,5-Dichloro-1-fluoro-pyridinium triflate (85%, 5.07 g) was added to a solution of 2,4-dimethoxy-nitrobenzene (1.0 g) in tetrachloroethane (10 mL) Heat to 120 < 0 > C for 5 hours. Additional 3,5-dichloro-1-fluoro-pyridinium triflate (85%, 0.25 g) is added and heating is continued for 1 hour. The solution is cooled to room temperature and passed through a silica gel column (using hexane followed by 30% ethyl acetate in hexanes as eluent). The product containing fractions were pooled, evaporated under reduced pressure and the residue crystallized with hexane to give the desired product as a tan solid.
    [879] Example 34 (Method 8)
    [880] 3-Chloro-4-trifluoromethyl-nitrobenzene
    [881] (2.26 g), trimethyl (trifluoromethyl) silane (5.68 g), copper (I) iodide (2.28 g) in N, N-dimethylformamide g) and potassium fluoride (0.56 g) in a sealed tube is heated to 80 < 0 > C for 40 hours. The solution is cooled, diluted with diethyl ether, filtered through diatomaceous earth, and the filtrate is successively washed with water, saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue chromatographed on silica gel (using 1% diethyl ether in hexanes followed by 10% ethyl acetate in hexanes as eluent) to give the desired product of a colorless oil.
    [882] Example 35 (Method 9)
    [883] (3-Chloro-4-methanesulfinyl-phenyl) -carbamic acid tert-butyl ester
    [884] To a solution of (3-chloro-4-thiomethyl-phenyl) -carbamic acid tert-butyl ester (0.89 g) in dichloromethane (15 mL) at 0 ° C was added a solution of dimethyldioxirane (~0.11 M in acetone, 34 mL) Is added and the mixture is stirred at 0 < 0 > C for 1 hour. The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane, washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Removal of the solvent under reduced pressure gives the desired product in the form of an orange foam.
    [885] Example 36 (Method 9B)
    [886] [4- (2-methylsulfinyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [887] To a solution of 2-methylsulfanyl-N- [4- (2,2,2-trifluoro-acetylamino) -phenyl] benzamide (234 mg) was added saturated sodium peridate solution (5 mL) Is stirred for 12 hours. The purple mixture is poured into water, extracted with ethyl acetate, dried over anhydrous potassium carbonate and evaporated to give 101 mg of a red solid.
    [888] Using the above procedure and the appropriate starting materials the following compounds were prepared.
    [889] [4- (2-Methanesulfinyl-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [890] 2-methanesulfinyl-N- [4- (2,2,2-trifluoro-acetylamino) -phenyl] -benzamide
    [891] Implementation 37 (Method 10)
    [892] (3-Chloro-4-methanesulfonyl-phenyl) -carbamic acid tert-butyl ester
    [893] A solution of dimethyldioxirane (~0.11 M in acetone, 80 mL) was added to a solution of (3-chloro-4-thiomethyl-phenyl) -carbamic acid tert- butyl ester (0.90 g) in dichloromethane (30 mL) Is added and the mixture is stirred at 0 < 0 > C for 1 hour. The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane, washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Removal of the solvent under reduced pressure gives the desired product of the orange foam.
    [894] Example 38 (Method 11)
    [895] 3-Chloro-4-vinyl-phenylamine
    [896] Oxygen removal of 3-chloro-4-iodo-aniline (6.95 g), triphenylarsine (0.67 g) and tris (dibenzylideneacetone) palladium (0) (0.50 g) in tetrahydrofuran Was added tributylvinyltin (10 g) at 50 < 0 > C and the mixture was stirred under an argon atmosphere at 50 < 0 > C for approximately 15 hours. The reaction is cooled, filtered through diatomaceous earth, and the filtrate is evaporated to dryness under reduced pressure. The residue is dissolved in hexane and extracted three times with 5% aqueous hydrochloric acid. This aqueous acidic extract is basified with solid potassium carbonate and extracted three times with ethyl acetate. The combined organic extracts are washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and the solvent is removed under reduced pressure. Chromatographing the resulting residue on silica gel (using hexane followed by 10% ethyl acetate in hexanes as eluent) gave the desired product of the amber oil.
    [897] Example 39 (Method 12)
    [898] [3-Chloro-4- (1-hydroxy-ethyl) -phenyl] -carbamic acid 2-trimethylsilanyl-ethyl ester
    [899] (2.6 g) was added to a solution of mercury acetate (3.48 g) in water (7 mL) and tetrahydrofuran (5.25 mL) And the mixture is stirred for approximately 15 hours. 3N Aqueous sodium hydroxide (8.7 mL) and a 0.5 M solution of sodium borohydride in 3N aqueous sodium hydroxide (8.7 mL) are added and stirred continuously for 6 hours. The solution is saturated with sodium chloride and extracted with ethyl acetate. This organic extract is washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. Removal of the solvent under reduced pressure and chromatography of the residue on silica gel (using 20% ethyl acetate in hexanes as eluent) gave the desired product as a white solid.
    [900] Example 40 (Method 13)
    [901] [3-Chloro-4- (2-hydroxy-ethyl) -phenyl] -carbamic acid tert-butyl ester
    [902] To a stirred suspension of sodium borohydride (0.45 g) in tetrahydrofuran (13 mL) at 0 C is added glacial acetic acid (0.75 mL) and the mixture is stirred at 0 < 0 > C for 1 hour. The solution is warmed to room temperature and (3-chloro-4-vinyl-phenyl) -carbamic acid 2-trimethylsilanyl-ethyl ester (1.0 g) is added. The reaction is stirred at room temperature for approximately 15 hours and then heated to reflux for approximately 20 hours. The mixture is cooled and a solution of 5 N aqueous sodium hydroxide (0.80 mL) and 30% aqueous hydrogen peroxide (0.56 mL) is added. After stirring for an additional 15 hours, the layers were separated, the aqueous layer was extracted three times with diethyl ether and the organic extracts were dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the residue is chromatographed on silica gel (using 40% ethyl acetate in hexanes as eluent) to give the desired product of the amber oil.
    [903] Example 41 (Method 14)
    [904] [4- (1-Azido-ethyl) -3-chloro-phenyl] -carbamic acid 2-trimethylsilanyl-ethyl ester
    [905] To a solution of 3-chloro-4- (1-hydroxy-ethyl) -phenyl] -carbamic acid 2-trimethylsilanyl-ethyl ester (1.25 g) in tetrahydrofuran (20 mL) Phenyl-phosphine (2.6 g), hydrazoic acid (approximately 2.5 molar equivalents in dichloromethane, prepared by the method of Fieser and Fieser, Reagents for Organic Synthesis, Vol.1, pg.444; Wiley, New York) Dicarboxylate (1.72 g) is added. After approximately 10 minutes, the solvent is removed under reduced pressure and the residue chromatographed on silica gel (using 5% ethyl acetate in hexanes as eluent) to give the desired product of a colorless oil.
    [906] Example 42 (Method 15)
    [907] [3-Chloro-4- (3-dimethylamino-prop-1-ynyl) -phenyl] -carbamic acid tert-butyl ester
    [908] To a degassed solution of (3-chloro-4-iodo-phenyl) -carbamic acid tert-butyl ester (10.0 g) in triethylamine (120 mL) (Triphenylphosphine) palladium (II) chloride (0.4 g), and cuprous iodide (0.054 g). The mixture is stirred at room temperature under an argon atmosphere for approximately 6 hours and then heated rapidly to 60 [deg.] C (10 minutes). The reaction mixture is cooled, filtered through diatomaceous earth, and then the solvent is removed by evaporation under reduced pressure. The residue was dissolved in ethyl acetate, washed three times with water, once with saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. The solvent was removed by evaporation under reduced pressure and the residue chromatographed on silica gel (eluting with 80% ethyl acetate in hexanes) to give a purified product of the amber oil which solidified on standing.
    [909] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [910] [3-Chloro-4- (3-dimethylamino-prop-1-ynyl) -phenyl] -carbamic acid tert-butyl ester
    [911] [3- (4-Methoxy-phenyl) -prop-2-ynyl] -dimethyl-amine
    [912] 4- (3-Dimethylamino-prop-1-ynyl) -benzonitrile
    [913] Dimethyl- [3- (4-nitro-phenyl) -prop-2-ynyl] -amine
    [914] Example 43 (Method 16)
    [915] [3-Chloro-4- (3-dimethylamino-acryloyl) -phenyl] -carbamic acid tert-butyl ester
    [916] To a cold solution of [3-chloro-4- (3-dimethylamino-prop-1 -inyl) -phenyl] carbamic acid tert-butyl ester (4.0 g) in dichloromethane (30 ml) was added a small amount of 3- Oxybenzoic acid (2.34 g). After stirring the reaction at 0 ° C for 20 minutes, the mixture is passed over 20 parts of basic alumina (Brockmann Grade I, 150 mesh) and the N-oxide is eluted with a 5% methanol solution in dichloromethane. All fractions containing the desired amine N-oxide are pooled and evaporated to dryness under reduced pressure. The residue is treated three times with a small amount of methanol (50 ml), evaporated to dryness under reduced pressure, and then the volume of the solution is adjusted to 250 mL by addition of methanol. The N-oxide methanol solution is heated to reflux for approximately 15 hours, then cooled, and the solvent is evaporated to dryness under reduced pressure. Purification of the residue by chromatography on silica gel (using 80% ethyl acetate in hexanes as eluent) gave the desired product as a pale yellow solid.
    [917] Example 44 (Method 17)
    [918] (3-Chloro-4-isoxazol-5-yl-phenyl) -carbamic acid tert-butyl ester
    [919] A solution of [3-chloro-4- (3-dimethylamino-acryloyl) -phenyl] -carbamic acid tert-butyl ester (270 mg) in dioxane (3 ml) was treated with hydroxylamine hydrochloride And the mixture is stirred at room temperature for 10 days. The mixture is diluted with ethyl acetate and washed successively with water, 5% aqueous sodium bicarbonate, saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The solvent is removed by evaporation under reduced pressure and the resulting residue is chromatographed on silica gel (eluting with 33% ethyl acetate in hexanes) to give the desired product as a colorless solid.
    [920] Example 45 (Method 18)
    [921] [3-Chloro-4- (lH-pyrazol-3-yl) -phenyl] -carbamic acid tert-butyl ester
    [922] A solution of [3-chloro-4- (3-dimethylamino-acryloyl) -phenyl] -carbamic acid tert-butyl ester (250 mg) in ethanol (1.25 ml) was treated with hydrazine hydrate (0.25 ml) Is stirred at room temperature for 3 hours. The mixture is diluted with 30 mL of diethyl ether, washed three times with water, once with saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. The solvent is removed by evaporation under reduced pressure and the resulting residue is chromatographed on silica gel (eluting with 67% ethyl acetate in hexanes) to give the desired product in the form of an oil.
    [923] Example 46 (Method 19A)
    [924] N- (2-chloro-4-nitrophenyl) -2-thiomorpholino-4-yl-acetamide
    [925] To a solution of N- (chloroacetyl) -2-chloro-4-nitroaniline (3.80 g) in tetrahydrofuran (50 mL) was added thiomorpholine (10 mL) and the solution was allowed to stand for 1 hour. The reaction mixture was poured into water, and a pale yellow solid was collected and then recrystallized from hot 2-propanol to obtain a pale yellow crystal solid.
    [926] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [927] (4- {2- [Bis- (2-hydroxy-ethyl) -amino] -acetylamino} -phenyl} -carbamic acid tert-butyl ester
    [928] [4- (2-Dimethylamino-acetylamino) -phenyl] -carbamic acid tert-butyl ester
    [929] {4- [3- (2-Dimethylamino-ethoxy) -benzoylamino] -phenyl} -carbamic acid tert-butyl ester
    [930] {4- [3- (2-Morpholin-4-yl-ethoxy) -benzoylamino] -phenyl} -carbamic acid tert-butyl ester
    [931] N- (2-Chloro-4-nitro-phenyl) -2-dimethylamino-acetamide
    [932] N- (2-Chloro-4-nitro-phenyl) -2-piperidin-1-yl-acetamide
    [933] N- (2-Chloro-4-nitro-phenyl) -2-morpholin-4-yl-acetamide
    [934] N- (2-chloro-4-nitro-phenyl) -2-dipropylamino-acetamide
    [935] N- (2-Chloro-4-nitro-phenyl) -2-thiomorpholin-4-yl-acetamide
    [936] N- (2-Chloro-4-nitro-phenyl) -2-diethylamino-acetamide
    [937] N- (2-Chloro-4-nitro-phenyl) -2-pyrrolidin- 1-yl-acetamide
    [938] 2-Azepan-1-yl-N- (2-chloro-4-nitro-phenyl) -acetamide
    [939] N- (2-Chloro-4-nitro-phenyl) -2- (2- methyl- piperidin- l-yl) -acetamide
    [940] N- (2-Chloro-4-nitro-phenyl) -2- (3- methyl- piperidin- l-yl) -acetamide
    [941] N- (2-Chloro-4-nitro-phenyl) -2- (4-methyl- piperidin- 1- yl) -acetamide
    [942] Example 47 (Method 19B)
    [943] N- (2-chloro-4-nitrophenyl) -2- (2-dimethylaminoethylsulfanyl) acetamide
    [944] To a solution of N- (chloroacetyl) -2-chloro-4-nitroaniline (3.01 g) in N, N-dimethylformamide (100 mL) was added powdered sodium carbonate (6.0 g) and 2-dimethylaminoethanethiol Chloride (6.0 g) is added. The mixture is stirred at 25 < 0 > C for 1 hour, poured into water and then extracted with ethyl acetate. The ethyl acetate solution is dried over anhydrous potassium carbonate and concentrated under reduced pressure to give an oil. The oil was crystallized from toluene-hexane (3: 1) to give a pale yellow crystalline solid.
    [945] Implementation 48 (Method 20)
    [946] (4-tert-Butoxycarbonylamino-2-chloro-phenyl) -carbamic acid 2-piperidin-1-yl-ethyl ester
    [947] To a suspension of 1,1-carbonyl-di- (1,2,4) -triazole (4.0 g) in dichloromethane (40 mL) was added a solution of (4-amino- Carbamic acid tert-butyl ester (5.0 g) was added dropwise over 20 minutes. When the reaction product is stirred at room temperature for 30 minutes, a precipitate is formed at this point. Piperidine ethanol (6.6 mL) is added to this mixture and tetra-hydofuran (20 mL) is added to keep it homogeneous. After heating at reflux overnight, the reaction is cooled and poured into water, and the organic layer is separated and washed with saturated aqueous sodium chloride. The solution was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to yield crude which was purified by chromatography on silica gel (using 5% methanol in dichloromethane as eluent) to give the desired product in the form of a white foam .
    [948] Example 49 (Method 21)
    [949] 5-phenyl- [1,2,3] thiadiazole-4-carboxylic acid methyl ester
    [950] A solution of ethyl benzoylacetate (1.1 g) in acetonitrile (10 mL) is treated with 4-methylbenzenesulfonyl azide (1.3 g) and triethylamine (1.6 g). After stirring at room temperature overnight, the reaction is concentrated under reduced pressure and the resulting crude product is dissolved in ethyl acetate and washed with 1N sodium hydroxide. The organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a yellow oil. This oil is taken up in dichloromethane, filtered through a functional magnesium silicate pad and eluted with dichloromethane to give a partially purified diazo ketone of a colorless oil. The diazo ketone sample (1.2 g) was dissolved in toluene (25 mL) and 2,4-bis -Disulfide < / RTI > (2.8 g) and the reaction is then heated to reflux. After 3 hours, the reaction was cooled to room temperature, loaded onto a silica gel pad and then eluted with dichloromethane. After removal of the solvent under reduced pressure, the resulting oil was purified by chromatography on silica gel (using 30% diethyl ether in petroleum ether as eluent) and recrystallization from hexanes to give the desired product in the form of a pale yellow needle.
    [951] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [952] 5-phenyl- [l, 2,3] thiadiazole-4-carboxylic acid ethyl ester
    [953] 5-phenyl- [1,2,3] thiadiazole-4-carboxylic acid methyl ester
    [954] Example 50
    [955] Ethyl benzoyl acetate < RTI ID = 0.0 >
    [956] Ethylbenzoyl acetate (5.0 g) is dissolved in methanol (10 mL) and added rapidly to a hot solution of water (130 mL) semicarbazide hydrochloride (29 g). To this was added pyridine (4.1 g) and heated at reflux for 5 min, then the reaction mixture was cooled to -20 < 0 > C overnight. The resulting solid semicarbazone is collected by filtration and washed with water followed by diethyl ether to yield the desired product of white crystals.
    [957] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [958] Ethyl (Z) -3 - [(aminocarbonyl) hydrazono] -4,4,4-trifluorobutanoate
    [959] 3 - [(Z) -2- (aminocarbonyl) hydrazono] -3-phenylpropanoic acid ethyl ester
    [960] 3 - [(E) -2- (aminocarbonyl) hydrazono] -3- (3-furyl) propanoic acid ethyl ester
    [961] Example 51
    [962] 5-phenyl- [l, 2,3] thiadiazole-5-carboxylic acid ethyl ester
    [963] A solution of ethyl benzoylacetate semicarbazone (2.5 g) in neat thionyl chloride (5 mL) was stirred at 0 < 0 > C for 1 hour. Dichloromethane (25 mL) is added and excess thionyl chloride is slowly destroyed with saturated aqueous sodium bicarbonate. The precipitate formed upon cooling is removed by filtration and the filtrate is extracted with dichloromethane. The combined organic extracts are dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Chromatography on silica gel (using 50% hexane in dichloromethane as eluent) gives the desired product of a colorless oil.
    [964] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [965] Methyl- [l, 2,3] thiadiazole-5-carboxylic acid methyl ester
    [966] 4-phenyl- [l, 2,3] thiadiazole-5-carboxylic acid ethyl ester
    [967] Furan-3-yl- [1,2,3] thiadiazole-5-carboxylic acid ethyl ester
    [968] Example 52
    [969] Methyl- [l, 2,3] thiadiazole-5-carboxylic acid
    [970] 4-Methyl- [l, 2,3] thiadiazole-5-carboxylic acid methyl ester (1.7 g) is dissolved in methanol (15 mL) and treated with 1 N sodium hydroxide (16 mL). After stirring at room temperature for 1 hour, the reaction was treated with concentrated hydrochloric acid (1.5 mL) and then concentrated under reduced pressure. The resulting cloudy water layer is extracted twice with diethyl ether, and the combined organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain the desired compound of white powder.
    [971] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [972] 3-Ethoxycarbonylmethoxy-benzoic acid
    [973] 5-furan-3-yl- [1,2,3] thiadiazole-4-carboxylic acid
    [974] Thiazole-4-carboxylic acid
    [975] Methyl- [l, 2,3] thiadiazole-5-carboxylic acid
    [976] 5-Methyl- [l, 2,3] thiadiazole-4-carboxylic acid
    [977] Example 53 (Method 25)
    [978] Trifluoro-methanesulfonic acid 4-chloro-5-methoxy-2-nitro-phenyl ester
    [979] To a solution of 4-chloro-5-methoxy-2-nitro-phenol (6.5 g) in dichloromethane (150 mL) at 0 C under argon atmosphere was added triethylamine (10 g) followed by dichloromethane (30 mL) Is added a solution of tri-fluoro-methanesulfonic anhydride (13.5 g). The solution is stirred at 0 < 0 > C for 10 min, then diluted with dichloromethane and then washed successively with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. After drying over anhydrous sodium sulfate, the solvent is removed by evaporation under reduced pressure, the residue is dissolved in 20% dichloromethane solution in hexane and a short column of dihydrate magnesium silicate is passed through (20% dichloromethane in hexane is used as eluent) . The fractions containing the product are collected and the solvent is removed by evaporation under reduced pressure to obtain the desired product of the yellow oil.
    [980] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [981] Trifluoro-methanesulfonic acid 4-chloro-5-methoxy-2-nitro-phenyl ester
    [982] Trifluoro-methanesulfonic acid 4-chloro-2-nitro-phenyl ester
    [983] Trifluoro-methanesulfonic acid 2-chloro-6-nitro-phenyl ester
    [984] Example 54 (Method 26)
    [985] [4- (3-Dimethylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [986] (505 mg), sodium cyanoborohydride (250 mg), acetic acid (3 drops) and 1: 2 tetrahydrofuran-2-carboxylic acid tert- A solution of 40% aqueous formaldehyde (4 mL) in methanol (15 mL) is stirred for 15 minutes, poured into saturated aqueous sodium bicarbonate and then extracted with ethyl acetate. The ethyl acetate solution was dried over anhydrous potassium carbonate and concentrated under reduced pressure to obtain a solid which was recrystallized from acetonitrile to give a pale pink crystalline solid.
    [987] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [988] [4- (3-Dimethylamino-benzoylamino) -phenyl] -carbamic acid tert-butyl ester
    [989] (3-Bromo-5-trifluoromethyl-phenyl) -dimethyl-amine
    [990] N- (3-chloro-5-dimethylamino-phenyl) -acetamide
    [991] Example 55 (Method 27)
    [992] N- (4-aminophenyl) -2-hydroxybenzamide
    [993] To a solution of 2- (4-aminophenylcarbamoyl) phenylacetate (580 mg) in methanol (10 mL) is added saturated sodium bicarbonate (2 mL) and water (3 mL). The mixture is heated at 80 < 0 > C for 30 minutes, poured into semi-saturated aqueous sodium chloride and then extracted with ethyl acetate. The ethyl acetate solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give an oil which is triturated with diethyl ether to give the desired product as a white solid.
    [994] Example 56 (Method 28)
    [995] [4- (3- (Hydroxybenzoylamino) phenyl} carbamic acid tert-butyl ester
    [996] To a solution of 3- (4-aminophenylcarbamoyl) phenylacetate (4.34 g) in methanol (75 mL) was added 0.1 N aqueous sodium hydroxide (25 mL) and tetrahydrofuran (25 mL). The solution is heated at 40 < 0 > C for 30 minutes, cooled, poured into 1 M hydrochloric acid and extracted with ethyl acetate. The ethyl acetate solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a white solid which is further purified by trituration with diethyl ether.
    [997] Example 57 (Method 29)
    [998] N- (4-aminophenyl) -2-hydroxymethylbenzamide
    [999] Lithium borohydride (1.0 g) was added to a solution of N- (4-aminophenyl) phthalimide (332 mg) in tetrahydrofuran (4 mL) and the mixture was stirred at 25 ° C for 1 hour. The mixture is poured into water and extracted with ethyl acetate. The ethyl acetate solution is dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a white foam which is triturated with diethyl ether to give the desired product of a white powder.
    [1000] Example 58 (Method 30)
    [1001] (3-Chloro-5-dimethylamino-phenyl) -carbamic acid tert-butyl ester
    [1002] To the solution of (3-amino-5-chloro-phenyl) -carbamic acid tert-butyl ester (0.32 g) in toluene (10 mL) was added aqueous formaldehyde (37%, 1.5 mL) followed by 10% palladium on carbon 0.50 g) is added and the mixture is stirred under a hydrogen atmosphere for approximately 15 hours. The solution is filtered through diatomaceous earth and the filtrate is concentrated under reduced pressure. Chromatographing the residue on silica gel (using 50% dichloromethane in hexane as eluent) gave the desired product as a white solid.
    [1003] Example 59 (Method 35)
    [1004] N- (4- {3- [3,5-Dichloro-4- (2-hydroxy-ethoxy) -phenyl] -thioureido} -phenyl) acetamide
    [1005] To a stirred solution of 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy} ethyl ester in a 1: 1 mixture of tetrahydrofuran and methanol (0.16 g) in 1 N aqueous sodium hydroxide (1 mL) is added and the mixture is stirred at room temperature for approximately 2 hours. The solution is poured into 2 M aqueous hydrochloric acid (3 mL), extracted with ethyl acetate, and the extract is dried over anhydrous sodium sulfate. The solvent is removed by evaporation under reduced pressure and the residue is triturated with diethyl ether to give the desired product of a white solid.
    [1006] Example 60 (Method 36)
    [1007] {4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy}
    [1008] To a solution of {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy} -acetic acid ethyl ester (0.29 g) in a 1: 1 mixture of tetrahydrofuran and methanol g) is added 1N aqueous sodium hydroxide (2 mL) and the mixture is stirred at room temperature for approximately 2 hours. The solution is poured into 2 M aqueous hydrochloric acid (5 mL), extracted with ethyl acetate, and the extract is dried over anhydrous sodium sulfate. The solvent is removed by evaporation under reduced pressure and the residue is triturated with diethyl ether to give the desired product of a white solid.
    [1009] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1010] {4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy}
    [1011] 2- {3- [4-Acetylamino-phenyl) -thioureido] -4-chloro-5-methoxy-phenoxy}
    [1012] 2-chloro-5-methoxy-phenoxy} -acetic acid < / RTI >
    [1013] Example 61 (Method 37)
    [1014] Benzoic acid 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy} -ethyl ester
    [1015] To a solution of N- (4- {3- [3,5-Dichloro-4- (2-hydroxy-ethoxy) -phenyl] thioureido} -phenyl) -methanone in pyridine (2 mL) and tetrahydrofuran ) Acetic acid (0.20 g) was added benzoyl chloride (0.08 g) and the mixture was stirred at 0 < 0 > C for 1.5 h. The mixture is diluted with ethyl acetate, washed twice with 2% aqueous hydrochloric acid, once with saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, the residue was chromatographed on silica gel (using 5% methanol in dichloromethane as eluent). The fractions containing the product were collected and evaporated under reduced pressure, and the residue was recrystallized from acetone-hexane A desired product of the white powder is obtained.
    [1016] Example 62 (Method 38)
    [1017] Methanesulfonic acid 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy} -ethyl ester
    [1018] To a solution of N- (4- {3- [3,5-Dichloro-4- (2-hydroxy-ethoxy) -phenyl] thioureido} -phenyl) -methanone in pyridine (2 mL) and tetrahydrofuran ) Acetamide (0.20 g) in methanesulfonyl chloride (0.11 g) was added and the solution was stirred at 0 ° C for 45 minutes. The reaction mixture is diluted with ethyl acetate, washed twice with 2% aqueous hydrochloric acid, once with saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. The solvent is removed by evaporation under reduced pressure, and the resulting residue is recrystallized from acetone-hexane to obtain the desired product of white powder.
    [1019] Example 63 (Method 39)
    [1020] (4- {3- [3,5-Dichloro-4- (2-dimethylamino-ethoxy) -phenyl] -thioureido} -phenyl) -acetamide
    [1021] To a solution of methanesulfonic acid 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichlorophenoxy} -ethyl ester (0.33 g) in tetrahydrofuran (6 mL) Aqueous dimethyl-amine (8.8 M, 0.5 mL) is added and the mixture is stirred at room temperature for 5 days. The reaction mixture is diluted with ethyl acetate, washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After removal of the solvent under reduced pressure, the residue is chromatographed on silica gel (using pure methanol as eluent). The fraction containing the collected product is evaporated under reduced pressure and the residue is recrystallized from acetonitrile to obtain the desired product of the white powder.
    [1022] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1023] - (4- {3- [3,5-Dichloro-4- (2-dimethylamino-ethoxy) -phenyl] -thioureido} -phenyl) acetamide
    [1024] Benzoic acid 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-dichloro-phenoxy} ethyl ester
    [1025] Example 64 (Method 40)
    [1026] 2-carboxylic acid (4- {3- [4- (1-amino-ethyl) -3-chloro-phenyl] -thioureido} phenyl)
    [1027] To a solution of furan-2-carboxylic acid (4- {3- [4- (1-azido-ethyl) -3-chloro-phenyl] -tetrahydroisoquinoline (0.25 g) in methanol (2.5 mL) -Ureido} -phenyl) -amide (0.22 g) is added and the solution is stirred at room temperature for approximately 15 hours. The solution is diluted with ethyl acetate, washed successively with saturated aqueous sodium bicarbonate followed by saturated aqueous sodium chloride, and dried over anhydrous sodium sulfate. After evaporation of the solvent under reduced pressure, the residue is chromatographed on silica gel (using 8% methanol in dichloromethane containing 1% triethylamine as eluent) to give the desired product as a yellow solid.
