Document Report Card

ID: ALA1126921

Journal: J Med Chem

Title: Heterocyclic lactam derivatives as dual angiotensin converting enzyme and neutral endopeptidase 24.11 inhibitors.

Authors: Stanton JL, Sperbeck DM, Trapani AJ, Cote D, Sakane Y, Berry CJ, Ghai RD.

Abstract: A series of 13- and 14-membered ring lactam derivatives 9a,b, 10, 11, and 12a-c was prepared from L-cysteine. Compounds 9a,b and 12a,b were tested in vitro for inhibition of neutral endopeptidase 24.11 (NEP) and angiotensin converting enzyme (ACE) inhibition. The structure-activity profile of the series is discussed. Compound 9b, a 13-membered ring macrocyclic lactam, had an NEP IC50 of 18 nM and an ACEIC50 of 12 nM in vitro and showed dual plasma inhibition after intravenous or oral administration.

CiteXplore: 8254612

DOI: 10.1021/jm00076a010