| 摘要 |
PURPOSE: Muscarinic antagonists of 1,4-I-substituted piperidine compounds, pharmaceutical compositions and methods of preparation are provided which are useful for treatment of cognitive disorders such as Alzheimer's disease. Synergistic combinations with acetyl-cholinesterase inhibitors of compounds capable of enhancing acetylcholine release and having the formula 1 is also provided. CONSTITUTION: A compound having the structural formula (I), a pharmaceutically acceptable salt, or solvate thereof, wherein: X is --O--, --S--, --SO--, -SO2 --, --CO--, -C(OR¬7)2-, -CH2-O-, -O-CH2-, -CH=CH-, -CH2-, -CH(C1-C6alkyl)-, -C(C1-C6alkyl)2- --, --CONR¬17 --, --NR¬17CO --SO2NR¬17 --, or --NR¬17SO2--; R is C3-C6cycloalkyl; R¬1 is hydrogen, -CN, -CF3, C1-C6alkyl, C3-C6alkenyl, C3-C6cycloalkyl, C3-C6cycloalkenyl, -COR15, COO(C1-C6alkyl), -COO(aryl), -COO(heteroaryl), -COO((C1-C6alkyl)aryl), COO((C1-C6alkyl)heteroaryl), -(C1-C6alkyl)aryl, -(C1-C6alkyl)heteroaryl, or -CON(R¬13)2; R¬2 is C3-C6cycloalkyl, C3-C6cycloalkenyl, or t-butoxycarbonyl; R¬3 and R¬4 are independently selected from the group consisting of H, -CF3, C1-C6alkyl, halo, C1-C6alkoxy and OH; R5 and R6 are independently selected from the group consisting of H, -CF3, C1-C6alkyl, halo, C1-C6alkoxy, C1-C6alkylcarbonyl, C1-C6alkoxycarbonyl, R¬13CONH-, R¬14OCONH-, R¬13NHCONH- and NH2CONR¬13.
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