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

• Published in: Bioorganic & medicinal chemistry letters Vol. 5; no. 18; pp. 2077 - 2080
• Main Authors: Alisi, Maria A., Brufani, Mario, Filocamo, Luigi, Gostoli, Gianluca, Licandro, Emanuela, Cesta, M.Candida, Lappa, Sperandina, Marchesini, Donata, Pagella, P.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 21-09-1995
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/0960-894X(95)00371-Y

Several new potent acetylcholinesterase inhibitors have been synthesised as potential drugs for the treatment of Alzheimer's 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.
Several new potent acetylcholinesterase inhibitors have been synthesised as potential drugs for the treatment of Alzheimer's disease. Heptylphysostigmine (MF201) is a drug analogue of physostigmine under clinical evaluation. In order to obtain new physostigmine analogues, the methylcarbamoyloxy 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.