Balanced AT1 and AT2 angiotensin II antagonists. I. New orally active 5-carboxyl imidazolyl biphenyl sulfonylureas

A series of substituted imidazolyl biphenyl sulfonylureas have been synthesized. Substitution on the imidazole ring but essentially on the urea side chain significantly increased AT2 binding with cyclohexylmethyl, cyclopentylmethyl and benzyl as the most effective substituents. Imidazole 13d, as a representative member of this series, displayed nanomolar binding affinity for both the AT1 and AT2 angiotensin II receptor subtypes as well as oral activity.