Dual metalloprotease inhibitors. 6. Incorporation of bicyclic and substituted monocyclic azepinones as dipeptide surrogates in angiotensin-converting enzyme/neutral endopeptidase inhibitors

J Med Chem. 1996 Jan 19;39(2):494-502. doi: 10.1021/jm950677a.


A series of substituted monocyclic and bicyclic azepinones were incorporated as dipeptide surrogates in mercaptoacetyl dipeptides with the desire to generate a single compound which would potently inhibit both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). Many of these compounds displayed excellent potency against both enzymes. Two of the most potent compounds, monocyclic azepinone 2n and bicyclic azepinone 3q, demonstrated a high level of activity versus ACE and NEP both in vitro and in vivo.

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Azepines / pharmacology*
  • Dipeptides / pharmacology*
  • Kidney / enzymology
  • Lung / enzymology
  • Male
  • Metalloendopeptidases / antagonists & inhibitors*
  • Molecular Sequence Data
  • Neprilysin / antagonists & inhibitors*
  • Protease Inhibitors / pharmacology*
  • Rats
  • Rats, Sprague-Dawley


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Azepines
  • Dipeptides
  • Protease Inhibitors
  • Metalloendopeptidases
  • Neprilysin