Patent ID: 6716846
Filing Date: 2004-04-06
Classification: A61K,A61P

Abstract:
A compound represented by the formula or a pharmaceutically acceptable salt or solvate thereof, wherein:X1 and X2 together form a spiro group of the formula m is 1 or 2; Q is â€”CH2â€”, â€”Oâ€”, â€”Sâ€”, â€”SOâ€”, â€”SO2â€” or â€”NR17â€”; R1, R2, R3 and R4 are independently selected from the group consisting of hydrogen and (C1-C6)alkyl; R5 is 1 to 3 substituents independently selected from the group consisting of H, R7-aryl, R6â€”(C3-C12)cycloalkyl, R8-heteroaryl, R10â€”(C3-C7)heterocycloalkyl, â€”NR19R20, â€”OR13 and â€”S(O)0-2R13; R6 is 1 to 3 substituents independently selected from the group consisting of H, (C1-C6)alkyl, R7-aryl, â€”NR19R20, â€”OR13 and â€”SR13; R7 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halo, (C1-C6)alkyl, R25-aryl, (C3-C12)cycloalkyl, â€”CN, â€”CF3, â€”OR19, â€”(C1-C6)alkyl-OR19, â€”OCF3, â€”NR19R20, â€”(C1-C6)alkyl-NR19R20, â€”NHSO2R19, â€”SO2N(R26)2, â€”SO2R19, â€”SOR19, â€”SR19, â€”NO2, â€”CONR19R20, â€”NR20COR19, â€”COR19, â€”COCF3, â€”OCOR19, â€”OCO2R19, â€”COOR19, â€”(C1-C6)alkyl-NHCOOC(CH3)3, â€”(C1-C6)alkyl-NHCOCF3, â€”(C1-C6)alkyl-NHSO2â€”(C1-C6)alkyl, â€”(C1-C6)alkyl-NHCONHâ€”(C1-C6)-alkyl or â€ƒwherein f is 0 to 6; or R7 substituents on adjacent ring carbon atoms may together form a methylenedioxy or ethylenedioxy ring; R8 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halo, (C1-C6)alkyl, R25-aryl, (C3-C12)cycloalkyl, â€”CN, â€”CF3, â€”OR19, â€”(C1-C6)alkyl-OR19, â€”OCF3, â€”NR19R20, â€”(C1-C6)alkyl-NR19R20, â€”NHSO2R19, â€”SO2N(R26)2, â€”NO2, â€”CONR19R20, â€”NR20COR19, â€”COR19, â€”OCOR19, â€”OCO2R19 and â€”COOR19; R10 is H, (C1-C6)alkyl, â€”OR19, â€”(C1-C6)alkyl-OR19, â€”NR19R20 or â€”(C1-C6)alkyl-NR19R20; R11 is independently selected from the group consisting of H, R5â€”(C1-C6)alkyl, R6â€”(C3-C12)cycloalkyl, â€”(C1-C6)alkyl(C3-C12)cycloalkyl, â€”(C1-C6)alkyl-OR19, â€”(C1-C6)alkyl-NR19R20 and â€ƒwherein q is 1 to 3 and a is 1 or 2; R13 is H, (C1-C6)alkyl, R7-aryl, â€”(C1-C6)alkyl-OR19, â€”(C1-C6)alkyl-NR19R20 or â€”(C1-C6)alkyl-SR19; each R17 is independently selected from the group consisting of hydrogen, R5â€”(C1-C6)alkyl, R7-aryl, (C3-C12)cycloalkyl, R8-heteroaryl, R8-heteroaryl(C1-C6)alkyl, â€”C(O)R28, â€”(C1-C6)alkyl(C3-C7)-heterocycloalkyl, â€”(C1-C6)alkyl-OR19 and â€”(C1-C6)alkyl-SR19; R19 and R20 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, (C3-C12)cycloalkyl, aryl and aryl(C1-C6)alkyl; Z1 is ortho-substituted phenyl wherein the substituents are halogen or (C1-C6 alkyl; Z2 is ortho-substituted phenyl wherein the substituents are halogen or (C1-C6 alkyl; Z3 is hydrogen or (C1-C6)alkyl; or Z1, Z2 and Z3, together with the carbon to which they are attached, form the group â€ƒwherein r is 0 to 3; w and u are each 0-3, provided that the sum of w and u is 1-3; and ring A is a fused R7-phenyl or R8-heteroaryl ring; R23 is 1 to 3 substituents independently selected from the group consisting of H, (C1-C6)alkyl, â€”OR19, â€”(C1-C6)alkyl-OR19, â€”NR19R20 and â€”(C1-C6)alkyl-NR19R20; R24 is 1 to 3 substituents independently selected from the group consisting of R23, â€”CF3, â€”OCF3, NO2 or halo, or R24 substituents on adjacent ring carbon atoms may together form a methylenedioxy or ethylenedioxy ring; R25 is 1-3 substituents independently selected from the group consisting of H, (C1-C6)alkyl, (C1-C6)alkoxy and halo; R26 is independently selected from the group consisting of H, (C1-C6)alkyl and R25â€”C6H4â€”CH2â€”; R28 is (C1-C6)alkyl, â€”(C1-C6)alkyl(C3-C12)cycloalkyl, R7-aryl, R7-aryl-(C1-C6)alkyl, R8-heteroaryl, â€”(C1-C6)alkyl-NR19R20, â€”(C1-C6)alkyl-OR19 or â€”(C1-C6)alkyl-SR19; provided that when Z1, Z2 and Z3, together with the carbon to which they are attached, form â€ƒX1 and X2 together are â€ƒR11 is â€”(C1-C6)alkyl-NR19R20 or