Patent ID: 6645987
Filing Date: 2003-11-11
Classification: A61P,C07D

Abstract:
A compound represented by the structural formula or a pharmaceutically acceptable salt thereof, wherein: Z is â€”CH2â€”; R1 is H, C1-C6 alkyl, fluoro(C1-C6)alkyl, difluoro(C1-C6)alkyl, trifluoro-(C1-C6)alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, aryl(C1-C6)alkyl, aryl(C2-C6)alkenyl, hydroxy-(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, amino-(C1-C6)alkyl, aryl or thio(C1-C6)alkyl; R2 is H; R3 is H, hydroxy, C1-C6 alkoxy, â€”NR18R19, â€”SOR16, â€”SO2R17, â€”C(O)OR17, â€”C(O)NR18R19, C1-C6 alkyl, halogen, fluoro(C1-C6)alkyl, difluoro(C1-C6)alkyl, trifluoro(C1-C6)alkyl, C3-C7 cycloalkyl, C2-C6 alkenyl, aryl(C1-C6)alkyl, aryl(C2-C6)alkenyl, hydroxy(C1-C6)alkyl, amino(C1-C6)alkyl, aryl, thio(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl or (C1-C6)alkylamino(C1-C6)alkyl; Het is pyridyl, wherein the ring nitrogen can form an N-oxide or a quaternary group with a C1-C4 alkyl group, wherein Het is attached to B by a carbon atom ring member, and wherein the Het group is substituted by 1 to 4 substituents of W, wherein W is independently selected from the group consisting of H; C1-C6 alkyl; fluoro(C1-C6)alkyl; difluoro(C1-C6)alkyl; trifluoro-(C1-C6)-alkyl; C3-C7 cycloalkyl; C2-C6 alkenyl; R21-aryl(C1-C6)alkyl; R21-aryl-(C1-C6)-alkenyl; R21-aryloxy; R21-aryl-NHâ€”; hydroxy(C1-C6)alkyl; dihydroxy(C1-C6)alkyl; amino(C1-C6)alkyl; (C1-C6)alkylamino-(C1-C6)alkyl; di-((C1-C6)alkyl)-amino-(C1-C6)alkyl; thio(C1-C6)alkyl; C1-C6 alkoxy; C2-C6 alkenyloxy; halogen; â€”NR4R5; â€”CN; â€”OH; â€”COOR17; â€”COR16; â€”OSO2CF3; â€”CH2OCH2CF3; (C1-C6)alkylthio; â€”C(O)NR4R5; â€”OCHR8-phenyl; phenoxy-(C1-C6)alkyl; â€”NHCOR16; â€”NHSO2R16; biphenyl; â€”OC(R6)2COOR7; â€”OC(R6)2C(O)NR4R5; (C1-C6)alkoxy: â€”C(&boxH;NOR17)R18; C1-C6 alkoxy substituted by (C1-C6)alkyl, amino, â€”OH, COOR17, â€”NHCOOR17, â€”CONR4R5, aryl, aryl substituted by 1 to 3 substutuents independently selected from the group consisting of halogen, â€”CF3, C1-C6 alkyl, C1-C6 alkoxy and â€”COOR17, â€”C(O)NR4R5; and R21-aryl; R4 and R5 are independently selected from the group consisting of H, C1-C6 alkyl, phenyl, benzyl and C3-C7 cycloalky; R6 is independently selected from the group consisting of H, C1-C6 alkyl, phenyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, hydroxy(C1-C6)alkyl and amino(C1-C6)alkyl; R7 is H or (C1-C6)alkyl; R8, R10 and R11 are each H; R9 is H, OH, C1-C6 alkoxy, halogen or halo(C1-C6)alkyl; B is â€”CH&boxH;CHâ€”; R16 is C1-C6 lower alkyl, phenyl or benzyl; R17, R18 and R19 are independently selected from the group consisting of H, C1-C6 alkyl, phenyl, benzyl; R21 is 1 to 3 substutuents independently selected from the group consisting of hydrogen, CN, â€”CF3, â€”OCF3, halogen, â€”NO2, C1-C6 alkyl, C1-C6alkoxy, (C1-C6)alkylamino, di-((C1-C6)alkyl)amino, amino(C1-C6)alkyl, (C1-C6)-alkylamino(C1-C6)alkyl, di-((C1-C6)alkyl)-amino(C1-C6)alkyl, hydroxy-(C1-C6)alkyl, â€”COOR17, â€”COR17, â€”NHCOR16, â€”NHSO2R16, â€”NHSO2CH2CF3, or