Aminoacetyl moiety as a potential surrogate for diacylhydrazine group of SC-51089, a potent PGE2 antagonist, and its analogs

J Med Chem. 1996 Jan 19;39(2):609-13. doi: 10.1021/jm950454k.

Abstract

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 Analogs of SC-51089, in which the diacylhydrazine functionality has been replaced by isosteric and isoelectronic groups, have been synthesized and have been shown to be analgesics and PGE2 antagonists of the EP1 subtype.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.

MeSH terms

  • Analgesics / chemistry
  • Analgesics / pharmacology*
  • Animals
  • Cells, Cultured
  • Dinoprostone / antagonists & inhibitors*
  • Guinea Pigs
  • Hydrazines / chemistry*
  • Hydrazines / pharmacology*
  • Ileum / drug effects
  • Ileum / metabolism
  • In Vitro Techniques
  • Liver / cytology
  • Liver / drug effects
  • Magnetic Resonance Spectroscopy
  • Oxazepines / chemistry
  • Oxazepines / pharmacology*
  • Prostaglandin Antagonists / chemistry
  • Prostaglandin Antagonists / pharmacology*
  • Rats

Substances

  • Analgesics
  • Hydrazines
  • Oxazepines
  • Prostaglandin Antagonists
  • SC 51089
  • hydrazine
  • Dinoprostone