Design, Synthesis and Biological Evaluation of Some Oxadiazole Derivatives as Novel Amide-Based Inhibitors of Soluble Epoxide Hydrolase
Elham Rezaee Zavareh, Mahdi Hedayati, Laleh Hoghooghi Rad, Azin Kiani, Soraya Shahhosseini, Mehrdad Faizi and Sayyed Abbas Tabatabai
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 invitro sEH inhibitory activity to 12-(3-Adamantan-1-yl-ureido)-dodecanoicacid (AUDA), a potent urea-based sEH inhibitor. The IC50 value of the most potent compound (15c) was 0.43 nM.
Department of Pharmaceutical Chemistry School of Pharmacy Pytochemistry Center Shahid Beheshti University of Medical Sciences Tehran Iran.