â€”C(&boxH;NOR17)R18; R22 and R23 are independently selected from the group consisting of hydrogen, R24â€”(C1-C10)alkyl, R24-(C2-C10)alkenyl, R24â€”(C2-C10)alkynyl, â€”R25-aryl, R25-aryl(C1-C6)alkyl, R29â€”(C3-C7)cycloalkyl, R29â€”(C3-C7)cyclo-alkenyl, â€”OH, â€”OC(O)R30, â€”C(O)OR30, â€”C(O)R30, â€”C(O)NR30R31, â€”NR30R31, â€”NR30C(O)R31, â€”NR30C(O)NR31R32, â€”NHSO2R30, â€”OC(O)NR30R31, R24â€”(C1-C10)alkoxy, R24â€”(C2-C10)-alkenyloxy, R24â€”(C2-C10)alkynyloxy, R29â€”(C3-C7)cycloalkyloxy, R29â€”(C3-C7)cyclo-alkenyloxy, R29â€”(C3-C7)cycloalkyl-NHâ€”, â€”NHSO2NHR16 and â€”CH(&boxH;NOR17); or R22 and R10 together with the carbon to which they are attached, or R23 and R11 together with the carbon to which they are attached, independently form a R42-substituted carbocyclic ring of 3-10 atoms; R24 is 1, 2 or 3 substituents independently selected from the group consisting of hydrogen, halogen, â€”OH, (C1-C6)alkoxy, R35-aryl, (C1-C10)-alkyl-C(O)â€”, (C2-C10)-alkenyl-C(O)â€”, (C2-C10)alkynyl-C(O)â€”, R26â€”(C3-C7)cycloalkyl, R26â€”(C3-C7)cycloalkenyl, â€”OC(O)R30, â€”C(O)OR30, â€”C(O)R30, â€”C(O)NR30R31, â€”NR30R31, â€”NR30C(O)R31, â€”NR30C(O)NR31R32, â€”NHSO2R30, â€”OC(O)NR30R31, R29â€”(C3-C7)-cycloalkyloxy, R29â€”(C3-C7)cyclo-alkenyloxy, R29â€”(C3-C7)cycloalkyl-NHâ€”, â€”NHSO2NHR16 and â€”CH(&boxH;NOR17); R25 is , 2 or 3 substituents independently selected from the group consisting of hydrogen. halogen, â€”COOR36, â€”CN, â€”C(O)NR37R38, â€”NR39C(O)R40, â€”OR36, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl-C1-C6)alkyl, (C1-C6)alkyl(C3-C7)cycloalkyl-(C1-C6)alkyl, halo(C1-C6)alkyl(C3-C7)cycloalkyl(C1-C6)alkyl, hydroxy(C1-C6)alkyl, and (C1-C6)alkoxy(C1-C6)alkyl; R26 is 1, 2, or 3 substituents independently selected from the group consisting of hydrogen, halogen and (C1-C6)alkoxy; R29 is 1, 2 or 3 substituents independently selected from the group consisting of hydrogen, (C1-C6)alkyl, â€”OH, (C1-C6)alkoxy and halogen; R30, R31 and R32 are independently selected from the group consisting of hydrogen, (C1-C10)-alkyl, (C1-C6)alkoxy(C1-C10)-alkyl, R25-aryl(C1-C6)-alkyl, R33â€”(C3-C7)cycloalkyl, R34-(C3-C7)cycloalkyl(C1-C6)alkyl, and R25-aryl; R33 is hydrogen, (C1-C6)alkyl, OHâ€”(C1-C6)alkyl or (C1-C6)alkoxy; R35 is 1 to 4 substituents independently selected from the group consisting of hydrogen, (C1-C6)alkyl, â€”OH, halogen, â€”CN, (C1-C6)alkoxy, trihalo(C1-C6)alkoxy, (C1-C6)alkylamino, di((C1-C6)alkyl)amino, â€”OCF3, OHâ€”(C1-C6)alkyl, â€”CHO, â€”C(O)(C1-C6)-alkylamino, â€”C(O)di((C1-C6)alkyl)amino, â€”NH2, â€”NHC(O)(C1-C6)alkyl and â€”N((C1-C6)alkyl)C(O)(C1-C6)alkyl; R36 is hydrogen, (C1-C6)alkyl, halo(C1-C6)alkyl, dihalo(C1-C6)alkyl or trifluoro(C1-C6)alkyl, R37 and R38 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, aryl(C1-C6)alkyl, phenyl and (C3-C15)cycloalkyl; R39 and R40 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, aryl(C1-C6)alkyl, phenyl and (C3-C15)-cycloalkyl; and R42 is 1 to 3 substituents independently selected from the group consisting of hydrogen, â€”OH, (C1-C6)alkyl and (C1-C6)alkoxy.