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Updated: Aug 14, 2026

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
Published on: June 7, 2016
Synthesis and structure-activity relationships of nonpeptide, potent triazolone-based angiotensin II receptor
H C Huang1, D B Reitz, T S Chamberlain
1Department of Chemistry, Searle R&D, St. Louis, Missouri 63198.
Abstract:
2,5-Dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4' - yl]methyl]-3H-1,2,4-triazol-3-one, SC-51316, was synthesized as a potent and orally active angiotensin II (AII) receptor antagonist with a long duration of action. To explore the lipophilic pocket in the AII receptor interacting with the substituent at the 2-position of triazolone-based antagonists, a series of compounds were prepared and evaluated for receptor binding affinity and antagonism of AII-contracted rabbit aortic rings. It has been found that the pocket is very spacious and can accommodate different sizes of lipophilic groups and various functionalities. Acidic groups generally result in a slight decrease in binding affinity. Branched chains are unfavorable. The freedom of rotation around C2-C3 in the flexible side chain is crucial for good binding. The 2-phenylethyl-substituted triazolone analogue exhibits the highest in vitro potency among all compounds that have been synthesized.
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