MnO2氧化.pdf

Asian Journal of Chemistry Vol. 21, No. 6 (2009), 4909-4913 A Convenient Method for the Preparation of Losartan Active Metabolite (EXP-3174) MORTEZA PIRALI-HAMEDANI†, ALIREZA ALIABADI, M. SHEKARCHI†, M. AMINI, MOHAMMAD REZA ROUINI‡, ABBAS SHAFIEE and ALIREZA FOROUMADI*§ Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14174, Iran Fax: (98)(21 Tel: (98)(21 E-mail: aforoumadi@ Losartan is an angiotensin antagonist with a 5-carboxylate active metabolite (EXP-3174). This active metabolite is the result of the oxida- tion of 5-hydroxymethyl group to the corresponding 5-carboxyl group in liver. The active metabolite (EXP-3174) is important in pharmaco- logical and biopharmaceutical studies of parent drug. Therefore, a con- venient two steps procedure has been developed based on the oxidation of hydroxymethyl group of losartan to aldehyde and subsequent oxidation to carboxylate using different oxidizing reagents. H O -KOH reagent 2 2 was found the most convenient and efficient method. Key Words: Synthesis, Losartan active metabolite, EXP-3174, Oxidation. INTRODUCTION Losartan is an angiotensin II type 1 receptor antagonist that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system. The renin-angiotensin system (RAS) plays an important role in the pathogenesis of heart failure and hyper- tension. Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers) are high