Aryloxyalkylamine derivatives as h3 receptor ligands

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

• wherein:
• R1 represents a group of formula (A):
• wherein R4a represents C1-6 alkyl, oxo, aryl, heteroaryl or heterocyclyl;
• R5a represents hydrogen, -C1 alkyl, -C1-6 alkylC1-6 alkoxy, -C1-6 alkoxycarbonyl, -C3-8 cycloalkyl, -aryl, -heterocyclyl, heteroaryl, -C1 alkyl-aryl, —CH(aryl)(aryl), -C1-6 alkyl-C3-8 cycloalkyl, -C1-6 alkyl-heteroaryl or -C1 alkyl-heterocyclyl,
• wherein R5a 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, oxo, haloC1-6 alkyl, polyhaloC1-6 alkyl, haloC1-6 alkoxy, polyhaloC1-6alkoxy, C1-6 alkyl, C1-6alkoxy, C1-6 alkylthio, C1-6 alkoxyC1-6 alkyl, C3-7 cycloalkylC1-6 alkoxy, C1-6alkanoyl, C1-6 alkoxycarbonyl, C1-6 alkylsulfonyl, C1-alkylsulfinyl, C1-6 alkylsulfonyloxy, C1-6 alkylsulfonylC1-6 alkyl, C1-6alkylsulfonamidoC1-6alkyl, C1-6 alkylamidoC1-6alkyl or a group NR15aR16a, —CONR15aR16a, —NR15aCOR16a, —NR15aSO2R16a or —SO2NR15aR16a, wherein R15a and R16a independently represent hydrogen, C1-6 alkyl, aryl or together with the nitrogen to which they are attached may form a nitrogen containing heterocyclyl group;
• m is 1 or 2;
• p is 0, 1, 2 or 3, or when p represents 2, said R4a groups may instead form a bridging group consisting of one or two methylene groups;
• or R1 represents a group of formula (B):
• wherein NR4bR5b represents an N-linked -heterocyclyl, -heterocyclyl-Xb-aryl, -heterocyclyl-Xb-heteroaryl, -heterocyclyl-Xb-heterocyclyl, -heteroaryl, -heteroaryl-Xb-aryl, -heteroaryl-Xb-heteroaryl or -heteroaryl-Xb-heterocyclyl group;
• wherein said aryl, heteroaryl and heterocyclyl groups of NR4bR5b 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, oxo, haloC1-6 alkyl, polyhaloC1-6 alkyl, haloC1-6 alkoxy, polyhaloC1-6 alkoxy, C1-6 alkyl, C1-6 alkoxy, arylC1-6 alkoxy, C1-6 alkylthio, C1-6 alkoxyC1-6 alkyl, C3-7 cycloalkylC1-6alkoxy, C1-6alkanoyl, C1-6 alkoxycarbonyl, arylC1-6 alkyl, heteroarylC1-6 alkyl, C1-6 alkylsulfonyl, C1-6alkylsulfinyl, C1-6 alkylsulfonyloxy, C1-6 alkylsulfonylC1-6 alkyl, arylsulfonyl, arylsulfonyloxy, arylsulfonylC1-6 alkyl, aryloxy, C1-6 alkylsulfonamidoC1-6 alkyl, C1-6 alkylamidoC1-6 alkyl, arylsulfonamido, arylaminosulfonyl, arylsulfonamidoC1-6 alkyl, arylcarboxamidoC1-6 alkyl, aroylC1-6 alkyl, arylC1-6 alkanoyl, or a group —NR15bR16b, —CONR15bR16b, —NR5bCOR16b, —NR15bSO2R16b or —SO2NR15bR16b, wherein R15b and R16b independently represent hydrogen or C1-6alkyl;
• Xb represents a bond, CO, NHCO or CONH;
• or R1 represents a group of formula (C):
• wherein R4c represents C1-6 alkyl, OH, aryl or heterocyclyl, wherein said aryl and heterocyclyl groups may be optionally substituted by halogen, C1-6 alkyl, C1-6 alkoxy, cyano, amino, oxo, trifluoromethyl or an aryl group;
• r is 0, 1 or 2;
• or R1 represents a group of formula (D):
• wherein R4d represents aryl or heteroaryl wherein said aryl and heteroaryl 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, C1-6 alkyl, C1-6 alkoxy, cyano, amino or trifluoromethyl;
