2-(1-OXO-1H-ISOQUINOLIN-2-YL) ACETAMIDE DERIVATIVES

摘要

The present invention relates to a 2-(1 -oxo-1 /-/-isoquinolin-2-yl)acetamide derivative of formula (I), wherein R1 is C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkylC1-2alkyl, C2-6alkenyl or C2-6alkynyl, said C1- 6alkyl, C3-6cycloalkyl and C3-6cycloalkylC1-2alkyl being optionally substituted with one or more halogens; R2 is C6-10aryl optionally substituted with one to three substituents selected from halogen, hydroxy, cyano, C1-6alkyl, C3.6cycloalkyl, C1-6alkyloxy and C3.6cycloalkyloxy, said C1-6alkyl, C3-6 cycloalkyl, C1 -6 alkyloxy and C3-6cycloalkyloxy being optionally substituted with one or more halogens or R2 is a 5-10 membered heteroaryl ring system comprising a heteroatom selected from N, O, S and optionally substituted with a substituent selected from methyl, C1-6alkyloxy and halogen; R3 is an optional substituent selected from C1-6alkyl, C1-6alkyloxy and halogen, said C1-6alky and C1-6alkyloxy being optionally substituted with one or more halogens; R4 is a group located at the 6- or 7- position of the oxoisoquinoline ring and is selected from formulas (II, III, IV, V, VI, VII,) each R5 is independently H or C1-6alkyl or one of R5 when joined together with one of R6 or R7 forms a 4-7 membered heterocyclic ring; R6 and R7 are independently H, C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkylC1-2alkyl, C6-10 aryl or C6-10arylC1-2alkyl; or R6 and R7 together with the nitrogen to which they are bonded form a 4 to 8 membered saturated or unsaturated heterocyclic ring optionally comprising a further heteroatomic moiety selected from O, S and NR10, said heterocyclic ring being optionally substituted with one or two substituents selected from halogen, hydroxyl, C1-6alkyl, C1-6alkyloxy, cyano and COOR11 and said heterocyclic ring being optionally fused at two adjacent carbon atoms to a phenyl ring; or one of R6 and R7 when joined together with one of R5 forms a 4-7 membered heterocyclic ring; or one of R6 and R7 when joined together with one of R8 forms a 5-6 membered heterocyclic ring; R8 is one or two substituents selected from H, C1-6alkyl, C1-6alkyloxy and halogen or one of R8 when joined together with one of R6 and R7 forms a 5-6 membered heterocyclic ring; or one of R8 when joined together with R9 forms a 5-6 membered ring R9 is H or C1-6alkyl or R9 when joined together with one of R8 forms a 5-6 membered ring; R10 is H, C1-6alkyl or C1-6acyl; R11 is H or C1-6alkyl; m is 2-4; n is 1-3; X is CH2, O, S, SO2 Or NR12; R12 is H, C1-6alkyl, C1 -6acyl or C6-10arylC1-2alkyl group, said C6-10arylC1-2alkyl group being optionally substituted with methyl or methoxy; Y is CH2, (CH2)2 or (CH2)3; Q, T, V and W are C or N with the proviso that one of Q, T, V and W is N and the others are C; Q', T and V are selected from C, O, N and S with the proviso that one of Q', T and V is O, N, or S and the others are C; or a pharmaceutically acceptable salt or solvate thereof. The present invention further relates to a pharmaceutical composition comprising a 2-(1 -oxo-7/-/-isoquinolin-2- yl)acetamide derivative according to the present invention and its use in therapy.