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[Angiotensin II receptor antagonist activities and mode of action of benzimidazole-7-carboxylic acid derivatives].

Blockade of the action of angiotensin II (A II) is a target for development of novel antihypertensive agents. We have recently discovered a novel and potent nonpeptide AT1 selective A II receptor antagonists, benzimidazole-7-carboxylic acid derivatives (CV-11194 and CV-11974), which are more potent than DuP 753. The prodrug analogue (TCV-116) of CV-11974 is an orally active, highly potent and long-acting antihypertensive agent. The structure-activity relationships (SAR) of benzimidazole derivatives showed the importance of presence of a 7-carboxyl group for the potent and functionally non-competitive (insurmountable) A II antagonism. The interactions between the A II antagonist and receptor on the basis of SAR studies as well as A II receptor modeling are also described.