Design and synthesis of new tetrazolyl- and carboxy-biphenylylmethyl-quinazolin-4-one derivatives as angiotensin II AT1 receptor antagonists. | LitMetric
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, ElKhalifa ElMaamoon St., 11566, Abbasseya, Cairo, Egypt.
Published: March 2006
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Article Abstract
A series of novel quinazolin-4-ones was designed and their molecular modeling simulation fitting to a new HipHop 3D pharmacophore model using CATALYST was examined. Several compounds showed significant high simulation fit values. The designed compounds were synthesized and eight of them were biologically evaluated in vitro using an AT1 receptor binding assay, where compound XX competed weakly against radiolabeled Sar1Ile8-angiotensin II (Ang II) binding, compounds XIV and XXII showed moderate competition, and compound XXV showed almost equal ability to displace radiolabeled Sar1Ile8-Ang II binding to AT1 receptors as losartan. In vivo biological evaluation study of compounds XIV, XXII, and XXV on both normotensive and hypertensive rats revealed that compound XXV demonstrated higher hypotensive and antihypertensive activity than the reference compound losartan. To obtain a highly active compound from a candidate set of only eight tested compounds illustrates the power and utility of our pharmacophore model.
Background: In patients with diabetes mellitus (DM), vascular endothelial dysfunction (VED) is the main reason for impaired life expectancy. Melatonin (MEL) demonstrates wide-ranging effects across various organs and exhibits pleiotropic characteristics. The current study aims to investigate the modulatory roles of MEL vascular response to angiotensin II (Ang II) and its receptors including angiotensin type 1 receptor (AT-1 R) and angiotensin type 2 receptor (AT-2 R) in isolated thoracic aorta of non-diabetes (non-DM) and diabetes (DM) rats.
Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, China. Electronic address:
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