    [1028] Example 65 (Method 41)
    [1029] [1,2,3] thiadiazole-4-carboxylic acid (4-isothiocyanato-phenyl) -amide
    [1030] To an ice cold solution of 1,1'-thiocarbonyldiimidazole (7.28 g) in tetrahydrofuran (50 mL) was added [1,2,3] -thiadiazole-4-carboxylic acid (4-amino-phenyl) amide (9.0 g). After approximately 1 hour the solvent is evaporated off and the residue is dissolved in ethyl acetate. Diethyl ether is added to precipitate the crude product, which is collected by filtration, dissolved in dichloromethane, and passed through a hydrous magnesium silicate plug. After removal of the solvent, the residue is recrystallized from ethyl acetate-hexane to give the desired product of a weak yellow solid.
    [1031] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1032] 2-fluoro-N- (4-isothiocyanato-phenyl) -benzamide
    [1033] Furan-2-carboxylic acid (4-isothiocyanato-phenyl) -amide
    [1034] [1,2,3] thiadiazole-4-carboxylic acid (4-isothiocyanato-phenyl) -amide
    [1035] Thiazole-4-carboxylic acid (4-isothiocyanato-phenyl) -amide
    [1036] Example 66 (Method 42)
    [1037] N, N-dimethyl-5-trifluoromethyl-benzene-1,3-diamine
    [1038] To a solution of 3-amino-5-bromo-benzotrifluoride (1.0 g) in degassed (argon) tetrahydrofuran (2 mL) was added bis- (tri- o- tolylphosphino) palladium (2 M, 4.2 mL) and a solution of lithium bis (trimethylsilyl) amide in tetrahydrofuran (1 M, 10.4 mL) in tetrahydrofuran were added. The reaction mixture is heated to 100 < 0 > C for about 2.5 hours in a sealed vessel to terminate the reaction. The mixture is cooled to room temperature, water is added, cooled and then diluted with ethyl acetate. The product is extracted three times with 5% aqueous hydrochloric acid, and the acidic extract is collected and then basified with cooling with addition of 5N aqueous sodium hydroxide. This basic solution is extracted with ethyl acetate and the combined organic extracts are washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure. Chromatographing the resulting residue on silica gel (using 20-30% ethyl acetate in hexanes as eluent) gives the desired product of a light pale solid.
    [1039] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1040] 3- (4-Methyl-piperazin-l-yl) -5-trifluoromethyl-phenylamine
    [1041] 3-Morpholin-4-yl-5-trifluoromethyl-phenylamine
    [1042] 3-Piperidin-l-yl-5-trifluoromethyl-phenylamine
    [1043] 3-pyrrolidin-l-yl-5-trifluoromethyl-phenylamine
    [1044] N, N-dimethyl-5-trifluoromethyl-benzene-1,3-diamine
    [1045] N-isobutyl-N-methyl-5-trifluoromethyl-benzene-1,3-diamine
    [1046] N-butyl-N-methyl-5-trifluoromethyl-benzene-1,3-diamine
    [1047] Example 67 (Method 43)
    [1048] (3-isobutyl-5-trifluoromethyl-phenyl) -carbamic acid tert-butyl ester
    [1049] Bubbled isobutylene in a sealed tube containing tetrahydrofuran (5 mL) capped with a rubber membrane and cooled in a dry ice-acetone bath for about 5 minutes. A solution of 9-borabicyclo [3.3.1] nonane in tetrahydrofuran (0.5 M, 11 mL) was added and the vessel was sealed with a Teflon cap, then warmed slowly to room temperature and maintained at room temperature for approximately 2.5 hours. The mixture is re-cooled in a dry ice-acetone bath, the Teflon cap is replaced with a rubber membrane, and excess isobutylene is removed by bubbling the mixture through argon. A solution of (3-bromo-5-trifluoromethyl-phenyl) -carbamic acid tert-butyl ester (1.7 g) in tetrahydrofuran (12 mL) Phosphino) -ferrocene] palladium (II) chloride-dichloromethane complex (0.12 g) and 3 N aqueous sodium hydroxide are added. The vessel is resealed with a Teflon cap and then heated to 65 ° C for approximately 15 hours. The mixture is cooled to room temperature, diluted with hexane, washed with water, saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. Chromatograph the resulting oil on silica gel (using 5% ethyl acetate in hexanes as eluent) to give the desired product of a white powder.
    [1050] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1051] [3- (2-Methyl-butyl) -5-trifluoromethyl-phenyl] -carbamic acid tert-butyl ester
    [1052] (3-isobutyl-5-trifluoromethyl-phenyl) -carbamic acid tert-butyl ester
    [1053] Example 68 (Method 44)
    [1054] 2- (3,5-Dichloro-phenylsulfanyl) -ethylamine
    [1055] 0.61 mL of 10 M borane dimethyl sulfide complex is added to a solution of (3,5-dichlorophenylthio) acetonitrile (1.2 g) in 3.0 mL of ethylene glycol dimethyl ether and the mixture is heated at reflux for 0.5 hour. Cool the reaction in an ice bath and add 2.0 mL of water and 2.0 mL of concentrated hydrochloric acid. This mixture is heated to reflux for 0.5 h. The clear solution is cooled, basified with 5N sodium hydroxide and extracted with ether. The ether extract is dried over potassium carbonate, filtered and concentrated to give 1.0 g of a colorless oil.
    [1056] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1057] 2- (3-Bromo-phenylsulfanyl) -ethylamine
    [1058] 2- (4-Bromo-phenoxy) -ethylamine
    [1059] 2- (4-Iodo-phenoxy) -ethylamine
    [1060] 2- (3,4-Dichloro-phenoxy) -ethylamine
    [1061] 2- (3-Chloro-phenylsulfanyl) -ethylamine
    [1062] 2- (3,4-Dichloro-phenylsulfanyl) -ethylamine
    [1063] 3- (4-Bromo-phenyl) -propylamine
    [1064] 2- (2-Fluoro-phenoxy) -ethylamine
    [1065] 2- (2-Chloro-phenoxy) -ethylamine
    [1066] 2- (3-Bromo-phenoxy) -ethylamine
    [1067] 2- (3-Fluoro-phenoxy) -ethylamine
    [1068] 2- (3-Iodo-phenoxy) -ethylamine
    [1069] 2- (3,5-Dichloro-phenylsulfanyl) -ethylamine
    [1070] 2-phenylsulfanyl-ethylamine
    [1071] L- (2-Chloro-phenyl) -ethylamine
    [1072] Example 69 (Method 45)
    [1073] N- (1-naphthalen-2-yl-ethyl) -formamide
    [1074] A mixture of 2-acetylnaphthylene (3.0 g), ammonium formate (11.0 g), formic acid (3.3 mL) and formamide (3.5 mL) was heated at 190 占 폚 for 3 hours. The mixture is cooled, poured into water and then extracted with ether. The ether extract was dried over anhydrous potassium carbonate, filtered and concentrated to give a yellow oil, which upon crystallization with toluene-hexane gave 1.97 g of a white solid.
    [1075] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1076] N- [1- (4-Fluoro-phenyl) -2-methyl-propyl] -formamide
    [1077] N- (1-naphthalen-2-yl-ethyl) -formamide
    [1078] Example 70 (Method 46)
    [1079] 1- (2-naphthyl) ethylamine
    [1080] A mixture of N- (1-naphthalen-2-yl-ethyl) -formamide (1.12 g), ethanol (10 mL) and 5N sodium hydroxide (10 mL) is heated at reflux for 1 hour. The solution is cooled, poured into water and extracted with ether. The ether solution is dried over anhydrous potassium carbonate, filtered and concentrated to give the product (0.95 g) as a pale yellow oil.
    [1081] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1082] 1- (3-Trifluoromethyl-phenyl) -ethylamine
    [1083] L- (4-Fluoro-phenyl) -2-methyl-propylamine
    [1084] [3- (1-Amino-ethyl) -phenyl] -dimethyl-amine
    [1085] 3- (1-Amino-ethyl) -benzonitrile
    [1086] Example 71 (Method 47)
    [1087] 1- (3-Trifluoromethyl-phenyl) -ethanone O-Methyl-oxime
    [1088] Methoxylamine hydrochloride (2.33 g) is added to a solution of 3 '- (trifluoromethyl) -acetophenone (1.5 g) in ethanol (20 mL) and pyridine (2 mL). The solution is heated at reflux for 45 minutes. The reaction mixture is cooled, concentrated under reduced pressure, and partitioned between water and ethyl acetate. The aqueous layer is extracted with ethyl acetate. The combined organic layers are washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the desired product (1.61 g) as a colorless solid.
    [1089] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1090] 3,5-Bis-trifluoromethyl-benzaldehyde oxime
    [1091] L- (4-Fluoro-phenyl) -propan-l-one O-Methyl-oxime
    [1092] 1- (2-Chloro-phenyl) -ethanone O-Methyl-oxime
    [1093] 1- (3-Bromo-phenyl) -ethanone O-methyl-oxime
    [1094] 1- (3-Chloro-phenyl) -ethanone O-methyl-oxime
    [1095] 1-o-tolyl-ethanone O-methyl-oxime
    [1096] 1- (4-Fluoro-phenyl) -pentan-l-one O-Methyl-oxime
    [1097] 1- (4-Fluoro-phenyl) -2-phenyl-ethanone O-Methyl-oxime
    [1098] 1-o-tolyl-ethanone O-methyl-oxime
    [1099] 1-m-Tolyl-ethanone O-methyl-oxime
    [1100] 1- (2-Fluoro-phenyl) -ethanone O-Methyl-oxime
    [1101] 3- (1-Methoxyimino-ethyl) -benzonitrile
    [1102] 4- (1-Methoxyimino-ethyl) -benzonitrile
    [1103] 1- (4-Methoxy-phenyl) -ethanone O-Methyl-oxime
    [1104] 1- (2-Methoxy-phenyl) -ethanone O-Methyl-oxime
    [1105] 1- (4-Dimethylamino-phenyl) -ethanone O-Methyl-oxime
    [1106] 1- (2-Trifluoromethyl-phenyl) -ethanone O-Methyl-oxime
    [1107] 1- (3-Methoxy-phenyl) -ethanone O-Methyl-oxime
    [1108] 1- (3-Trifluoromethyl-phenyl) -ethanone O-Methyl-oxime
    [1109] 1- (4-Trifluoromethyl-phenyl) -ethanone O-Methyl-oxime
    [1110] 1-furan-2-yl-ethanone O-methyl-oxime
    [1111] 1-pyridin-4-yl-ethanone O-methyl-oxime
    [1112] 1- (l-Methyl-lH-pyrrol-2-yl) -ethanone O-
    [1113] 1-Thiophen-3-yl-ethanone O-methyl-oxime
    [1114] (4-Fluoro-phenyl) -phenyl-methanone O-Methyl-oxime
    [1115] 1- (4-Methoxyphenyl) ethanone O-Methyl-oxime
    [1116] 1- (3-Chloro-4-methoxy-phenyl) -ethanone O-Methyl-oxime
    [1117] 4- (1-Methoxyimino-ethyl) -benzenesulfonamide
    [1118] 4- (1-Methoxyimino-ethyl) -N, N-dimethyl-benzenesulfonamide
    [1119] 1- [4- (Piperidine-l-sulfonyl) -phenyl] -ethanone O-Methyl-oxime
    [1120] 4- (1-methoxyimino-ethyl) -N, N-dipropyl-benzenesulfonamide
    [1121] 2-Fluoro-N- [4- (1-methoxyimino-ethyl) -phenyl] -benzamide
    [1122] 1- (3,5-Bis-trifluoromethyl-phenyl) -ethanone O-Methyl-oxime
    [1123] 1- [4- (1H-imidazol-1-yl) phenyl] -1-ethanone, O-
    [1124] 1- [4- (trifluoromethyl) phenyl] -1-ethanone, O-methyl oxime
    [1125] 1- [1,1'-biphenyl] -4-yl-1-ethanone, O-methyloxime
    [1126] 1- (4-methylphenyl) -1-ethanone, O-methyl oxime
    [1127] 1- [4-fluoro-3- (trifluoromethyl) phenyl] ethanone O-methyl oxime
    [1128] 1- [3,5-bis (trifluoromethyl) phenyl] ethanone O-Benzyl oxime
    [1129] 1- [4-chloro-3- (trifluoromethyl) phenyl] ethanone O-methyl oxime
    [1130] 1- [3-fluoro-5- (trifluoromethyl) phenyl] ethanone O-methyl oxime
    [1131] 1- [2-fluoro-4- (trifluoromethyl) phenyl] ethanone O-methyl oxime
    [1132] 1- [2-fluoro-5- (trifluoromethyl) phenyl] ethanone O-methyl oxime
    [1133] 1- (2, 4-dichlorophenyl) ethanone O-methyloxime
    [1134] 1- (2,4-dimethylphenyl) ethanone O-methyloxime
    [1135] 1- [2,4-bis (trifluoromethyl) phenyl] ethanone O-methyl oxime
    [1136] 1- (3-bromophenyl) ethanone O-methyl oxime
    [1137] 1- (3-methylphenyl) ethanone O-methyl oxime
    [1138] 1- [4- (4-morpholinyl) phenyl] ethanone O-Methyl oxime
    [1139] 1- (2-Chloro-4-fluorophenyl) ethanone O-Methyl oxime
    [1140] 1- (4-Bromo-2-fluorophenyl) ethanone O-Methyl oxime
    [1141] 1- (3,4-difluorophenyl) ethanone O-methyl oxime
    [1142] 1- [3- (trifluoromethyl) phenyl] ethanone O-methyl oxime
    [1143] 1- [2- (trifluoromethyl) phenyl] ethanone O-methyl oxime
    [1144] 1- (2,4-difluorophenyl) ethanone O-Methyl oxime
    [1145] 1- [3-fluoro-4- (trifluoromethyl) phenyl] ethanone O-Methyl oxime
    [1146] 1- (3,4-Dichlorophenyl) ethanone O-Methyl oxime
    [1147] 1- [4-fluoro-2- (trifluoromethyl) phenyl] ethanone O-methyl oxime
    [1148] 1- (3-Chloro-4-fluorophenyl) ethanone O-Methyl oxime
    [1149] 1- (4-Chloro-3-fluorophenyl) ethanone O-Methyl oxime
    [1150] 1- (2,5-difluorophenyl) ethanone O-Methyl oxime
    [1151] 1- (2-bromo-4-fluorophenyl) ethanone O-Methyl oxime
    [1152] 1- (3,4-dibromophenyl) ethanone O-methyloxime
    [1153] 1- (2-bromophenyl) ethanone O-Methyl oxime
    [1154] Example 72 (Method 48)
    [1155] L- (2-Trifluoromethyl-phenyl) -ethylamine
    [1156] Sodium borohydride (1.17 g) is slowly added to a flask containing zirconium tetrachloride (1.8 g) in tetrahydrofuran (27 mL). A solution of 1- (2-trifluoromethylphenyl) -ethanone O-methyl-oxime (1.34 g) in tetrahydrofuran (7,7 mL) is added and the resulting solution is stirred at 25 ° C for 12 hours. The reaction mixture is cooled to 0 < 0 > C and water (16 mL) is slowly added. Excess ammonium hydroxide is added and the solution is extracted twice with ethyl acetate. The organic portion is washed twice with 1N hydrochloric acid. The aqueous (acid) layer is basified with sodium hydroxide and extracted twice with ethyl acetate. The organic layer is washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Removal of the solvent under reduced pressure gave the desired product (0.20 g) of a yellow oil.
    [1157] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1158] 1- (3-Methoxy-phenyl) -ethylamine
    [1159] 1- (4-Fluoro-phenyl) -propylamine
    [1160] 1-naphthalen-2-yl-ethylamine
    [1161] 4- (1-Amino-ethyl) -benzonitrile
    [1162] L- (4-Trifluoromethyl-phenyl) -ethylamine
    [1163] 1- (4-Methoxy-phenyl) -ethylamine
    [1164] 1-prop-2-ynyl-pyrrolidine
    [1165] L- (2-Methoxy-phenyl) -ethylamine
    [1166] 1-m-Tolyl-ethylamine
    [1167] L- (2-Bromo-phenyl) -ethylamine
    [1168] 1-o-tolyl-ethylamine
    [1169] C- (4-Fluoro-phenyl) -C-phenyl-methylamine
    [1170] 1- (4-Fluoro-phenyl) -pentylamine
    [1171] L- (4-Fluoro-phenyl) -2-phenyl-ethylamine
    [1172] L- (2-Trifluoromethyl-phenyl) -ethylamine
    [1173] L- (3-Bromo-phenyl) -ethylamine
    [1174] L- (3-Chloro-phenyl) -ethylamine
    [1175] [4- (1-Amino-ethyl) -phenyl] -dimethyl-amine
    [1176] L- (l-Methyl-lH-pyrrol-2-yl) -ethylamine
    [1177] Example 73 (Method 49)
    [1178] (2-fluoro-5-trifluoromethyl-phenoxy) -acetonitrile
    [1179] A solution of 2-fluoro-5-trifluoromethylphenol (25 g) in tentacetate acetone (0.55 L) is treated with solid potassium carbonate (7.7 g) followed by rapid addition of pure bromoacetonitrile (10 mL). The heterogeneous mixture is vigorously stirred for approximately 20 hours under water and extracted with diethyl ether. The combined ether extracts are washed with saturated sodium chloride and dried over anhydrous potassium carbonate. Filtration and concentration under reduced pressure gave a pale orange solid which was chromatographed on silica gel eluting with dichloromethane to give the desired product (28.3 g) as a white solid.
    [1180] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1181] (3-bromo-phenylsulfanyl) -acetonitrile
    [1182] (3-chloro-phenylsulfanyl) -acetonitrile
    [1183] (4-Iodo-phenoxy) -acetonitrile < / RTI >
    [1184] (3-Trifluoromethyl-phenylsulfanyl) -acetonitrile < / RTI >
    [1185] (3,5-Dichloro-phenylsulfanyl) -acetonitrile
    [1186] (3,4-Dichloro-phenylsulfanyl) -acetonitrile
    [1187] (3,4-Dichloro-phenoxy) -acetonitrile
    [1188] (2-Fluoro-phenoxy) -acetonitrile < / RTI >
    [1189] (3-Fluoro-phenoxy) -acetonitrile < / RTI >
    [1190] (2-Chloro-phenoxy) -acetonitrile
    [1191] (3-Bromo-phenoxy) -acetonitrile < / RTI >
    [1192] (2-fluoro-5-trifluoromethyl-phenoxy) -acetonitrile
    [1193] (3-Iodo-phenoxy) -acetonitrile
    [1194] (4-Bromo-phenoxy) -acetonitrile < / RTI >
    [1195] Example 74 (Method 50)
    [1196] 3-fluoro-5-trifluoromethylphenethylamine tosylate
    [1197] To a solution of 2.5 g of 3-fluoro-5-trifluoromethylphenylacetonitrile and 2.34 g (12.3 mmol) of p-toluenesulfonic acid in 75 ml of ethylene glycol monomethyl ether was added 200 mg of 10% palladium on carbon catalyst at 40 psi at room temperature ≪ / RTI > for 3 hours. The catalyst is filtered and the solvent is evaporated to half its volume. Upon standing, the desired p-toluenesulfonic acid salt of 3-fluoro-5-trifluoromethylphenethylamine is crystallized. Filtration gave 4.26 g (91%) of white crystals.
    [1198] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1199] 2- (3,5-Difluoro-phenyl) -ethylamine
    [1200] 2- (4-Trifluoromethyl-phenyl) -ethylamine
    [1201] 2- (3,4-Difluoro-phenyl) -ethylamine
    [1202] 2- (2-Fluoro-phenyl) -ethylamine
    [1203] 2- (3-Fluoro-5-trifluoromethyl-phenyl) -ethylamine
    [1204] 2- (2-Fluoro-3-trifluoromethyl-phenyl) -ethylamine
    [1205] 2- (2,4-Bis-trifluoromethyl-phenyl) -ethylamine
    [1206] 2- (4-Fluoro-3-trifluoromethyl-phenyl) -ethylamine
    [1207] Example 75 (Method 51)
    [1208] (4-Aminomethyl-2-trifluoromethyl-phenyl) -dimethyl-amine
    [1209] A solution of 4-dimethylamino-3-trifluoromethylbenzonitrile (0.35 g) in tetrahydrofuran (2 mL) was slowly added to a suspension of lithium aluminum hydride (0.1 g) in tetrahydrofuran (2 mL) at 0 ° C And stirred under an argon atmosphere for 2 hours. Water (0.1 mL) is slowly added at 0 ° C followed by 5% sodium hydroxide (0.1 mL) and water (0.3 mL). The resulting gray solid is filtered off and washed with tetrahydrofuran. The filtrate was collected and concentrated under reduced pressure, and the resulting oil was chromatographed on silica gel (using 15% methanol in methylene chloride as eluent) to give the desired product (0.164 g) as a pale orange oil.
    [1210] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1211] 4-Piperidin-1-yl-3-trifluoromethyl-benzylamine
    [1212] (4-Aminomethyl-2-trifluoromethyl-phenyl) -dimethyl-amine
    [1213] 4- (4-Methyl-piperazin-1-yl) -3-trifluoromethyl-benzylamine
    [1214] (3-Aminomethyl-5-trifluoromethyl-phenyl) -dimethyl-amine
    [1215] [3- (2-Amino-ethyl) -5-trifluoromethyl-phenyl] -dimethyl-amine
    [1216] [4- (2-Amino-ethyl) -2-methyl-phenyl] -dimethyl-amine
    [1217] Example 76 (Method 52)
    [1218] 3-Dimethylamino-5-trifluoromethyl-benzaldehyde
    [1219] Diisobutyl aluminum hydride (10 mL of a 1 M solution of methylene chloride) was added dropwise to a solution of 3-dimethylamino-5-trifluoromethylbenzonitrile (1.06 g) in methylene chloride (25 mL) at 0 ° C and the mixture was stirred for 2 hours Lt; / RTI > A saturated aqueous solution of sodium potassium tartrate (8 mL) is slowly added at 0 ° C and the solution is stirred for 1.5 hours. The reaction mixture is extracted with ethyl acetate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the desired product (0.97 g) as a yellow solid.
    [1220] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1221] 3-Dimethylamino-5-trifluoromethyl-benzaldehyde
    [1222] 4-Dimethylamino-3-methyl-benzaldehyde
    [1223] Example 77 (Method 53)
    [1224] Dimethyl- [3- (2-nitro-vinyl) -5-trifluoromethyl-phenyl] -amine
    [1225] Nitromethane (0.473 g) is added to a solution of 3-dimethylamino-5-trifluoromethylbenzaldehyde (0.885 g) and ammonium acetate (0.339 g) in acetic acid (3.4 mL) and the solution is heated at 110 C for 6 h . The reaction mixture is cooled to 0 < 0 > C, filtered and washed with 1: 1 water-acetic acid to form a solid. Recrystallization of this solid with ethanol gave the desired product (0.39 g) as a red solid.
    [1226] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1227] Dimethyl- [3- (2-nitro-vinyl) -5-trifluoromethyl-phenyl] -amine
    [1228] Dimethyl- [2-methyl-4- (2-nitro-vinyl) -phenyl] -amine
    [1229] Example 78 (Method 54)
    [1230] 3- (4-Bromo-phenyl) -propionitrile
    [1231] Diethyl azodicarboxylate (5.2 g) is added dropwise to a solution of 4-bromo-phenethyl alcohol (2.01 g) and triphenylphosphine (7.9 g) in diethyl ether (16 mL) at 0 ° C. The reaction mixture is stirred for 10 minutes and a solution of acetone cyanohydrin (2.6 g) in diethyl ether (10 mL) is added. The clear orange solution is stirred at 0 < 0 > C for 5 min followed by 25 < 0 > C for 12 h. The reaction mixture is filtered and washed with diethyl ether. The filtrate is concentrated under reduced pressure and chromatographed on silica gel (10% ethyl acetate-hexane as eluent) to give the desired product (2.04 g) as a pale yellow oil.
    [1232] Example 79 (Method 55)
    [1233] 3-Dimethylamino-2-isocyano-acrylic acid ethyl ester
    [1234] N, N-dimethyl-formamide dimethyl acetal (6.5 g) was added dropwise over 10 minutes to a solution of ethyl isocyanoacetate (5.0 g) in ethanol (100 mL) while stirring. The reaction is stirred for 24 h and the ethanol is evaporated. The oil produced using 50% ethyl acetate-hexane as an eluent is passed through magnesium silicate. The solvent was removed and the resulting oil was crystallized from ethyl acetate-hexane to give 3.0 g of a light yellow needle.
    [1235] Example 80 (Method 56)
    [1236] 4-Carboethoxytriazole
    [1237] A solution of 3-dimethylamino-2-isocyano-acrylic acid ethyl ester (1.0 g) and triethylamine (3.0 g) in tetrahydrofuran (30 mL) is treated with gaseous hydrogen sulfide until all starting material is consumed . The mixture is concentrated to an oil and purified by column chromatography using silica and 25% ethyl acetate-hexane as eluent. The purified material (0.61 g) is isolated in oil form.
    [1238] Example 81 (Method 34)
    [1239] - {[(5-chloro-2,4-dimethoxy-phenyl) -ureido] -phenyl} -2-fluoro-benzamide
    [1240] A suspension of N- (4-amino-phenyl) -2-fluoro-benzamide (0.43 g) in acetonitrile (4 mL) is treated with 5-chloro-2,4-dimethoxyphenyl isocyanate (0.40 g) . The mixture becomes a solution and it is allowed to stand for 12 hours. A white solid forms and is collected by filtration (0.79 g). [M + H] < / RTI > 444.
