Discovery of novel 2-benzylisoquinolin-1(2H)-ones as potent vasodilative agents

作者：Kang Bo Rui; Li Sen; Mao Shuai; Cao Yong Xiao; Zhang San Qi^*

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(24): 5808-5812.

DOI：10.1016/j.bmcl.2015.10.018

• 2-Benzylisoquinolin-1(2H)-ones
• Synthesis
• Vasodilation
• Antihypertension

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 60 mM 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 4 h at a dosage of 4.0 mg/kg. These findings suggest that the title compounds can serve as novel vasodilative agents and promising antihypertensive agents.

• 出版日期2015-12-15
• 单位西安交通大学