Discovery of novel 3-benzylquinazolin-4(3H)-ones as potent vasodilative agents |
| |
| Institution: | 1. Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, PR China;2. Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, PR China;1. Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;2. Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;1. LUNAM Université, Oniris, UPSP 5304 de physiopathologie animale et de pharmacologie fonctionnelle, Atlanpole La Chantrerie, B.P. 40706, Nantes F-44307, France;2. UR 1268 Biopolymères Interactions Assemblages, INRA, équipe Fonctions et Interactions des Protéines, B.P. 71627, 44316 Nantes, Cedex 3, France;3. EA 4324 ORPHY, European University of Brittany, University of Brest, 6 avenue Le Gorgeu, CS 93837, 29238 Brest, France;1. Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN 37203, USA;2. Royal Marsden Hospital, London, United Kingdom;3. National Heart and Lung Hospital, Imperial College London, United Kingdom;4. Kent Cancer Centre, Maidstone, Kent, United Kingdom |
| |
| 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 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. |
| |
| Keywords: | Synthesis Vasodilation Antihypertension |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