    [1241] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1242] Example M + H Compound Name
    [1243] 81 445 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) ureido] phenyl} -2-
    [1244] Oro-benzamide
    [1245] 82 441 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) ureido] phenyl} -2-
    [1246] Benzamide
    [1247] 83 435 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (5-chloro-2,4-
    [1248] Phenyl) ureido] phenyl} -amide
    [1249] 84 443 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-chloro-3-
    [1250] Phenyl) ureido] phenyl} -amide < / RTI >
    [1251] 85 453 N- {4- [3- (4-Chloro-3-trifluoromethyl-phenyl) ureido] phenyl} -2-
    [1252] Fluoro-benzamide
    [1253] 86 409 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl) urea
    [1254] Iso] phenyl} -amide
    [1255] 87 486 N- {4- [3- (3,5-Bis-trifluoromethyl-phenyl) ureido] phenyl} -2-
    [1256] ≪ RTI ID = 0.0 >
    [1257] 88 458 furan-2-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-phenyl) urea
    [1258] Iso] phenyl} -amide
    [1259] 89 476 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,5-bis-trifluoro-
    [1260] Yl-phenyl) ureido] phenyl} -amide
    [1261] 90 423 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,4-dichloro-benzyl) urea
    [1262] Isopropyl] -amide < / RTI >
    [1263] Example 91 (Method 31)
    [1264] (Trifluoromethyl) phenyl] ethyl} amino) carbothioyl] amino} -2-pyridinyl) -1,3- Thiazole-4-carboxamide
    [1265] Synthesis of (S) -alpha-methyl-3,5-bis (trifluoromethoxy) -3-thiazole-4-carboxamide with 0.36 g of N- (5-isothiocyanato- Methyl) -benzenemethanamine (0.36 g) is heated with acetonitrile (10 mL) until all solids are dissolved. The solution is allowed to stand for 12 hours. A white solid forms and is collected by filtration (0.40 g). [M + H] < / RTI >
    [1266] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [1267] Example M + H Compound Name
    [1268] 92 506 [3-Chloro-5- (3- {4 - ([1,2,3] thiadiazole-
    [1269] Thioureido) phenyl] carbamic acid tert-butyl ester
    [1270] 93 409 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (4-morpholin-
    [1271] Thiourea
    [1272] 94 370 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (4-methylsulfanyl-
    [1273] Thiourea
    [1274] 95 338 1- (5-Chloro-2,4-dimethoxy-phenyl) -3-p-tolyl-thiourea
    [1275] 96 414 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) thioureido] phenylsulfanyl}
    [1276] Acetic acid
    [1277] 97 384 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- [4- (2-hydroxy-
    [1278] Phenyl] -thiourea
    [1279] 98 340 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (4-hydroxy-phenyl) -thiourea
    [1280] 99 395 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -N-
    [1281] Methyl acetamide
    [1282] 100 381 N- {3- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1283] Acetamide
    [1284] 101 411 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) thioureido] phenyl} carbamic acid
    [1285] Ethyl ester
    [1286] 102 319 1- (2,4-Dimethoxy-phenyl) -3- (4-methoxy-phenyl) -thiourea
    [1287] 103 346 N- {4- [3- (2,4-Dimethoxy-phenyl) -thioureido] -phenyl} -acetamide
    [1288] 104 316 N- {4- [3- (4-Methoxy-phenyl) -thioureido] -phenyl} -acetamide
    [1289] 105 316 N- {4- [3- (2-Methoxy-phenyl) -thioureido] -phenyl} -acetamide
    [1290] 106 351 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl}
    [1291] mid
    [1292] 107 351 N- {4- [3- (5-Chloro-2-methoxy-phenyl) -thioureido] -phenyl}
    [1293] mid
    [1294] 108 371 N- {4- [3- (3,5-Dichloro-4-hydroxy-phenyl) -thioureido] -phenyl} -
    [1295] Acetamide
    [1296] 109 385 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -
    [1297] Acetamide
    [1298] 110 381 N- {4- [3- (4-Chloro-2,5-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1299] Acetamide
    [1300] 111 389 N- {4- [3- (2-Chloro-5-trifluoromethyl-phenyl) -thioureido] -
    [1301] Phenyl} -acetamide
    [1302] 112 389 N- {4- [3- (4-Chloro-3-trifluoromethyl-phenyl) -thioureido]
    [1303] Phenyl} -acetamide
    [1304] 113 422 benzoic acid 4- [3- (4-acetylamino-phenyl) thioureido] -3-hydroxy-
    [1305] Phenyl ester
    [1306] 114 457 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [1307] Methylbenzamide
    [1308] 115 501 Acetic acid 2- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) thioureido]
    [1309] Phenylcarbamoyl} phenyl ester
    [1310] 116 461 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -4-
    [1311] Fluoro-benzamide
    [1312] 117 461 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-
    [1313] Fluoro-benzamide
    [1314] 118 461 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [1315] Fluoro-benzamide
    [1316] 119 473 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [1317] Methoxy-benzamide
    [1318] 120 473 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-
    [1319] Methoxy-benzamide
    [1320] 121 473 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -4-
    [1321] Methoxy-benzamide
    [1322] 122 443 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1323] Benzamide
    [1324] 123 417 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1325] Methane-sulfonamide
    [1326] 124 331 N- {4- [3- (3-Nitro-phenyl) -thioureido] -phenyl} -acetamide
    [1327] 125 339 1- (3-Chloro-4-methoxy-phenyl) -3- (3-nitro-phenyl) -thiourea
    [1328] 126 337 N- {4- [3- (5-Chloro-2-hydroxy-phenyl) -thioureido] -phenyl} -
    [1329] Acetamide
    [1330] 127 439 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1331] Carbamic acid tert-butyl ester
    [1332] 128 351 N- {4- [3- (3-Chloro-4-hydroxy-5-methyl-phenyl) -thioureido]
    [1333] Phenyl} -acetamide
    [1334] 129 385 N- {4- [3- (3,5-Dichloro-4-hydroxy-2-methyl-phenyl) -thioureido]
    [1335] Phenyl} -acetamide
    [1336] 130 318 N- {4- [3- (2,4-Dihydroxy-phenyl) -thioureido] -phenyl} -acetamide
    [1337] 131 414 N- {4- [3- (2,4-Dimethoxy-5-trifluoromethyl-phenyl) -thioureido]
    [1338] Phenyl} -acetamide
    [1339] 132 332 N- {4- [3- (2-Hydroxy-4-methoxy-phenyl) -thioureido] -phenyl} -
    [1340] Acetamide
    [1341] 133 465 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -4-
    [1342] Fluoro-benzamide
    [1343] 134 500 3-Acetylamino-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thiourea
    [1344] Iso] -phenyl} -benzamide < / RTI >
    [1345] 135 488 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-
    [1346] Nitro-benzamide
    [1347] 136 486 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-
    [1348] Dimethylamino-benzamide
    [1349] 137 536 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-
    [1350] Methanesulfonyl-amino-benzamide
    [1351] 138 511 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [1352] Trifluoromethyl-benzamide < RTI ID = 0.0 >
    [1353] 139 459 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [1354] Hydroxy-benzamide
    [1355] 140 479 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1356] 2,6-difluoro-benzamide
    [1357] 141 477 2-Chloro-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1358] Phenyl} -benzamide
    [1359] 142 522 2-Bromo-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1360] Phenyl} -benzamide
    [1361] 143 488 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [1362] Nitro-benzamide
    [1363] 144 445 pyrazine-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1364] Iso] -phenyl} -amide
    [1365] 145 463 5-Methyl-thiophene-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-
    [1366] Thioureido] -phenyl} -amide < / RTI >
    [1367] 146 494 Quinoline-8-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thiourea
    [1368] Iso] -phenyl} -amide
    [1369] 147 446 1 -Methyl-1 H-pyrrole-2-carboxylic acid {4- [3- (5- chloro-2,4-
    [1370] Thioureido] -phenyl} -amide < / RTI >
    [1371] 148 369 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (2-nitro- phenyl) -thiourea
    [1372] 149 369 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (4-nitro- phenyl) -thiourea
    [1373] 150 425 N- {4- [3- (5-Bromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1374] Acetamide
    [1375] 151 376 N- {4- [3- (3,4,5-trimethoxy-phenyl) -thioureido] -phenyl} -
    [1376] Acetamide
    [1377] 152 399 N- {4- [3- (3,5-Dichloro-2-methoxy-4-methyl-phenyl) -thioureido]
    [1378] Phenyl} -acetamide
    [1379] 153 499 Benzo [b] thiophene-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-
    [1380] Thioureido] -phenyl} -amide < / RTI >
    [1381] 154 483 benzofuran-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1382] Yl] -phenyl} -amide < / RTI >
    [1383] 155 444 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1384] Isonicotinamide
    [1385] 156 493 Naphthalene-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy- phenyl)
    [1386] Thioureido] -phenyl} -amide < / RTI >
    [1387] 157 493 naphthalene-1-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1388] Thioureido] -phenyl} -amide < / RTI >
    [1389] 158 494 isoquinoline-1-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1390] Thioureido] -phenyl} -amide < / RTI >
    [1391] 159 494 Quinoline-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1392] Thioureido] -phenyl} -amide < / RTI >
    [1393] 160 444 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1394] Nicotinamide
    [1395] 161 478 5-Nitro-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-
    [1396] Thioureido] -phenyl} - amide carbamic acid phenyl ester
    [1397] 162 459 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1398] 163 467 5-Chloro-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-
    [1399] Thioureido] -phenyl} -amide < / RTI >
    [1400] 164 439 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1401] Carbamic acid isobutyl ester
    [1402] 165 397 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1403] Carbamic acid methyl ester
    [1404] 166 433 Furan-3-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1405] Thioureido] -phenyl} -amide < / RTI >
    [1406] 167 447 3-Methyl-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-
    [1407] Thioureido] -phenyl} -amide < / RTI >
    [1408] 168 512 5-Bromo-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-
    [1409] Thioureido] -phenyl} -amide < / RTI >
    [1410] 169 512 4-Bromo-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-
    [1411] Thioureido] -phenyl} -amide < / RTI >
    [1412] 170 433 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1413] Thioureido] -phenyl} -amide < / RTI >
    [1414] 171 467 {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1415] Carbamic acid hexyl ester
    [1416] 172 494 isoquinoline-4-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1417] Thioureido] -phenyl} -amide < / RTI >
    [1418] 173 451 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (5-chloro-2,4-
    [1419] Phenyl) -thioureido] -phenyl} -amide
    [1420] 174 434 1H- [1,2,3] triazole-4-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-
    [1421] Phenyl) -thioureido] -phenyl} -amide
    [1422] 175 528 3-Bromo-thiophene-2-carboxylic acid {4- [3- (5-chloro-2,4-
    [1423] -Thioureido] -phenyl} -amide < / RTI >
    [1424] 176 399 N- {4- [3- (3,5-Dichloro-4-ethoxy-phenyl) -thioureido] -phenyl} -
    [1425] Acetamide
    [1426] 177 427 N- {4- [3- (4-Butoxy-3,5-dichloro-phenyl) -thioureido] -phenyl} -
    [1427] Acetamide
    [1428] 178 461 N- {4- [3- (4-Benzyloxy-3,5-dichloro-phenyl) -thioureido] -phenyl} -
    [1429] Acetamide
    [1430] 179 381 N- {4- [3- (3-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1431] Acetamide
    [1432] 180 530 (3- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1433] Phenylcarbamoyl} -phenyl) -carbamic acid ethyl ester
    [1434] 181 458 2-Amino-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1435] Phenyl} -benzamide
    [1436] 182 519 biphenyl-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1437] Thioureido] -phenyl} -amide < / RTI >
    [1438] 183 469 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- [4- (1,3- dioxo-1,3-
    [1439] - isoindol-2-yl) -phenyl] -thiourea
    [1440] 184 487 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1441] Phthalamic acid
    [1442] 185 473 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [1443] Hydroxy-methyl-benzamide
    [1444] 186 479 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1445] 2,3-difluoro-benzamide
    [1446] 187 479 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1447] 2,5-difluoro-benzamide
    [1448] 188 479 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1449] 2,4-difluoro-benzamide
    [1450] 189 500 2-Acetylamino-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1451] Thioureido] -phenyl} -benzamide < / RTI >
    [1452] 190 441 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (6-oxo-5,6-
    [1453] Phenanthridin-2-yl) -thiourea
    [1454] 191 536 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [1455] Methanesulfonylamino-benzamide
    [1456] 192 497 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1457] 2,3,4-Trifluoro-benzamide
    [1458] 193 533 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1459] 2,3,4,5,6-pentafluoro-benzamide
    [1460] 194 489 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [1461] Methyl-sulfanyl-benzamide
    [1462] 195 431 5-Methyl-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-
    [1463] Thioureido] -phenyl} -amide < / RTI >
    [1464] 196 467 5-Difluoromethyl-furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-
    [1465] Phenyl) -thioureido] -phenyl} -amide
    [1466] 197 472 N- {4- [3- (5-Iodo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1467] Acetamide
    [1468] 198 364 N- {4- [3- (5-Fluoro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1469] Acetamide
    [1470] 199 365 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido] -phenyl}
    [1471] Acetamide
    [1472] 200 459 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl-
    [1473] Yl-phenyl) -thioureido] -phenyl} -amide
    [1474] 201 455 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro-
    [1475] Phenyl) -thioureido] -phenyl} -amide
    [1476] 202 392 N- {4- [3- (3-Chloro-4-diethylamino-phenyl) -thioureido] -phenyl} -
    [1477] Acetamide
    [1478] 203 432 N- (4- {3- [3-Chloro-4- (cyanohexyl-methyl-amino) -phenyl] -
    [1479] Thioureido} -phenyl) -acetamide < / RTI >
    [1480] 204 506 1 -Hydroxy-naphthalene-2-carboxylic acid {4- [3- (4-acetylamino-phenyl)
    [1481] Thioureido] -2-chloro-phenyl} -amide
    [1482] 205 406 N- {4- [3- (3-Chloro-4-morpholin-4-yl-phenyl) -thioureido] -phenyl} -
    [1483] Acetamide
    [1484] 206 443 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (3-chloro-
    [1485] Phenyl) -thiourea
    [1486] 207 372 1- (5-Chloro-2,4-dimethoxy-phenyl) -3- (5-chloro-
    [1487] Thiourea
    [1488] 208 501 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1489] Isophthalamic acid methyl ester
    [1490] 209 487 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1491] Isophthalamic acid
    [1492] 210 549 3-Benzyloxy-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1493] Thioureido] -phenyl} -benzamide < / RTI >
    [1494] 211 434 N- (4- {3- [5-Chloro-2-methoxy-4- (4-nitrilo-butoxy) -phenyl]
    [1495] Thioureido} -phenyl) -acetamide < / RTI >
    [1496] 212 406 N- (4- {3- [5-Chloro-2-methoxy-4- (2-nitrilo-ethoxy) -phenyl] -
    [1497] Thioureido} phenyl) acetamide
    [1498] 213 406 N- (4- {3- [5-Chloro-4-methoxy-2- (2-nitrilo-ethoxy) -phenyl] -
    [1499] Thioureido} phenyl) acetamide
    [1500] 214 411 N- (4- {3- [5-Chloro-2- (2-hydroxy-ethoxy) -4- methoxy-
    [1501] Thioureido} phenyl) acetamide
    [1502] 215 411 N- (4- {3- [5-Chloro-4- (2-hydroxy-ethoxy) -2- methoxy-
    [1503] Thioureido} phenyl) -acetamide
    [1504] 216 481 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-5-methoxy-
    [1505] Phenoxy} -acetic acid tert-butyl ester
    [1506] 217 439 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-5-methoxy-
    [1507] Phenoxy} acetic acid methyl ester
    [1508] 218 481 {2- [3- (4-Acetylamino-phenyl) -thioureido] -4-chloro-5-methoxy-
    [1509] Phenoxy} acetic acid tert-butyl ester
    [1510] 219 515 3-Butoxy-N- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1511] Phenyl} -benzamide
    [1512] 220 505 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [1513] Methane-sulfinyl-benzamide
    [1514] 221 545 (3- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1515] Phenylcarbamoyl} -phenoxy) acetic acid ethyl ester
    [1516] 222 517 (3- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1517] Phenylcarbamoyl} -phenoxy) -acetic < / RTI > acid
    [1518] 223 367 N- {4- [3- (5-Chloro-4-hydroxy-2-methoxy-phenyl) -thioureido]
    [1519] Phenyl} -acetamide
    [1520] 224 444 Pyridine-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1521] Thioureido] -phenyl} -amide < / RTI >
    [1522] 225 494 Quinoline-4-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1523] Thioureido] -phenyl} -amide < / RTI >
    [1524] 226 436 N- {4- [3- (5-Chloro-4-methoxy-2-morpholin-
    [1525] Thioureido] -phenyl} -acetamide < / RTI >
    [1526] 227 394 N- {4- [3- (5-Chloro-2-dimethylamino-4-methoxy-phenyl)
    [1527] Thioureido] -phenyl} -acetamide < / RTI >
    [1528] 228 420 N- {4- [3- (5-Chloro-4-methoxy-2-pyrrolidin-
    [1529] Thioureido] -phenyl} -acetamide < / RTI >
    [1530] 229 434 N- {4- [3- (5-Chloro-4-methoxy-2-piperidin-
    [1531] Thioureido] -phenyl} -acetamide < / RTI >
    [1532] 230 405 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-methyl-
    [1533] Thioureido] -phenyl} -amide < / RTI >
    [1534] 231 415 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -phenyl} -2-
    [1535] Fluoro-benzamide
    [1536] 232 427 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -phenyl} -3-methoxy-
    [1537] Benzamide
    [1538] 233 387 furan-2-carboxylic acid {4- [3- (3-chloro-4-methyl- phenyl) -thioureido]
    [1539] Phenyl} -amide
    [1540] 234 411 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -phenyl}
    [1541] Benzamide
    [1542] 235 433 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -phenyl}
    [1543] Difluoro-benzamide
    [1544] 236 398 Pyridine-2-carboxylic acid {4- [3- (3-chloro-4-methyl- phenyl) -thioureido]
    [1545] Phenyl} -amide
    [1546] 237 502 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3-chloro-4- (cyclohexyl-
    [1547] Methyl-amino) -phenyl] -thioureido} -phenyl) -amide
    [1548] 238 512 N- (4- {3- [3-Chloro-4- (cyclohexyl-methyl-amino) -phenyl] -
    [1549] Thioureido} -phenyl) -2-fluoro-benzamide
    [1550] 239 404 N- {4- [3- (3-Chloro-4-piperidin-l-yl-phenyl) -thioureido] -phenyl} -
    [1551] Acetamide
    [1552] 240 364 N- {4- [3- (3-Chloro-4-dimethylamino-phenyl) -thioureido] -phenyl} -
    [1553] Acetamide
    [1554] 241 426 N- {4- [3- (4-Benzylamino-3-chloro-phenyl) -thioureido] -phenyl} -
    [1555] Acetamide
    [1556] 242 390 N- {4- [3- (3-Chloro-4-pyrrolidin- 1 -yl-phenyl) -thioureido] -phenyl} -
    [1557] Acetamide
    [1558] 243 419 N- (4- {3- [3-Chloro-4- (4-methyl-piperazin- 1- yl) -phenyl] -
    [1559] Thioureido} -phenyl) -acetamide < / RTI >
    [1560] 244 469 N- {4- [3- (4-Chloro-3-trifluoromethyl-phenyl) -thioureido]
    [1561] Phenyl} -2-fluoro-benzamide
    [1562] 245 422 N- {4- [3- (2-Benzylamino-4-methoxy-phenyl) -thioureido] -phenyl} -
    [1563] Acetamide
    [1564] 246 484 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (cyclohexyl- methyl-
    [1565] Phenyl] thioureido} phenyl) -amide
    [1566] 247 508 N- (4- {3- [3-Chloro-4- (cyclohexyl-methyl-amino) -phenyl] -
    [1567] Thioureido} -phenyl) -2-methyl-benzamide
    [1568] 248 530 N- (4- {3- [3-Chloro-4- (cyclohexyl-methyl-amino) -phenyl] -
    [1569] Thioureido} -phenyl) -2,6-difluoro-benzamide
    [1570] 249 495 Pyridine-2-carboxylic acid (4- {3- [3-chloro-4- (cyclohexyl-
    [1571] Amino) -phenyl] -thioureido} -phenyl) -amide
    [1572] 250 524 N- (4- {3- [3-Chloro-4- (cyclohexyl-methyl-amino) -phenyl] -
    [1573] Thioureido} -phenyl) -3-methoxy-benzamide
    [1574] 251 376 N- (4- {3- [3-Chloro-4- (2-nitrilo-ethoxy) -phenyl] -thioureido}
    [1575] Phenyl) -acetamide
    [1576] 252 393 N- {4- [3- (4-sec-Butoxy-3-chloro-phenyl) -thioureido] -phenyl} -
    [1577] Acetamide
    [1578] 253 501 Acetic acid 3- {4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1579] Phenyl-carbamoyl} -phenyl ester
    [1580] 254 459 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-
    [1581] Hydroxy-benzamide
    [1582] 255 487 Benzo [1, 3] dioxole-4-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-
    [1583] Thioureido] -phenyl} -amide < / RTI >
    [1584] 256 527 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-
    [1585] Trifluoromethoxy-benzamide < RTI ID = 0.0 >
    [1586] 257 530 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-
    [1587] (2-dimethylamino-ethoxy) -benzamide
    [1588] 258 572 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -3-
    [1589] (2-morpholin-4-yl-ethoxy) -benzamide
    [1590] 259 406 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-cyano-
    [1591] Phenyl} -acetamide
    [1592] 260 521 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2,5-
    [1593] Dimethoxy-phenyl} -2-fluoro-benzamide < / RTI >
    [1594] 261 441 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2,5-
    [1595] Dimethoxy-phenyl} -acetamide < / RTI >
    [1596] 262 527 2- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenoxy} -
    [1597] 5-Chlorobenzenesulfonic acid
    [1598] 263 562 2- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenoxy} -
    [1599] 4,5-Dichlorobenzenesulfonic acid
    [1600] 264 527 4-Phenyl [l, 2,3] thiadiazole-5-carboxylic acid {4- [3- (5-
    [1601] Dimethoxyphenyl) -thioureido] -phenyl} -amide < / RTI >
    [1602] 265 381 N- (4- {3- [3-Chloro-4- (2-hydroxy-ethoxy) -phenyl] -thioureido}
    [1603] Phenyl) acetamide
    [1604] 266 393 N- {4- [3- (4-Butoxy-3-chloro-phenyl) -thioureido] -phenyl} -
    [1605] Acetamide
    [1606] 267 446 N- (4- {3- [3-Chloro-4- (cyclohexyl-ethyl-amino) -phenyl] -
    [1607] Thioureido} -phenyl) acetamide < / RTI >
    [1608] 268 365 N- {4- [3- (3-Chloro-4-ethoxy-phenyl) -thioureido] -phenyl} -
    [1609] Acetamide
    [1610] 269 427 N- {4- [3- (4-Benzyloxy-3-chloro-phenyl) -thioureido] -phenyl} -
    [1611] Acetamide
    [1612] 270 317 {4- [(3-Methyl-furan-2-carbonyl) amino] phenyl} -carbamic acid tert- butyl
    [1613] ester
    [1614] 271 456 N- {4- [3- (2-Benzylamino-5-chloro-4-methoxy-phenyl) -thioureido]
    [1615] Phenyl} -acetamide
    [1616] 272 420 N- {4- [3- (3-Chloro-4-dipropylamino-phenyl) -thioureido] -phenyl} -
    [1617] Acetamide
    [1618] 273 458 N- (4- {3- [4- (Allyl-cyclohexyl-amino) -3-chloro-phenyl] -
    [1619] Thioureido} -phenyl) acetamide < / RTI >
    [1620] 274 411 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy-
    [1621] Phenyl} -acetamide
    [1622] 275 415 N- {2-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1623] Phenyl} acetamide
    [1624] 276 493 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1625] Thioureido] -2,5-dimethoxy-phenyl} -amide
    [1626] 277 486 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-cyano-
    [1627] Phenyl} -2-fluoro-benzamide
    [1628] 278 495 N- {2-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1629] Phenyl} -2-fluoro-benzamide
    [1630] 279 465 5-Methyl- [l, 2,3] thiadiazole-4-carboxylic acid {4- [3- (5-
    [1631] Dimethoxy-phenyl) -thioureido] -phenyl} -amide
    [1632] 280 517 5-Furan-3-yl- [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (5-
    [1633] Dimethoxy-phenyl) thioureido] -phenyl} amide
    [1634] 281 527 5-Phenyl- [l, 2,3] thiadiazole-4-carboxylic acid {4- [3- (5-
    [1635] Dimethoxy-phenyl) thioureido] -phenyl} amide
    [1636] 282 458 N- (4- {3- [3-Chloro-4- (octahydro-quinolin- 1 -yl) -phenyl] -
    [1637] Thioureido} phenyl) acetamide
    [1638] 283 458 N- [5 - [[[(5-chloro-2,4-dimethoxyphenyl) amino] thioxomethyl]
    [1639] 2-pyridinyl] -2-methylbenzamide
    [1640] 284 434 furan-2-carboxylic acid {5- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1641] Thioureido] -pyridin-2-yl} -amide
    [1642] 285 425 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy-
    [1643] 5-methylphenyl} -acetamide
    [1644] 286 505 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy-
    [1645] 5-methylphenyl} -2-fluoro-benzamide
    [1646] 287 477 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1647] Thioureido] -2-methoxy-5-methyl-phenyl} -amide
    [1648] 288 517 4-Furan-3-yl- [1,2,3] thiadiazole-5-carboxylic acid {4- [3- (5-
    [1649] Dimethoxy-phenyl) -thioureido] -phenyl} -amide
    [1650] 289 462 N- {5- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -pyridin-
    [1651] Yl} -2-fluoro-benzamide
    [1652] 290 384 N- {4- [3- (4-Methoxy-3-trifluoromethyl-phenyl) -thioureido]
    [1653] Phenyl} -acetamide
    [1654] 291 394 N- {4- [3- (3-Chloro-4 - [(2-hydroxy- ethyl) -methyl-
    [1655] Thioureido) -phenyl] -acetamide < / RTI >
    [1656] 292 485 N- {2-Benzoyl-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1657] Phenyl} -acetamide
    [1658] 293 565 N- {2-Benzoyl-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1659] Phenyl} -2-fluoro-benzamide
    [1660] 294 537 furan-2-carboxylic acid {2-benzoyl-4- [3- (5-chloro-2,4-dimethoxy- phenyl)
    [1661] Thioureido] -phenyl} -amide < / RTI >
    [1662] 295 475 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1663] Phenyl} -2-fluoro-benzamide
