Piperidin-1-yl and azepin-1-yl carboxylates as muscarinic M4 receptor agonists

摘要

The present invention provides muscarinic M4 receptor agonists of formula (I) and pharmaceutically acceptable salts thereof, wherein m, n, p, q, R, R2 and R3 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases such as schizophrenia, Alzheimer's disease and various cognitive disorders as well as in the treatment or alleviation of pain.;

主权项

1. A compound of formula (I) or a pharmaceutically acceptable salt thereofwherein
m, p and q each independently represent 0 or 1; n represents an integer 2; R1 is selected from hydrogen, fluorine, cyano, hydroxyl, amino, and a C1-C9 non-aromatic hydrocarbon group which is optionally substituted with from one to six fluorine atoms and wherein one, two or three carbon atoms of the hydrocarbon group may optionally be replaced by one, two or three heteroatoms independently selected from nitrogen, oxygen and sulphur; R2 is hydrogen or a C1-C6 non-aromatic hydrocarbon group which is optionally substituted with from one to six fluorine atoms and wherein one, two or three carbon atoms of the hydrocarbon group may optionally be replaced by one, two or three heteroatoms independently selected from nitrogen, oxygen and sulphur; R3 represents a 5-or 6-membered monocyclic aromatic heterocyclic group containing 1, 2, 3or 4 ring heteroatoms independently selected from nitrogen, oxygen and sulphur, which heterocyclic group may be optionally substituted by at least one substituent selected from halogen, cyano, oxo, —NR4R5, —C(O)NR6R7, C1-C6 haloalkyl, C1-C6 haloalkoxy, —R8, —OCH2R8, C1-C6 alkoxy, C3-C8 cycloalkyl and C1-C6 alkyl, the alkyl substituent itself being optionally substituted by at least one substituent selected from cyano, —C(O)NR9R10, C1-C6 alkoxy and —NHC(O)R11, or R3 represents a group of formula (II)in which X represents a bond, C(O), C(O)O, C(O)NR13 or SO2, and R12 represents a C1-C6 alkyl group or a 3-to 10-membered saturated or unsaturated carbocyclic or heterocyclic ring system, each of which may be optionally substituted by at least one substituent selected from halogen, hydroxyl, cyano, oxo, C1-C6 alkyl, C2-C6 alkenyl, 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, —N(R14)2, —CON(R15)2, C3-C6 cycloalkyl, C3-C6 cycloalkyloxy and C3-C6 cycloalkylmethyl;
R4, R5, R6 and R7 each independently represent a hydrogen atom, C1-C6 alkyl, C3-C6 cycloalkyl or C3-C6 cycloalkylmethyl; R8 represents a 5-or 6-membered monocyclic aromatic group optionally containing 1, 2, 3 or 4 ring heteroatoms independently selected from nitrogen, oxygen and sulphur, the aromatic group being optionally substituted by at least one substituent selected from halogen and C1-C6 alkyl; R9, R10 and R11 each independently represent a hydrogen atom, C1-C6 alkyl or C3-C6 cycloalkyl; and each R13, R14 and R15 independently represents a hydrogen atom or C1-C6 alkyl group.