Synthesis and biological properties of novel sphingosine derivatives

Bioorg Med Chem Lett. 2005 Feb 15;15(4):1115-9. doi: 10.1016/j.bmcl.2004.12.010.

Abstract

Sphingosine-1-phosphate (S-1P) derivatives such as threo-(2S,3S)-analogues, which are C-3 stereoisomers of natural erythro-(2S,3R)-S-1P, have been synthesized starting from l-serine or (1S,2S)-2-amino-1-aryl-1,3-propanediols (6). threo-(1S,2R)-2-Amino-1-aryl-3-bromopropanols (HBr salt) have also been prepared from 6. The threo-S-1Ps and the threo-amino-bromide derivatives have shown potent inhibitory activity against Ca(2+) ion mobilization in HL60 cells induced by erythro-S-1P, suggesting that these compounds would compete with cell surface EDG/S1P receptors.

MeSH terms

  • Calcium Signaling / drug effects*
  • HL-60 Cells
  • Humans
  • Lysophospholipids / chemical synthesis*
  • Lysophospholipids / pharmacology
  • Receptors, Lysosphingolipid / agonists
  • Receptors, Lysosphingolipid / antagonists & inhibitors
  • Sphingosine / analogs & derivatives*
  • Sphingosine / chemical synthesis*
  • Sphingosine / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Lysophospholipids
  • Receptors, Lysosphingolipid
  • erythro-(2R,3S)-sphingosine
  • sphingosine 1-phosphate
  • Sphingosine