There was a two-fold or greater increase in the activity of sulfisoxazole against S. pyogenes 4 in combination with 3a-d (2.1-, 3.8-, 2.6-, and 6.2-fold, respectively); against D. pneumoniae 6301 in combination with 3b,c,e (2.1-, 2.1-, and 3.8-fold, respectively); against S. aureus 209 in combination with 3a-e (>5.0-, 4.0-, >3.5-, 2.5-, and >11.0-fold, respectively); against E. coli 257 in combination with 3a-e (2.0-, 5.7-, 4.7-, 2.5-, and >8.9-fold, respectively); against K. pneumoniae KA in combination with 3b and 3e (3.1-, and 4.1-fold, respectively); against P. vulgaris 190 in combination with 3a,b,c,e (2.3-, 2.6-, 11.1-, and 9.2-fold, respectively); in combination with 3b and 3e against S. typhosa P58a (11.0-and 4.0-fold, respectively) and in combination with 3b against S. schottmuelleri (5.4-fold). No potentiation of sulfisoxazole was observed with any compound against P. aeruginosa. These results are summarized in Table III.

8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a functional PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activity. During metabolism in cultured rat hepatocytes, SC-51089, which contains a diacylhydrazine moiety, has been shown to release hydrazine. Analogs of SC-51089, in which the diacylhydrazine functionality has been replaced by isosteric and isoelectronic groups, have been synthesized and have been shown to be analgesics and PGE2 antagonists of the EP1 subtype. This report discusses the structure-activity relationships within these series.

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