Discovery of novel sphingosine kinase-1 inhibitors. Part 2

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4550-4. doi: 10.1016/j.bmcl.2010.06.019. Epub 2010 Jun 17.

Abstract

Building on our initial work, we have identified additional novel inhibitors of sphingosine kinase-1 (SK1). These new analogs address the shortcomings found in our previously reported compounds. Inhibitors 51 and 54 demonstrated oral bioavailability in a rat PK study.

MeSH terms

  • Animals
  • Benzaldehydes / chemical synthesis
  • Benzaldehydes / chemistry*
  • Benzaldehydes / pharmacokinetics
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacokinetics
  • Humans
  • Lithium / chemistry*
  • Microsomes, Liver / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Rats

Substances

  • Benzaldehydes
  • Enzyme Inhibitors
  • Lithium
  • 4-cyanobenzaldehyde
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase