Design and synthesis of novel heterocyclic derivatives as soluble epoxide hydrolase inhibitors

Soluble epoxide hydrolase (sEH), is an enzyme belongs to serine hydrolase family. sEH inhibition provides a novel approach to treat common ailments such as hypertension and inflammation. We designed and synthesized novel inhibitors, having tetrazole core to improve pharmacokinetic profile and potency.1 In this study, 5-phenyl-5H-tetrazole (1) was prepared by the reaction of benzonitrile and sodium azide using freshly synthesized ZnBr2 as the catalyst.2 Then N-benzylation of the compound 1 with 4-nitrobenzylbromide leads to crystalline compound 2.3 Then the compound 3 is resulted by reduction of nitro group of compound 2 with a mixture of iron powder, glacial acetic acid, ethanol and water under sonication for one hour.4 The final products (4) were afforded by treating of 4-((5-phenyl-2H-tetrazol-2-yl)methyl)aniline (3) with different benzoyl chlorides at room temperature in dry tetrahydrofuran (Fig. 1).3Finally, some novel compounds bearing a tetrazole ring were designed. The designed compounds showed high affinity to the active site of the sEH enzyme and were synthesized in good yield and were characterized by IR, Mass, HNMR, and CNMR.

کلیدواژه ها:

Soluble epoxide hydrolase ، Tetrazole ، Synthesis