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) an
d angiotensin converting enzyme (ACE) inhibition. The structure-activi
ty profile of the series is discussed. Compound 9b, a 13-membered ring
macrocyclic lactam, had an NEP IC50 Of 18 nM and an ACE IC50 of 12 nM
in vitro and showed dual plasma inhibition after intravenous or oral
administration.