title: Rational design, synthesis, biological evaluation, homology and docking studies of coumarin derivatives as α1 -adrenoceptor antagonists.
abstract: According to a three-point pharmacophore for some uro-selective α(1) -adrenoceptor (AR) antagonists, a novel class of coumarin (=2H-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 (pK(i) value of 8.77), among those coumarins, tolylpiperazine-substituted derivatives, 7 and 8, have comparable pK(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).
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, 210009 Nanjing, P. R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.forename: Ya-Dong
authors.initials: YD
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wang
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D003374:Coumarins; D018340:Receptors, Adrenergic, alpha-1; C030123:coumarin