Synthesis and structure-activity relationships of new acetylcholinesterase inhibitors: Morpholinoalkylcarbamoyloxyeseroline derivatives

Several new potent acetylcholinesterase inhibitors have been synthesised as potential drugs for the treatment of Alzheimerʹs disease. Heptylphysostigmine (MF201) is a drug analogue of physostigmine under clinical evaluation. In order to obtain new physostigmine analogues, the methylcarbomoyloxy group was substituted with ω-morpholinoalkylcarbamoyloxy moieties of different chain lengths (C2–C12). Potent in vitro inhibition is seen when the chain length is composed of eight to twelve methylene groups. The inhibitory activity of the C10 and C11 is 7-fold greater with respect to heptylphysostigmine.