Design, synthesis, and biological evaluation of some 1,2,3-triazole derivatives as novel amide-based inhibitors of soluble epoxide hydrolase

Epoxyeicosatrienoic acids (EETs) are produced by the effect of cytochrome P 450 (CYP) on arachidonic acid (AA), and have a beneficial performance to renal and cardiovascular systems. In recent decades, many new pharmacological agents have been developed to inhibit the soluble epoxide hydrolase (sEH) and consequently, maintain EETs serum level in high concentrations. In the present study, a series of novel amide derivatives were designed and investigated with a 1,2,3-triazole ring as a secondary pharmacophore against sEH enzyme. Based on docking studies, these novel structures were suitably located in the active site of the enzyme. All final compounds showed satisfactory inhibitory activity against sEH with proper IC 50 values (0.9–55.5 nM). Compound 5l , as the most potent compound, could be a valuable structure for further investigation. According to in silico ADME calculations, these novel compounds could be formulated as orally active agents. In this study, some new amide-based derivatives of 1,2,3-triazole as soluble epoxide hydrolase inhibitors were designed, synthesized, and biologically evaluated. Most of the synthesized compounds provided nanomolar range inhibition against sEH enzyme. The best observed IC 50 value was 0.9 nM for compound 5l . In silico ADME calculations showed that these novel compounds could be formulated as orally active agents.