SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF NEW ACETYLCHOLINESTERASE INHIBITORS - MORPHOLINOALKYLCARBAMOYLOXYESEROLINE DERIVATIVES

Several new potent acetylcholinesterase inhibitors have been synthesis ed as potential drugs for the treatment of Alzheimer's disease. Heptyl physostigmine (MF201) is a drug analogue of physostigmine under clinic al evaluation. In order to obtain new physostigmine analogues, the met hylcarbamoyloxy group was substituted with omega-morpholinoalkylcarbam oyloxy moieties of different chain lengths (C2-C12). Potent in vitro i nhibition is seen when the chain length is composed of eight to twelve methylene groups. The inhibitory activity of the C10 and C11 is 7-fol d greater with respect to heptylphysostigmine.