Discovery of novel S1P2 antagonists. Part 1: discovery of 1,3-bis(aryloxy)benzene derivatives

Bioorg Med Chem Lett. 2015 Apr 1;25(7):1479-82. doi: 10.1016/j.bmcl.2015.02.029. Epub 2015 Feb 23.

Abstract

The structure-activity relationships of a novel series of sphingosine-1-phosphate receptor antagonists have been examined in detail. The initial hit compound 1 was modified through synthesis to improve its S1P2 activity. The synthesis of a series of analogs revealed that 1,3-bis(aryloxy)benzene derivatives, as represented by 22, are potent and selective S1P2 antagonists.

Keywords: Antagonist; G protein-coupled receptors; Sphingosine-1-phosphate receptor 2.

MeSH terms

  • Benzene Derivatives / chemical synthesis
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Molecular Structure
  • Receptors, Lysosphingolipid / antagonists & inhibitors*
  • Sphingosine-1-Phosphate Receptors
  • Structure-Activity Relationship

Substances

  • Benzene Derivatives
  • Receptors, Lysosphingolipid
  • S1PR2 protein, human
  • Sphingosine-1-Phosphate Receptors