A novel series of potent and selective EP(4) receptor ligands: facile modulation of agonism and antagonism

Bioorg Med Chem Lett. 2011 Jan 1;21(1):484-7. doi: 10.1016/j.bmcl.2010.10.106. Epub 2010 Oct 28.

Abstract

A novel series of EP(4) ligands, based on a benzyl indoline scaffold, has been discovered. It was found that agonism and antagonism in this series can be easily modulated by minor modifications on the benzyl group. The pharmacokinetic, metabolic and pharmacological profiles of these compounds was explored. It was found that these compounds show good pharmacokinetics in rat and are efficacious in pre-clinical models of pain and inflammation.

MeSH terms

  • Animals
  • Arthritis / chemically induced
  • Arthritis / drug therapy
  • Drug Evaluation, Preclinical
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy
  • Indoles / chemistry*
  • Indoles / pharmacokinetics
  • Indoles / therapeutic use
  • Ligands
  • Rats
  • Receptors, Prostaglandin E, EP2 Subtype / agonists
  • Receptors, Prostaglandin E, EP2 Subtype / antagonists & inhibitors
  • Receptors, Prostaglandin E, EP2 Subtype / metabolism
  • Receptors, Prostaglandin E, EP4 Subtype / agonists*
  • Receptors, Prostaglandin E, EP4 Subtype / antagonists & inhibitors*
  • Receptors, Prostaglandin E, EP4 Subtype / metabolism
  • Structure-Activity Relationship

Substances

  • Indoles
  • Ligands
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • indoline