Synthesis and Biological Activity of Modified Peptide Inhibitors of Angiotensin-Converting Enzyme

Article abstract of DOI:10.1021/jm00147a030

A series of non-sulfhydryl modified dipeptides related to CI-906, CI-907 and enalapril was prepared in which various isosteric moieties (O, S, SO, SO2) have been substituted for the amino group and in which the proline residue has been replaced with various hydrophobic amino acids.The compounds were evaluated in vivo for inhibition of angiotensin-converting enzyme and in vitro for antihypertensive activity.Compound 7c, the most potent member of this series, had an in vitro IC50 1.4*10^-8 M and showed modest oral antihypertensive activity at 30 mg/kg in conscious, two kidney, one clip Goldblatt hypertensive rats.Structure-activity relationships are discussed.