    [1664] 296 447 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1665] Thioureido] -3-methyl-phenyl} -amide
    [1666] 297 395 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1667] Phenyl} -acetamide
    [1668] 298 435 N- [4- (3- {3-Chloro-4 - [(3-dimethylamino-propyl)
    [1669] Phenyl} -thioureido) -phenyl] -acetamide < / RTI >
    [1670] 299 418 N- {4- [3- (3-Chloro-4-cyclohexylamino-phenyl) -thioureido]
    [1671] Phenyl} -acetamide
    [1672] 300 421 N- [4- (3- {3-Chloro-4 - [(2- dimethylamino-ethyl) -methyl-
    [1673] Thioureido) -phenyl] -acetamide < / RTI >
    [1674] 301 580 5 - [[[(5-chloro-2,4-dimethoxyphenyl) amino] thioxomethyl]
    [1675] [(2-fluorobenzoyl) amino] -N-phenyl-benzamide
    [1676] 302 552 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1677] Thioureido] -2-phenylcarbamoyl-phenyl} -amide
    [1678] 303 491 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-methoxy-
    [1679] Phenyl} -2-fluoro-benzamide
    [1680] 304 463 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1681] Thioureido] -2-methoxy-phenyl} -amide
    [1682] 305 449 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-
    [1683] Trifluoromethyl-phenyl} -acetamide < / RTI >
    [1684] 306 458 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1685] Thioureido] -2-cyano-phenyl} -amide
    [1686] 307 467 furan-2-carboxylic acid {2-chloro-4- [3- (5-chloro-2,4-dimethoxy-
    [1687] Thioureido] -phenyl} -amide < / RTI >
    [1688] 308 501 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1689] Thioureido] -2-trifluoromethyl-phenyl} -amide
    [1690] 309 395 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1691] Phenyl} -acetamide
    [1692] 310 475 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1693] Phenyl} -2-fluoro-benzamide
    [1694] 311 447 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1695] Thioureido] -2-methyl-phenyl} -amide
    [1696] 312 378 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -
    [1697] Acetamide
    [1698] 313 408 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -
    [1699] Carbamic acid ethyl ester
    [1700] 314 382 N- {5- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -pyridin-
    [1701] Yl} -acetamide
    [1702] 315 509 N- (4- {3- [4- (l-Benzyl-piperidin-4-ylamino) -3-chloro-
    [1703] Thioureido} -phenyl) -acetamide < / RTI >
    [1704] 316 407 N- (4- {3- [3-Chloro-4- (2-dimethylamino-ethylamino) -phenyl] -
    [1705] Thioureido} -phenyl) -acetamide < / RTI >
    [1706] 317 408 N- [4- (3- {3-Chloro-4 - [(2- methoxy-ethyl) -methyl-
    [1707] Thioureido) phenyl] -acetamide
    [1708] 318 421 N- (4- {3- [3-Chloro-4- (3-dimethylamino-propylamino) -phenyl] -
    [1709] Thioureido} -phenyl) -acetamide < / RTI >
    [1710] 319 495 N- (4- {3- [4- (l-Benzyl-pyrrolidin-3- ylamino) -3-chloro-
    [1711] Thioureido} -phenyl) -acetamide < / RTI >
    [1712] 320 483 Furan-2-carboxylic acid {5-chloro-4- [3- (5-chloro-2,4-dimethoxy-
    [1713] Thioureido] -2-hydroxy-phenyl} -amide
    [1714] 321 431 N- {5-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1715] 2-hydroxy-phenyl} -acetamide
    [1716] 322 511 (5H, 11H-benzo [e] pyrrolo [1,2-a] [1,4] diazepin-
    [1717] Yl-phenyl) -methanone < / RTI >
    [1718] 323 451 [1,2,3] Thiadiazole-5-carboxylic acid {4- [3- (5-chloro-2,4-
    [1719] Phenyl) thioureido] -phenyl} -amide
    [1720] 324 483 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1721] Thioureido] naphthalen-l-yl} -amide
    [1722] 325 511 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -naphthalene-
    [1723] Yl} -2-fluoro-benzamide < / RTI >
    [1724] 326 429 N- {5-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1725] 2-methyl-phenyl} -acetamide
    [1726] 327 509 N- {5-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1727] 2-methylphenyl} -2-fluoro-benzamide
    [1728] 328 481 furan-2-carboxylic acid {5-chloro-4- [3- (5-chloro-2,4-dimethoxy-
    [1729] Thioureido] -2-methyl-phenyl} -amide
    [1730] 329 431 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -naphthalene-
    [1731] 1-yl} -acetamide < / RTI >
    [1732] 330 416 furan-2-carboxylic acid {4- [3- (3-chloro-4-dimethylamino-
    [1733] Thioureido] -phenyl} -amide < / RTI >
    [1734] 331 561 furan-2-carboxylic acid [4- (3- {4 - [(1-benzyl- pyrrolidin-
    [1735] 3-chloro-phenyl} -thioureido) -phenyl] -amide
    [1736] 332 513 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl-pyrrolidin-
    [1737] Phenyl} thioureido) -phenyl] -2-fluoro-benzamide
    [1738] 333 463 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido] -phenyl}
    [1739] 2,6-difluoro-benzamide
    [1740] 334 420 N- (4- {3- [3-Chloro-4- (l-methyl-pyrrolidin-3- yloxy) -phenyl] -
    [1741] Thioureido} phenyl) -acetamide
    [1742] 335 434 N- (4- {3- [3-Chloro-4- (1 -methyl-piperidin-4- yloxy) -phenyl] -
    [1743] Thioureido} phenyl) -acetamide
    [1744] 336 422 N- (4- {3- [3-Chloro-4- (3-dimethylamino-propoxy) -phenyl] -
    [1745] Thioureido} phenyl) -acetamide
    [1746] 337 425 2-Acetylamino-5- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1747] Thioureido] benzoic acid
    [1748] 338 505 5- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2- (2-
    [1749] Benzoylamino) -benzoic acid
    [1750] 339 477 5- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2 - [(furan-
    [1751] Carbonyl) amino) -benzoic acid
    [1752] 340 545 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl- piperidin-
    [1753] Phenyl} thioureido) -phenyl] -2,6-difluoro-benzamide
    [1754] 341 503 [1,2,3] thiadiazole-4-carboxylic acid [4- (3- {3-chloro-4- [methyl-
    [1755] Pyrrolidin-3-yl) -amino] -phenyl} -thioureido) -phenyl] -amide
    [1756] 342 443 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido] -phenyl} -2-
    [1757] Methyl-benzamide
    [1758] 343 408 N- (4- {3- [3-Chloro-4- (2-dimethylamino-ethoxy) -phenyl] -
    [1759] Thioureido} -phenyl) -acetamide < / RTI >
    [1760] 344 499 Furan-2-carboxylic acid [4- (3- {3-chloro-4- [methyl- (1 -methyl-piperidin-
    [1761] Amino] -phenyl} -thioureido) -phenyl] -amide
    [1762] 345 419 N- {4- [3- (3-Chloro-4-cyclohexyloxy-phenyl) -thioureido] -
    [1763] Phenyl} -acetamide
    [1764] 346 440 N- {4- [3- (3-Chloro-4-dimethylamino-phenyl) -thioureido] -phenyl} -2-
    [1765] Methyl-benzamide
    [1766] 347 493 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1767] Phenyl} -2,6-difluoro-benzamide
    [1768] 348 462 N- {4- [3- (3-Chloro-4-dimethylamino-phenyl) -thioureido] -phenyl} -
    [1769] 2,6-difluoro-benzamide
    [1770] 349 531 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl-pyrrolidin-
    [1771] Phenyl} -thioureido) -phenyl] -2,6-difluoro-benzamide
    [1772] 350 427 Pyridine-2-carboxylic acid {4- [3- (3-chloro-4-dimethylamino-
    [1773] Thioureido] -phenyl} -amide < / RTI >
    [1774] 351 430 Pyridine-2-carboxylic acid {4- [3- (3-chloro-4-methylsulfanyl- phenyl)
    [1775] Thioureido] -phenyl} -amide < / RTI >
    [1776] 352 428 Pyridine-2-carboxylic acid {4- [3- (5-chloro-2-methoxy-
    [1777] Thioureido] -phenyl} -amide < / RTI >
    [1778] 353 417 furan-2-carboxylic acid {4- [3- (5-chloro-2-methoxy-
    [1779] Thioureido] -phenyl} -amide < / RTI >
    [1780] 354 496 Pyridine-2-carboxylic acid {4- [3- (3-chloro-4- [methyl-
    [1781] Yl) -amino] -phenyl} -thioureido) -phenyl] -amide
    [1782] 355 495 N- {3-Chloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl) -thioureido]
    [1783] Phenyl} -2-fluoro-benzamide
    [1784] 356 467 furan-2-carboxylic acid {3-chloro-4- [3- (5- chloro-2,4-dimethoxy- phenyl)
    [1785] Thioureido] -phenyl} -amide < / RTI >
    [1786] 357 515 N- {4- [3- (3-Chloro-4-cyclohexylsulfanyl-phenyl) -thioureido] -
    [1787] Phenyl} -2-fluoro-benzamide
    [1788] 358 449 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-
    [1789] Trifluoromethylphenyl} -acetamide < / RTI >
    [1790] 359 529 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-
    [1791] Trifluoromethylphenyl} -2-fluoro-benzamide < / RTI >
    [1792] 360 421 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-
    [1793] Dimethylamino-acetamide
    [1794] 361 473 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-
    [1795] Acetylamino) phenyl] -thioureido} -phenyl) -amide
    [1796] 362 501 N- (4- {3- [3-Chloro-4- (2-dimethylamino-acetylamino) -phenyl] -
    [1797] Thioureido} -phenyl) -2-fluoro-benzamide
    [1798] 363 461 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-
    [1799] Piperidin-1-yl-acetamide
    [1800] 364 541 N- (4- {3- [3-Chloro-4- (2-piperidin- 1- yl-acetylamino) -phenyl] -
    [1801] Thioureido} -phenyl) -2-fluoro-benzamide
    [1802] 365 513 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-
    [1803] Acetylamino) phenyl] -thioureido} -phenyl) -amide
    [1804] 366 463 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-
    [1805] Morpholin-4-yl-acetamide
    [1806] 367 543 N- (4- {3- [3-Chloro-4- (2-morpholin-4- yl- acetylamino) -phenyl] -
    [1807] Thioureido} -phenyl) -2-fluoro-benzamide
    [1808] 368 515 furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-morpholin-
    [1809] Acetylamino) phenyl] -thioureido} -phenyl) -amide
    [1810] 369 414 N- {4- [3- (3-Chloro-4-methanesulfonylamino-phenyl) -thioureido]
    [1811] Phenyl} -acetamide
    [1812] 370 494 N- {4- [3- (3-Chloro-4-methanesulfonylamino-phenyl) -thioureido]
    [1813] Phenyl} -2-fluoro-benzamide
    [1814] 371 466 furan-2-carboxylic acid {4- [3- (3-chloro-4-methanesulfonylamino-phenyl)
    [1815] Thioureido] -phenyl} -amide < / RTI >
    [1816] 372 481 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-
    [1817] (2-dimethylamino-ethylsulfanyl) -acetamide
    [1818] 373 561 N- [4- (3- {3-Chloro-4- [2- (2-dimethylamino-ethylsulfanyl)
    [1819] Acetylamino] -phenyl} -thioureido) -phenyl] -2-fluoro-benzamide
    [1820] 374 585 N- [4- (3- {4 - [(1-Benzyl-pyrrolidin-3- yl) -methyl-
    [1821] Phenyl} -thioureido) -phenyl] -2-methyl-benzamide
    [1822] 375 523 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl- piperidin-
    [1823] Phenyl} -thioureido) -phenyl] -2-methyl-benzamide
    [1824] 376 510 Pyridine-2-carboxylic acid [4- (3- {3-chloro-4- [methyl- (1 -methyl-piperidin-
    [1825] Yl) -amino] phenyl} -thioureido) -phenyl] -amide
    [1826] 377 347 N- {4- [3- (3-Chloro-4-vinyl-phenyl) -thioureido] phenyl} -acetamide]
    [1827] 378 441 furan-2-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl- phenyl)
    [1828] Thioureido] -phenyl} -amide < / RTI >
    [1829] 379 452 Pyridine-2-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl- phenyl)
    [1830] Thioureido] -phenyl} -amide < / RTI >
    [1831] 380 487 N- {4- [3- (4-Chloro-3-trifluoromethyl-phenyl) -thioureido]
    [1832] Phenyl} -2,6-difluoro-benzamide
    [1833] 381 486 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-
    [1834] Phenyl} -2-fluoro-benzamide
    [1835] 382 458 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1836] Thioureido] -3-cyano-phenyl} -amide
    [1837] 383 406 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-
    [1838] Phenyl} -acetamide
    [1839] 384 395 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -2-methyl-isothioureido]
    [1840] Phenyl} -acetamide
    [1841] 385 396 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -2-methyl-isothioureido]
    [1842] Phenyl} -acetamide
    [1843] 386 461 N- {4- [3- (3-Chloro-4-ethylsulfanyl-phenyl) -thioureido] -phenyl} -2-
    [1844] Fluoro-benzamide
    [1845] 387 489 N- {4- [3- (4-Butylsulfanyl-3-chloro-phenyl) -thioureido] -phenyl} -2-
    [1846] Fluoro-benzamide
    [1847] 388 411 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-methoxy-
    [1848] Phenyl} -acetamide
    [1849] 389 491 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -3-methoxy-
    [1850] Phenyl} -2-fluoro-benzamide
    [1851] 390 463 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [1852] Thioureido] -3-methoxy-phenyl} -amide
    [1853] 391 531 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3-chloro-4- (2-piperidin-
    [1854] Yl-acetyl-amino) -phenyl] -thioureido} -phenyl) -amide
    [1855] 392 481 N- {4- [3- (3-Chloro-4-methanesulfinyl-phenyl) -thioureido] -phenyl}
    [1856] Difluoro-benzamide
    [1857] 393 497 N- {4- [3- (3-Chloro-4-methanesulfonyl-phenyl) -thioureido] -phenyl}
    [1858] Difluoro-benzamide
    [1859] 394 459 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido]
    [1860] Phenyl} -2-fluoro-benzamide
    [1861] 395 429 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -2-methyl-
    [1862] Fluoro-benzamide
    [1863] 396 533 furan-2-carboxylic acid [4- (3- {3-chloro-4- [2- (2-
    [1864] Ethylsulfanyl) acetylamino] -phenyl} -thioureido) -phenyl] -amide
    [1865] 397 458 N- {4- [3- (4-Acetylamino-3-chloro-phenyl) -thioureido] -phenyl} -2-
    [1866] Fluoro-benzamide
    [1867] 398 460 [2-Chloro-4- (3- {4- [(furan-2-carbonyl) -amino] -phenyl}
    [1868] Thioureido) -phenyl] -carbamic acid ethyl ester
    [1869] 399 488 (2-Chloro-4- {3- [4- (2-fluoro-benzoylamino) -phenyl] -
    [1870] Thioureido} -phenyl) carbamic acid ethyl ester
    [1871] 400 440 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -
    [1872] Benzamide
    [1873] 401 520 N- {4 - [({[4- (Benzoylamino) -3-chloro-phenyl] -amino} -thioxomethyl)
    [1874] Amino] -phenyl} -2-fluoro-benzamide
    [1875] 402 529 N- {4- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -2-
    [1876] Trifluoromethyl-phenyl} -2-fluoro-benzamide < / RTI >
    [1877] 403 492 Furan-2-carboxylic acid {4- [3- (4-benzoylamino-3-chloro-phenyl)
    [1878] Thioureido] -phenyl} -amide < / RTI >
    [1879] 404 416 N- {4- [3- (4-Amino-3-chloro-phenyl) -thioureido] -phenyl} -2-
    [1880] Fluoro-benzamide
    [1881] 405 479 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-
    [1882] Thiomorpholin-4-yl-acetamide
    [1883] 406 531 furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-thiomorpholin-
    [1884] Acetylamino) phenyl] -thioureido} -phenyl) -amide
    [1885] 407 559 N- (4- {3- [3-Chloro-4- (2-thiomorpholin-4- yl- acetylamino) -phenyl] -
    [1886] Thioureido} -phenyl) -2-fluoro-benzamide
    [1887] 408 461 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido]
    [1888] Phenyl} -2-fluoro-benzamide
    [1889] 409 430 furan-2-carboxylic acid {4- [3- (4-acetylamino-3-chloro-phenyl)
    [1890] Thioureido] phenyl} -amide
    [1891] 410 477 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-
    [1892] Dipropylamino-acetamide
    [1893] 411 529 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-
    [1894] Acetylamino) phenyl] -thioureido} -phenyl) -amide
    [1895] 412 449 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-
    [1896] Diethylamino-acetamide
    [1897] 413 501 furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-
    [1898] Acetylamino) -phenyl] -thioureido} -phenyl) -amide < / RTI >
    [1899] 414 529 N- (4- {3- [3-Chloro-4- (2-diethylamino-acetylamino) -phenyl] -
    [1900] Thioureido} -phenyl) -2-fluoro-benzamide
    [1901] 415 447 N- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-phenyl} -2-
    [1902] Pyrrolidin-1-yl-acetamide
    [1903] 416 499 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (2-pyrrolidin-
    [1904] Acetylamino) phenyl] -thioureido} -phenyl) -amide
    [1905] 417 527 N- (4- {3- [3-Chloro-4- (2-pyrrolidin- 1 -yl- acetylamino) -phenyl] -
    [1906] Thioureido} -phenyl) -2-fluoro-benzamide
    [1907] 418 475 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido] -3-
    [1908] Methoxy-phenyl} -2-fluoro-benzamide
    [1909] 419 445 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -3-methoxy-
    [1910] 2-Fluoro-benzamide
    [1911] 420 477 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido] -3-methoxy-
    [1912] Phenyl} -2-fluoro-benzamide
    [1913] 421 388 furan-2-carboxylic acid {4- [3- (4-amino-3-chloro-phenyl) -thioureido]
    [1914] Phenyl} -amide
    [1915] 422 527 furan-2-carboxylic acid (4- {3- [4- (2-azepan-1-yl- acetylamino)
    [1916] Phenyl] -thioureido} -phenyl) -amide
    [1917] 423 555 N- (4- {3- [4- (2-Azepan-1-yl-acetylamino)
    [1918] Thioureido} -phenyl) -2-fluoro-benzamide
    [1919] 424 527 furan-2-carboxylic acid [4- (3- {3-chloro-4- [2-
    [1920] Acetyl-amino] -phenyl} -thioureido) -phenyl] -amide
    [1921] 425 555 N- [4- (3- {3-Chloro-4- [2- (2-methyl- piperidin- 1- yl) -acetylamino]
    [1922] Phenyl} -thioureido) -phenyl] -2-fluoro-benzamide
    [1923] 426 339 furan-2-carboxylic acid [4- (3-pyridin-2-yl-thioureido) -phenyl]
    [1924] 427 339 Furan-2-carboxylic acid [4- (3-pyridin-4-yl-thioureido) -phenyl]
    [1925] 428 367 2-Fluoro-N- [4- (3-pyridin-3-yl-thioureido) -phenyl] -benzamide
    [1926] 429 339 furan-2-carboxylic acid [4- (3-pyridin-3-yl-thioureido) -phenyl]
    [1927] 430 353 Furan-2-carboxylic acid {4- [3- (3-amino-phenyl) -thioureido] -phenyl}
    [1928] 431 406 furan-2-carboxylic acid {4- [3- (3-trifluoromethyl-phenyl) -thioureido]
    [1929] Phenyl} -amide
    [1930] 432 380 2-Fluoro-N- [4- (3-m-tolyl-thioureido) -phenyl] -benzamide
    [1931] 433 434 2-Fluoro-N- {4- [3- (3-trifluoromethyl-phenyl) -thioureido] -
    [1932] Phenyl} benzamide
    [1933] 434 381 N- {4- [3- (3-Amino-phenyl) -thioureido] -phenyl} -2-fluoro-
    [1934] Benzamide
    [1935] 435 388 furan-2-carboxylic acid {4- [3- (3-amino-5-chloro-phenyl) -thioureido]
    [1936] Phenyl} -amide
    [1937] 436 352 Furan-2-carboxylic acid [4- (3-m-tolyl-thioureido) -phenyl] -amide
    [1938] 437 416 N- {4- [3- (2-Amino-5-chloro-phenyl) -thioureido] -phenyl} -2-
    [1939] Fluoro-benzamide
    [1940] 438 571 (2-Chloro-4- {3- [4- (2-fluoro-benzoylamino) -phenyl] -
    [1941] Thioureido} -phenyl) -carbamic acid 2-piperidin-1-yl-ethyl ester
    [1942] 439 543 [2-Chloro-4- (3- {4- [(furan-2-carbonyl) -amino] -phenyl}
    [1943] Thioureido) -phenyl] -carbamic acid 2-piperidin-1-yl-ethyl ester
    [1944] 440 388 furan-2-carboxylic acid {4- [3- (2-amino-5-chloro-phenyl) -thioureido]
    [1945] Phenyl} -amide
    [1946] 441 363 furan-2-carboxylic acid {4- [3- (3-cyano-phenyl) -thioureido] -phenyl} -
    [1947] amides
    [1948] 442 416 N- {4- [3- (3-Amino-5-chloro-phenyl) -thioureido] -phenyl} -2-
    [1949] Fluoro-benzamide
    [1950] 443 367 2-Fluoro-N- [4- (3-pyridin-2-yl-thioureido) -phenyl] -benzamide
    [1951] 444 367 2-Fluoro-N- [4- (3-pyridin-4-yl-thioureido) -phenyl] -benzamide
    [1952] 445 374 furan-2-carboxylic acid {4- [3- (6-chloro-pyridin-3- yl) -thioureido]
    [1953] Phenyl} -amide
    [1954] 446 388 furan-2-carboxylic acid {4- [3- (2-amino-3-chloro-phenyl) -thioureido]
    [1955] Phenyl} -amide
    [1956] 447 396 Furan-2-carboxylic acid {4- [3- (3-hydrazinocarbonyl-phenyl)] - thioureido]
    [1957] Phenyl} -amide
    [1958] 448 410 2-Fluoro-N- (4- {3- [3- (1 -hydroxy-ethyl) -phenyl] -thioureido}
    [1959] Phenyl) -benzamide
    [1960] 449 414 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-hydrazinocarbonyl- phenyl)
    [1961] Thioureido] -phenyl} -amide < / RTI >
    [1962] 450 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3- isopropyl- phenyl)
    [1963] Thioureido] -phenyl} -amide < / RTI >
    [1964] 451 380 Furan-2-carboxylic acid {4- [3- (3-isopropyl-phenyl) -thioureido] -phenyl} -
    [1965] amides
    [1966] 452 409 2-Fluoro-N- {4- [3- (3-isopropyl-phenyl) -thioureido] -phenyl} -
    [1967] Benzamide
    [1968] 453 381 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-cyano- phenyl)
    [1969] Thioureido] -phenyl} -amide < / RTI >
    [1970] 454 410 N- {4- [3- (3-Dimethylamino-phenyl) -thioureido] -phenyl} -2-fluoro-
    [1971] Benzamide
    [1972] 455 381 furan-2-carboxylic acid {4- [3- (3-dimethylamino-phenyl) -thioureido]
    [1973] Phenyl} -amide
    [1974] 456 370 [1,2,3] Thiadiazole-4-carboxylic acid [4- (3-m-tolyl-thioureido) -phenyl] -
    [1975] amides
    [1976] 457 424 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-trifluoromethyl- phenyl)
    [1977] Thioureido] -phenyl} -amide < / RTI >
    [1978] 458 479 N- {3-Chloro-4- [3- (5-chloro-2-methoxy-4-methyl- phenyl) -thioureido]
    [1979] Phenyl} -2-fluoro-benzamide
    [1980] 459 449 N- {3-Chloro-4- [3- (3-chloro-4-methyl-phenyl) -thioureido] -phenyl}
    [1981] 2-Fluoro-benzamide
    [1982] 460 481 N- {3-Chloro-4- [3- (3-chloro-4-methylsulfanyl- phenyl) -thioureido]
    [1983] Phenyl} -2-fluoro-benzamide
    [1984] 461 391 N- {4- [3- (3-Cyano-phenyl) -thioureido] -phenyl} -2-fluoro-
    [1985] Benzamide
    [1986] 462 395 Furan-2-carboxylic acid {4- [3- (3-acetylamino-phenyl) -thioureido]
    [1987] Phenyl} -amide
    [1988] 463 424 2-Fluoro-N- {4- [3- (3-hydrazinocarbonyl-phenyl) -thioureido] -
    [1989] Phenyl} -benzamide
    [1990] 464 400 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (1 -hydroxy-
    [1991] Thioureido} -phenyl) -amide < / RTI >
    [1992] 465 434 N- {4- [3- (2-Amino-3-chloro-phenyl) -thioureido] -phenyl}
    [1993] Difluoro-benzamide
    [1994] 466 406 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-amino-
    [1995] Thioureido] -phenyl} -amide < / RTI >
    [1996] 467 398 furan-2-carboxylic acid {4- [3- (3,5-dimethoxy-phenyl) -thioureido] -phenyl} -
    [1997] amides
    [1998] 468 416 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-dimethoxy- phenyl)
    [1999] Thioureido] -phenyl} -amide < / RTI >
    [2000] 469 454 5- (3- {4 - [(Furan-2-carbonyl) -amino} -phenyl} -thioureido)
    [2001] Isophthalic acid dimethyl ester
    [2002] 470 434 isoxazole-5-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [2003] Thioureido] -phenyl} -amide < / RTI >
    [2004] 471 392 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (6-chloro-pyridin-
    [2005] Thioureido] -phenyl} -amide < / RTI >
    [2006] 472 382 Furan-2-carboxylic acid (4- {3- [3- (1 -hydroxy-ethyl) -phenyl] -thioureido}
    [2007] Phenyl) -amide
    [2008] 473 368 Furan-2-carboxylic acid {4- [3- (3-methoxy-phenyl) -thioureido] -phenyl} -
    [2009] amides
    [2010] 474 354 Furan-2-carboxylic acid {4- [3- (3-hydroxy-phenyl) -thioureido] -phenyl} -
    [2011] amides
    [2012] 475 382 2-Fluoro-N- {4- [3- (3-hydroxy-phenyl) -thioureido] -phenyl} -
    [2013] Benzamide
    [2014] 476 396 2-Fluoro-N- {4- [3- (3-hydroxymethyl-phenyl) -thioureido] -phenyl} -
    [2015] Benzamide
    [2016] 477 423 N- {4- [3- (3-Acetylamino-phenyl) -thioureido] -phenyl} -2-fluoro-
    [2017] Benzamide
    [2018] 478 413 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-acetylamino- phenyl)
    [2019] Thioureido] -phenyl} -amide < / RTI >
    [2020] 479 400 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-dimethylamino-
    [2021] Thioureido] -phenyl} -amide < / RTI >
    [2022] 480 340 furan-2-carboxylic acid [4- (3-pyrimidin-4-yl-thioureido) -phenyl]
    [2023] 481 378 furan-2-carboxylic acid {4- [3- (lH-indazol-5-yl) -thioureido] -phenyl}
    [2024] amides
    [2025] 482 395 Furan-2-carboxylic acid [4- (3-benzothiazol-5-yl-thioureido) -phenyl] -
    [2026] amides
    [2027] 483 406 2-Fluoro-N- {4- [3- (lH-indazol-5-yl) -thioureido] -phenyl} -
    [2028] Benzamide
    [2029] 484 424 N- [4- (3-Benzothiazol-5-yl-thioureido) -phenyl] -2-fluoro-
    [2030] Benzamide
    [2031] 485 473 5- (3- {4 - ([1,2,3] thiadiazole-4-carbonyl) -amino]
    [2032] Thioureido) -isophthalic acid dimethyl ester
    [2033] 486 442 furan-2-carboxylic acid (4- {3- [4- (1-azido-ethyl)
    [2034] Thioureido} -phenyl) -amide < / RTI >
    [2035] 487 396 2-Fluoro-N- {4- [3- (3-methoxy-phenyl) -thioureido] -phenyl} -
    [2036] Benzamide
    [2037] 488 368 Furan-2-carboxylic acid {4- [3- (3-hydroxymethyl-phenyl) -thioureido]
    [2038] Phenyl} -amide
    [2039] 489 416 furan-2-carboxylic acid {4- [3- (5-chloro-2-dimethylamino-
    [2040] Thioureido] -phenyl} -amide < / RTI >
    [2041] 490 444 N- {4- [3- (5-Chloro-2-dimethylamino-phenyl) -thioureido] -phenyl} -2-
    [2042] Fluoro-benzamide
    [2043] 491 506 [3-Chloro-5- (3- {4 - [([1,2,3] thiadiazole-4-carbonyl) -amino]
    [2044] Thioureido) -phenyl] -carbamic acid tert-butyl ester
    [2045] 492 470 N- (4- {3- [4- (1-Azido-ethyl) -3-chloro-phenyl] -thioureido} -phenyl) -
    [2046] 2-Fluoro-benzamide
    [2047] 493 337 Furan-2-carboxylic acid [4- (1H-thiazolo [5,4- b] pyridin- 2- ylideneamino)
    [2048] Phenyl] -amide
    [2049] 494 378 furan-2-carboxylic acid {4- [3- (lH-benzoimidazol-5-yl) -thioureido]
    [2050] Phenyl} -amide
    [2051] 495 392 Furan-2-carboxylic acid {4- [3- (2-methyl-lH-benzoimidazol-
    [2052] Thioureido] -phenyl} -amide < / RTI >
    [2053] 496 406 N- {4- [3- (lH-Benzoimidazol-5-yl) -thioureido] -phenyl} -2-fluoro-
    [2054] Benzamide
    [2055] 497 420 2-Fluoro-N- {4- [3- (2-methyl-lH-benzoimidazol-
    [2056] Thioureido] -phenyl} -benzamide < / RTI >
    [2057] 498 452 [1,2,3] Thiadiazole-4-carboxylic acid {5- [3- (5-chloro-2,4-dimethoxy-
    [2058] Phenyl) -thioureido] -pyridin-2-yl} -amide
    [2059] 499 445 Pyridine-2-carboxylic acid {5- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [2060] Thioureido] -pyridin-2-yl} -amide
    [2061] 500 434 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (5-chloro-2-dimethylamino-
    [2062] Phenyl) -thioureido] -phenyl} -amide
    [2063] 501 484 [1,2,3] Thiadiazole-4-carboxylic acid (4- {3- [4- (2- amino-pyrimidin-
    [2064] Yl) -3-chloro-phenyl] -thioureido} -phenyl) -amide
    [2065] 502 494 N- (4- {3- [4- (2-Amino-pyrimidin-4-yl) -3-chloro-
    [2066] Thioureido} -phenyl) -2-fluoro-benzamide
    [2067] 503 434 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-2-
