[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.
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Discovery Research Laboratories I, Takeda Chemical Industries, LTD.
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011355:Prodrugs; D013777:Tetrazoles; C081672:CV 11194; C077793:candesartan cilexetil; C081643:candesartan