A new class of angiotensin II receptor antagonists with a novel acidic bioisostere

The synthesis and angiotensin II (AII) antagonistic activity of 2-substituted benzimidazole-7-carboxylic acids (8) bearing a novel acidic bioisostere, a 5-oxo-1,2,4-oxadiazole ring, are described. These compounds had in vitro and in vivo AII receptor antagonistic activity comparable to that of tetrazole analogs. The representative compound, TAK-536 (8e) is a potent, orally active and specific AII receptor antagonist.