Potent Triazolinone-Based Angiotensin-Ii Receptor Antagonists With Equivalent Affinity For Both The At(1) And At(2) Subtypes

A series of subnanomolar (IC50) triazolinone-based AT(1)/AT(2)-balanced AII antagonists has been identified. The 70-240-fold gain in AT(2) activity relative to prototype compounds was achieved by the introduction of a 5-acylamino group on the N-2-aryl moiety and the addition of (3'-F-5'-Pr)biphenyl substituents on 4. These analogues exhibited AT(2)/AT(1) IC50 ratios of I 1 in multiple assay systems including human adrenal.