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.
Webster L Santos  1 ,  Brian H Heasley ,  Renata Jarosz ,  Karen M Carter ,  Kevin R Lynch ,  Timothy L Macdonald
Affiliations
  • 1. Department of Chemistry and Chemical Biology, 12 Oxford Street, Cambridge, MA 02138, USA.
PMID: 15177455 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.

Products