Design, Synthesis and Biological Evaluation of 4-Benzamidobenzoic Acid Hydrazide Derivatives as Novel Soluble Epoxide Hydrolase Inhibitors

Document Type : Research article

Authors

1 a) Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Cellular & Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 a) Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

Inhibitors of soluble epoxide hydrolase (sEH) represent one of the novel pharmaceutical approaches for treating hypertension, vascular inflammation, pain and other cardiovascular related diseases. Most of the potent sEH inhibitors reported in literature often suffer from poor solubility and bioavailability. Toward improving pharmacokinetic profile beside favorable potency, two series of 4-benzamidobenzoic acid hydrazide derivatives with hydrazide group as a novel secondary pharmacophore against sEH enzyme were developed. The designed compounds were synthesized in acceptable yield and their in vitro assay was determined. Most of the synthesized compounds have appropriate physical properties and exhibited considerable in vitro sEH in comparison with 12-(3-Adamantan-1-yl-ureido)-dodecanoicacid(AUDA), a potent urea-based sEH inhibitor. 4-(2-(4-(4-chlorobenzamido)benzoyl)hydrazinyl)-4-oxobutanoic acid 6c was found to be the most potent inhibitor with inhibitory activity of 72% targeting sEH enzyme.

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