Patent TW-200827352-A (TW)
Title: Quinazolinone and isoquinolinone acetamide derivatives
Inventor: LETOURNEAU JEFFREY
IPC: C07D471/08
Filed: 2007-09-11
Abstract: The present invention relates to a quinazolinone or isoquinolinone derivative of formula I, formula I wherein R1 is C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkylC1-3alkyl, C2-6alkenyl, C2-6alkenyl, said C1-6alkyl, C3-6cycloalkyl and C3-5cycloalkylC1-3alkyl being optionally substituted with hydroxy, C1-6 alkyloxy, cyano or 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 cycloalky, C1-6alkyloxy 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 and S and optionally substituted with a substituent selected from methyl, C1-6alkyloxy and halogen; or R2 is C4-7cycloalkyl; R3 is an optional substituent selected from C1-6alkyl, C1-6alkyloxy and halogen, said C1-6alkyl and C1-6alkyloxy being optionally substituted with one or more halogens; R4 is a group located at the 6- or 7- position of the quinazolinone or isoquinolinone ring having the formula II formula II wherein R5 together with one of R6 forms a 4-8 membered saturated or unsaturated heterocyclic ring optionally comprising a further heteroatomic moiety selected from O, S and NR9, said heterocyclic ring being optionally substituted with one or two substituents selected from methyl, halogen, hydroxy and oxo or R5 together with one of R7 and R8 forms a 6-8 membered heterocyclic ring optionally substituted with one or two substituents selected from methyl, halogen, hydroxy and oxo; Each R6 is independently H, halogen or C1-4alkyl optionally substituted with halogen or SO2CH3 or one of R6 together with R5 forms a 4-8 membered saturated or unsaturated heterocyclic ring optionally comprising a further heteroatomic moiety selected from O, S and NR9, said heterocyclic ring being optionally substituted with one or two substituents selected from methyl, halogen, hydroxy and oxo; R7 and R8 are independently H, C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkylC1-3alkyl, cyanoC1-3alkyl, C6-10aryl, C6-10arylC1-3alkyl, C1-3alkyloxyC1-3alkyl or C1-6acyl said C1-6alkyl, C3-6cycloalkyl and C3-6cycloalkylC1-3alkyl being optionally substituted with hydroxy, 1 or more halogens or diC1-2alkylamino; or R7 and R8 together with the nitrogen to which they are bonded form a 4-8 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 C1-6alkyl, halogen, hydroxy, C1-6alkyloxy, cyano and COOR11; or one of R7 and R8 is Y, CH2Y or CH2CH2Y, wherein Y is a 4-6 membered saturated heterocyclic ring comprising a heterocyclic moiety selected from O, SO2 and NR10, said ring being optionally substituted with 1-2 substituents selected from methyl or halogen; or one of R7 or R8 together with R5 forms a 6-8 membered heterocyclic ring being optionally substituted with one or two substituents selected from methyl, halogen, hydroxy and oxo or one of R7 and R8 together with R12 forms a 4-8 membered saturated or unsaturated heterocyclic ring optionally comprising a further heteroatomic moiety selected from O, S and NR13, said heterocyclic ring being optionally substituted with one or two substituents selected from methyl, hydroxy and oxo; R9 and R10 are independently H, C1-6alkyl or C1-6acyl; R11 is H or C1-6alkyl; Each R12 is independently H or C1-4alkyl or one of R12 together with one of R7 or R8 forms a 4-8 membered saturated or unsaturated heterocyclic ring optionally comprising a further heteroatomic moiety selected from O, S and NR13, said heterocyclic ring being optionally substituted with one or two substituents selected from methyl, hydroxy and oxo; R13 is H, C1-6alkyl or C1-6acyl; m is 2-3 and X is N or CH or a pharmaceutically acceptable salt or solvate thereof. The present invention further relates to a pharmaceutical composition comprising a quinazolinone or isoquinolinone according to the present invention and its use in therapy.