• Xd represents a bond or NHCO, such that when Xd represents NHCO, the group R4d—Xd is attached at the 3-position of the pyrrolidinyl ring;
• or R1 represents a group of formula —CO-E, wherein E represents a group of formula Ea, Eb or Ec:
• wherein Xe represents O or N—R8e;
• Ye represents —C(HR9e)— or —C(═O)—;
• R4e, R5e, R8e and R9e independently represent hydrogen, C1 alkyl, aryl, heteroaryl, —C1-6alkyl-aryl or -C1-6alkyl-heteroaryl;
• R6e and R7e independently represent hydrogen, C1-6 alkyl, aryl, heteroaryl, -C1-6 alkyl-aryl, -C1-6 alkyl-heteroaryl or R6e and R7e together with the carbon atoms to which they are attached may form a benzene ring;
• is a single or double bond;
• wherein said aryl or heteroaryl groups of R4e, R5e, R6e, R7e and R9e 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 C1-6 alkyl, CF3, C1-6 alkoxy, halogen, cyano, sulfonamide or C1-6 alkylsulfonyl;
• or R1 represents a group of formula (F):
• wherein t is 0, 1 or 2;
• u is 1 or 2;
• R4f represents C1-6 alkyl or when t represents 2, said R4f groups may instead form a bridging group consisting of one or two methylene groups;
• R5f represents -C1-6 alkyl, -C1-6 alkylC1-6alkoxy, -C1-6 cycloalkyl, aryl, heterocyclyl, heteroaryl, -C1-6 alkyl-aryl, -C1-6 alkyl-C3-8 cycloalkyl, -C1-6 alkyl-heteroaryl, -C1-6 alkyl-heterocyclyl, -aryl-aryl, -aryl-heteroaryl, -aryl-heterocyclyl, -heteroaryl-aryl, -heteroaryl-heteroaryl, -heteroaryl-heterocyclyl, -heterocyclyl-aryl, -heterocyclyl-heteroaryl or -heterocyclyl-heterocyclyl;
• wherein R5f 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, oxo, haloC1-6alkyl, polyhaloC1-6alkyl, haloC1-6alkoxy, polyhaloC1-6alkoxy, C1— alkyl, C1-6alkoxy, C1-6alkylthio, C1-6alkoxyC1-6alkyl, C3-7 cycloalkylC1-6alkoxy, C1-6alkanoyl, C1-6alkoxycarbonyl, C1-6alkylsulfonyl, C1-6alkylsulfinyl, C1-6alkylsulfonyloxy, C1-6alkylsulfonylC1-6alkyl, C1-6alkylsulfonamidoC1-6alkyl, C1-6alkylamidoC1-6alkyl, arylsulfonyl, arylsulfonyloxy, aryloxy, arylsulfonamido, arylcarboxamido, aroyl, or a group NR15fR16f, —CONR15fR16f, —NR15fCOR16f, —NR15SO2R16f or —SO2NR15fR16f, wherein R15f and R16f independently represent hydrogen or C1-6alkyl or together form a heterocyclic ring;
• Zf represents CO or SO2;
• R2 represents halogen, C1-6alkyl, C1-6alkoxy, cyano, amino or trifluoromethyl;
• n is 0, 1 or 2;
• R3 represents —(CH2)q—NR11R12 or a group of formula (i):
• wherein q is 2, 3 or 4;
• R11 and R12 independently represent C1-6alkyl or together with the nitrogen atom to which they are attached represent an N-linked heterocyclic group selected from pyrrolidine, piperidine and homopiperidine optionally substituted by one or two R17 groups;
• R13 represents C1-6alkyl, C3-6 cycloalkyl or -C1-6 alkyl-C3-6cycloalkyl;
• R14 and R17 independently represent halogen, C1-6alkyl, haloC1-6 alkyl, OH, diC1-6 alkylamino or C1— alkoxy;
• f and k independently represent 0, 1 or 2;
• g is 0, 1 or 2 and h is 0, 1, 2 or 3, such that g and h cannot both be 0;
• or solvates thereof.