S1P receptor mediated activity of FTY720 phosphate mimics

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1485-7. doi: 10.1016/j.bmcl.2010.01.118. Epub 2010 Jan 28.

Abstract

Various carboxylic acids, phosphonic acids, sulfonic acids, tetrazoles as well as sulfonylhydantoins were prepared as phosphate mimics of the chiral aminophosphate 1-P to act as agonists on the S1P(1) receptor. It was found that amino phosphonates and amino carboxylates are potent S1P(1) binders. beta-Amino acid 11 could be shown to reversibly reduce blood lymphocyte counts in rats after po administration.

MeSH terms

  • Administration, Oral
  • Amino Acids / chemistry
  • Animals
  • Fingolimod Hydrochloride
  • Immunosuppressive Agents / chemical synthesis
  • Immunosuppressive Agents / chemistry*
  • Immunosuppressive Agents / pharmacology
  • Isoleucine / analogs & derivatives*
  • Isoleucine / chemical synthesis
  • Isoleucine / chemistry
  • Isoleucine / pharmacology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Phosphates / chemistry*
  • Phosphorylation
  • Propylene Glycols / chemistry*
  • Propylene Glycols / pharmacology
  • Rats
  • Receptors, Lysosphingolipid / agonists*
  • Receptors, Lysosphingolipid / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / chemistry
  • Sphingosine / pharmacology

Substances

  • Amino Acids
  • Immunosuppressive Agents
  • Phosphates
  • Propylene Glycols
  • Receptors, Lysosphingolipid
  • Isoleucine
  • Fingolimod Hydrochloride
  • Sphingosine