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Design, synthesis and structure-activity relationships of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease

Authors :
Hiroshi Kogen
Yasuyuki Abe
Takao Hara
Naho Yamada
Reina Yamazaki
Kazumi Abe
Shinji Marumoto
Kazuo Koyama
Kazuko Takami
Shunji Naruto
Tsugio Kaneko
Mayuko Ori
Atsushi Aoyagi
Narihiro Toda
Keiko Tago
Source :
Bioorganicmedicinal chemistry. 11(9)
Publication Year :
2003

Abstract

We have designed and synthesized a dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT) as a novel class of treatment drugs for Alzheimer's disease on the basis of a hypothetical model of the AChE active site. Dual inhibitions of AChE and SERT would bring about greater therapeutic effects than AChE inhibition alone and avoid adverse peripheral effects caused by excessive AChE inhibition. Compound ( S )- 6j exhibited potent inhibitory activities against AChE (IC 50 =101 nM) and SERT (IC 50 =42 nM). Furthermore, ( S )- 6j showed inhibitory activities of both AChE and SERT in mice brain following oral administration.

Details

ISSN :
09680896
Volume :
11
Issue :
9
Database :
OpenAIRE
Journal :
Bioorganicmedicinal chemistry
Accession number :
edsair.doi.dedup.....91a96bcff5bc7c24c9f92075fec506f8