Discovery of novel 3-benzylquinazolin-4(3H)-ones as potent vasodilative agents

作者：Zuo Sai Jie; Li Sen; Yu Rui Hong; Zheng Guo Xun; Cao Yong Xiao; Zhang San Qi^*

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(24): 5597-5601.

DOI：10.1016/j.bmcl.2014.10.092

• 3-Benzylquinazolin-4(3H)-ones
• Synthesis
• Vasodilation
• Antihypertension

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 60 mM 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 6 h at a dosage of 4.0 mg/kg. These findings suggest that the title compounds are novel vasodilative agents, representing a novel series of promising antihypertensive agents.

• 出版日期2014-12-15
• 单位西安交通大学