Design and synthesis of a selective EP4-receptor agonist. Part 4: practical synthesis and biological evaluation of a novel highly selective EP4-receptor agonist

Bioorg Med Chem. 2002 Jul;10(7):2103-10. doi: 10.1016/s0968-0896(02)00085-8.

Abstract

A practical method of synthesizing a highly selective EP4-receptor agonist 1 using Corey lactone 2 as a key intermediate was developed. Selective methanesulfonylation of the primary alcohol of the diol 8 under the newly devised conditions followed by the protection of the remaining secondary alcohol are key reactions in this new method. Further biological evaluation of 1a-b is also reported.

MeSH terms

  • Animals
  • Blood Cells / drug effects
  • Blood Cells / metabolism
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / blood
  • Lipopolysaccharides / pharmacology
  • Rats
  • Receptors, Prostaglandin E / agonists*
  • Receptors, Prostaglandin E, EP4 Subtype
  • Signal Transduction
  • Spectrum Analysis
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Lipopolysaccharides
  • PTGER4 protein, human
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP4 Subtype
  • Tumor Necrosis Factor-alpha
  • Interleukin-10