3-(2-Aminocarbonylphenyl)propanoic acid analogs as potent and selective EP3 receptor antagonists. Part 3: Synthesis, metabolic stability, and biological evaluation of optically active analogs

Bioorg Med Chem. 2010 May 1;18(9):3212-23. doi: 10.1016/j.bmc.2010.03.028. Epub 2010 Mar 17.


A series of 3-(2-aminocarbonylphenyl)propanoic acid analogs possessing the (1R)-1-(3,5-dimethylphenyl)-3-methylbutylamine moiety on the carboxyamide side chain were synthesized and evaluated for their binding affinity for the EP1-4 receptors and their antagonist activity for the EP3 receptor. Rational drug design based on the structure of the metabolites in human liver microsomes led us to the discovery of another series of analogs. Several compounds were further evaluated for their in vivo efficacy in rats after oral administration and also for their pharmacokinetic profiles including in vitro stability in the liver microsomes.

MeSH terms

  • Administration, Oral
  • Animals
  • Binding, Competitive
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Drug Stability
  • Female
  • Humans
  • Microsomes, Liver / chemistry
  • Microsomes, Liver / metabolism*
  • Molecular Structure
  • Phenyl Ethers
  • Pregnancy
  • Pregnancy, Animal
  • Propionates* / chemical synthesis
  • Propionates* / chemistry
  • Radioligand Assay
  • Rats
  • Receptors, Prostaglandin E / antagonists & inhibitors*
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E, EP3 Subtype


  • 3-(2-aminocarbonyl-4-phenoxymethylphenyl)propanoic acid
  • PTGER3 protein, human
  • Phenyl Ethers
  • Propionates
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP3 Subtype