synthesis of new indole derivatives structurally related to donepezil and their biological evaluation as acetylcholinesterase inhibitors新的吲哚衍生物的合成结构与多奈哌齐和他们的生物评价乙酰胆碱酯酶抑制剂.pdf

Molecules 2012, 17, 4811-4823; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Articles Synthesis of New Indole Derivatives Structurally Related to Donepezil and Their Biological Evaluation as Acetylcholinesterase Inhibitors Mohamed M. Ismail, Mona M. Kamel, Lamia W. Mohamed * and Samar I. Faggal Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt * Author to whom correspondence should be addressed; E-Mail: lamiawagdy@; Tel.: +202-2363-2245; Fax: +202-2532-1900. Received: 26 March 2012; in revised form: 16 April 2012 / Accepted: 17 April 2012 / Published: 25 April 2012 Abstract: New series of indole derivatives analogous to donepezil, a well known anti-Alzheimer and acetylcholinesterase inhibitor drug, was synthesized. A full chemical characterization of the new compounds is provided. Biological evaluation of the new compounds as acetylcholinesterase inhibitors was performed. Most of the compounds were found to have potent acetylcholinesterase inhibitor activity compared to donepezil as standard. The compound 1-(2-(4-(2-fluorobenzyl) piperazin-1-yl)acetyl)indoline-2,3-dione (IIId) was found to be the most potent. Keywords: indole; isatin; oxindole; acetylcholinesterase inhibitors; Alzheimer; donepezil 1. Introduction Among many pharmacological agents, acetylcholinesterase inhibitors (AChEI) are the only class of compounds that have consistently proven to be effic