Facile synthesis of novel nonpeptide angiotensin - II - Receptor antagonists

A series of Losartan analogues 1-12 with different functional groups were synthesized and characterized. In comparison with the previous reports, the synthetic procedures described in this paper have been optimized as follows below: 1) preparation of aromatic amine 15 and 18 through hydrogenation by employing Raney Ni and hydrazine as catalysts in place of palladium; 2) preparation of nitro-compound 17 by using pure fuming nitric acid at -20 - -15 degreesC; 3) alkylation of 21 with 22 or 23 in the presence of sodium hydride in place of potassium tert-butylate; 4) preparation of carboxylic acid 4 by ester cleavage rather than hydrolysis of cyano group.