By introducing the novel fragment [N-(1H-tetrazol-5-yl)-amide], a series of 4′-[(benzimidazol-1-yl)methyl]biphenyl-2-amides (1a–1w) was designed, synthesized and biologically evaluated. 1d, 1k and 1p showed potent antagonistic activities against the angiotensin II receptor (AT₁) and the endothelin A receptor (ET_A). The evaluation in spontaneous hypertensive rats indicated that the oral activity of compound 1p was more potent than Irbesartan. Structural biological studies of 1p revealed that strong interactions to the AT₁ and ET_A receptors were explicit and the tetrazol-5-ylamide could be an important moiety for the binding to the proteins.