Orally Active, Nonpeptide Oxytocin Antagonists

J Med Chem. 1992 Oct 16;35(21):3919-27. doi: 10.1021/jm00099a020.

Abstract

The first nonpeptide antagonists of the neurohypophyseal hormone, oxytocin (OT) are described. Derivatives of the spiroindenepiperidine ring system, these compounds include L-366,509, an orally bioavailable OT antagonist with good in vivo duration. The potential use of these agents for treatment of preterm labor and their significance as new nonpeptide ligands for peptide receptors are discussed.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Female
  • Magnetic Resonance Spectroscopy
  • Obstetric Labor, Premature / drug therapy
  • Oxytocin / antagonists & inhibitors*
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Pregnancy
  • Rats
  • Receptors, Angiotensin / metabolism
  • Receptors, Oxytocin
  • Receptors, Vasopressin / metabolism
  • Spiro Compounds / administration & dosage
  • Spiro Compounds / pharmacology*
  • Spiro Compounds / therapeutic use
  • Structure-Activity Relationship

Substances

  • Piperidines
  • Receptors, Angiotensin
  • Receptors, Oxytocin
  • Receptors, Vasopressin
  • Spiro Compounds
  • L 366509
  • Oxytocin