title: Design, synthesis and biological evaluation of novel 7-mercaptocoumarin derivatives as α(1)-adrenoceptor antagonists.
abstract: Study on the pharmacophore model of α(1)-adrenoceptor (α(1)-AR) antagonists led to design a series of novel 7-mercaptocoumarin derivatives as α(1)-AR antagonists. All designed compounds have been synthesized and biologically evaluated. The results showed that most of them exhibited strong antagonistic activity. Especially compound 6 showed excellent activity, which was better than that of the reference compound prazosin. Structure-activity relationship studies revealed that small hydrophobic group at the terminal heterocyclic ring and ortho substituents on the phenyl ring of phenylpiperazine moiety were the essential structural factors for α(1)-AR antagonistic activity. The pharmacophore modeling studies further clarified their structural contributions to antagonistic activity and also demonstrated that 7-mercaptocoumarin moiety could be a useful scaffold for design of α(1)-AR antagonists.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
authors.forename: Sai-Sai
authors.initials: SS
authors.lastname: Xie
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wang
authors.forename: Jiang-Yan
authors.initials: JY
authors.lastname: Li
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*; D000818:Animals; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D008297:Male; D008958:Models, Molecular; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: C581751:7-((4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)thio)-4-methyl-2H-chromen-2-one; D058668:Adrenergic alpha-1 Receptor Antagonists; D003374:Coumarins; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C031503:phenylpiperazine