Synthesis and in vitro activity of a non-epimerizable analog of the angiotensin-converting enzyme inhibitor A58365A

Abstract

The 3-methyl-substituted analog (±)-3 of the angiotensin converting enzyme inhibitor A58365A (1) was synthesized from lactone 4 and amino acid ester 16, via key intermediates 18, 19 and 21a,b. Compound (±)-3 was found to possess powerful ACE inhibitory activity (IC₅₀ = ca 500 nM), as judged by in vitro tests against porcine kidney ACE, under conditions in which the commercial drug captopril has IC₅₀ = 280 nM.