By introduced a 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 angiotensin II receptor (AT1) and endothelin A receptor (ETA). The evaluation in spontaneous hypertensive rats indicated that the oral activity of compound 1p was more potent than Irbersartan. Structural biology studies of 1p exhibited that strong interactions were contributed to the AT1 and ETA receptors and the tetrazol‐5‐ylamide could be an important moiety for the binding to the proteins.