Fluorinated triazole-containing sphingosine analogues. Syntheses and in vitro evaluation as SPHK inhibitors

Org Biomol Chem. 2018 Oct 10;16(39):7230-7235. doi: 10.1039/c8ob01867g.

Abstract

Sphingosine analogues with a rigid triazole moiety in the aliphatic chain and systematic modifications in the polar head and different degrees of fluorination at the terminus of the alkylic chain were synthesized from a common alkynyl aziridine key synthon. This key synthon was obtained by enantioselective organocatalyzed aziridination and it was subsequently ring opened in a regioselective manner in acidic medium. Up to 16 sphingosine analogues were prepared in a straightforward manner. The in vitro activity of the obtained products as SPHK1 and SPHK2 inhibitors was evaluated, displaying comparable activity to that of DMS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry Techniques, Synthetic
  • Click Chemistry
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Halogenation*
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
  • Sphingosine / chemical synthesis*
  • Sphingosine / chemistry
  • Sphingosine / pharmacology*
  • Stereoisomerism
  • Triazoles / chemistry*

Substances

  • Enzyme Inhibitors
  • Triazoles
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase
  • Sphingosine