HETEROCYCLES, Vol. 71, No. 11, 2007, pp. 2413 - 2425. © The Japan Institute of Heterocyclic Chemistry Received, 9th June, 2007, Accepted, 6th August, 2007, Published online, 8th August, 2007. COM-07-11136 SYNTHESES AND ANTICHOLINESTERASE ACTIVITIES OF NOVEL 3-AMINOCARBONYLMETHYLENE-3-METHYL-2,3- DIHYDROBENZOFURAN-5-YL CARBAMATES Weiming Luo,* Qian-sheng Yu,* Harold W. Holloway,* David Tweedie,* Damon Parrish,  Arnold Brossi # and Nigel H. Greig*  *Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA  Laboratory for the Structure of Matter, Department of the Navy, Naval Research Laboratory, Washington, D.C. 20375, USA # School of Pharmacy, University of North Carolina at Chapel Hill, North Carolina 27599-7361, USA Abstract - Novel carbamates 4 and 5 were synthesized from starting material 5- hydroxy-3-methyl-3H-benzofuran-2-one, 17. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of 4 and 5 were determined against fresh human enzyme, are in the realm of clinically valuable compounds and are discussed. In addition, the reductive properties of the 2-carbonyl group of 3H-benzofuran-2-one, possessing an unsaturated substituted group in its 3 position (9, 11 and 14), were studied. Carbamates based on physostigmine series 1a-1c, on physovenine series 2a-2c and on tetrahydrofuro- benzofuran series 3a-3c have been proven to be potent inhibitors of the enzymes acetylcholinesterase (AChE) or butyrylcholinesterase (BChE), with specific compounds exhibiting remarkable selectivity for one form of the enzyme over the other. These enzymes are validated targets in the treatment of Alzheimer’s disease (AD), and their characterization is leading to the development of new and better tolerated drug candidates with actions that may impact disease course. There are numerous reports in the literature describing the synthesis of agents from each of these series. 1-17 Herein, we report the chemical synthesis and anticholinesterase properties of the novel and unexpected carbamates, 4 and 5.  Corresponding Author: Phone: 410-558-8278; Fax: 410-558-8323; E-mail: GreigN@grc.nia.nih.gov HETEROCYCLES, Vol. 71, No. 11, 2007 2413