Lactams as EP4 prostanoid receptor subtype selective agonists. Part 1: 2-Pyrrolidinones-stereochemical and lower side-chain optimization

Bioorg Med Chem Lett. 2004 Apr 5;14(7):1655-9. doi: 10.1016/j.bmcl.2004.01.063.

Abstract

A series of 7-[(5R)-substituted 2-oxo-1-pyrrolidinyl]-heptanoic acids were prepared, their isomeric purity determined, and pharmacologically evaluated. Lactams with affinity for the EP(4) receptor displayed agonist behavior. The lower side-chain of the lactam template could be substituted to afford ligands (e.g., 17, 24, 30, 31, and 33) of high potency and greater than 1000-fold affinity for EP(4) versus the other EP prostanoid receptors.

MeSH terms

  • Lactams / chemistry*
  • Lactams / metabolism
  • Protein Binding
  • Pyrrolidinones / chemistry*
  • Pyrrolidinones / metabolism
  • Receptors, Prostaglandin E / agonists*
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E, EP4 Subtype
  • Stereoisomerism

Substances

  • Lactams
  • Pyrrolidinones
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP4 Subtype
  • 2-pyrrolidone