    [2068] Phenyl) -thioureido] -phenyl} -amide
    [2069] 504 462 N- {4- [3- (3-Chloro-2-dimethylamino-phenyl) -thioureido] -phenyl} -
    [2070] 2,6-difluoro-benzamide
    [2071] 505 416 furan-2-carboxylic acid {4- [3- (3-chloro-2-dimethylamino-
    [2072] Thioureido] -phenyl} -amide < / RTI >
    [2073] 506 445 Pyridine-2-carboxylic acid {6- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [2074] Thioureido] -pyridin-3-yl} -amide
    [2075] 507 462 N- {6- [3- (5-Chloro-2,4-dimethoxy-phenyl) -thioureido] -pyridin-
    [2076] Yl} -2-fluoro-benzamide
    [2077] 508 482 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-iodo-phenyl)
    [2078] Thioureido] -phenyl} -amide < / RTI >
    [2079] 509 413 [l, 2,3] Thiadiazole-4-carboxylic acid {4- [3- (3- tert-
    [2080] Thioureido] -amide
    [2081] 510 387 Furan-2-carboxylic acid {4- [3- (3-chloro-benzyl) -thioureido] -phenyl} -
    [2082] amides
    [2083] 511 415 N- {4- [3- (3-Chloro-benzyl) -thioureido] -phenyl} -2-fluoro-
    [2084] Benzamide
    [2085] 512 434 furan-2-carboxylic acid {6- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [2086] Thioureido] -pyridin-3-yl} -amide
    [2087] 513 435 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-bromo-phenyl)
    [2088] Thioureido] -phenyl} -amide < / RTI >
    [2089] 514 452 [1,2,3] Thiadiazole-4-carboxylic acid {6- [3- (5-chloro-2,4-
    [2090] Phenyl) -thioureido] -pyridin-3-yl} -amide
    [2091] 515 426 [1,2,3] Thiadiazole-4-carboxylic acid {5- [3- (3,5-dichloro- phenyl)
    [2092] Thioureido] -pyridin-2-yl} -amide
    [2093] 516 474 furan-2-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-phenyl)
    [2094] Thioureido] -phenyl} -amide < / RTI >
    [2095] 517 502 N- {4- [3- (3,5-Bis-trifluoromethyl-phenyl) -thioureido] -phenyl} -
    [2096] 2-Fluoro-benzamide
    [2097] 518 450 N- {4- [3- (4-Amino-3,5-dichloro-phenyl) -thioureido] -phenyl} -2-
    [2098] Fluoro-benzamide
    [2099] 519 539 N- {4- [3- (4-Amino-3,5-dibromo-phenyl) -thioureido] -phenyl} -2-
    [2100] Fluoro-benzamide
    [2101] 520 392 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (5-chloro-pyridin-
    [2102] Thioureido] -phenyl} -amide < / RTI >
    [2103] 521 529 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-amino-3,5-dibromo-
    [2104] Phenyl) -thioureido] -phenyl} -amide
    [2105] 522 434 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-5-dimethylamino-
    [2106] Phenyl) -thioureido] -phenyl} -amide
    [2107] 523 444 N- {4- [3- (3-Chloro-5-dimethylamino-phenyl) -thioureido] -phenyl} -2-
    [2108] Fluoro-benzamide
    [2109] 524 416 furan-2-carboxylic acid {4- [3- (3-chloro-5-dimethylamino-
    [2110] Thioureido] -phenyl} -amide < / RTI >
    [2111] 525 436 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (5-bromo-pyridin-
    [2112] Thioureido] -phenyl} -amide < / RTI >
    [2113] 526 379 furan-2-carboxylic acid {4- [3- (lH-benzotriazol-5-yl) -thioureido]
    [2114] Phenyl} -amide
    [2115] 527 425 N- {4- [3- (1H-Benzotriazol-5-yl) -thioureido] -phenyl} -2,6-
    [2116] Difluoro-benzamide
    [2117] 528 388 N- [4 - ({[2- (3-Chloro-phenyl) -hydrazino] -thioxomethyl}
    [2118] Phenyl] -furan-2-carboxamide
    [2119] 529 416 N- [4 - ({[2- (3-Chloro-phenyl) -hydrazino] -thioxomethyl}
    [2120] Phenyl] -2-fluoro-benzamide
    [2121] 530 456 Furan-2-carboxylic acid {4- [3- (2-amino-3-chloro-5-trifluoromethyl-
    [2122] Phenyl) -thioureido] -phenyl} -amide
    [2123] 531 513 N- {4- [3- (3-Bromo-5-trifluoromethyl-phenyl) -thioureido] -
    [2124] Phenyl} -2-fluoro-benzamide
    [2125] 532 503 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-bromo-5-trifluoro
    [2126] Methyl-phenyl) -thioureido] -phenyl} -amide
    [2127] 533 374 {4- [(furan-2-carbonyl) -amino] -phenyl} -thiocarbamic acid O- (3-chloro-
    [2128] Phenyl) ester
    [2129] 534 474 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-amino-
    [2130] Trifluoromethyl-phenyl) -thioureido] -phenyl} -amide < / RTI >
    [2131] 535 508 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-piperidin-
    [2132] Trifluoromethyl-phenyl) -thioureido] -phenyl} -amide < / RTI >
    [2133] 536 380 N- [4- (3-Benzyl-thioureido) -phenyl] -2-fluoro-benzamide
    [2134] 537 439 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,4-dichloro-benzyl) -
    [2135] Thioureido] -phenyl} -amide < / RTI >
    [2136] 538 449 N- {4- [3- (3,4-Dichloro-benzyl) -thioureido] -phenyl} -2-fluoro-
    [2137] Benzamide
    [2138] 539 370 [1,2,3] thiadiazole-4-carboxylic acid [4- (3-benzyl-thioureido) -phenyl] -
    [2139] amides
    [2140] 540 424 N- [4- (3-Benzo [1,3] dioxol-5-ylmethyl-thioureido) -phenyl] -2-
    [2141] Fluoro-benzamide
    [2142] 541 414 [1,2,3] Thiadiazole-4-carboxylic acid [4- (3-benzo [1,3] dioxol-
    [2143] Thioureido) -phenyl] -amide < / RTI >
    [2144] 542 506 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-
    [2145] Benzyl) -thioureido] -phenyl} -amide
    [2146] 543 516 N- {4- [3- (3,5-Bis-trifluoromethyl-benzyl) -thioureido] -phenyl} -
    [2147] 2-Fluoro-benzamide
    [2148] 544 352 Furan-2-carboxylic acid [4- (3-benzyl-thioureido) -phenyl] -amide
    [2149] 545 421 furan-2-carboxylic acid {4- [3- (3,4-dichloro-benzyl) -thioureido] -phenyl} -
    [2150] amides
    [2151] 546 396 Furan-2-carboxylic acid [4- (3-benzo [1,3] dioxol-5-ylmethyl-thioureido)
    [2152] Phenyl] -amide
    [2153] 547 488 furan-2-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-benzyl) -
    [2154] Thioureido] -phenyl} -amide < / RTI >
    [2155] 548 503 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-bromo-3- trifluoro
    [2156] Methyl-phenyl) -thioureido] -phenyl} -amide
    [2157] 549 529 N- {4- [3- (3-Bromo-4-trifluoromethoxy-phenyl) -thioureido] -
    [2158] Phenyl} -2-fluoro-benzamide
    [2159] 550 519 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-bromo-4-trifluoro
    [2160] Methoxy-phenyl) -thioureido] -phenyl} -amide
    [2161] 551 473 furan-2-carboxylic acid {4- [3- (3-chloro-4-trifluoromethylsulfanyl- phenyl)
    [2162] Ureido] -phenyl} -amide
    [2163] 552 412 2-Fluoro-N- (4- {3- [2- (3-fluoro-phenyl) -ethyl] -thioureido}
    [2164] Phenyl) -benzamide
    [2165] 553 412 2-Fluoro-N- (4- {3- [2- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2166] Phenyl) -benzamide
    [2167] 554 402 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-fluoro-
    [2168] Thioureido} -phenyl) -amide < / RTI >
    [2169] 555 402 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-fluoro-
    [2170] Thioureido} -phenyl) -amide < / RTI >
    [2171] 556 495 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (2-methyl-
    [2172] Trifluoromethyl-phenyl] -thioureido} -phenyl) -amide < / RTI >
    [2173] 557 481 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-isobutyl-5-trifluoro
    [2174] Methyl-phenyl) -thioureido] -phenyl} -amide
    [2175] 558 523 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (4- methyl- piperazin-
    [2176] 5-trifluoromethyl-phenyl] -thioureido} -phenyl) -amide
    [2177] 559 510 [1,2,3] thiadiazole-4-carboxylic acid {4- {3- (3-morpholin-
    [2178] Trifluoromethyl-phenyl) -thioureido] -phenyl} -amide < / RTI >
    [2179] 560 494 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-pyrrolidin-
    [2180] Trifluoromethyl-phenyl) -thioureido] -phenyl} -amide < / RTI >
    [2181] 561 384 furan-2-carboxylic acid (4- {3- [2- (4-fluoro-phenyl)
    [2182] Thioureido} -phenyl) amide
    [2183] 562 419 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-chloro-phenyl)
    [2184] Thioureido} -phenyl) -amide < / RTI >
    [2185] 563 429 N- (4- {3- [2- (3-Chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2186] Fluoro-benzamide
    [2187] 564 401 furan-2-carboxylic acid (4- {3- [2- (3-chloro-phenyl) -ethyl] -thioureido}
    [2188] Phenyl) -amide
    [2189] 565 402 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [1- (4-fluoro-
    [2190] Thioureido} -phenyl) -amide < / RTI >
    [2191] 566 504 2-Fluoro-N- {4- [3- (3-pyrrolidin-1-yl-5-trifluoromethyl- phenyl)
    [2192] Thioureido] -phenyl} -benzamide < / RTI >
    [2193] 567 477 N- {4- [3- (3-Dimethylamino-5-trifluoromethyl-phenyl) -
    [2194] Thioureido] -phenyl} -2-fluoro-benzamide
    [2195] 568 520 2-Fluoro-N- {4- [3- (3-morpholin-4-yl-5-trifluoromethyl-
    [2196] Thioureido] -phenyl] -benzamide < / RTI >
    [2197] 569 533 2-Fluoro-N- (4- {3- (4-methyl-piperazin- 1 -yl) -5- trifluoromethyl-
    [2198] Phenyl] -thioureido} -phenyl) -benzamide < / RTI >
    [2199] 570 518 2-Fluoro-N- {4- [3- (3-piperidin-l-yl-5-trifluoromethyl- phenyl)
    [2200] Thioureido] -phenyl} -benzamide < / RTI >
    [2201] 571 468 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-dimethylamino-
    [2202] Trifluoromethyl-phenyl) -thioureido] -phenyl} -amide < / RTI >
    [2203] 572 405 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-benzyl) -
    [2204] Thioureido] -phenyl} -amide < / RTI >
    [2205] 573 384 furan-2-carboxylic acid (4- {3- [2- (3-fluoro-phenyl) -ethyl] -thioureido}
    [2206] Phenyl) -amide
    [2207] 574 366 Furan-2-carboxylic acid [4- (3-phenethyl-thioureido) -phenyl] -amide
    [2208] 575 384 [1,2,3] thiadiazole-4-carboxylic acid [4- (3-phenethyl-thioureido) -phenyl] -
    [2209] amides
    [2210] 576 394 2-Fluoro-N- [4- (3-phenethyl-thioureido) -phenyl] -benzamide
    [2211] 577 505 2-Fluoro-N- (4- {3- [3- (2-methyl-butyl) -5- trifluoromethyl-
    [2212] Thioureido} -phenyl) -benzamide < / RTI >
    [2213] 578 491 2-Fluoro-N- {4- [3- (3-isobutyl-5-trifluoromethyl-phenyl)
    [2214] Thioureido] -phenyl} -benzamide < / RTI >
    [2215] 579 388 furan-2-carboxylic acid {4- [3- (3,5-difluoro-benzyl) -thioureido]
    [2216] Phenyl} -amide
    [2217] 580 416 N- {4- [3- (3,5-Difluoro-benzyl) -thioureido] -phenyl} -2-fluoro-
    [2218] Benzamide
    [2219] 581 406 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-difluoro-benzyl) -
    [2220] Thioureido] -phenyl} -amide < / RTI >
    [2221] 582 421 furan-2-carboxylic acid {4- [3- (3,5-dichloro-benzyl) -thioureido] -phenyl}
    [2222] amides
    [2223] 583 449 N- {4- [3- (3,5-Dichloro-benzyl) -thioureido] -phenyl} -2-fluoro-
    [2224] Benzamide
    [2225] 584 439 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro-
    [2226] Thioureido] -phenyl} -amide < / RTI >
    [2227] 585 438 Furan-2-carboxylic acid {4- [3- (3-fluoro-5-trifluoromethyl-
    [2228] Thioureido] -phenyl} -amide < / RTI >
    [2229] 586 466 2-Fluoro-N- {4- [3- (3-fluoro-5-trifluoromethyl-benzyl) -
    [2230] Thioureido] -phenyl} -benzamide < / RTI >
    [2231] 587 456 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-fluoro-
    [2232] Trifluoromethyl-benzyl) -thioureido] -phenyl} -amide < / RTI >
    [2233] 588 384 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (1-phenyl- ethyl) -thioureido]
    [2234] Phenyl} -amide
    [2235] 589 394 2-Fluoro-N- {4- [3- (1-phenyl-ethyl) -thioureido] -phenyl} -
    [2236] Benzamide
    [2237] 590 366 Furan-2-carboxylic acid {4- [3- (1-phenyl-ethyl) -thioureido] -phenyl}
    [2238] 591 412 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2239] Phenyl) -benzamide
    [2240] 592 384 Furan-2-carboxylic acid (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2241] Phenyl) -amide
    [2242] 593 413 N- {4- [3- (1-tert-Butyl-1H-imidazol-2-yl) -thioureido] -phenyl} -2-
    [2243] Fluorobenzamide
    [2244] 594 510 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (isobutyl-
    [2245] 5-trifluoromethyl-phenyl] -thioureido} -phenyl) -amide
    [2246] 595 510 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (3-hydroxy-pyrrolidin-
    [2247] Yl) -5-trifluoromethyl-phenyl] -thioureido} -phenyl) -amide
    [2248] 596 520 2-Fluoro-N- (4- {3- [3- (isobutyl-methyl-amino) -5-trifluoro
    [2249] Methyl-phenyl] -thioureido} -phenyl) -benzamide < / RTI >
    [2250] 597 510 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (butyl- methyl-
    [2251] Trifluoromethyl-phenyl] -thioureido} -phenyl) -amide < / RTI >
    [2252] 598 520 N- (4- {3- [3- (Butyl-methyl-amino) -5-trifluoromethyl-phenyl]
    [2253] Thioureido} -phenyl) -2-fluoro-benzamide
    [2254] 599 520 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,5-
    [2255] Methylphenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >
    [2256] 600 442 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-fluoro-3-
    [2257] Methylphenyl) -thioureido] -phenyl} -amide
    [2258] 601 522 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-piperidin-
    [2259] Trifluoromethyl-benzyl) -thioureido] -phenyl} -amide < / RTI >
    [2260] 602 482 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-dimethylamino-
    [2261] Trifluoromethyl-benzyl) -thioureido] -phenyl} -amide < / RTI >
    [2262] 603 381 Furan-2-carboxylic acid (4- {3- [2- (4-amino- phenyl) -ethyl] -thioureido}
    [2263] Phenyl) -amide
    [2264] 604 445 Furan-2-carboxylic acid (4- {3- [2- (4-bromo-phenyl) -ethyl] -thioureido}
    [2265] Phenyl) -amide
    [2266] 605 380 Furan-2-carboxylic acid {4- [3- (2-p-tolyl-ethyl) -thioureido] -phenyl} -
    [2267] amides
    [2268] 606 463 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (4-bromo- phenyl)
    [2269] Thioureido} -phenyl) -amide < / RTI >
    [2270] 607 396 Furan-2-carboxylic acid (4- {3- [2- (3-methoxy-phenyl) -ethyl] -thioureido}
    [2271] Phenyl) -amide
    [2272] 608 403 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (1-tert- butyl-
    [2273] Yl) -thioureido] -phenyl} -amide
    [2274] 609 384 furan-2-carboxylic acid {4- [3- (l-tert-butyl- lH-imidazol-
    [2275] Thioureido] -phenyl} -amide < / RTI >
    [2276] 610 492 N- {4- [3- (4-Dimethylamino-3-trifluoromethyl-benzyl) -
    [2277] Thioureido] -phenyl} -2-fluoro-benzamide
    [2278] 611 427 furan-2-carboxylic acid (4- {3- [2- (3,4-dimethoxy-phenyl)
    [2279] Thioureido} -phenyl) -amide < / RTI >
    [2280] 612 380 Furan-2-carboxylic acid {4- [3- (3-phenyl-propyl) -thioureido] -phenyl} -
    [2281] amides
    [2282] 613 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-phenyl-
    [2283] Thioureido] -phenyl} -amide < / RTI >
    [2284] 614 502 furan-2-carboxylic acid (4- {3- [2- (3,5-bis-trifluoromethyl-phenyl)
    [2285] Ethyl] -thioureido} -phenyl) -amide
    [2286] 615 550 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-iodo-3- trifluoro
    [2287] Methyl-phenyl) -thioureido] -phenyl} -amide
    [2288] 616 532 2-Fluoro-N- {4- [3- (4-piperidin-l-yl-3- trifluoromethyl-
    [2289] Thioureido] -phenyl} -benzamide < / RTI >
    [2290] 617 537 [l, 2,3] Thiadiazole-4-carboxylic acid (4- {3- [4- (4-methyl-piperazin-
    [2291] 3-trifluoromethyl-benzyl] -thioureido} -phenyl) -amide
    [2292] 618 482 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-dimethylamino-
    [2293] Trifluoromethyl-benzyl) -thioureido] -phenyl} -amide < / RTI >
    [2294] 619 488 furan-2-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-phenyl)
    [2295] Thioureido-methyl] -phenyl} -amide < / RTI >
    [2296] 620 421 furan-2-carboxylic acid {4- [3- (3,5-dichloro-phenyl) -thioureidomethyl] -
    [2297] Phenyl} -amide
    [2298] 621 421 furan-2-carboxylic acid {4- [3- (3,4-dichloro-phenyl) -thioureidomethyl] -
    [2299] Phenyl} -amide
    [2300] 622 455 furan-2-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl- phenyl)
    [2301] Thioureido-methyl] -phenyl} -amide < / RTI >
    [2302] 623 466 2-Fluoro-N- {4- [3- (4-fluoro-3-trifluoromethyl-benzyl) -
    [2303] Thioureido] -phenyl} -benzamide < / RTI >
    [2304] 624 456 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-fluoro-
    [2305] Trifluoromethyl-benzyl) -thioureido] -phenyl} -amide < / RTI >
    [2306] 625 410 2-Fluoro-N- {4- [3- (2-phenoxy-ethyl) -thioureido] -phenyl} -
    [2307] Benzamide
    [2308] 626 382 furan-2-carboxylic acid {4- [3- (2-phenoxy-ethyl) -thioureido] -phenyl} -
    [2309] amides
    [2310] 627 400 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-phenoxy- ethyl)
    [2311] Thioureido] -phenyl} -amide < / RTI >
    [2312] 628 409 2-Fluoro-N- {4- [3- (3-phenyl-propyl) -thioureido] -phenyl} -
    [2313] Benzamide
    [2314] 629 425 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (5-trifluoromethyl-
    [2315] 3-yl) -thioureido] -phenyl} -amide
    [2316] 630 439 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)
    [2317] Thioureido-methyl] -phenyl} -amide < / RTI >
    [2318] 631 473 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-chloro-3-trifluoro
    [2319] Methyl-phenyl) -thioureidomethyl] -phenyl} -amide
    [2320] 632 381 2-Fluoro-N- [4- (3-pyridin-3-ylmethyl-thioureido) -phenyl] -
    [2321] Benzamide
    [2322] 633 353 Furan-2-carboxylic acid [4- (3-pyridin-3-ylmethyl-thioureido) -phenyl] -
    [2323] amides
    [2324] 634 371 [l, 2,3] Thiadiazole-4-carboxylic acid [4- (3-pyridin-
    [2325] Thioureido) phenyl] -amide
    [2326] 635 439 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl)
    [2327] Thioureidomethyl] -phenyl} -amide < / RTI >
    [2328] 636 492 N- {4- [3- (3-Dimethylamino-5-trifluoromethyl-benzyl) -
    [2329] Thioureido] -phenyl} -2-fluoro-benzamide
    [2330] 637 415 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-methoxy- phenyl)
    [2331] Thioureido} -phenyl) -amide < / RTI >
    [2332] 638 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-p-
    [2333] Thioureido] -phenyl} -amide < / RTI >
    [2334] 639 445 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,4- dimethoxy- phenyl)
    [2335] Ethyl] -thioureido} -phenyl) -amide
    [2336] 640 506 [l, 2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,5-bis-
    [2337] Phenyl) -thioureidomethyl] -phenyl} -amide
    [2338] 641 516 N- {4- [3- (3,5-Bis-trifluoromethyl-phenyl) -thioureidomethyl] -
    [2339] Phenyl} -2-fluoro-benzamide
    [2340] 642 449 N- {4- [3- (3,5-Dichloro-phenyl) -thioureidomethyl] -phenyl} -2-
    [2341] Fluoro-benzamide
    [2342] 644 448 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-acetylamino-
    [2343] Phenyl) -thioureido] -phenyl} -amide
    [2344] 645 453 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,4-
    [2345] Ethyl] -thioureido} -phenyl) -amide
    [2346] 646 413 [l, 2,3] Thiadiazole-4-carboxylic acid {4- [3- (l-
    [2347] Thioureido] -phenyl} -amide < / RTI >
    [2348] 647 463 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [1- (4-bromo- phenyl)
    [2349] Thioureido} -phenyl) -amide < / RTI >
    [2350] 648 413 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-phenyl-
    [2351] Thioureido] -phenyl} -amide < / RTI >
    [2352] 649 397 [1,2,3] Thiadiazole-4-carboxylic acid [4- (3-indan-1-yl-thioureido)
    [2353] Phenyl] -amide
    [2354] 650 400 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-methoxy-benzyl) -
    [2355] Thioureido] -phenyl} -amide < / RTI >
    [2356] 651 415 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-methoxy- phenyl)
    [2357] Thioureido} -phenyl) -amide < / RTI >
    [2358] 652 415 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-methoxy- phenyl)
    [2359] Thioureido} -phenyl) -amide < / RTI >
    [2360] 653 506 N- (4- {3- [2- (3-Dimethylamino-5-trifluoromethyl-phenyl) -ethyl] -
    [2361] Thioureido} -phenyl) -2-fluoro-benzamide
    [2362] 654 510 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3- (3- dimethylamino-
    [2363] 5-trifluoromethyl-phenyl] -thioureido} -phenyl) -amide
    [2364] 655 417 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (2-phenylsulfanyl- ethyl)
    [2365] Thioureido] -phenyl} -amide < / RTI >
    [2366] 656 427 2-Fluoro-N- {4- (2-phenylsulfanyl-ethyl) -thioureido] -phenyl} -
    [2367] Benzamide
    [2368] 657 399 furan-2-carboxylic acid {4- [3- (2-phenylsulfanyl-ethyl) -thioureido] -phenyl} -
    [2369] amides
    [2370] 658 381 2-Fluoro-N- [4- (3-pyridin-4-ylmethyl-thioureido) -phenyl] -
    [2371] Benzamide
    [2372] 659 353 Furan-2-carboxylic acid [4- (3-pyridin-4-ylmethyl-thioureido) -phenyl] -
    [2373] amides
    [2374] 660 371 [l, 2,3] Thiadiazole-4-carboxylic acid [4- (3-pyridin-
    [2375] Thioureido) phenyl] -amide
    [2376] 661 506 2-Fluoro-N- {4- [3- (3-iodo-benzyl) -thioureido] -phenyl} -
    [2377] Benzamide
    [2378] 662 478 furan-2-carboxylic acid {4- [3- (3-iodo-benzyl) -thioureido] -phenyl} -
    [2379] amides
    [2380] 663 496 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-iodo-benzyl) -
    [2381] Thioureido] phenyl} -amide
    [2382] 664 479 N- (4- {3- [2- (3,5-Dichloro-phenoxy) -ethyl] -thioureido} -phenyl) -2-
    [2383] Fluoro-benzamide
    [2384] 665 451 Furan-2-carboxylic acid (4- {3- [2- (3,5-dichloro-phenoxy)
    [2385] Thioureido} -phenyl) -amide < / RTI >
    [2386] 666 445 N- (4- {3- [2- (3-Chloro-phenoxy) -ethyl] -thioureido} -phenyl) -2-
    [2387] Fluoro-benzamide
    [2388] 667 417 Furan-2-carboxylic acid (4- {3- [2- (3-chloro-phenoxy) -ethyl] -thioureido}
    [2389] Phenyl) -amide
    [2390] 668 435 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-chloro-phenoxy)
    [2391] Thioureido} -phenyl) -amide < / RTI >
    [2392] 669 466 2-Fluoro-N- {4- [3- (2-fluoro-5-trifluoromethyl-benzyl) -
    [2393] Thioureido] -phenyl} -benzamide < / RTI >
    [2394] 670 438 furan-2-carboxylic acid {4- [3- (2-fluoro-5-trifluoromethyl-benzyl) -
    [2395] Thioureido] -phenyl} -amide < / RTI >
    [2396] 671 456 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (2-fluoro-5-trifluoro
    [2397] Methyl-benzyl) -thioureido] -phenyl} -amide
    [2398] 672 416 N- {4- [3- (3,4-Difluoro-benzyl) -thioureido] -phenyl} -2-fluoro-
    [2399] Benzamide
    [2400] 673 452 N- (4- {3- [2- (4-Dimethylamino-3-methyl-phenyl) -ethyl] -thioureido}
    [2401] Phenyl) -2-fluoro-benzamide
    [2402] 674 496 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-dimethylamino-
    [2403] Trifluoromethylphenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >
    [2404] 675 388 furan-2-carboxylic acid {4- [3- (3,4-difluoro-benzyl) -thioureido]
    [2405] Phenyl} -amide
    [2406] 676 406 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,4-difluoro-benzyl) -
    [2407] Thioureido] -phenyl} -amide < / RTI >
    [2408] 677 433 N- {4- [3- (3-Chloro-4-fluoro-benzyl) -thioureido] -phenyl} -2-
    [2409] Fluoro-benzamide
    [2410] 678 495 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-bromo- phenylsulfanyl)
    [2411] Ethyl] -thioureido} -phenyl) -amide
    [2412] 679 477 furan-2-carboxylic acid (4- {3- [2- (3-bromo-phenylsulfanyl)
    [2413] Thioureido} -phenyl) -amide < / RTI >
    [2414] 680 505 N- (4- {3- [2- (3-Bromo-phenylsulfanyl) -ethyl] -thioureido} -phenyl) -2-
    [2415] Fluoro-benzamide
    [2416] 681 493 [l, 2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (3-bromo-4-
    [2417] Ethyl] -thioureido} -phenyl) -amide
    [2418] 682 493 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (5-bromo-2-methoxy-
    [2419] Ethyl] -thioureido} -phenyl) -amide
    [2420] 683 419 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-
    [2421] Thioureido} -phenyl) -amide < / RTI >
    [2422] 684 402 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2- fluoro-
    [2423] Thioureido} -phenyl) -amide < / RTI >
    [2424] 685 419 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-chloro-phenyl)
    [2425] Thioureido} -phenyl) -amide < / RTI >
    [2426] 686 475 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,3-diphenyl-
    [2427] Thioureido] -phenyl} -amide < / RTI >
    [2428] 687 547 2-Fluoro-N- (4- {3- [4- (4-methyl-piperazin- 1- yl) -3-trifluoro
    [2429] Methyl-benzyl] -thioureido} -phenyl) -benzamide < / RTI >
    [2430] 688 469 [1,2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (3,5- dichloro-phenoxy)
    [2431] Ethyl] -thioureido} -phenyl) -amide
    [2432] 689 423 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-fluoro-
    [2433] Thioureido] -phenyl} -amide < / RTI >
    [2434] 690 427 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4- tert- butyl-
    [2435] Thioureido] -phenyl} -amide < / RTI >
    [2436] 691 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,5-dimethyl-
    [2437] Thioureido] -phenyl} -amide < / RTI >
    [2438] 692 442 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-
    [2439] Phenyl) -ethyl] -thioureido} -phenyl) -amide
    [2440] 693 479 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-bromo- phenoxy)
    [2441] Thioureido} -phenyl) -amide < / RTI >
    [2442] 694 526 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-iodo-phenoxy)
    [2443] Thioureido} -phenyl) -amide < / RTI >
    [2444] 695 489 N- (4- {3- [2- (4-Bromo-phenoxy) -ethyl] -thioureido} -phenyl) -2-
    [2445] Fluoro-benzamide
    [2446] 696 536 2-Fluoro-N- (4- {3- [2- (4-iodo-phenoxy) -ethyl] -thioureido}
    [2447] Phenyl) -benzamide
    [2448] 697 461 Furan-2-carboxylic acid (4- {3- [2- (4-bromo-phenoxy) -ethyl] -thioureido}
    [2449] Phenyl) -amide
    [2450] 698 508 Furan-2-carboxylic acid (4- {3- [2- (4-iodo-phenoxy) -ethyl] -thioureido}
    [2451] Phenyl) -amide
    [2452] 699 408 Oxazole-4-carboxylic acid {4- [3- (3,4-dichloro-phenyl) -thioureido]
    [2453] Phenyl} -amide
    [2454] 700 424 Thiazole-4-carboxylic acid {4- [3- (3,5-dichloro-phenyl) -thioureido]
    [2455] Phenyl} -amide
    [2456] 701 491 Thiazole-4-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-phenyl)
    [2457] Thioureido] -phenyl} -amide < / RTI >
    [2458] 702 408 Oxazole-4-carboxylic acid {4- [3- (3,5-dichloro-phenyl) -thioureido]
    [2459] Phenyl} -amide
    [2460] 703 469 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,4- dichloro-phenoxy) -
