Design, Synthesis and Biological Evaluation of Some Oxadiazole Derivatives as Novel Amide-Based Inhibitors of Soluble Epoxide Hydrolase

Author(s): Elham Rezaee Zavareh, Mahdi Hedayati, Laleh Hoghooghi Rad, Azin Kiani, Soraya Shahhosseini, Mehrdad Faizi, Sayyed Abbas Tabatabai.

Journal Name:Letters in Drug Design & Discovery

Volume 11 , Issue 6 , 2014

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Abstract:

Soluble epoxide hydrolase (sEH) enzyme plays an important role in the metabolism of endogenous chemical mediators which are involved in the regulation of blood pressure and inflammation. Although the most reported potent sEH inhibitors are urea derivatives, these compounds have limited pharmacokinetic profile. In order to improve physicochemical properties, besides having favorable potency, amide non-urea derivatives with oxadiazole ring as a novel secondary pharmacophore against sEH enzyme were developed. Most of the novel compounds with appropriate physical properties, had comparable in vitro sEH inhibitory activity to 12-(3-Adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a potent urea-based sEH inhibitor. The IC50 value of the most potent compound (15c) was 0.43 nM.

Keywords: Biological evaluation, Docking, Oxadiazole, Physical properties, Soluble epoxide hydrolase, Synthesis.

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Article Details

VOLUME: 11
ISSUE: 6
Year: 2014
Page: [721 - 730]
Pages: 10
DOI: 10.2174/1570180811666140220005530
Price: $58