Synthesis of para-alkyl aryl amide analogues of sphingosine-1-phosphate: discovery of potent S1P receptor agonists

Bioorg Med Chem Lett. 2003 Oct 20;13(20):3401-4. doi: 10.1016/s0960-894x(03)00812-6.


Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid with the capacity to induce a broad range of cellular responses via its interaction with the S1P family of G-protein coupled receptors. This report describes the synthesis of several potent S1P receptor agonists. For instance, compound 9c displayed an EC(50)=8.6 nM at the S1P(1) receptor using a [gamma-35S]GTP binding assay as compared to an EC(50)=4.5 nM for the endogenous ligand. We also report the effects associated with introduction of a phenyl ring between the 'linker' and 'lipophilic tail' regions of the analogues, for example total loss of activity at S1P(2) and increased agonism at S1P(5).

Publication types

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

MeSH terms

  • Amides / chemistry*
  • Cell Line
  • Humans
  • Lysophospholipids*
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, Lysophospholipid
  • Sphingosine / analogs & derivatives*
  • Sphingosine / chemical synthesis
  • Sphingosine / chemistry*


  • Amides
  • Lysophospholipids
  • Receptors, G-Protein-Coupled
  • Receptors, Lysophospholipid
  • sphingosine 1-phosphate
  • Sphingosine