synthesis and biological evaluation of thiophene derivatives as acetylcholinesterase inhibitors噻吩衍生物的合成和生物评价乙酰胆碱酯酶抑制剂.pdf

Molecules 2012, 17, 7217-7231; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and Biological Evaluation of Thiophene Derivatives as Acetylcholinesterase Inhibitors Mohamed M. Ismail 1, Mona M. Kamel 1, Lamia W. Mohamed 1,*, Samar I. Faggal 1 and 2 Mai A. Galal 1 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, El-Kasr El-Aini Street, Cairo 11562, Egypt 2 Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt * Author to whom correspondence should be addressed; E-Mail: lamiawagdy@; Tel.: +20-22-535-3100 or +20-12-2237-7861; Fax: +20-22-532-1900. Received: 26 April 2012; in revised form: 31 May 2012 / Accepted : 5 June 2012 / Published: 12 June 2012 Abstract: A series of new thiophene derivatives has been synthesized using the Gewald protocol. The acetylcholinesterase inhibition activity was assayed according to Ellman’s method using donepezil as reference. Some of the compounds were found to be more potent inhibitors than the reference. 2-(2-(4-(4-Methoxyphenyl)piperazin-1-yl)acetamido)- 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (IIId) showed 60% inhibition, compared to only 40% inhibition by donepezil. Keywords: thiophene; Gewald; Ellman; acetylcholinesterase; Alzheimer ’s disease 1. Introduction Alzheimer ’s disease (AD) is a neurodegenerative disorder of the central nervous system (CNS) characterized by pr