AMINOACETYL MOIETY AS A POTENTIAL SURROGATE FOR DIACYLHYDRAZINE GROUPOF SC-51089, A POTENT PGE(2) ANTAGONIST, AND ITS ANALOGS

Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4 -pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a func tional PGE(2) antagonist selective for the EP(1) receptor subtype with antinociceptive activity. During metabolism in cultured rat hepatocyt es, SC-51089, which contains a diacylhydrazine moiety, has been shown to release hydrazine. Analogs of SC-51089, in which the diacylhydrazin e functionality has been replaced by isosteric and isoelectronic group s, have been synthesized and have been shown to be analgesics and PGE( 2) antagonists of the EP(1) subtype. This report discusses the structu re-activity relationships within these series.