    [2461] Ethyl] -thioureido} -phenyl) -amide
    [2462] 704 424 Thiazole-4-carboxylic acid {4- [3- (3,4-dichloro-phenyl) -thioureido]
    [2463] Phenyl} -amide
    [2464] 705 458 Thiazole-4-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl- phenyl)
    [2465] Thioureido] -phenyl} -amide < / RTI >
    [2466] 706 400 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-phenylamino-ethyl)
    [2467] Thioureido] -phenyl} -amide < / RTI >
    [2468] 707 453 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2,4-
    [2469] Ethyl] -thioureido} -phenyl) -amide
    [2470] 708 452 [1,2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (3- trifluoromethyl-
    [2471] Phenyl) -ethyl] -thioureido} -phenyl) -amide
    [2472] 709 453 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2,6-dichloro- phenyl)
    [2473] Ethyl] -thioureido} -phenyl) -amide
    [2474] 710 485 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,4-
    [2475] Phenylsulfanyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >
    [2476] 711 503 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-fluoro-
    [2477] Trifluoromethyl-phenylsulfanyl) -ethyl] -thioureido} -phenyl) -amide
    [2478] 712 668 N- (4- {3- [3-Chloro-5- (3- {4 - [(1,2,3] thiadiazole-
    [2479] Amino] -phenyl} -thioureido) -phenyl] -thioureido} -phenyl) - [l, 2,3]
    [2480] Thiadiazole-4-carboxamide
    [2481] 713 413 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-ethyl-
    [2482] Thioureido} -phenyl) -amide < / RTI >
    [2483] 714 442 OXAZOLE-4-CARBOXYLIC ACID {4- [3- (4-Chloro-3-trifluoromethyl-phenyl)
    [2484] Thioureido] -phenyl} -amide < / RTI >
    [2485] 715 475 < / RTI > Oxazole-4-carboxylic acid {4- [3- (3,5-bis- trifluoromethyl- phenyl)
    [2486] Thioureido] -phenyl} -amide < / RTI >
    [2487] 716 420 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,4- difluoro-
    [2488] Ethyl] -thioureido} -phenyl) -amide
    [2489] 717 452 [l, 2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (4-trifluoromethyl-
    [2490] Phenyl) -ethyl] -thioureido} -phenyl) -amide
    [2491] 718 435 Furan-2-carboxylic acid (4- {3- [2- (3,4-dichloro-phenyl)
    [2492] Thioureido} -phenyl) -amide < / RTI >
    [2493] 719 463 N- (4- {3- [2- (3,4-Dichloro-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2494] Fluoro-benzamide
    [2495] 720 420 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3,5- difluoro-
    [2496] Ethyl] -thioureido} -phenyl) -amide
    [2497] 721 412 2-Fluoro-N- (4- {3- [2- (2-fluoro-phenyl) -ethyl] -thioureido}
    [2498] Phenyl) -benzamide
    [2499] 722 429 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-nitro- phenyl)
    [2500] Thioureido} -phenyl) -amide < / RTI >
    [2501] 723 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (1-methyl-
    [2502] Thioureido] -phenyl} -amide < / RTI >
    [2503] 724 437 N- {4- [3- (4-tert-Butyl-benzyl) -thioureido] -phenyl} -2-fluoro-
    [2504] Benzamide
    [2505] 725 409 N- {4- [3- (3,5-Dimethyl-benzyl) -thioureido] -phenyl} -2-fluoro-
    [2506] Benzamide
    [2507] 726 400 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-hydroxy-
    [2508] Thioureido] -phenyl} -amide < / RTI >
    [2509] 727 409 2-Fluoro-N- {4- [3- (1 -methyl-1-phenyl- ethyl) -thioureido] -phenyl} -
    [2510] Benzamide
    [2511] 728 399 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (1-methyl-
    [2512] Thioureido] -phenyl} -amide < / RTI >
    [2513] 729 405 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (2-chloro-benzyl) -
    [2514] Thioureido] -phenyl} -amide < / RTI >
    [2515] 730 388 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (2-fluoro-
    [2516] Thioureido] -phenyl} -amide < / RTI >
    [2517] 731 438 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-trifluoromethyl-benzyl) -
    [2518] Thioureido] -phenyl} -amide < / RTI >
    [2519] 732 388 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-fluoro-
    [2520] Thioureido] -phenyl} -amide < / RTI >
    [2521] 733 435 [l, 2,3] Thiadiazole-4-carboxylic acid (4- [3- [2- (2-chloro-phenoxy)
    [2522] Thioureido} -phenyl) -amide < / RTI >
    [2523] 734 479 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-bromo- phenoxy)
    [2524] Thioureido} -phenyl) -amide < / RTI >
    [2525] 735 418 [1,2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (2-fluoro-phenoxy)
    [2526] Ethyl] -thioureido} -phenyl) -amide
    [2527] 736 418 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-fluoro-phenoxy)
    [2528] Ethyl] -thioureido} -phenyl) -amide
    [2529] 737 486 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-fluoro-
    [2530] Trifluoromethyl-phenoxy) -ethyl] -thioureido} -phenyl) -amide < / RTI >
    [2531] 738 384 furan-2-carboxylic acid (4- {3- [2- (2-fluoro-phenyl)
    [2532] Thioureido} -phenyl) -amide < / RTI >
    [2533] 739 435 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-bromo-phenyl)
    [2534] Thioureido] -phenyl} -amide < / RTI >
    [2535] 740 374 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-fluoro-
    [2536] Thioureido] -phenyl} -amide < / RTI >
    [2537] 741 388 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-fluoro-
    [2538] Thioureido] -phenyl} -amide < / RTI >
    [2539] 742 405 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-chloro-benzyl) -
    [2540] Thioureido] -phenyl} -amide < / RTI >
    [2541] 743 449 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-bromo-benzyl)
    [2542] Thioureido] -phenyl} -amide < / RTI >
    [2543] 744 332 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -
    [2544] Acetamide
    [2545] 745 438 Thiazole-4-carboxylic acid {4- [3- (3,4-dichloro-benzyl) -thioureido]
    [2546] Phenyl} -amide
    [2547] 746 455 Thiazole-4-carboxylic acid {4- [3- (2-fluoro-5-trifluoromethyl-benzyl) -
    [2548] Thioureido] -phenyl} -amide < / RTI >
    [2549] 747 426 Thiazole-4-carboxylic acid {4- [3- (4-tert-butyl-benzyl) -thioureido]
    [2550] Phenyl} -amide
    [2551] 748 374 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (2-fluoro-phenyl)
    [2552] Thioureido] -phenyl} -amide < / RTI >
    [2553] 749 374 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-fluoro- phenyl)
    [2554] Thioureido] -phenyl} -amide < / RTI >
    [2555] 750 526 [l, 2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (3-iodo-phenoxy)
    [2556] Thioureido} -phenyl) -amide < / RTI >
    [2557] 751 409 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl)
    [2558] Acetamide
    [2559] 752 425 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2560] Methoxy-benzamide
    [2561] 753 425 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -3-
    [2562] Methoxy-benzamide
    [2563] 754 425 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -4-
    [2564] Methoxy-benzamide
    [2565] 755 429 2-Chloro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2566] Phenyl) -benzamide
    [2567] 756 429 4-Chloro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2568] Phenyl) -benzamide
    [2569] 757 453 Acetic acid 4- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2570] Phenylcarbamoyl) -phenyl ester
    [2571] 758 394 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -
    [2572] Benzamide
    [2573] 759 395 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -
    [2574] Isonicotinamide
    [2575] 760 410 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -4-
    [2576] Hydroxy-benzamide
    [2577] 761 429 3-Chloro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2578] Phenyl) -benzamide
    [2579] 762 470 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-fluoro-
    [2580] Trifluoromethyl-phenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >
    [2581] 763 520 [l, 2,3] Thiadiazole-4-carboxylic acid (4- {3- [2- (2,4-
    [2582] Methyl-phenyl) -ethyl] -thioureido} -phenyl) -amide
    [2583] 764 470 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4- fluoro-3- trifluoro
    [2584] Methyl-phenyl) -ethyl] -thioureido} -phenyl) -amide
    [2585] 765 438 4-Dimethylamino-N- (4- {3- [1- (4-fluoro- phenyl)
    [2586] Thioureido} -phenyl) -benzamide < / RTI >
    [2587] 766 470 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-fluoro-
    [2588] Trifluoromethyl-phenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >
    [2589] 767 470 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (2-fluoro-
    [2590] Trifluoromethyl-phenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >
    [2591] 768 510 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-
    [2592] Thioureido} -phenyl) -amide < / RTI >
    [2593] 769 470 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (4-
    [2594] Trifluoromethyl-phenyl) -ethyl] -thioureido} -phenyl) -amide < / RTI >
    [2595] 770 463 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [2- (3-bromo- phenyl)
    [2596] Thioureido} -phenyl) -amide < / RTI >
    [2597] 771 427 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -propyl] -thioureido}
    [2598] Phenyl) -benzamide
    [2599] 772 475 2-Fluoro-N- (4- {3 - [(4-fluoro-phenyl) -phenyl- methyl] -thioureido}
    [2600] Phenyl) -benzamide
    [2601] 773 455 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -pentyl] -thioureido}
    [2602] Phenyl) -benzamide
    [2603] 774 489 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -2-
    [2604] Thioureido} -phenyl) -benzamide < / RTI >
    [2605] 775 409 2-Fluoro-N- {4- [3- (1-o-tolyl-ethyl) -thioureido] -phenyl} -
    [2606] Benzamide
    [2607] 776 409 2-Fluoro-N- {4- [3- (1-m-tolyl-ethyl) -thioureido] -phenyl} -
    [2608] Benzamide
    [2609] 777 425 2-Fluoro-N- (4- {3- [1- (4-methoxy-phenyl) -ethyl] -thioureido}
    [2610] Phenyl) -benzamide
    [2611] 778 412 2-Fluoro-N- (4- {3- [1- (2-fluoro-phenyl) -ethyl] -thioureido}
    [2612] Phenyl) -benzamide
    [2613] 779 429 N- (4- {3- [l- (3-Chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2614] Fluoro-benzamide
    [2615] 780 473 N- (4- {3- [1- (3-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2616] Fluoro-benzamide
    [2617] 781 429 N- (4- {3- [l- (4-Chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2618] Fluoro-benzamide
    [2619] 782 409 2-Fluoro-N- {4- [3- (1-p-tolyl-ethyl) -thioureido] -phenyl} -
    [2620] Benzamide
    [2621] 783 473 N- (4- {3- [1- (2-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2622] Fluoro-benzamide
    [2623] 784 429 N- (4- {3- [l- (2-Chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2624] Fluoro-benzamide
    [2625] 785 462 2-Fluoro-N- (4- {3- [1- (2-trifluoromethyl-phenyl)
    [2626] Thioureido} -phenyl) -benzamide < / RTI >
    [2627] 786 462 2-Fluoro-N- (4- {3- [1- (3-trifluoromethyl-phenyl) -ethyl] -
    [2628] Thioureido} -phenyl) -benzamide < / RTI >
    [2629] 787 462 2-Fluoro-N- (4- {3- [l- (4-trifluoromethyl-phenyl) -ethyl] -
    [2630] Thioureido} -phenyl) -benzamide < / RTI >
    [2631] 788 425 2-Fluoro-N- (4- {3- [1- (2-methoxy-phenyl) -ethyl] -thioureido}
    [2632] Phenyl) -benzamide
    [2633] 789 425 2-Fluoro-N- (4- {3- [1- (3-methoxy- phenyl) -ethyl] -thioureido}
    [2634] Phenyl) -benzamide
    [2635] 790 441 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -2-methyl-
    [2636] Thioureido} -phenyl) -benzamide < / RTI >
    [2637] 791 419 N- (4- {3- [1- (3-Cyano-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2638] Fluoro-benzamide
    [2639] 792 419 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2640] Fluoro-benzamide
    [2641] 793 438 N- (4- {3- [1- (4-Dimethylamino-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2642] Fluoro-benzamide
    [2643] 794 438 N- (4- {3- [1- (3-Dimethylamino-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2644] Fluoro-benzamide
    [2645] 795 473 2-Bromo-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2646] Phenyl) -benzamide
    [2647] 796 446 Quinoline-2-carboxylic acid- (4- {3- [l- (4-fluoro-phenyl)
    [2648] Thioureido} -phenyl) -amide < / RTI >
    [2649] 797 410 2-Fluoro-N- {4- [3- (2-hydroxy-1-phenyl- ethyl) -thioureido]
    [2650] Phenyl} -benzamide
    [2651] 798 332 2-Fluoro-N- [4- (3-isopropyl-thioureido) -phenyl] -benzamide
    [2652] 799 445 2-Fluoro-N- {4- [3- (1 -naphthalen-2-yl-ethyl) -thioureido] -phenyl} -
    [2653] Benzamide
    [2654] 800 412 3-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2655] Phenyl) -benzamide
    [2656] 801 412 4-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2657] Phenyl) -benzamide
    [2658] 802 384 2-Fluoro-N- {4- [3- (1-furan-2-yl-ethyl) -thioureido] -phenyl}
    [2659] Benzamide
    [2660] 803 395 2-Fluoro-N- {4- [3- (1-pyridin-4- yl- ethyl) -thioureido] -phenyl} -
    [2661] Benzamide
    [2662] 804 397 2-Fluoro-N- (4- {3- [l- (1 -methyl-lH-pyrrol-
    [2663] Thioureido} -phenyl) -benzamide < / RTI >
    [2664] 805 401 2-Fluoro-N- {4- [3- (1 -thiophen-3-yl-ethyl) -thioureido] -phenyl} -
    [2665] Benzamide
    [2666] 806 445 N- {4- [3- (3-Chloro-4-ethoxy-phenyl) -thioureido] -phenyl} -2-
    [2667] Fluoro-benzamide
    [2668] 807 459 N- {4- [3- (3-Chloro-4-propoxy-phenyl) -thioureido] -phenyl} -2-
    [2669] Fluoro-benzamide
    [2670] 808 459 N- {4- [3- (3-Chloro-4-isopropoxy-phenyl) -thioureido] -phenyl} -2-
    [2671] Fluoro-benzamide
    [2672] 809 473 N- {4- [3- (4-Butoxy-3-chloro-phenyl) -thioureido] -phenyl} -2-
    [2673] Fluoro-benzamide
    [2674] 810 522 2-Fluoro-N- {4- [3- (3-iodo-4-methoxy-phenyl) -thioureido]
    [2675] Phenyl} -benzamide
    [2676] 811 475 N- {4- [3- (3-Bromo-4-methoxy-phenyl) -thioureido] -phenyl} -2-
    [2677] Fluoro-benzamide
    [2678] 812 520 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2679] Iodo-benzamide
    [2680] 813 346 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -
    [2681] Propionamide
    [2682] 814 286 N- [4- (3-Phenyl-thioureido) -phenyl] -acetamide
    [2683] 1102 473 N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2684] Fluoro-benzamide
    [2685] 1103 473 N- (4- {3 - [(1S) -1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -4-
    [2686] Fluoro-benzamide
    [2687] 1104 485 N- (4- {3 - [(1S) -1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2688] Methoxy-benzamide
    [2689] 1105 485 N- (4- {3 - [(1 R) -1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2690] Methoxy-benzamide
    [2691] 1106 480 2-Fluoro-N- (4 - {[({1- [2-fluoro-4- (trifluoromethyl) phenyl]
    [2692] Ethyl} amino) carbothioyl] amino} phenyl) benzamide
    [2693] 1107 506 Isoquinoline-1-carboxylic acid (4- {3 - [(1S) -1- (4-bromo-
    [2694] Thioureido} -phenyl) -amide < / RTI >
    [2695] 1108 506 Isoquinoline-3-carboxylic acid (4- {3 - [(1S) -1- (4-bromo-
    [2696] Thioureido} -phenyl) -amide < / RTI >
    [2697] 1109 461 isoquinoline-1-carboxylic acid (4- {3 - [(1S) -1- (4- chloro-phenyl)
    [2698] Thioureido} -phenyl) -amide < / RTI >
    [2699] 1110 445 isoquinoline-1-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [2700] Thioureido} -phenyl) -amide < / RTI >
    [2701] 1111 452 N- {4 - [({[(1S) -1- (4-cyanophenyl) ethyl] amino} carbothioyl) amino]
    [2702] Phenyl} -1-nonenyl) ethyl] amino} carbothioyl) amino] phenyl} -1-
    [2703] Isoquinolinecarboxamide
    [2704] Example 815 (Method 32)
    [2705] [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2,5-dichloro-phenyl) -thioureido] phenyl}
    [2706] To the solution of 2,5-dichloroaniline (0.16 g) in tetrahydrofuran (20 mL) is added newly prepared 1,1'-thiocarbonyldiimidazole (0.20 g) and the mixture is stirred at room temperature for about 30 minutes. [1,2,3] thiadiazole-4-carboxylic acid (4-amino-phenyl) amide (0.22 g) is added to the reaction flask and the mixture is stirred for approximately 6 hours. The solvent is removed by evaporation under reduced pressure and warm acetonitrile (3 mL) is added. After 15 hours the mixture is filtered and the collected precipitate is washed with acetonitrile followed by diethyl ether and air dried to give the desired product of a white powder.
    [2707] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [2708] Example M + H Compound Name
    [2709] 816 321 N- {4- [3- (3-Chloro-phenyl) -thioureido] -phenyl} -acetamide
    [2710] 817 413 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -
    [2711] Benzamide
    [2712] 818 443 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -2-
    [2713] Methoxy-benzamide
    [2714] 819 443 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -3-
    [2715] Methoxy-benzamide
    [2716] 820 443 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -4-
    [2717] Methoxy-benzamide
    [2718] 821 431 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -4-
    [2719] Methoxy-benzamide
    [2720] 822 431 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -3-
    [2721] Fluoro-benzamide
    [2722] 823 431 N- {4- [3- (3-Chloro-4-methoxy-phenyl) -thioureido] -phenyl} -4-
    [2723] Fluoro-benzamide
    [2724] 824 437 furan-2-carboxylic acid {4- [3- (3,5-dichloro-4-methoxy- phenyl)
    [2725] Thioureido] -phenyl} -amide < / RTI >
    [2726] 825 511 {4- [3- (5-Bromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [2727] Carbamic acid hexyl ester
    [2728] 826 481 hexanoic acid {4- [3- (5-bromo-2,4-dimethoxy-phenyl) -thioureido]
    [2729] Phenyl} -amide
    [2730] 827 505 N- {4- [3- (5-Bromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [2731] Fluoro-benzamide
    [2732] 828 477 furan-2-carboxylic acid {4- [3- (5-bromo-2,4-dimethoxy-phenyl)
    [2733] Thioureido] -phenyl} -amide < / RTI >
    [2734] 829 501 N- {4- [3- (5-Bromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -2-
    [2735] Methoxy-benzamide
    [2736] 830 517 N- {4- [3- (5-Bromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -4-
    [2737] Methoxy-benzamide
    [2738] 831 395 N- {4- [3- (5-Chloro-2-ethoxy-4-methoxy-phenyl) -thioureido]
    [2739] Phenyl} -acetamide
    [2740] 832 395 N- {4- [3- (5-Chloro-4-ethoxy-2-methoxy-phenyl) -thioureido]
    [2741] Phenyl} -acetamide
    [2742] 833 423 N- {4- [3- (2-Butoxy-5-chloro-4-methoxy-phenyl) -thioureido]
    [2743] Phenyl} -acetamide
    [2744] 834 423 N- {4- [3- (4-Butoxy-5-chloro-2-methoxy-phenyl) -thioureido]
    [2745] Phenyl} -acetamide
    [2746] 835 457 N- {4- [3- (2-Benzyloxy-5-chloro-4-methoxy-phenyl) -thioureido]
    [2747] Phenyl} -acetamide
    [2748] 836 457 N- {4- [3- (4-Benzyloxy-5-chloro-2-methoxy-phenyl) -thioureido]
    [2749] Phenyl} -acetamide
    [2750] 837 421 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-methoxy- phenyl)
    [2751] Thioureido] -phenyl} -amide < / RTI >
    [2752] 838 424 2- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-5-methoxy-
    [2753] Phenoxy} -acetamide
    [2754] 839 367 N- {4- [3- (5-Chloro-2-hydroxy-4-methoxy-phenyl) -thioureido]
    [2755] Phenyl} -acetamide
    [2756] 840 367 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido] -phenyl} -
    [2757] Acetamide
    [2758] 841 447 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl- piperidin-
    [2759] Phenyl} -thioureido) -phenyl] -acetamide < / RTI >
    [2760] 842 426 N- (4- {3- [3-Chloro-4- (methyl-phenyl-amino) -phenyl] -thioureido}
    [2761] Phenyl) -acetamide
    [2762] 843 509 N- [4- (3- {4 - [(1-Benzyl-pyrrolidin-3- yl) -methyl-
    [2763] Phenyl} -thioureido) -phenyl] -acetamide < / RTI >
    [2764] 844 418 N- (4- {3- [3-Chloro-4- (cyclopentyl-phenyl-amino) -phenyl] -
    [2765] Thioureido} -phenyl) -acetamide < / RTI >
    [2766] 845 433 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl-pyrrolidin-
    [2767] Phenyl} -thioureido) -phenyl] -acetamide < / RTI >
    [2768] 846 419 furan-2-carboxylic acid {4- [3- (3-chloro-4-methylsulfanyl- phenyl)
    [2769] Thioureido] phenyl} -amide
    [2770] 847 447 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido] -phenyl} -2-
    [2771] Fluorobenzamide
    [2772] 848 465 N- {4- [3- (3-Chloro-4-methylsulfanyl-phenyl) -thioureido] -phenyl} -2,6-
    [2773] Difluorobenzamide
    [2774] 849 445 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido] -phenyl}
    [2775] 2-fluorobenzamide
    [2776] 850 441 N- {4- [3- (5-Chloro-2-methoxy-4-methyl-phenyl) -thioureido] -phenyl} -
    [2777] 2-methyl-benzamide
    [2778] 851 434 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-chloro-
    [2779] Phenyl) -thioureido] -phenyl} -amide
    [2780] 852 444 N- {4- [3- (3-Chloro-4-dimethylamino-phenyl) -thioureido] -phenyl} -2-
    [2781] Fluorobenzamide
    [2782] 853 517 [1,2,3] Thiadiazole-4-carboxylic acid [4- (3- {3-chloro-4- [methyl-
    [2783] Piperidin-4-yl) -amino] -phenyl} -thioureido) -phenyl] -amide
    [2784] 854 579 [1,2,3] thiadiazole-4-carboxylic acid [4- (3- {4 - [(1 -benzyl- pyrrolidin-
    [2785] Methyl-amino] -3-chloro-phenyl} -thioureido) -phenyl] -amide
    [2786] 855 527 N- [4- (3- {3-Chloro-4- [methyl- (1 -methyl- piperidin-
    [2787] Phenyl} -thioureido) -phenyl] -2-fluoro-benzamide
    [2788] 856 435 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (5-chloro-2-methoxy-
    [2789] Methylphenyl) -thioureido] -phenyl} -amide
    [2790] 857 589 N- [4- (3- {4 - [(1-Benzyl-pyrrolidin-3- yl) -methyl-
    [2791] Phenyl} -thioureido) -phenyl] -2-fluoro-benzamide
    [2792] 858 501 furan-2-carboxylic acid {4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [2793] Thioureido] -3-trifluoromethyl-phenyl} -amide
    [2794] 859 366 2-Fluoro-N- [4- (3-phenyl-thioureido) -phenyl] -benzamide
    [2795] 860 338 Furan-2-carboxylic acid [4- (3-phenyl-thioureido) -phenyl] -amide
    [2796] 861 356 [1,2,3] thiadiazole-4-carboxylic acid [4- (3-phenyl-thioureido) -phenyl] -
    [2797] amides
    [2798] 862 365 N- (4- {3- [3-Chloro-4- (l-hydroxy-ethyl) -phenyl] -thioureido}
    [2799] Phenyl) -acetamide
    [2800] 863 435 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3-chloro-4- (1-
    [2801] Ethyl) -phenyl} -thioureido) -phenyl] -amide
    [2802] 864 365 N- (4- {3- [3-Chloro-4- (2-hydroxy-ethyl) -phenyl] -thioureido}
    [2803] Phenyl) -acetamide
    [2804] 865 445 N- (4- {3- [3-Chloro-4- (l-hydroxy-ethyl) -phenyl] -thioureido}
    [2805] Phenyl) -2-fluoro-benzamide
    [2806] 866 417 Furan-2-carboxylic acid (4- {3- [3-chloro-4- (1-
    [2807] Thioureido} -phenyl) -amide < / RTI >
    [2808] 867 371 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-amino-
    [2809] Thioureido] -phenyl} -amide < / RTI >
    [2810] 868 501 furan-2-carboxylic acid {4- [3- (3-bromo-4-trifluoromethoxy-phenyl)
    [2811] Thioureido] phenyl} -amide
    [2812] 869 423 N- {4- [3- (3-tert-Butyl-phenyl) -thioureido] -phenyl} -2-fluoro-
    [2813] Benzamide
    [2814] 870 440 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-chloro-3,5-
    [2815] Phenyl) -thioureido] -phenyl} -amide
    [2816] 974 485 N- {4- [3- (1-Benzofuran-2-yl-ethyl) -thioureido] -phenyl} -2-
    [2817] Trifluoromethyl-benzamide < RTI ID = 0.0 >
    [2818] 975 412 N- (4-Fluoro-phenyl) -4- {3- [l- (4-fluoro- phenyl)
    [2819] Thioureido} -benzamide
    [2820] 976 446 isoquinoline-1-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [2821] Thioureido} -phenyl) -amide < / RTI >
    [2822] 977 468 isoquinoline-1-carboxylic acid {4- [3- (1-benzofuran-2-yl-ethyl)
    [2823] Thioureido] -phenyl} -amide < / RTI >
    [2824] 978 506 isoquinoline-1-carboxylic acid (4- {3- [l- (4-bromo-phenyl)
    [2825] Thioureido} -phenyl) -amide < / RTI >
    [2826] 979 453 isoquinoline-1-carboxylic acid (4- {3- [1- (4-cyano-phenyl)
    [2827] Thioureido} -phenyl) -amide < / RTI >
    [2828] 980 435 Benzofuran-2-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [2829] Thioureido} -phenyl) -amide < / RTI >
    [2830] 981 457 Benzofuran-2-carboxylic acid {4- [3- (1-benzofuran-2-yl-ethyl) -thioureido]
    [2831] Phenyl} -amide
    [2832] 982 495 Benzofuran-2-carboxylic acid (4- {3- [l- (4-bromo-phenyl)
    [2833] Thioureido} -phenyl) -amide < / RTI >
    [2834] 983 442 Benzofuran-2-carboxylic acid (4- {3- [1- (4-cyano-phenyl)
    [2835] Thioureido} -phenyl) -amide < / RTI >
    [2836] 984 446 isoquinoline-3-carboxylic acid (4- {3- [l- (4-fluoro- phenyl)
    [2837] Thioureido} -phenyl) -amide < / RTI >
    [2838] 985 468 isoquinoline-3-carboxylic acid {4- [3- (1-benzofuran-2-yl-ethyl)
    [2839] Thioureido] -phenyl} -amide < / RTI >
    [2840] 986 453 isoquinoline-3-carboxylic acid (4- {3- [1- (4-cyano-phenyl)
    [2841] Thioureido} -phenyl) -amide < / RTI >
    [2842] 987 506 Isoquinoline-3-carboxylic acid (4- {3- [l- (4-bromo-phenyl)
    [2843] Thioureido} -phenyl) -amide < / RTI >
    [2844] 988 446 Quinoline-3-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [2845] Thioureido} -phenyl) -amide < / RTI >
    [2846] 989 446 Quinoline-4-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [2847] Thioureido} -phenyl) -amide < / RTI >
    [2848] 6-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -
    [2849] Thioureido} -phenyl) -amide < / RTI >
    [2850] 8-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -
    [2851] Thioureido} -phenyl-amide
    [2852] 992 462 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2853] Trifluoromethyl-benzamide < RTI ID = 0.0 >
    [2854] 993 419 2-Cyano-N- (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2855] Phenyl) -benzamide
    [2856] 994 473 N- {4- [3- (3-Chloro-4-isobutoxy-phenyl) -thioureido] -phenyl} -
    [2857] Fluoro-benzamide
    [2858] 995 414 2-Fluoro-N- {4- [3- (3-fluoro-4-methoxy-phenyl) -thioureido]
    [2859] Phenyl} -benzamide
    [2860] 996 475 N- (4- {3- [3-Chloro-4- (2-methoxy-ethoxy) -phenyl] thioureido}
    [2861] Phenyl) -2-fluoro-benzamide
