DUAL METALLOPROTEASE INHIBITORS .6. INCORPORATION OF BICYCLIC AND SUBSTITUTED MONOCYCLIC AZEPINONES AS DIPEPTIDE SURROGATES IN ANGIOTENSIN-CONVERTING ENZYME NEUTRAL ENDOPEPTIDASE INHIBITORS

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