Synthesis of Brominated 2-Phenitidine Derivatives as Valuable Inhibitors of Cholinesterases for the Treatment of Alzheimer’s Disease

Document Type : Research article


1 Department of Chemistry, GC University, Lahore.

2 Department of Chemistry, Government College University, Lahore-54000, Pakistan

3 Department of Chemistry, Government College University, Lahore-54000, Pakistan.

4 HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.

5 Department of Biochemistry and Biotechnology

6 Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur- 63100, Pakistan.


The present study reports the synthesis of a series N-substituted derivatives of brominated 2-phenitidine. First, the reaction of 2-phenitidine (1) with benzenesulfonyl chloride (2) in aqueous media yielded N-(2-ethoxyphenyl) benzenesulfonamide (3), which was then subjected to bromination with bromine in the presence of glacial acetic acid to give N-(4,5-dibromo-2-ethoxyphenyl)benzenesulfonamide (4). Secondly, the product (4) on further treatment with alkyl/aryl halides (5a-l) in the presence of lithium hydride (LiH) produced twelve new derivatives of N-substituted sulfonamides (6a-l). These were characterized by 1H-NMR spectrum and screened against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and lipoxygenase (LOX) and were found to be valuable inhibitors of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). Few of these synthesized derivatives were also active against lipoxygenase (LOX). It was concluded from this investigation that these derivatives were moderate inhibitors of cholinesterases and are also ideally suited for further structural modification to obtain more potent and less cytotoxic therapeutic agents for the treatment of Alzheimer’s disease.


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