Synthesis and evaluation of novel phosphate ester analogs as neutral sphingomyelinase inhibitors

Bioorg Med Chem Lett. 2010 Jul 1;20(13):3868-71. doi: 10.1016/j.bmcl.2010.05.042. Epub 2010 May 15.

Abstract

A novel sphingomyelin inhibitor RY221B-a, which contains a bipyridyl moiety as a metal coordination site was designed based upon the mechanism of phosphate ester hydrolysis. RY221B-a was synthesized from N-Boc-sphingosine in three steps via selective etherification using stannyl acetal. Synthesized RY221B-a exhibited relatively-strong inhibitory activity against Bc-SMase (IC(50)=1.2microM).

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / analogs & derivatives*
  • 2,2'-Dipyridyl / chemical synthesis
  • 2,2'-Dipyridyl / chemistry
  • 2,2'-Dipyridyl / pharmacology
  • Bacillus cereus / enzymology
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Sphingomyelin Phosphodiesterase / antagonists & inhibitors*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / chemical synthesis
  • Sphingosine / chemistry
  • Sphingosine / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • RY221B-a
  • 2,2'-Dipyridyl
  • Sphingomyelin Phosphodiesterase
  • Sphingosine