NEW ORALLY-ACTIVE ENKEPHALINASE INHIBITORS - THEIR SYNTHESIS, BIOLOGICAL-ACTIVITY, AND ANALGESIC PROPERTIES

A series of captopropionylamino]-4-(N-phenylcarbamoyl)-butyric acids h as been identified as potent systemically active enkephalinase inhibit ors. Structure-activity relationships (SAR) are discussed. Further che mical modification of the inhibitors was carried out in order to ident ify the inhibitors which are orally active in an animal model. Compoun ds of particular interest are the prodrug-like analogues, including 5b (ONO-9902). Their analgesic effects after oral administration were ev aluated. (C) 1998 Elsevier Science Ltd. All rights reserved.