title: Discovery of novel 3-benzylquinazolin-4(3H)-ones as potent vasodilative agents.
abstract: In the present study, a series of 3-benzylquinazolin-4(3H)-ones were synthesized and characterized. Their vasodilative effects were evaluated by wire myograph on isolated rat mesenteric arterial ring induced contraction with 60mM KCl. The SAR of target compounds was discussed preliminarily. Among these compounds, 2a and 2c displayed potent vasodilatation action and could compete significantly the rat mesenteric arterial rings induced contraction with phenylephrine. Compounds 2a and 2c were further tested for their antihypertensive effects in SHR by oral administration. The results indicated that 2a and 2c could reduce significantly both diastolic and systolic blood pressure. Moreover, 2c displayed antihypertensive effect in a dose dependent manner, and could maintain the effects for 6h at a dosage of 4.0mg/kg. These findings suggest that the title compounds are novel vasodilative agents, representing a novel series of promising antihypertensive agents.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Sai-Jie
authors.initials: SJ
authors.lastname: Zuo
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Sen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Rui-Hong
authors.initials: RH
authors.lastname: Yu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Guo-Xun
authors.initials: GX
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, 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, Health Science Center, 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; D001593:Benzyl Compounds / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D052999:Quinazolinones / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D014665:Vasodilator Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001593:Benzyl Compounds; D052999:Quinazolinones; D014665:Vasodilator Agents
keywords: 3-Benzylquinazolin-4(3H)-ones; Antihypertension; Synthesis; Vasodilation