Design and Synthesis of Angiotensin Converting Enzyme (ACE) Inhibitors: Analysis of the Role of Tetrazole Ring Appended to Biphenyl Moiety

摘要

Novel biphenyl compounds bearing triazolones have been designed and synthesized with an aim to explore the paramount set of molecules as antihypertensive agents. Our efforts have been directed towards the synthesis of Triazolyl-biphenyl compounds containing different groups at ortho position of the biphenyl ring. In particular, cyano, tetrazole and oxadiazole substituents at the ortho position of biphenyl ring were synthesized and structures of all these previously unknown 16 molecules were confirmed by their spectral characterizations. Binding modes for these compounds were evaluated by docking in a theoretical Human angiotensin converting enzyme (ACE) in complex with Lisinopril. These novel compounds were evaluated for the in vitro ACE inhibition and the results were compared to Lisinopril. Results indicated that the tetrazole containing compounds have shown significant inhibitory activity than the other compounds which are in good agreement with the docking results.