title: Discovery of novel 2-benzylisoquinolin-1(2H)-ones as potent vasodilative agents.
abstract: 2-Benzylisoquinolin-1(2H)-ones has been proposed as vasodilative agents on the basis of scaffold hopping. In the present study, a series of 2-benzylisoquinolin-1(2H)-ones were synthesized. Their vasodilative effects were evaluated by wire myograph on isolated rat mesenteric arterial ring induced contraction with 60mM KCl. The structure-activity relationships of target compounds were discussed. Among these compounds, C7 and C8 displayed potent vasodilative effects and significantly inhibited the contraction of rat mesenteric arterial rings induced by phenylephrine. The antihypertensive effects of compounds C7 and C8 on SHR were further evaluated. The results indicated that oral administrational C7 and C8 can significantly reduce both diastolic and systolic blood pressure in a dose-dependent manner. Moreover, C7 maintained the effects for 4h at a dosage of 4.0mg/kg. These findings suggest that the title compounds can serve as novel vasodilative agents and promising antihypertensive agents.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Bo-Rui
authors.initials: BR
authors.lastname: Kang
authors.affiliation: Department of Pharmacology, School of Basic Medical Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Mao
authors.affiliation: Department of Pharmacology, School of Basic Medical Science, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Cao
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China. Electronic address: sqzhang@xjtu.edu.cn.
authors.forename: San-Qi
authors.initials: SQ
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006973:Hypertension / Q000188:drug therapy; D008638:Mesenteric Arteries / Q000187:drug effects; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D015363:Quinolones; D014665:Vasodilator Agents
keywords: 2-Benzylisoquinolin-1(2H)-ones; Antihypertension; Synthesis; Vasodilation