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Rational Design, Synthesis, Biological Evaluation, Homology and Docking Studies of Coumarin Derivatives as α 1 ‐Adrenoceptor Antagonists
Author(s) -
Zhou Xiang,
Chen YaDong,
Wang Tao,
Wang XiaoBing,
Kong LingYi
Publication year - 2011
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201000135
Subject(s) - pharmacophore , coumarin , chemistry , prazosin , in vitro , docking (animal) , stereochemistry , combinatorial chemistry , pharmacology , antagonist , receptor , biochemistry , organic chemistry , medicine , nursing
According to a three‐point pharmacophore for some uro‐selective α 1 ‐adrenoceptor (AR) antagonists, a novel class of coumarin (=2 H ‐1‐benzopyran‐2‐one) derivatives have been successfully designed and synthesized with high efficacies for α 1 ‐AR. These synthesized coumarin derivatives exhibited high efficacies towards α 1 ‐AR in in vitro pharmacological assays. Compared with prazosin (p K i value of 8.77), among those coumarins, tolylpiperazine‐substituted derivatives, 7 and 8 , have comparable p K i values of 8.81 and 8.77, respectively. The trend in efficacies of these coumarin derivatives towards α 1A ‐adrenoceptor was further rationalized by intensive molecular docking. Our work demonstrated that the designed coumarin derivatives can inhibit α 1 ‐AR in vitro. These findings will provide a guide for further studies of the medical therapy of benign prostatic hyperplasia (BPH).