DESIGN, SYNTHESIS AND CONFORMATIONAL ANALYSIS OF POTENT ANGIOTENSIN II LOSARTAN BASED ANTAGONIST

摘要

The octapeptide Angiotensin II (H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-OH) is the major factor of the Renin -Angiotensin System (RAS) and plays a significant role in the regulation of arterial blood pressure. A number of AngII antagonist non-peptide mimetics (Irbesartan, Tasosartan) analogues is currently used for the treatment of hypertension. In the present study, a Losartan based analogue, 2-methoxy-carbonyl N-[(tetrazol-5"-yl)phenyl-4'-yl] methylimidazol, was rationally designed and synthesized using the imidazole template on which phenyl, tetrazol and esteric groups are bound, according to Angll structure. The conformational analysis was carried out comparing the 3D structure of the synthesized analogue with the lowest energy 3D structure of [Sar~1, Ile~8]AngII (Sarilesin) and EXP3174 (bioactive metabolite of Losartan).