    [2862] 997 398 2-Fluoro-N- {4- [3- (3-fluoro-4-methyl-phenyl) -thioureido]
    [2863] Phenyl} -benzamide
    [2864] 998 464 2-Fluoro-N- {4- [3- (4-methoxy-3-trifluoromethyl-phenyl)
    [2865] Thioureido] -phenyl} -benzamide < / RTI >
    [2866] 999 449 N- {4- [3- (2-Amino-5-trifluoromethyl-phenyl) -thioureido] -
    [2867] Phenyl} -2-fluoro-benzamide
    [2868] 1000 459 N- (4- {3- [1- (3-Chloro-4-methoxy-phenyl) -ethyl] -thioureido}
    [2869] Phenyl) -2-fluoro-benzamide
    [2870] 1001 417 N- {4- [3- (5-Chloro-2-hydroxy-phenyl) -thioureido] -phenyl} -2-
    [2871] Fluoro-benzamide
    [2872] 1002 435 N- {4- [3- (1-Benzofuran-2-yl-ethyl) -thioureido] -phenyl} -2-
    [2873] Fluoro-benzamide
    [2874] 1003 448 2-Fluoro-N- {4- [3- (4-methyl-3-trifluoromethyl- phenyl)
    [2875] Thioureido] -phenyl} -benzamide < / RTI >
    [2876] 1004 473 (S) -N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2877] Fluoro-benzamide
    [2878] 1005 473 N- (4- {3 - [(1 R) -1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2879] Fluoro-benzamide
    [2880] 1006 494 2-Fluoro-N- (4- {3- [2-methoxy-4- (2,2,2- trifluoro-ethoxy)
    [2881] Phenyl] -thioureido} -phenyl) -benzamide < / RTI >
    [2882] 1007 399 N- {4- [3- (2-Amino-5-fluoro-phenyl) -thioureido] -phenyl} -2-
    [2883] Fluoro-benzamide
    [2884] 1008 502 N- (4- {3- [1- (4-Dimethylsulfamoyl-phenyl) -ethyl] -thioureido} -phenyl) -
    [2885] 2-Fluoro-benzamide
    [2886] 1009 542 2-Fluoro-N- [4- (3- {1- [4- (piperidine-1 -sulfonyl) -phenyl] -ethyl}
    [2887] Thioureido) -phenyl] -benzamide < / RTI >
    [2888] 1010 562 N- (4- {3- [2,4-Bis- (2,2,2-trifluoro-ethoxy) -phenyl] -
    [2889] Thioureido} -phenyl) -2-fluoro-benzamide
    [2890] 1011 409 2-Fluoro-N- {4- [3 - ((1S) -1-p-tolyl-ethyl) -thioureido] -phenyl}
    [2891] Benzamide
    [2892] 1012 409 2-Fluoro-N- {4- [3 - ((1 R) -1-p-tolyl-ethyl) -thioureido] -phenyl}
    [2893] Benzamide
    [2894] 1013 394 2-Fluoro-N- {4- [3 - ((1S) -1-phenyl- ethyl) -thioureido] -phenyl} -
    [2895] Benzamide
    [2896] (4-chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2897] Fluoro-benzamide
    [2898] 1015 429 N- (4- {3 - [(1S) -1- (4-Chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2899] Fluoro-benzamide
    [2900] 1016 394 2-Fluoro-N- {4- [3 - ((1 R) -1-phenyl- ethyl) -thioureido] -phenyl} -
    [2901] Benzamide
    [2902] 1017 432 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2903] Methoxy-benzamide
    [2904] 1018 447 N- {4- [3- (1-Benzofuran-2-yl-ethyl) -thioureido] -phenyl} -2-methoxy-
    [2905] Benzamide
    [2906] 1019 485 N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-
    [2907] Methoxy-benzamide
    [2908] 1020 419 3-Cyano-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2909] Phenyl) -benzamide
    [2910] 1021 462 N- (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -4-
    [2911] Trifluoromethyl-benzamide < RTI ID = 0.0 >
    [2912] 1022 419 4-Cyano-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2913] Phenyl) -benzamide
    [2914] 1023 469 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2915] 2,3,5,6-tetramethylphenyl) -benzamide
    [2916] 1024 480 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -2,5-dimethoxy-
    [2917] Phenyl) -2-fluoro-benzamide
    [2918] 1025 473 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2919] 2,5-dimethoxy-phenyl) -benzamide < / RTI >
    [2920] 1026 530 N- {3,5-Dichloro-4- [3- (5-chloro-2,4-dimethoxy-phenyl)
    [2921] Thioureido] -phenyl} -2-fluoro-benzamide
    [2922] 1027 447 N- (3-Chloro-4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2923] Phenyl) -2-fluoro-benzamide
    [2924] 1028 447 2,3,4,5-Tetrafluoro-N- (4- {3- [1- (4-fluoro-phenyl)
    [2925] Thioureido} -3-methyl-phenyl) -benzamide
    [2926] 1029 462 2,4,5-Trifluoro-N- (4- {3- [1- (4-fluoro-phenyl)
    [2927] Thioureido} -3-methyl-phenyl) -benzamide
    [2928] 1030 427 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2929] 3-methyl-phenyl) -benzamide < / RTI >
    [2930] 1031 457 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2931] Methoxy-5-methyl-phenyl) -benzamide < / RTI >
    [2932] 1032 443 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2933] 3-methoxy-phenyl) -benzamide < / RTI >
    [2934] 1033 570 N- (2,6-dibromo-4- {3- [l- (4-fluoro-phenyl)
    [2935] Thioureido} -phenyl) -2-fluoro-benzamide
    [2936] 1034 480 2-Fluoro-N- (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2937] 2-trifluoromethyl-phenyl) -benzamide < / RTI >
    [2938] 1035 541 N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2-
    [2939] Trifluoromethyl-phenyl) -2-fluoro-benzamide < / RTI >
    [2940] 1036 487 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -2-
    [2941] Trifluoromethyl-phenyl) -2-fluoro-benzamide < / RTI >
    [2942] 1037 503 N- {4- [3- (1-Benzofuran-2-yl-ethyl) -thioureido] -2-
    [2943] Trifluoromethyl-phenyl} -2-fluoro-benzamide < / RTI >
    [2944] 1038 447 N- (2-Chloro-4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2945] Phenyl) -2-fluoro-benzamide
    [2946] 1039 454 N- (2-Chloro-4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido}
    [2947] Phenyl) -2-fluoro-benzamide
    [2948] 1040 437 N- (2-Cyano-4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2949] Phenyl) -2-fluoro-benzamide
    [2950] 1041 498 N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2-cyano-
    [2951] Phenyl) -2-fluoro-benzamide
    [2952] 1042 445 N- (2-Cyano-4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido}
    [2953] Phenyl) -2-fluoro-benzamide
    [2954] 1043 460 N- {4- [3- (1-Benzofuran-2-yl-ethyl) -thioureido] -2-cyano-
    [2955] 2-Fluoro-benzamide
    [2956] 1044 517 N- (2-Benzoyl-4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2957] Phenyl) -2-fluoro-benzamide
    [2958] 1045 427 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2959] 2-methyl-phenyl) -benzamide < / RTI >
    [2960] 1046 487 N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2-methyl-
    [2961] 2-Fluoro-benzamide
    [2962] 1047 434 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -2- methyl-
    [2963] 2-Fluoro-benzamide
    [2964] 2-yl-ethyl) -thioureido] -2-methyl-phenyl} -2- (4-methoxy-
    [2965] Fluoro-benzamide
    [2966] 1049 456 N- (2-Dimethylamino-4- {3- [l- (4-fluoro-phenyl)
    [2967] Thioureido} -phenyl) -2-fluoro-benzamide
    [2968] 1050 526 N- (2-Benzyloxy-4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido} -2-
    [2969] Fluoro-benzamide
    [2970] 1051 519 N- (2-Benzyloxy-4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2971] Phenyl) -2-fluoro-benzamide
    [2972] 1052 603 N- [4- {3- [l- (4-Bromo-phenyl) -ethyl] -thioureido} -2- (2-
    [2973] 4-yl-ethoxy) phenyl] -2-fluoro-benzamide
    [2974] 1053 603 N- [4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2- (2-
    [2975] 4-yl-ethoxy) phenyl] -2-fluoro-benzamide
    [2976] 1054 542 2-Fluoro-N- [4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2977] 2- (2-morpholin-4-yl-ethoxy) phenyl] -benzamide
    [2978] 1055 485 N- (2-Butoxy-4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2979] Phenyl) -2-fluoro-benzamide
    [2980] 1056 492 N- (2-Butoxy-4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido} -phenyl) -
    [2981] 2-Fluoro-benzamide
    [2982] 1057 589 N- [4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2-
    [2983] Amino-ethoxy) phenyl] -2-fluoro-benzamide
    [2984] 4- {3- [1- (4-fluoro-phenyl) -ethyl] -
    [2985] Thioureido} -phenyl) -2-fluoro-benzamide
    [2986] 1059 589 N- [4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -2-
    [2987] Amino-ethoxy) phenyl] -2-fluoro-benzamide
    [2988] 1060 457 N- (2-Ethoxy-4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2989] Phenyl) -2-fluoro-benzamide
    [2990] 1061 464 N- (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -2-ethoxy-
    [2991] Phenyl) -2-fluoro-benzamide
    [2992] 1062 468 2-Fluoro-N- [4- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2993] 2- (2-Nitrilo-ethoxy) -phenyl] -benzamide
    [2994] 1063 475 N- [4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -2- (2-
    [2995] Ethoxy) -phenyl] -2-fluoro-benzamide
    [2996] 1064 443 2-Fluoro-N- (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2997] 2-methoxy-phenyl) -benzamide < / RTI >
    [2998] 1065 489 2-Fluoro-N- (5- {3- [l- (4-fluoro-phenyl) -ethyl] -thioureido}
    [2999] Biphenyl-2-yl) -benzamide
    [3000] 1066 514 isoquinoline-1-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [3001] Thioureido} -2-trifluoromethyl-phenyl) -amide
    [3002] 1067 503 Benzofuran-2-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [3003] Thioureido} -2-trifluoromethyl-phenyl) -amide
    [3004] 1068 514 isoquinoline-3-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [3005] Thioureido} -2-trifluoromethyl-phenyl) -amide
    [3006] 1069 471 Preparation of isoquinoline-1-carboxylic acid (2-cyano-4- {3- [1- (4-
    [3007] Ethyl] -thioureido} -phenyl) -amide
    [3008] 1070 460 Benzofuran-2-carboxylic acid (2- cyano-4- {3- [l- (4-fluoro-
    [3009] Thioureido} -phenyl) -amide < / RTI >
    [3010] 1071 471 isoquinoline-3-carboxylic acid (2-cyano-4- {3- [1- (4-fluoro-
    [3011] Ethyl] -thioureido} -phenyl) -amide
    [3012] 1072 460 Isoquinoline-1-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [3013] Thioureido} -2-methyl-phenyl) -amide
    [3014] 1073 449 Benzofuran-2-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [3015] Thioureido} -2-methyl-phenyl) -amide
    [3016] 1074 460 Isoquinoline-3-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [3017] Thioureido} -2-methyl-phenyl) -amide
    [3018] 1075 396 Pyrazine-2-carboxylic acid (4- {3- [1- (4-fluoro-phenyl)
    [3019] Thioureido} -phenyl) -amide < / RTI >
    [3020] 1076 401 Thiophene-2-carboxylic acid (4- {3- [l- (4-fluoro-phenyl)
    [3021] Thioureido} -phenyl) -amide < / RTI >
    [3022] 1077 401 Thiophene-3-carboxylic acid (4- {3- [l- (4-fluoro-phenyl) -ethyl] -thiourea
    [3023] Yl} -phenyl) -amide
    [3024] 1078 500 2-Isopropyl-thiazole-4-carboxylic acid {4- [3- (4-chloro-3-
    [3025] Methyl-phenyl) -thioureido] -phenyl} -amide
    [3026] 1079 466 2-Isopropyl-thiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl)
    [3027] Thioureido] -phenyl} -amide < / RTI >
    [3028] 1080 466 2-Isopropyl-thiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)
    [3029] Thioureido] -phenyl} -amide < / RTI >
    [3030] 1081 534 2-Isopropyl-thiazole-4-carboxylic acid {4- [3- (3,5-bis-trifluoro
    [3031] Methyl-phenyl) -thioureido] -phenyl} -amide
    [3032] 1082 480 2-Butyl-thiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)
    [3033] Iso] -phenyl} -amide
    [3034] 1083 514 2-Butyl-thiazole-4-carboxylic acid {4- [3- (4-chloro-3-trifluoromethyl-
    [3035] Phenyl) -thioureido] -phenyl} -amide
    [3036] 1084 480 2-Butyl-thiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl)
    [3037] Iso] -phenyl} -amide
    [3038] 1085 548 2-Butyl-thiazole-4-carboxylic acid {4- [3- (3,5-bis- trifluoromethyl-
    [3039] Phenyl) -thioureido] -phenyl} -amide
    [3040] 1086 438 2-Methyl-thiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl)
    [3041] Iso] -phenyl} -amide
    [3042] 1087 438 2-Methyl-thiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)
    [3043] Iso] -phenyl} -amide
    [3044] 1088 505 2-Methyl-thiazole-4-carboxylic acid {4- [3- (3,5-bis- trifluoromethyl-
    [3045] Phenyl) -thioureido] -phenyl} -amide
    [3046] 1089 534 2-Phenyl-thiazole-4-carboxylic acid {4- [3- (4-chloro-3- trifluoromethyl-
    [3047] Phenyl) -thioureido] -phenyl} -amide
    [3048] 1090 500 2-Phenyl-thiazole-4-carboxylic acid {4- [3- (3,5-dichloro- phenyl)
    [3049] Iso] -phenyl} -amide
    [3050] 1091 500 2-Phenyl-thiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)
    [3051] Iso] -phenyl} -amide
    [3052] 1092 568 2-Phenylthiazole-4-carboxylic acid {4- [3- (3,5-bis-trifluoromethyl-
    [3053] Phenyl) -thioureido] -phenyl} -amide
    [3054] 1093 401 2-Fluoro-N- {4- [3- (1 -thiazol-2-yl-ethyl) -thioureido] -phenyl} -
    [3055] Benzamide
    [3056] 1094 588 2-Fluoro-N- [4- (3- {1- [1- (toluene-4-sulfonyl) -lH- indol-
    [3057] Ethyl} -thioureido) -phenyl] -benzamide < / RTI >
    [3058] 1095 446 2-Fluoro-N- {4- [3- (l-quinolin-2-yl-ethyl) -thioureido] -phenyl} -
    [3059] Benzamide
    [3060] 1096 446 2-Fluoro-N- {4- [3- (l-quinolin-4-yl-ethyl) -thioureido] -phenyl}
    [3061] Benzamide
    [3062] 1097 446 2-Fluoro-N- {4- [3- (1-isoquinolin-3-yl-ethyl) -thioureido]
    [3063] Phenyl} -benzamide
    [3064] 1098 446 2-Fluoro-N- {4- [3- (1-isoquinolin-1-yl-ethyl) -thioureido]
    [3065] Phenyl} -benzamide
    [3066] 1099 446 2-Fluoro-N- {4- [3- (l-quinolin-6-yl-ethyl) -thioureido] -phenyl} -
    [3067] Benzamide
    [3068] 1100 446 2-Fluoro-N- {4- [3- (l-quinolin-3-yl-ethyl) -thioureido] -phenyl}
    [3069] Benzamide
    [3070] 1101 413 2-Methoxy-N- {4- [3- (1 -thiophen-3-yl-ethyl) -thioureido] -phenyl}
    [3071] Benzamide
    [3072] Example 871 (Method 33)
    [3073] [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro-phenyl) -thioureido] -phenyl}
    [3074] To a solution of 3,5-dichloroaniline (0.16 g) in tetrahydrofuran (20 mL) was added 1,1'-thiocarbonyl-di- (1,2,4) -thiazole (0.20 g) And the mixture is stirred at room temperature for approximately 30 minutes. [1,2,3] -thiadiazole-4-carboxylic acid (4-amino-phenyl) amide (0.22 g) is added to the reaction flask and the mixture is stirred for approximately 6 hours. The solvent is removed by evaporation under reduced pressure and warm acetonitrile (3 mL) is added. After 15 h the mixture is filtered and the collected precipitate is washed with acetonitrile followed by diethyl ether and air dried to give the desired product of a white powder. [M + H] < / RTI > 424.
    [3075] Using the above procedure and the appropriate starting materials the following compounds were prepared:
    [3076] Example M + H Compound name
    [3077] 872 465 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -3-
    [3078] Fluoro-benzamide
    [3079] 873 467 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -2-
    [3080] Methoxy-benzamide
    [3081] 874 465 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -2-
    [3082] Fluoro-benzamide
    [3083] 875 477 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -3-
    [3084] Methoxy-benzamide
    [3085] 876 399 N- {4- [3- (3,5-Dichloro-2-methoxy-4-methyl-phenyl) -thioureido]
    [3086] Phenyl} -acetamide
    [3087] 877 365 N- {4- [3- (3-Chloro-4-methoxy-5-methyl-phenyl) -thioureido] -phenyl} -
    [3088] Acetamide
    [3089] 878 331 N- {4- [3- (2-Nitro-phenyl) -thioureido] -phenyl} -acetamide
    [3090] 879 331 N- {4- [3- (4-Nitro-phenyl) -thioureido] -phenyl} -acetamide
    [3091] 880 477 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -4-
    [3092] Methoxy-benzamide
    [3093] 881 351 N- {4- [3- (2-Chloro-5-methoxy-phenyl) -thioureido] -phenyl}
    [3094] mid
    [3095] 882 428 2- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-
    [3096] Glacial} -acetamide
    [3097] 883 443 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-
    [3098] } -Acetic acid
    [3099] 884 457 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-
    [3100] Yl} -acetic acid ethyl ester
    [3101] 885 447 N- {4- [3- (3,5-Dichloro-4-phenoxy-phenyl) -thioureido] -phenyl}
    [3102] Cetamide
    [3103] 886 410 N- (4- {3- [3,5-Dichloro-4- (2-nitrilo-ethoxy) -phenyl] -thiourea
    [3104] Yl} -phenyl) -acetamide < / RTI >
    [3105] 887 485 {4- [3- (4-Acetylamino-phenyl) -thioureido] -2,6-dichloro-
    [3106] Yl} acetic acid tert-butyl ester
    [3107] 888 469 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,5-dichloro-
    [3108] Yl-phenyl) -thioureido] -phenyl} -amide
    [3109] 889 335 N- {4- [3- (3-Chloro-4-methyl-phenyl) -thioureido] -phenyl} -acetamide
    [3110] 890 335 N- {4- [3- (5-Chloro-2-methyl-phenyl) -thioureido] -phenyl}
    [3111] De
    [3112] 891 703 N- {4- [3- (4- {4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-
    [3113] Phenyldisulfanyl} -3-chloro-phenyl) -thioureido] -phenyl} -acetamide
    [3114] 892 369 N- {4- [3- (3,5-Dichloro-4-methoxy-phenyl) -thioureido] -phenyl} -acetic acid
    [3115] Tamide
    [3116] 893 598 N- {4- [3- (3,5-Diiodo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [3117] Acetamide
    [3118] 894 504 N- {4- [3- (3,5-Dibromo-2,4-dimethoxy-phenyl) -thioureido] -phenyl} -
    [3119] Acetamide
    [3120] 895 317 N- {4- [3- (6-Methoxy-pyridin-3-yl) -thioureido] -phenyl} -acetamide
    [3121] 896 347 N- {4- [3- (2,6-Dimethoxy-pyridin-3-yl) -thioureido] -phenyl}
    [3122] mid
    [3123] 897 457 Acetic acid 2- {4- [3- (4-acetylamino-phenyl) -thioureido] -2,6-
    [3124] Chloro-phenoxy} -ethyl ester
    [3125] 898 365 4- [3- (4-Acetylamino-phenyl) -thioureido] -2-chloro-benzoic acid
    [3126] 899 346 N- {4- [3- (3-Chloro-4-cyano-phenyl) -thioureido] -phenyl} -acetamide
    [3127] 900 512 N- (4- {3- [5-Chloro-2- (4-chloro-phenoxy) -4-pyrrol-
    [3128] Ureido} -phenyl) -acetamide < / RTI >
    [3129] 901 355 N- {4- [3- (3,4-Dichloro-phenyl) -thioureido] -phenyl} -acetamide
    [3130] 902 339 N- {4- [3- (3-Chloro-4-fluoro-phenyl) -thioureido] -phenyl}
    [3131] mid
    [3132] 903 447 N- {4- [3- (3-Chloro-4-iodo-phenyl) -thioureido] -phenyl}
    [3133] De
    [3134] 904 400 N- {4- [3- (4-Bromo-3-chloro-phenyl) -thioureido] -phenyl}
    [3135] De
    [3136] 905 424 N- [4- (3- {4- [Bis- (2-hydroxy-ethyl) -amino] -3-chloro-phenyl}
    [3137] ≪ RTI ID = 0.0 > oureido) -phenyl] -acetamide &
    [3138] 906 434 N- (4- {3- [3-Chloro-4- (hexyl-methyl-amino) -phenyl] -thioureido}
    [3139] Yl) -acetamide
    [3140] 907 406 N- (4- {3- [3-Chloro-4- (isobutyl-methyl-amino) -phenyl] -thiourea
    [3141] Yl} -phenyl) -acetamide < / RTI >
    [3142] 908 389 N- {4- [3- (3-Chloro-4-trifluoromethyl-phenyl) -thioureido] -phe
    [3143] Yl} -acetamide
    [3144] 909 441 furan-2-carboxylic acid {4- [3- (3-chloro-4-trifluoromethyl- phenyl)
    [3145] Ureido] -phenyl} -amide
    [3146] 910 459 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-trifluoromethyl-
    [3147] Yl-phenyl) -thioureido] -phenyl} -amide
    [3148] 911 469 N- {4- [3- (3-Chloro-4-trifluoromethyl-phenyl) -thioureido] -phe
    [3149] Yl} -2-fluoro-benzamide < / RTI >
    [3150] 912 435 N- {4- [3- (3,4-Dichloro-phenyl) -thioureido] -phenyl} -2-fluoro-
    [3151] Zeamide
    [3152] 913 407 furan-2-carboxylic acid {4- [3- (3,4-dichloro-phenyl) -thioureido] -phenyl}
    [3153] -amides
    [3154] 914 425 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3,4-dichloro- phenyl)
    [3155] Yl] -phenyl} -amide < / RTI >
    [3156] 915 480 N- {4- [3- (4-Bromo-3-chloro-phenyl) -thioureido] -phenyl} -2-
    [3157] Benzamide
    [3158] 916 527 N- {4- [3- (3-Chloro-4-iodo-phenyl) -thioureido] -phenyl} -2-fluoro
    [3159] Benzamide
    [3160] 917 452 Furan-2-carboxylic acid {4- [3- (4-bromo-3-chloro-phenyl) -thioureido]
    [3161] Phenyl} -amide
    [3162] 918 499 furan-2-carboxylic acid {4- [3- (3-chloro-4-iodo-phenyl) -thioureido]
    [3163] Phenyl} -amide
    [3164] 919 391 Furan-2-carboxylic acid {4- [3- (3-chloro-4-fluoro-phenyl) -thiourea
    [3165] Iso] -phenyl} -amide
    [3166] 920 470 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (4-bromo-3-
    [3167] Thioureido] -phenyl} -amide < / RTI >
    [3168] 921 517 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-
    [3169] Thioureido] -phenyl} -amide < / RTI >
    [3170] 922 419 N- {4- [3- (3-Chloro-4-fluoro-phenyl) -thioureido] -phenyl} -2-
    [3171] Oro-benzamide
    [3172] 923 409 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-fluoro-
    [3173] Thioureido] -phenyl} -amide < / RTI >
    [3174] 924 388 N- {4- [3- (3-Chloro-4-isoxazol-5-yl-phenyl) -thioureido] -phenyl} -
    [3175] Acetamide
    [3176] 925 387 N- (4- {3- [3-Chloro-4- (lH-pyrazol-3-yl) -phenyl] -thioureido}
    [3177] Yl) -acetamide
    [3178] 926 355 N- {4- [3- (2,3-Dichloro-phenyl) -thioureido] -phenyl} -acetamide
    [3179] 927 435 N- {4- [3- (2,3-Dichloro-phenyl) -thioureido] -phenyl} -2-fluoro-
    [3180] Zeamide
    [3181] 928 407 furan-2-carboxylic acid {4- [3- (2,3-dichloro-phenyl) -thioureido] -phenyl} -
    [3182] amides
    [3183] 929 425 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2,3-dichloro- phenyl)
    [3184] Yl] -phenyl} -amide < / RTI >
    [3185] 930 355 N- {4- [3- (2,5-Dichloro-phenyl) -thioureido] -phenyl} -acetamide
    [3186] 931 435 N- {4- [3- (2,5-Dichloro-phenyl) -thioureido] -phenyl} -2-fluoro-
    [3187] Zeamide
    [3188] 932 407 furan-2-carboxylic acid {4- [3- (2,5-dichloro-phenyl) -thioureido] -phenyl} -
    [3189] amides
    [3190] 933 355 N- {4- [3- (3,5-Dichloro-phenyl) -thioureido] -phenyl} -acetamide
    [3191] 934 435 N- {4- [3- (3,5-Dichloro-phenyl) -thioureido] -phenyl} -2-fluoro-
    [3192] Zeamide
    [3193] 935 407 furan-2-carboxylic acid {4- [3- (3,5-dichloro-phenyl) -thioureido] -phenyl} -
    [3194] amides
    [3195] 936 390 N- {4- [3- (3,4,5-Trichloro-phenyl) -thioureido] -phenyl} -acetamide
    [3196] 937 470 2-Fluoro-N- {4- [3- (3,4,5-trichloro-phenyl) -thioureido]
    [3197] Phenyl} -benzamide
    [3198] 938 442 furan-2-carboxylic acid {4- [3- (3,4,5-trichloro-phenyl) -thioureido]
    [3199] Phenyl} -amide
    [3200] 939 460 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3,4,5-trichloro-phenyl)
    [3201] Oureido] -phenyl} -amide < / RTI >
    [3202] 940 458 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-chloro-4-isoxazol-
    [3203] Phenyl) -thioureido] -phenyl} -amide
    [3204] 941 457 [1,2,3] thiadiazole-4-carboxylic acid (4- {3- [3-chloro-4- (lH-
    [3205] Yl) -phenyl] -thioureido} -phenyl) -amide
    [3206] 942 391 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (3-chloro-phenyl)
    [3207] Iso] -phenyl} -amide
    [3208] 943 373 Furan-2-carboxylic acid {4- [3- (3-chloro-phenyl) -thioureido] -phenyl}
    [3209] mid
    [3210] 944 401 N- {4- [3- (3-Chloro-phenyl) -thioureido] -phenyl} -2-fluoro-
    [3211] mid
    [3212] 945 373 Furan-2-carboxylic acid {4- [3- (4-chloro-phenyl) -thioureido] -phenyl}
    [3213] mid
    [3214] 946 401 N- {4- [3- (4-Chloro-phenyl) -thioureido] -phenyl} -2-fluoro-
    [3215] mid
    [3216] 947 391 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (4-chloro-phenyl)
    [3217] Iso] -phenyl} -amide
    [3218] 948 401 N- {4- [3- (2-Chloro-phenyl) -thioureido] -phenyl} -2-fluoro-
    [3219] mid
    [3220] 949 396 3- (3- {4- [(furan-2-carbonyl) -amino] -phenyl} -thioureido) -benzoic acid
    [3221] Methyl ester
    [3222] 950 424 3- {3- [4- (2-Fluoro-benzoylamino) -phenyl] -thioureido} -benzoic acid
    [3223] Methyl ester
    [3224] 951 414 3- (3- {4 - [([[1,2,3] thiadiazole-4-carbonyl) -amino] -phenyl} -thiourea
    [3225] Iso) -benzoic acid methyl ester
    [3226] 952 409 N- [4 - [[[[3- (aminocarbonyl) phenyl] amino] thioxomethyl]
    [3227] 2-Fluoro-benzamide
    [3228] 953 373 Furan-2-carboxylic acid {4- [3- (2-chloro-phenyl) -thioureido] -phenyl}
    [3229] mid
    [3230] 954 381 furan-2-carboxylic acid {4- [3- (3-carbamoyl-phenyl) -thioureido] -phenyl} -
    [3231] amides
    [3232] 955 399 [1,2,3] Thiadiazole-4-carboxylic acid {4- [3- (3-carbamoyl-phenyl) -thiourea
    [3233] Iso] -phenyl} -amide
    [3234] 956 391 [1,2,3] thiadiazole-4-carboxylic acid {4- [3- (2-chloro-phenyl)
    [3235] Iso] -phenyl} -amide
    [3236] 957 356 Furan-2-carboxylic acid {4- [3- (3-fluoro-phenyl) -thioureido] -phenyl} -
    [3237] amides
    [3238] 958 383 Furan-2-carboxylic acid {4- [3- (3-nitro-phenyl) -thioureido] -phenyl}
    [3239] mid
    [3240] 959 411 2-Fluoro-N- {4- [3- (3-nitro-phenyl) -thioureido] -phenyl}
    [3241] mid
    [3242] 960 422 Furan-2-carboxylic acid {4- [3- (3-trifluoromethoxy-phenyl) -thiourea
    [3243] Iso] -phenyl} -amide
    [3244] 961 450 2-Fluoro-N- {4- [3- (3-trifluoromethoxy-phenyl) -thioureido] -
    [3245] Phenyl} -benzamide
    [3246] 962 384 2-Fluoro-N- {4- [3- (3-fluoro-phenyl) -thioureido] -phenyl}
    [3247] amides
    [3248] 963 410 3- {3- [4- (2-Fluoro-benzoylamino) -phenyl] -thioureido} -benzoic acid
    [3249] 964 382 3- (3- {4- [(furan-2-carbonyl) -amino] -phenyl} -thioureido) -benzoic acid
    [3250] 965 408 N- {4- [3- (3-Acetyl-phenyl) -thioureido] -phenyl} -2-fluoro-
    [3251] mid
    [3252] 966 502 N- {4- [3- (3-Butylsulfamoyl-phenyl) -thioureido] -phenyl} -2-fluoro-
    [3253] Benzamide
    [3254] 967 380 Furan-2-carboxylic acid {4- [3- (3-acetyl-phenyl) -thioureido] -phenyl}
    [3255] mid
    [3256] 968 447 furan-2-carboxylic acid (4- {3- [3- (2-hydroxy-ethanesulfonyl) -phenyl] -thio
    [3257] Yl-phenyl) -amide < / RTI >
    [3258] 969 475 2-Fluoro-N- (4- {3- [3- (2-hydroxy-ethanesulfonyl) -phenyl] -thiourea
    [3259] Iso} -phenyl) -benzamide < / RTI >
    [3260] 970 474 furan-2-carboxylic acid {4- [3- (3-butylsulfamoyl-phenyl) -thioureido] -phe
    [3261] Yl} -amide
    [3262] Example 971 (method 57)
    [3263] 1- (4-Fluoro-phenyl) -2-methyl-propan-
    [3264] To a solution of 4-fluorobenzaldehyde (2.0 g) in diethyl ether (40 mL) at 0 ° C is added isopropyl magnesium bromide (2.0 M, 9.6 mL) with stirring. After 1.5 h, the reaction is quenched with aqueous ammonium chloride and extracted with diethyl ether. The diethyl ether extract is washed with saturated sodium chloride, dried over anhydrous magnesium sulfate, filtered and evaporated to give an oil. Purify the oil by silica gel chromatography eluting with 10% dichloromethane-hexane to give the product (1.76 g) of a yellow oil.
