Benzo d!azepine derivatives for the treatment of neurological disorders

A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof comprising:

• wherein:
• R1 represents —C3-7 cycloalkyl optionally substituted by, C1-3 alkyl;
• R2 represents hydrogen, —C1-6 alkyl, —X—C3-8 cycloalkyl, —X-aryl, —X-heterocyclyl, —X-heteroaryl, —X—C3-8 cycloalkyl-Y—C3-8 cycloalkyl, —X—C3-8 cycloalkyl-Y-aryl, —X—C3-8 cycloalkyl-Y-heteroaryl, —X—C3-8 cycloalkyl-Y-heterocyclyl, —X-aryl-Y—C3-8 cycloalkyl, —X-aryl-Y-aryl, —X-aryl-Y-heteroaryl, —X-aryl-Y-heterocyclyl, —X-heteroaryl-Y—C3-8 cycloalkyl, —X-heteroaryl-Y-aryl, —X-heteroaryl-Y-heteroaryl, —X-heteroaryl-Y-heterocyclyl, —X-heterocyclyl-Y—C3-8 cycloalkyl, —X-heterocyclyl-Y-aryl, —X-heterocyclyl-Y-heteroaryl, —X-heterocyclyl-Y-heterocyclyl;
• X represents a bond or C1-6 alkyl;
• Y represents a bond, C1-6 alkyl, CO, COC2-6 alkenyl, O or SO2;
• R3 represents halogen, C1-6 alkyl, C1-6 alkoxy, cyano, amino or trifluoromethyl;
• n is 0, 1 or 2;
• wherein said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl groups of R2 may be optionally substituted by one or more substituents which may be the same or different, and which are selected from the group consisting of halogen, hydroxy, cyano, nitro, ═O, trifluoromethyl, trifluoromethoxy, fluoromethoxy, difluoromethoxy, C1-6 alkyl, pentafluoroethyl, C1-6 alkoxy, arylC1-6 alkoxy, C1-6 alkylthio, C1-6 alkoxyC1-6 alkyl, C3-7 cycloalkylC1-6 alkoxy, C1-6 alkanoyl, C1-6 alkoxycarbonyl, C1-6 alkylsulfonyl, C1-6 alkyl sulfinyl, C1-6 alkylsulfonyloxy, C1-6 alkylsulfonylC1-6 alkyl, sulfonyl, arylsulfonyl, arylsulfonyloxy, arylsulfonylC1-6 alkyl, aryloxy, C1-6 alkylsulfonamido, C1-6 alkylamino, C1-6 alkylamido, —R4, —CO2R , —COR4, C1-6 alkylsulfonamidoC1-6 alkyl, C1-6 alkylamidoC1-6 alkyl, arylsulfonamido, arylcarboxamido, arylsulfonamidoC1-6 alkyl, arylcarboxamidoC1-6 alkyl, aroyl, aroylC1-6 alkyl, arylC1-6 alkanoyl, or a group —NR5R5, —C1-6 alkyl-NR5R6, —C3-8 cycloalkyl-NR5R6, —CONR5R6, —NR5COR6, —NR5SO2R6, —OCONR5R6—NR5CO2R6, —NR4CONR5R6 or —SO2NR5R6, wherein R4, R5 and R6 independently represent hydrogen, C1-6 alkyl, —C3-8 cycloalkyl, —C1-6 alkyl-C3-8 cycloalkyl, aryl, heterocyclyl or heteroaryl or —NR5R6 may represent a nitrogen containing heterocyclyl group, wherein said R4, R5 and R6 groups may be optionally substituted by one or more substituents which may be the same or different, and which are selected from the group consisting of halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, cyano, amino, ═O or trifluoromethyl.

A method of treatment of neurological diseases which comprises administering to a host in need thereof an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof:

• wherein:
• R1 represents —C3-7 cycloalkyl optionally substituted by C1-3 alkyl;
• R2 represents hydrogen, —C1-6 alkyl, —X—C3-8 cycloalkyl, —X-aryl, —X-heterocyclyl, —X-heteroaryl, —X—C3-8 cycloalkyl-Y—C3-8 cycloalkyl, —X—C3-8 cycloalkyl-Y-aryl, —X—C3-8 cycloalkyl-Y-heteroaryl, —X—C3-8 cycloalkyl-Y-heterocyclyl, —X-aryl-Y—C3-8 cycloalkyl, —X-aryl-Y-aryl, —X-aryl-Y-heteroaryl, —X-aryl-Y-heterocyclyl, —X-heteroaryl-Y—C3-8 cycloalkyl, —X-heteroaryl-Y-aryl, —X-heteroaryl-Y-heteroaryl, —X-heteroaryl-Y-heterocyclyl, —X-heterocyclyl-Y—C3-8 cycloalkyl, —X-heterocyclyl-Y-aryl, —X-heterocyclyl-Y-heteroaryl, —X-heterocyclyl-Y-heterocyclyl;
• X represents a bond or C1-6 alkyl;
• Y represents a bond, C1-6 alkyl, CO, COC2-6 alkenyl, O or SO2;
• R3 represents halogen, C1-6 alkyl, C1-6 alkoxy, cyano, amino or trifluoromethyl;
• n is 0, 1 or 2;
• wherein said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl groups of R2 may be optionally substituted by one or more substituents which may be the same or different, and which are selected from the group consisting of halogen, hydroxy, cyano, nitro, ═O, trifluoromethyl, trifluoromethoxy, fluoromethoxy, difluoromethoxy, C1-6 alkyl, pentafluoroethyl, C1-6 alkoxy, arylC1-6 alkoxy, C1-6 alkylthio, C1-6 alkoxyC1-6 alkyl, C3-7 cycloalkylC1-6 alkoxy, C1-6 alkanoyl, C1-6 alkoxycarbonyl, C1-6 alkylsulfonyl, C1-6 alkylsulfinyl, C1-6 alkylsulfonyloxy, C1-6 alkylsulfonylC1-6 alkyl, sulfonyl, arylsulfonyl, arylsulfonyloxy, arylsulfonylC1-6 alkyl, aryloxy, C1-6 alkylsulfonamido, C1-6 alkylamino, C1-6 alkylamido, —R4, —CO2R4, —COR4, C1-6 alkylsulfonamidoC1-6 alkyl, C1-6 alkylamidoC1-6 alkyl, arylsulfonamido, arylcarboxamido, arylsulfonamidoC1-6 alkyl, arylcarboxamidoC1-6 alkyl, aroyl, aroylC1-6 alkyl, arylC1-6 alkanoyl, or a group —NR5R6, —C1-6 alkyl-NR5R6, —C3-8 cycloalkyl-NR5R , —CONR5R6, —NR5COR6, —NR5SO2R6, —OCONR5R6, —NR5CO2R6, —NR4CONR5R6 or —SO2NR5R6, wherein R4, R5 and R6 independently represent hydrogen, C1-6 alkyl, —C3-8 cycloalkyl, —C1-6 alkyl-C3-8 cycloalkyl, aryl, heterocyclyl or heteroaryl or —NR5R6 may represent a nitrogen containing heterocyclyl group, wherein said R4, R5 and R6 groups may be optionally substituted by one or more substituents which may be the same or different, and which are selected from the group consisting of halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, cyano, amino, ═O or trifluoromethyl.