Synthesis and Evaluation of Novel Nonpeptide Angiotensin II Receptor Antagonists : Imidazo[4, 5-c]pyridine Derivatives with an Aromatic Substituent

Abstract

Starting from recently reported nonpeptidic angiotensin II (AII) receptor antagonists, we have designed and prepared a new series of 6-arylimidazo[4, 5-c]pyridine derivatives. Variation of phenyl groups at the 4-, 6- or 7-position of imidazo[4, 5-c]pyridine showed that substitution at the 6-position resulted in receptor-binding activity almost as potent as that of DuP 753. This led to synthesis and evaluation of an extensive series of 6-aryl-imidazo[4, 5-c]pyridine derivatives. Some of them were 4-fold more potent in vitro than DuP 753, but only showed weak antihypertensive activity in vivo when given orally to rats.