Patent TN-2010000603-A1 (TN)
Title: Benzazepine derivatives and their use as histamine h3 antagonists
Inventor: POONI PARMINDER KAUR
IPC: C07D417/12
Filed: 2010-12-24
Abstract: A compound having the formula (1) wherein: R1 is a group selected from C3-8 cycloalkyl, C1-6 alkyl, C1-6 alkylene-C3-8 cycloalkyl, each of which groups may optionally be substituted with C1-6 alkyl, halogen, haloC1-6 alkyl or OR15, or R1 is heterocyclyl, optionally substituted with C1-6 alkyl, haloC1-6 alkyl or OR15; n is 0, 1, 2, 3 or 4, the alkylene group -(CH2)n- formed thereby being optionally substituted with a group selected from C1-4 alkyl, C3-8 cycloalkyl and arylsulfonyl; A is a group selected from -N(R2)CO-, -CON(R2)-, -OC(O)-, -C(O)O-, -CO-, -C(R2)(OR3)-, -C(=N-O-R3)-, - C(=CR2R3)-, -C3-8 cycloalkylene-, -C(R2)(haloC1-6 alkyl)-, C1-4 alkylene and -C(OR3)(haloC1-6 alkyl)-; R2 and R3 are each independently selected from H, C1-6 alkyl, and C3-8 cycloalkyl, or, when A is -N(R2)CO- and X is absent, R2 may form, together with the adjacent nitrogen atom and Z, an N-containing heterocyclyl group, which may optionally be substituted; X is absent or is C1-4 alkylene or C2-4 alkenylene, each of which may optionally be substituted with one or more C1-4 alkyl groups, OR16, halogen or haloC1-6 alkyl; Z is selected from aryl, heteroaryl, C3-8 cycloalkyl, and heterocyclyl, each of which may optionally be substituted by a group selected from -Y-aryl, -Y-heteroaryl, -Y-C3-8 cycloalkyl and -Y-heterocyclyl, or, when X is present, Z may be H, or, when X is absent and A is -C(R2)(OR3)- or -N(R2)CO-, Z may be H, or, when A is -N(R2)CO- and X is absent, Z may form, together with the adjacent nitrogen atom and R2, an N-containing heterocyclyl group which may optionally be substituted, wherein, when A is -CO-, Z is linked to X or A via a carbon atom and wherein, when A is -N(R2)CO- and Z is H, R1 is C3-8 cycloalkyl; and Y represents a bond, C1-6 alkylene, CO, NR14, COC2-6 alkenylene, O, SO2 or NHCOC1-6 alkylene; wherein said cycloalkyl, aryl, heteroaryl and heterocyclyl groups Z may be optionally substituted by one or more substituents which may be the same or different, and which are selected from halogen, haloC1-6 alkyl, hydroxy, cyano, nitro, =O, -R4, -CO2R4, -COR4, -NR5R6, -C1-6 alkyl-NR5R6, -C3-8 cycloalkyl-NR5R6, - CONR12R13, -NR12COR13, -NR5SO2R6, -OCONR5R6, -NR5CO2R6, -NR4CONR5R6 or -SO2NR5R6- SHR8, -alkyl-OR8, -SOR8, -OR9, -SO2R9, -OSO2R9, -alkyl-SO2R9, -alkyl-CONHR9, -alkyl-SONHR9, -alkyl-COR10, -CO-alkyl-R10, -O-alkyl-R11 (wherein R4, R5 and R6 independently represent hydrogen, C1-6 alkyl, -C3-8 cycloalkyl, -C1-6 alkylene-C3-8 cycloalkyl, aryl, heterocyclyl or heteroaryl, wherein R8 represents C1-6 alkyl, wherein R9 represents C1-6 alkyl or aryl, wherein R10 represents aryl, wherein R11 represents C3-8 cycloalkyl or aryl, R12, R13, R14, R15 and R16 each independently represent H or C1-6 alkyl, and wherein -NR5R6 and -NR12R13 may represent a nitrogen containing heterocyclyl group); wherein said R4, R5, R6 R8, R9, R11 and R11 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; and wherein substituents of Z selected from -Y-aryl, -Y-heteroaryl, -Y-C3-8cycloalkyl and -Y-heterocyclyl may be optionally substituted by one or more substituents selected from =O, hydroxy, cyano, nitro, halogen, haloC1-6 alkyl and C1-6alkyl; and wherein, when A is C1-4 alkylene, said cycloalkyl, aryl, heteroaryl or heterocyclyl group Z (such as a heterocyclyl group Z) is substituted at least with hydroxy, CF3, or =0; and wherein, when A is CON(R2) n is 1; or a pharmaceutically acceptable salt or ester thereof, provided that: when A is -CO-, R1 is CH3, C3-8 cycloalkyl-substituted C1-6 alkylene or n-butyl, n is 0 and X is -CH2CH2-, Z is not N-benzyl substituted 4-piperidinyl, N-(3-fluorobenzyl)-substituted 4-piperidinyl or N-acetyl substituted 4-piperidinyl; when A is -OC(O)-, R1 is cyclobutyl, n is 0 and X is -CH2CH2-, Z is not H; when A is -OC(O)-, R1 is n-propyl, n is 0 and X is -CH2-, Z is not H; and when A is -CO-, R1 is CH3, n is 0 and X is CH2, Z is not H.