Synthesis and biological evaluation of phosphonic and thiophosphoric acid derivatives of lysophosphatidic acid

Bioorg Med Chem Lett. 2004 Jul 5;14(13):3473-6. doi: 10.1016/j.bmcl.2004.04.061.

Abstract

Using an N-oleoyl ethanolamide scaffold, a series of phosphate polar head group analogues of LPA comprised of various alpha-substituted phosphonates and thiophosphates was prepared. In a broken cell GTP[gamma35S] binding assay, agonist activity was evaluated at the three LPA receptors of the endothelial differentiation gene (Edg) family. This study has resulted in the discovery of a nonhydrolyzable LPA1-selective agonist (11). Additionally, thiophosphate 19 bears an isosteric phosphate mimetic that confers agonism at the LPA1 receptor but not LPA2.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amides / chemistry
  • Animals
  • Cells, Cultured
  • Lysophospholipids / chemical synthesis*
  • Lysophospholipids / pharmacology
  • Oleic Acids / chemistry
  • Phosphates / chemistry*
  • Phosphoric Acids / chemistry*
  • Radioligand Assay / methods
  • Receptors, Lysophosphatidic Acid / agonists*
  • Receptors, Lysophosphatidic Acid / metabolism
  • Stearic Acids / chemistry

Substances

  • Amides
  • Lysophospholipids
  • Oleic Acids
  • Phosphates
  • Phosphoric Acids
  • Receptors, Lysophosphatidic Acid
  • Stearic Acids
  • phosphoric acid
  • thiophosphoric acid
  • isostearic acid