Balanced AT1 and AT2 angiotensin II antagonists. III. potent and orally active 5-β-ketosulfoxide imidazolyl biphenyl sulfonylureas

In the imidazolyl biphenyl sulfonylurea series, effects of substitution in position 5 of the imidazole ring with enolic ketone moiety were studied on AT2 binding. β-ketosulfoxide, β-ketosulfone and β-ketoester proved to be highly effective substituents for potent nanomolar binding affinity on both AT1 and AT2 receptor subtypes. This led to the identification of β-ketophenylsulfoxide RU 64276 as a potent and orally active AT1 antagonist and AT2 binding inhibitor