Novel tail and head group prostamide probes

Bioorg Med Chem Lett. 2015 Mar 15;25(6):1228-31. doi: 10.1016/j.bmcl.2015.01.064. Epub 2015 Feb 4.

Abstract

We report the design and synthesis of novel prostaglandin-ethanolamide (PGE2-EA) analogs containing head and tail group modifications to aid in the characterization of a putative prostamide receptor(s). Our synthetic approach utilizes Horner-Wadsworth-Emmons and Wittig reactions to construct the head and the tail moieties of the key PGE2 precursor, which leads to the final products through a peptide coupling, Swern oxidation and HF/pyridine assisted desilylation. The synthesized analogs were shown not to interact significantly with endocannabinoid proteins and recombinant EP1, EP3 and EP4 receptors and suggest a yet to be identified prostamide receptor as their site(s) of action.

Keywords: Cyclooxygenase-2; Endocannabinoids; Prostamides.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / metabolism
  • Amidohydrolases / antagonists & inhibitors
  • Amidohydrolases / metabolism
  • Animals
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Humans
  • Mice
  • Monoacylglycerol Lipases / antagonists & inhibitors
  • Monoacylglycerol Lipases / metabolism
  • Prostaglandins / biosynthesis
  • Prostaglandins / chemistry*
  • Protein Binding
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB2 / metabolism
  • Stereoisomerism

Substances

  • Amides
  • Enzyme Inhibitors
  • Prostaglandins
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Monoacylglycerol Lipases
  • Amidohydrolases
  • NAAA protein, human
  • fatty-acid amide hydrolase