    [3265] Example 972 (Method 58)
    [3266] 1- (4-Fluoro-phenyl) -2-methyl-propan-1-
    [3267] To a solution of 1- (4-fluoro-phenyl) -2-methyl-propan-1-ol (1.6 g) in acetone (10 mL) at 0 ° C was added Jones ture (20 mL) with stirring. After 10 minutes isopropyl alcohol is added to destroy excess Jones tense. Diethyl ether is added followed by anhydrous magnesium and the mixture is filtered and evaporated to give the product (1.2 g) of a yellow oil.
    [3268] Example 973 (Method 59)
    [3269] 3-Dimethylamino-5-trifluoromethyl-benzonitrile
    [3270] To a solution of 3-dimethylamino-5-trifluoromethylbromobenzene (7.3 g) in N, N-dimethylformamide (20 mL) was added primary copper cyanide (2.7 g) and the reaction was refluxed for 12 h Lt; / RTI > Dilute the reaction with water (40 mL) and add dichloromethane. The dichloromethane fraction is washed with concentrated ammonium hydroxide followed by water. The solution was dried over anhydrous magnesium sulfate, filtered and concentrated to give a yellow solid which was recrystallized from hexane to give a yellow solid (4.7 g).
    [3271] The compounds were tested for their activity as a Huff's virus inhibitor.
    [3272] Human cytomegalovirus
    [3273] Yield analysis. A monolayer culture of human foreskin fibroblasts is infected with HCMV wild type in the presence of inhibitory compounds (various concentrations), typically at an infection duplication of 0.2. On the third day after infection, the virus was collected from the cultured human phallic fibroblast 12-well plate and the concentration was measured to evaluate the total virus (i.e., virus yield) produced in the culture solution (performed in the absence of inhibitor). Plaque is quantified at 2 weeks after infection. The presence of an inhibitor of HCMV is confirmed by a decrease in the viral yield titer in the presence of the compound as compared to the titer under the absence of the compound. In this assay, the relative anti-HCMV activity of the inhibitor is typically measured by calculating the IC 50 or IC 90 value, the amount required to reduce the virus yield to 50% or 90%, respectively. Table I describes IC 50 data for compounds tested against HCMV.
    [3274] Microtiter plate analysis . To the 96-well culture medium of human foreskin fibroblasts in the presence of the inhibitor compound was added the HCMV recombinant mutant virus (the genome of which is the prokaryotic beta-glucuronidase gene (Jefferson, RA, SMBurgess, and D. Hirsh. 1986. Beta-glucuronidase from Escherichia coli as a gene fusion marker, Proc Natl Acad Sci USA 83: 8447-8451) and its expression is controlled by a viral promoter. An example of such a virus is RV145 (Jones, TR, VP Muzithras, and Y. Gluzman, 1991. Replacement mutagenesis of the human cytomegalovirus genome: US10 and US11 gene products are nonessential.J Virol. 65: 5860-5872). Since it is under the control of a viral promoter, beta-glucuronidase expression is an indirect indicator of the growth and replication of HCMV in this assay. Infected cell lysates were prepared at 96 hours post infection (using 50 mM sodium phosphate [H 7.0] containing 0.1% Triton X-100 and 0.1% sarkosyl) and analyzed by colorimetry or spectrophotometry on a microphotometer Beta-glucuronidase activity is assessed using a substrate for an enzyme that produces a product whose fluorescence can be measured. Examples of such substrates are p-nitrophenyl-beta-D-glucuronide and methylumbelliferyl glucuronide, respectively. The presence of the antiviral compound is known by the reduced expression of the beta-glucuronidase gene present in the HCMV genome compared to the absence of the inhibitor. Thus, the generation of chromophores or fluorophores in this assay is correspondingly reduced. The IC 50 values of the inhibitor compounds are assessed using data from these assays performed with varying amounts of inhibitor compounds.
    [3275] HSV antiviral (ELISA) analysis
    [3276] 100 ㎕ tissue culture DMEM (Dulbecco's modified Eagle media) per 3.5 x 10 Ting 4 play a 96-well tissue culture medium Vero cells (ATCC # CCL-81) on the plate of cells, and each well 2% state bovine serum (FBS) . Cells were either not treated or treated with the test compound (multiple concentrations) or the reference standard drug control 30 minutes before incubation (5% CO 2 ) at 37 ° C and 30 minutes before infection with HSV-1 . After incubation at 37 ° C (5% CO 2 ) for approximately 24 hours post infection, cells are fixed for ELISA analysis. The primary antibody is a rat anti-HSV glycoprotein D monoclonal primary antibody and the secondary antibody is a goat anti-mouse IgG linked to beta -galactosidase. After adding methylumbelliferyl-beta-D-galactoside (Sigma # M1633) substrate onto a microfluorescent analyzer (365 nm in the excited state and 450 nm in the emissive state), 4-methylumbelliferone fluorescence The cleavage product is quantitated to evaluate the activity of β-galactosidase to measure the degree of viral replication. The antiviral activity (IC 50 ) of the test compound is measured by comparing the fluorescence obtained in the presence of the compound with the fluorescence obtained in the absence of the compound. The data are shown in Table 1.
    [3277] VZV antiviral (ELISA) analysis
    [3278] For stock VZV generated to be used for analysis, VZV strain Ellen (ATCC # VR-1367) using the infecting road (0.1) overlapping a lower human foreskin fibroblasts (HFF), incubated overnight in 5% CO 2 and 37 ℃ do. After overnight incubation, a mixture of uninfected cells and VZV-infected HFF infected cells was harvested and resuspended in 96-well plates (3.5 x 10 4 cells in 100 μl DMEM containing 2% FBS) containing the test compound or reference standard drug control, (In 100 [mu] L DMEM supplemented with 2% FBS per well). The cells are incubated for 3 days at 5% CO 2 and 37 ° C and then fixed for ELISA analysis. The primary antibody is a rat anti-VZV glycoprotein II monoclonal antibody (Applied Biosystems, Inc. # 13-145-100) and the secondary antibody is a goat anti-mouse IgG linked to beta -galactosidase. After adding methylumbelliferyl-beta-D-galactoside (Sigma # M1633) substrate onto a microfluorescent analyzer (365 nm in the excited state and 450 nm in the emissive state), 4-methylumbelliferone fluorescence The cleavage product is quantitated to evaluate the activity of β-galactosidase to measure the degree of viral replication. The antiviral activity (IC 50 ) of the test compound is measured by comparing the fluorescence obtained in the presence of the compound with the fluorescence obtained in the absence of the compound. The data are shown in Table 1.
    [3279] Table I
    [3280]
    [3281]
    [3282]
    [3283] Accordingly, the compounds of the present invention are potent inhibitors of the growth and replication of HERPV viruses, including HCMV, VZV, and HSV, effectively inhibiting viral yield.
    [3284] According to the present invention, the compounds of the present invention can be administered to patients suffering from Herns virus diseases including HCMV, VZV and HSV in an amount effective to inhibit the virus. The compounds of the present invention are useful for attenuating or eliminating the symptoms of Houghts virus infection in mammals, including humans.
    [3285] The compounds of the present invention may be administered to a patient without or in association with conventional pharmaceutical carriers.
    [3286] Applicable solid carriers may include one or more substances which may act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, excipients, compression aids, binders or tablet-dispersing or encapsulating materials. In powders, the carrier is a finely divided solid present in admixture with the finely divided active component. In tablets, the active ingredient is mixed with the carrier having the necessary compressibility in suitable proportions and compressed to the desired shape and size. The powders and tablets preferably contain up to 99% of the active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugar, lactose, dextrin, starch, gelatin, cellulose, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidine, low melting wax, .
    [3287] Liquid carriers can be used to prepare solutions, suspensions, emulsions, syrups and elixirs. The active ingredient of the present invention may be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of the two, or a pharmaceutically acceptable oil or fat. The liquid carrier may contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavors, suspensions, thickeners, pigments, viscosity modifiers, stabilizers or osmo-regulators. Suitable examples of liquid carriers for oral and parenteral administration include water (especially those containing such additives, such as cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (monohydric and polyhydric alcohols, e.g., For example, glycols, and derivatives thereof, and oils (e.g., fractionated coconut oil and arachis oil). For parenteral administration, the carrier may also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid carriers are used in sterile liquid compositions for parenteral administration.
    [3288] Liquid pharmaceutical compositions that are sterile solutions or suspensions may be used, for example, for intramuscular, intraperitoneal, or subcutaneous injection. The sterile solution may also be administered intravenously. Oral administration can be in the form of a liquid or solid composition.
    [3289] Preferably, the pharmaceutical composition is in unit dosage form, for example a tablet or capsule. In this form, the composition is subdivided into unit doses containing the appropriate amount of active ingredient; The unit dosage form can be a package composition, for example, packet powder, vial, ampoule, pre-filled syringe or liquid containing sachet. The unit dosage form may be, for example, a capsule or tablet itself, or it may be a suitable number of such compositions in packaged form.
    [3290] Effective dosages for treatment used in the treatment of a Huff's virus infection are subjectively determined by the primary care physician. The relevant variables include the patient's health status, age and weight. A novel method of the present invention for treating a Houghts virus infection comprises the step of administering to a subject, including a human, an effective amount of at least one compound of formula I or a non-toxic pharmaceutically acceptable salt thereof. The compounds may be administered orally, rectally, parenterally or topically to the skin and mucous membranes. The usual daily dosage will depend on the particular compound, the method of treatment and the condition of the patient. The usual daily dosage is 0.01-1000 mg / Kg, preferably 0.5-500 mg / Kg for oral administration, 0.1-100 mg / Kg for parenteral administration, preferably 0.5-50 mg / Kg.
    权利要求:
    Claims (27)
    [1" claim-type="Currently amended] Or a pharmaceutically acceptable salt thereof,
    Formula I

    In this formula,
    R 1 -R 5 is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, 10 carbon atoms, cycloalkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, halogen, -CN, -NO 2, -CO 2 R 6, -COR 6, -OR 6, -SR 6 , -SOR 6, -SO 2 R 6 , -CONR 7 R 8, -NR 6 n (R 7 R 8), -N (R 7 R 8) or WY- (CH 2) n -Z ( R 1 - And at least one of R < 5 > is not hydrogen; R 2 and R 3 or R 3 and R 4 together form a 3- to 7-membered heterocycloalkyl or a 3- to 7-membered heteroaryl;
    R 6 and R 7 are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl;
    R 8 is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, 3 to 10 membered heterocycloalkyl, aryl or heteroaryl ,
    R 7 and R 8 taken together may form a 3- to 7-membered heterocycloalkyl;
    W is O, NR < 6 > or absent;
    Y is - (CO) - or - (CO 2 ), or is absent;
    Z is alkyl of 1 to 4 carbon atoms, -CN, -CO 2 R 6, COR 6, -CONR 7 R 8, -OCOR 6, -NR 6 COR 7, -OCONR 6, -OR 6, -SR 6 , -SOR 6 , -SO 2 R 6 , SR 6 N (R 7 R 8 ), -N (R 7 R 8 ) or phenyl;
    G is aryl or fused bicyclic heteroaryl;
    X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J;
    J is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl;
    n is an integer of 1 to 6;
    [2" claim-type="Currently amended] The compound of claim 1, wherein R 1 -R 5 are independently alkyl of 1 to 6 carbon atoms, halogen, perhaloalkyl of 1 to 6 carbon atoms, OR 6 or N (R 7 R 8 ).
    [3" claim-type="Currently amended] 2. Compounds according to claim 1, wherein R < 4 > is halogen, trifluoromethyl or cyano.
    [4" claim-type="Currently amended] The compound of claim 1, wherein G is selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, 10 carbon atoms, cycloalkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, halogen, -CN, -NO 2, -CO 2 R 6, -COR 6, -OR 6, -SR 6 , -SOR 6 , -SO 2 R 6 , -CONR 7 R 8 , -NR 6 N (R 7 R 8 ), -N (R 7 R 8 ) or WY- (CH 2 ) ≪ / RTI >
    [5" claim-type="Currently amended] 2. The compound according to claim 1, wherein G is phenyl.
    [6" claim-type="Currently amended] 6. The compound according to claim 5, wherein G is substituted phenyl.
    [7" claim-type="Currently amended] According to claim 1, G is alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 alkyl carbon atoms, halogen, -SR 6, -SOR 6, -N (R 7 R 8) or WY- ( CH 2 ) nZ.
    [8" claim-type="Currently amended] 3. The compound of claim 1, wherein G is 2-fluorophenyl.
    [9" claim-type="Currently amended] 7. The compound of claim 1, wherein G is fused bicycloheteroaryl.
    [10" claim-type="Currently amended] 10. The compound of claim 9, wherein G is quinoline, isoquinoline or benzofuran.
    [11" claim-type="Currently amended] 2. The compound according to claim 1, wherein X is a bond.
    [12" claim-type="Currently amended] 2. The compound of claim 1, wherein X is straight chain alkyl.
    [13" claim-type="Currently amended] 2. The compound of claim 1, wherein X is straight chain alkyl of 1 to 4 carbon atoms.
    [14" claim-type="Currently amended] The compound according to claim 1, wherein X is CH (J).
    [15" claim-type="Currently amended] 2. The compound according to claim 1, wherein J is methyl.
    [16" claim-type="Currently amended] 4. The compound of claim 1 which is N- {4- [3- (1-benzofuran-2-yl-ethyl) -thioureido] -phenyl} -2- trifluoromethyl-
    4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -benzamide,
    (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    1-carboxylic acid {4- [3- (1-benzofuran-2-yl-ethyl) -thioureido] -phenyl}
    (4- {3- [1- (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    (4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    2-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    Benzofuran-2-carboxylic acid {4- [3- (1-benzofuran-2-yl-ethyl) -thioureido] -phenyl}
    2-carboxylic acid (4- {3- [1- (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    2-carboxylic acid (4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    (4- {3- [1- (1-benzofuran-2-yl-ethyl) -thioureido] -phenyl} -amide,
    3-carboxylic acid (4- {3- [1- (4-cyano-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    (4- {3- [1- (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    4-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    6-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    8-carboxylic acid (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    - (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -2-trifluoromethyl-
    2-Cyano-N- (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -benzamide,
    - (3-chloro-4-isobutoxy-phenyl) -thioureido] -phenyl} -2-fluoro-benzamide,
    2-fluoro-N- {4- [3- (3-fluoro-4-methoxy-phenyl) -thioureido] -phenyl}
    - (3-chloro-4- (2-methoxy-ethoxy) -phenyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    2-fluoro-N- {4- [3- (3-fluoro-4-methyl-phenyl) -thioureido] -phenyl}
    2-fluoro-N- {4- [3- (4-methoxy-3-trifluoromethyl-phenyl) -thioureido] -phenyl} -benzamide,
    -Thioureido] -phenyl} -2-fluoro-benzamide, < / RTI >
    - (3-chloro-4-methoxy-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    - {4- [3- (5-chloro-2-hydroxy-phenyl) -thioureido] -phenyl} -2-fluoro-benzamide,
    Yl} -thioureido] -phenyl} -2-fluoro-benzamide, < RTI ID = 0.0 &
    2-Fluoro-N- {4- [3- (4-methyl-3-trifluoromethyl-phenyl) -thioureido] -phenyl} -benzamide,
    (S) -N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    - (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    2-fluoro-ethoxy) -phenyl] -thioureido} -phenyl) -benzamide < / RTI > ,
    - (4- [3- (2-Amino-5-fluoro-phenyl) -thioureido] -phenyl} -2-fluoro-benzamide,
    (4- {3- [1- (4-Dimethylsulfamoyl-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    Phenyl] -ethyl} -thioureido) -phenyl] -benzamide, < / RTI > < RTI ID = 0.0 &
    - (2, 2-trifluoro-ethoxy) -phenyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    2-fluoro-N- {4- [3 - ((1S) -1-p-tolyl-ethyl) -thioureido] -phenyl}
    2-fluoro-N- {4- [3 - ((1 R) -1-p-tolyl-ethyl) -thioureido] -phenyl}
    2-Fluoro-N- {4- [3 - ((1S) -1-phenyl- ethyl) -thioureido] -phenyl} -benzamide,
    (4-chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    - (4-chloro-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    2-fluoro-N- {4- [3 - ((1 R) -1-phenyl- ethyl) -thioureido] -phenyl}
    (4- {3- [1- (4-Cyano-phenyl) -ethyl] -thioureido} -phenyl) -2-methoxy-
    Yl} -thioureido] -phenyl} -2-methoxy-benzamide, < RTI ID = 0.0 &
    N- (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-methoxy-
    - (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -benzamide,
    - (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -4-trifluoromethyl-benzamide,
    (4- {3- [1- (4-Fluoro-phenyl) -ethyl] -thioureido} -phenyl) -benzamide,
    (4- {3- [1- (4-Bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-fluoro-benzamide,
    - (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -4-fluoro-benzamide,
    Phenyl) -ethyl] -thioureido} -phenyl) -2-methoxy-benzamide, < RTI ID = 0.0 &
    - (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -2-methoxy-benzamide,
    (Trifluoromethyl) phenyl] ethyl} amino) carbothioyl] amino} phenyl) benzamide, 2-fluoro-N-
    (4- {3 - [(1S) -1- (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    (4- {3 - [(1S) -1- (4-bromo-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    (4- {3 - [(1S) -1- (4-chloro-phenyl) -ethyl] -thioureido} -phenyl) -amide,
    (4- {3- [1- (4-fluoro-phenyl) -ethyl] -thioureido} -phenyl) -amide, and
    Amino] phenyl} -1-naphthyl) ethyl] amino} carbothioyl) amino] -1H- Phenyl} -1-isoquinolinecarboxamide, and a pharmaceutical salt thereof.
    [17" claim-type="Currently amended] A pharmaceutical composition comprising a compound of the formula: or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent:
    Formula I

    In this formula,
    R 1 -R 5 is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, 10 carbon atoms, cycloalkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, halogen, -CN, -NO 2, -CO 2 R 6, -COR 6, -OR 6, -SR 6 , -SOR 6, -SO 2 R 6 , -CONR 7 R 8, -NR 6 n (R 7 R 8), -N (R 7 R 8) or WY- (CH 2) n -Z ( R 1 - And at least one of R < 5 > is not hydrogen; R 2 and R 3 or R 3 and R 4 together form a 3- to 7-membered heterocycloalkyl or a 3- to 7-membered heteroaryl;
    R 6 and R 7 are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl;
    R 8 is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, 3 to 10 membered heterocycloalkyl, aryl or heteroaryl ,
    R 7 and R 8 taken together may form a 3- to 7-membered heterocycloalkyl;
    W is O, NR < 6 > or absent;
    Y is - (CO) - or - (CO 2 ), or is absent;
    Z is alkyl of 1 to 4 carbon atoms, -CN, -CO 2 R 6, COR 6, -CONR 7 R 8, -OCOR 6, -NR 6 COR 7, -OCONR 6, -OR 6, -SR 6 , -SOR 6 , -SO 2 R 6 , SR 6 N (R 7 R 8 ), -N (R 7 R 8 ) or phenyl;
    G is aryl or fused bicyclic heteroaryl;
    X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J;
    J is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl;
    n is an integer of 1 to 6;
    [18" claim-type="Currently amended] CLAIMS 1. A method for inhibiting the replication of a Huff's virus, comprising contacting a compound of the formula: or a pharmaceutically acceptable salt thereof with a Huff's virus:
    Formula I

    In this formula,
    R 1 -R 5 is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, 10 carbon atoms, cycloalkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, halogen, -CN, -NO 2, -CO 2 R 6, -COR 6, -OR 6, -SR 6 , -SOR 6, -SO 2 R 6 , -CONR 7 R 8, -NR 6 n (R 7 R 8), -N (R 7 R 8) or WY- (CH 2) n -Z ( R 1 - And at least one of R < 5 > is not hydrogen; R 2 and R 3 or R 3 and R 4 together form a 3- to 7-membered heterocycloalkyl or a 3- to 7-membered heteroaryl;
    R 6 and R 7 are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl;
    R 8 is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, 3 to 10 membered heterocycloalkyl, aryl or heteroaryl ,
    R 7 and R 8 taken together may form a 3- to 7-membered heterocycloalkyl;
    W is O, NR < 6 > or absent;
    Y is - (CO) - or - (CO 2 ), or is absent;
    Z is alkyl of 1 to 4 carbon atoms, -CN, -CO 2 R 6, COR 6, -CONR 7 R 8, -OCOR 6, -NR 6 COR 7, -OCONR 6, -OR 6, -SR 6 , -SOR 6 , -SO 2 R 6 , SR 6 N (R 7 R 8 ), -N (R 7 R 8 ) or phenyl;
    G is aryl or fused bicyclic heteroaryl;
    X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J;
    J is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl;
    n is an integer of 1 to 6;
    [19" claim-type="Currently amended] 19. The method of claim 18, wherein the Huff's virus is human cytomegalovirus.
    [20" claim-type="Currently amended] 19. The method according to claim 18, wherein the Huff's virus is Varicella zoster virus.
    [21" claim-type="Currently amended] 21. The method of claim 20, wherein the compound is a substantially pure (S) optical isomer.
    [22" claim-type="Currently amended] 19. The method of claim 18, wherein the Huffs virus is Huffs simplex virus.
    [23" claim-type="Currently amended] Comprising administering to a patient a therapeutically effective amount of a compound of formula < RTI ID = 0.0 > or a < / RTI > pharmaceutically acceptable salt thereof:
    Formula I

    In this formula,
    R 1 -R 5 is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, 10 carbon atoms, cycloalkyl, heterocycloalkyl of 3 to 10 carbon members, aryl, heteroaryl, halogen, -CN, -NO 2, -CO 2 R 6, -COR 6, -OR 6, -SR 6 , -SOR 6, -SO 2 R 6 , -CONR 7 R 8, -NR 6 n (R 7 R 8), -N (R 7 R 8) or WY- (CH 2) n -Z ( R 1 - And at least one of R < 5 > is not hydrogen; R 2 and R 3 or R 3 and R 4 together form a 3- to 7-membered heterocycloalkyl or a 3- to 7-membered heteroaryl;
    R 6 and R 7 are independently hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, or aryl;
    R 8 is hydrogen, alkyl of 1 to 6 carbon atoms, perhaloalkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, 3 to 10 membered heterocycloalkyl, aryl or heteroaryl ,
    R 7 and R 8 taken together may form a 3- to 7-membered heterocycloalkyl;
    W is O, NR < 6 > or absent;
    Y is - (CO) - or - (CO 2 ), or is absent;
    Z is alkyl of 1 to 4 carbon atoms, -CN, -CO 2 R 6, COR 6, -CONR 7 R 8, -OCOR 6, -NR 6 COR 7, -OCONR 6, -OR 6, -SR 6 , -SOR 6 , -SO 2 R 6 , SR 6 N (R 7 R 8 ), -N (R 7 R 8 ) or phenyl;
    G is aryl or fused bicyclic heteroaryl;
    X is a bond, -NH, alkyl of 1 to 6 carbon atoms, alkenyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, thioalkyl of 1 to 6 carbon atoms, 1 to 6 carbons Alkylamino of the atom or (CH) J;
    J is alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, phenyl or benzyl;
    n is an integer of 1 to 6;
    [24" claim-type="Currently amended] 24. The method of claim 23, wherein the Huffs virus is human cytomegalovirus.
    [25" claim-type="Currently amended] 24. The method according to claim 23, wherein the Huff's virus is Varicella zoster virus.
    [26" claim-type="Currently amended] 26. The method of claim 25, wherein the compound is a substantially pure (S) isomer.
    [27" claim-type="Currently amended] 24. The method of claim 23, wherein the Huff's virus is Huffs simplex virus.
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    同族专利:
    公开号 | 公开日
    CN1329608A|2002-01-02|
    EA200100638A1|2001-12-24|
    EP1137645B1|2004-05-26|
    NO20012833L|2001-08-02|
    WO2000034260A3|2000-09-08|
    CN1165531C|2004-09-08|
    DK1137645T3|2004-08-09|
    AT267824T|2004-06-15|
    HU0104492A2|2002-04-29|
    BR9916084A|2001-09-04|
    EP1137645A2|2001-10-04|
    ES2221470T3|2004-12-16|
    DE69917673T2|2005-06-09|
    CZ20012067A3|2001-10-17|
    EA004205B1|2004-02-26|
    JP2002531555A|2002-09-24|
    WO2000034260A2|2000-06-15|
    NO20012833D0|2001-06-08|
    PT1137645E|2004-09-30|
    NZ512135A|2003-12-19|
    DE69917673D1|2004-07-01|
    IL143183D0|2002-04-21|
    AU1934600A|2000-06-26|
    HU0104492A3|2002-12-28|
    ZA200104376B|2002-08-28|
    AR035308A1|2004-05-12|
    CA2350833A1|2000-06-15|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    1998-12-09|Priority to US20890298A
    1998-12-09|Priority to US09/208,902
    1999-12-06|Application filed by 이곤 이 버그, 아메리칸 홈 푸로닥츠 코포레이션
    1999-12-06|Priority to PCT/US1999/028839
    2001-10-06|Publication of KR20010089551A
    优先权:
    申请号 | 申请日 | 专利标题
    US20890298A| true| 1998-12-09|1998-12-09|
    US09/208,902|1998-12-09|
    PCT/US1999/028839|WO2000034260A2|1998-12-09|1999-12-06|Alpha-methylbenzyl-containing thiourea inhibitors of herpes viruses containing a phenylenediamine group|
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