Patent ID: 6420365
Filing Date: 2002-07-16
Classification: A61P,C07D

Abstract:
A compound of the formula: or the Pharmaceutically acceptable non-toxic salts thereof wherein: represents a nitrogen-containing ring system, in which the dashed lines represent double, single or aromatic bonds, and in which not more than two of A, B, C, or D represent nitrogen and remaining ring members are carbon, and which nitrogen-containing ring system is optionally substituted with up to four substituents independently selected from: (i) hydroxyl, halogen, trifluoromethyl, C1-C6 alkyl, trifluoromethoxy, C1-C6 alkoxy, aminomethyl, mono or di(C1-C6)alkylamino, mono or dialkylaminomethyl (wherein each alkyl is independently lower C1-C6 alkyl), (ii) C1-C6alkoxyNR7R8, NR7R8, NR7COR8, CONR7R8, wherein R7 and R8 are the same or different and represent hydrogen, or straight or branched chain lower alkyl, or R7 and R8 are joined together to form a 5, 6, or 7 membered heterocyclic ring, which is optionally substituted with halogen, nitro, trifluoromethyl, cyano, hydroxyl, C1-C6 alkyl, amino, mono or di(C1-C6)alkylamino, or C1-C6 alkoxy, and (iii) O(CH2)nCO2RA (where n=1,2,3, or 4), CORA, and CO2RA wherein RA represents hydrogen, or straight or branched chain lower alkyl; R1 is arylalkyl, heteroarylalkyl, or allyl each of which is optionally substituted directly or through a O(CH2)n linker (where n=1,2,3 or 4) with up to three substituents independently selected from: (i) halogen (with the proviso that R1 may not be 3-Fluorobenzyl), nitro, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, C1-C6 alkyl, amino, C1-C6 alkoxy, aminomethyl, mono or di(C1-C6)alkylamino, mono or dialkylaminomethyl (wherein each alkyl is independently lower C1-C6 alkyl), (ii) C1-C6alkoxyNR7â€²R8â€², NR7â€²R8â€², NR7â€²COR8â€², CONR7â€²R8â€², wherein R7â€² and R8â€² are the same or different and represent hydrogen, or straight or branched chain lower alkyl, or R7â€² and R8â€² are joined together to form a 5, 6, or 7 membered heterocyclic ring, which is optionally substituted with halogen, nitro, trifluoromethyl, cyano, hydroxyl, C1-C6 alkyl, amino, mono or di(C1-C6)alkylamino, or C1-C6 alkoxy, (iii) O(CH2)nCO2RAâ€² (where n=1,2,3, or 4), CORAâ€², CO2RAâ€², wherein RAâ€² represents hydrogen, or straight or branched chain lower alkyl, (iv) SO2RAâ€², NHSO2RAâ€², SO2NHRAâ€², SO2NHCORAâ€², CONHSO2RAâ€², wherein RAâ€² is as defined above, (v) tetrazole, triazole, imidazole, thiazole, oxazole, thiophene, naphthyl, and pyridyl (each of which may be optionally substituted with halogen, hydroxyl, amino, nitro, cyano, C1-C6 alkyl, and C1-C6 alkoxy); R3 represents straight or branched chain lower alkyl; R4 represents halogen or trifluoromethyl; R5, R6, and R6â€² are the same or different and represent (i)hydrogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, lower alkyl, halogen, aminomethyl, mono or dialkylamino, mono or dialkylaminomethyl, wherein each alkyl is independently lower alkyl, or C1-C6alkoxyaminoalkyl where the amino is mono or disubstituted with straight or branched chain lower alkyl; (ii) C1-C6 alkoxy (with the proviso that R5, R6, or R6â€² may not be C1-C6 alkoxy when located ortho to Y) which is optionally substituted with (a) C1-C6 alkoxy, C1-C6 alkylthio, amino, hydroxy, halogen, haloalkyl, mono or di(C1-C6)alkylamino, morpholino, pyrrolidino, piperidino, or thiomorpholino (b)mono or di(C1-C10)alkylamino1, wherein said mono or di(C1-C10)alkylamino1 is substituted with aryl, arylalkyl, heteroarylalkyl, heteroarylalkyl, C3-C7 cycloalkyl, (C3-C7 cycloalkyl)C1-C4alkyl, C3-C7heterocycloalkyl, or (C3-C7 cycloalkyl)C1-C4alkyl wherein each aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group substituting said mono or di(C1-C10)alkylamino, is optionally substituted by alkyl, oxo, halogen, hydroxyl, trifluoromethyl, trifluromethoxy, or alkoxy; or R4 and R5 are joined to form a 5, 6, or 7 membered carbocyclic or heterocyclic aromatic ring which is optionally substituted with up to four substitutents selected from: (i) halogen, nitro, trifluoromethyl, cyano, hydroxyl, C1-C6 alkyl, amino, C1-C6 alkoxy, aminomethyl, mono or dialkylamino, mono or dialkylaminomethyl (wherein each alkyl is independently lower alkyl), (ii)C1-C6alkoxyNR7â€³R8â€³, NR7â€³R8â€³, CONR7â€³R8â€³, NR7â€³COR8â€³, where R7â€³ and R8â€³ are the same or different and represent hydrogen or straight or branched chain lower alkyl, or R7â€³ and R8â€³ may be a 5, 6, or 7 membered heterocyclic ring, which is optionally substituted with halogen, nitro, trifluoromethyl, cyano, hydroxyl, lower alkyl, amino, mono or dialkylamino (wherein each alkyl is independently lower alkyl) or C1-C6 alkoxy, (iii)O(CH2)nCO2RAâ€³ where n=1,2,3,4, CORAâ€³, or CO2RAâ€³ where RAâ€³ represents hydrogen or straight or branched chain lower alkyl having 1-6 carbon atoms; and R6 and R6â€² are as defined above; and Y represents a bond or CH2, when Y=CH2 it may be mono or disubstituted with a straight or branched chain lower alkyl, or straight or branched chain lower alkoxy having 1-6 carbon atoms.