Design and synthesis of sulfamoyl benzoic acid analogues with subnanomolar agonist activity specific to the LPA2 receptor

J Med Chem. 2014 Aug 28;57(16):7136-40. doi: 10.1021/jm5007116. Epub 2014 Aug 12.

Abstract

Lysophosphatidic acid (LPA) is a growth factor-like mediator and a ligand for multiple GPCR. The LPA2 GPCR mediates antiapoptotic and mucosal barrier-protective effects in the gut. We synthesized sulfamoyl benzoic acid (SBA) analogues that are the first specific agonists of LPA2, some with subnanomolar activity. We developed an experimental SAR that is supported and rationalized by computational docking analysis of the SBA compounds into the LPA2 ligand-binding pocket.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoates / chemistry*
  • Binding Sites
  • Chemistry Techniques, Synthetic
  • Drug Design
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Molecular Docking Simulation
  • Receptors, Lysophosphatidic Acid / agonists*
  • Receptors, Lysophosphatidic Acid / chemistry
  • Receptors, Lysophosphatidic Acid / metabolism
  • Structure-Activity Relationship

Substances

  • Benzoates
  • Receptors, Lysophosphatidic Acid
  • carzenide