Quinuclidine derivatives and their use as muscarinic M3 receptor ligands.

摘要

A compound according to formula (I) wherein: custom-character file="US20030055080A1-20030320-P00900.TIF" wi="20" he="20" id="custom-character-00001"/is a phenyl ring, a C4 to C9 heteroaromatic compound containing one or more heteroatoms, or a naphthalenyl, 5,6,7,8-tetrahydronaphthalenyl or biphenyl group; R1, R2 and R3 each independently represent a hydrogen or halogen atom, or a hydroxy group, or a phenyl, -OR4, -SR4, -NR4R5, -NHCOR4, -CONR4R5, -CN, -NO2, -COOR4 or -CF3 group, or a straight or branched lower alkyl group which may optionally be substituted, for example, with a hydroxy or alcoxy group, wherein R4 and R5 each independently represent a hydrogen atom, straight or branched lower alkyl group, or together form an alicyclic ring; or R1 and R2 together form an aromatic, alicyclic or heterocyclic ring; n is an integer from 0 to 4; A represents a -CH2-, -CH=CR6, -CR6=CH-, -CR6R7-, -CO-, -O-, -S-, -S(O)-, SO2 or -NR6- group, wherein R6 and R7 each independently represent a hydrogen atom, straight or branched lower alkyl group, or R6 and R7 together form an alicyclic ring; m is an integer from 0 to 8; provided that when m=0, A is not -CH2-; p is an integer from 1 to 2 and the substitution in the azoniabicyclic ring may be in the 2, 3 or 4 position including all possible configurations of the asymmetric carbons; B represents a group of formula i) or ii): wherein R10 represents a hydrogen atom, a hydroxy or methyl group; and R8 and R9 each independently represents wherein R11 represents a hydrogen or halogen atom, or a straight or branched lower alkyl group and Q represents a single bond, -CH2-, -CH2-CH2-, -O-, -O-CH2-, -S-, -S-CH2- or -CH=CH-, and when i) or ii) contain a chiral centre they may represent either configuration; X represents a pharmaceutically acceptable a