| 摘要 |
<p>1,4-Di-substituted piperidine muscarinic antagonists of formula (I) or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein X is a bond, -O-, -S-, -SO-, -SO2-, -CO-, -C(OR7)2-, -CH2-O-, -O-CH2-, -CH=CH-, -CH2-, -CH(C1-C6 alkyl)-, -C(C1-C6 alkyl)2-, -CONR?17-, -NR17¿CO-, -SO¿2NR?17- or -NR17SO2-; R is C3-C6 cycloalkyl, (a), (b), (c), (d), (e), optionally substituted phenyl or optionally substituted pyridyl; R1 is H, -CN, -CF¿3?, alkyl, cycloalkyl, cycloalkenyl, alkenyl, -COR?15¿, -COO(alkyl, aryl, heteroaryl, alkylaryl or alkylheteroaryl), alkylaryl, alkylheteroaryl or -CON(R13)2; R2 is cycloalkyl, cycloalkenyl, t-butoxycarbonyl or optionally substituted 4-piperidinyl; R?3 and R4¿ are H, halo, -CF¿3?, alkyl, alkoxy or -OH; R?5 and R6¿ are H, alkyl, -CF¿3?, alkoxy, -OH, alkylcarbonyl, alkoxycarbonyl, R?13¿CONH-, R14OCONH-, R13NHCONH- or NH¿2?CONR?13-; R7¿ is H or alkyl, or the two R7 groups may form -(CH¿2?)2-4; R?13¿ is H, alkyl, cycloalkyl, -(alkyl)COOR15, aryl, heteroaryl, alkylaryl, alkylheteroaryl and adamantyl; R14 is H or alkyl; R15 is H, C¿1?-C20 alkyl, C1-C6 cycloalkyl, aryl or heteroaryl; and R?17¿ is H, C¿1?-C6 alkyl, aryl or heteroaryl; useful for treating cognitive disorders such as Alzheimer's disease are disclosed, as well as pharmaceutical compositions and methods of preparation. Also disclosed are combinations of compounds of formula (I) capable of enhancing ACh release with ACh'ase inhibitors.</p> |
