Muscarinic antagonists

摘要

Di-N-substituted piperazine or 1,4 di-substituted piperadine compounds of formula I <IMAGE> I wherein one of Y and Z is N and the other is N, CH, or C-alkyl; X is -O-, -SO0-2-, amino, substituted amino, -CO-, -CH2-, mono or di-substituted methylene, -CS-, -CONR20-, -NR20-SO2-, -NR20CO-, -SO2NR20-, -CH=CH-, -C 3BOND C- or -NHC(O)NH-; R is optionally substituted phenyl, aryl or cycloalkyl, or other substituents as defined in the specification; R1 and R21 are H, CN or optionally substituted alkyl, or other substituents as defined in the specification; R2 is optionally substituted cycloalkyl or piperidyl, or other substituents as defined in the specification; and R3, R4, R5, R20, R27 and R28 are as defined in the specification; are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease; pharmaceutical compositions and methods of preparation are also disclosed, as well as synergistic combinations of compounds of the above formula or other compounds capable of enhancing acetylcholine release with acetylcholinesterase inhibitors.