Sulfonyl piperidine derivatives and their use for treating prokineticin mediated diseases

摘要

The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof: (I) in which m, n, W, X, Y, Z, R1, R2, R3 and R4 are as defined in the specification, for use in the treatment or prevention of a diseases o conition mediated by a prokineticin, such as psychiatric and neurological conditions.;

主权项

1. A compound of formula (Ia) or a pharmaceutically acceptable salt thereof,wherein
W1, X1, Y1 and Z1 each independently represent N, NH or CH, wherein at least two of W1, X1, Y1 and Z1 represent N or NH; p is 0, 1, 2 or 3; each R11 independently represents halogen, cyano, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 alkylcarbonyl, or C1-C6 alkyl optionally substituted by carboxyl or C1-C6 alkoxycarbonyl; q is 0, 1, 2, 3 or 4; each R12 independently represents halogen, cyano, carboxyl, hydroxyl, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 hydroxyalkyl, C1-C6 alkoxycarbonyl, C1-C6 alkoxyC1-C6 alkyl or a 5- to 9-membered heterocyclic ring system; R13 represents an oxygen atom, or a group NR15 or CR16R17, with the provisos that (i) when R13 represents NH and ring A represents pyrazol-4-yl or imidazol-4-yl, then p must be 3 and R14 represents a substituted phenyl, substituted pyridinyl or substituted naphthyl ring system, and (ii) when R13 represents CH2 and ring A represents pyrazol-4-yl or imidazol-4-yl, then either p is 3, or, p is 2 and q is at least 1; R15 represents a hydrogen atom or a C1-C6 alkyl group; R16 and R17 each independently represent a hydrogen or halogen atom or cyano, carboxyl, hydroxyl, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 hydroxyalkyl, C1-C6 alkoxycarbonyl, C1-C6 alkoxyC1-C6 alkyl or a 5- to 9-membered heterocyclic ring system; R14 represents a ring system chosen from substituted phenyl, substituted naphthyl or unsubstituted or substituted pyridinyl, wherein the substituted ring system includes at least one substituent selected from halogen, hydroxyl, cyano, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 alkylsulphinyl, C1-C6 alkylsulphonyl, C1-C6 alkylcarbonyl, C1-C6 alkylcarbonyloxy, C1-C6 alkoxycarbonyl, amino, —CON(R18)2, C1-C6 alkylamino, di-(C1-C6 alkyl)amino, C3-C6 cycloalkyl, C3-C6 cycloalkyloxy or C3-C6 cycloalkylmethyl; and each R18 independently represents a hydrogen atom or a C1-C6 alkyl group; but excluding the following compounds: 1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]-4-(4-methylphenoxy)piperidine, 1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]-4-(4-fluorophenoxy)piperidine, 1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]-4-(4-methoxyphenoxy)piperidine, 1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]-4-(3-ethylphenoxy)piperidine, 4-(3-chlorophenoxy)-1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]piperidine, 1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]-4-(2-methylphenoxy)piperidine, 1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]-4-[[2-(trifluoromethyl)phenyl]methyl]-4-piperidinemethanol, 1-[(3,5-dimethyl-1H-pyrazol-4-yl)sulfonyl]-4-[(4-methoxyphenyl)methyl]-4-piperidinecarboxylic acid, ethyl ester, 4-[[1-[(1-methyl-1H-pyrazol-4-yl)sulfonyl]-4-piperidinyl]oxy]benzonitrile, N-(2-methylphenyl)-1-[(1,3,5-trimethyl-1H-pyrazol-4-yl)sulfonyl]-4-piperidineamine, 1-[[1-(difluoromethyl)-3-methyl-1H-pyrazol-4-yl]sulfonyl]-4-(4-fluorophenoxy)piperidine, 4-(3-fluorophenoxy)-1-[(3-methyl-1-propyl-1H-pyrazol-4-yl)sulfonyl]piperidine, 1-[[1-(difluoromethyl)-3,5-dimethyl-1H-pyrazol-4-yl]sulfonyl]-4-(2-fluorophenoxy)piperidine, (4-(4-Methoxybenzyl)-1-(1,3,5-trimethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-yl)methanol, (4-(4-Chlorobenzyl)-1-(1,3,5-trimethyl-1H-pyrazol-4-yl)sulfonyl)piperidin-4-yl)methanol, and 1-[(5-chloro-1,3-dimethyl-1H-pyrazol-4-yl)sulfonyl]-4-[(4-methoxyphenyl)methyl]-4-piperidinemethanol.