Development of carbohydrate-derived inhibitors of acid sphingomyelinase

Bioorg Med Chem. 2010 Jan 15;18(2):939-44. doi: 10.1016/j.bmc.2009.11.030. Epub 2009 Dec 11.


The acid sphingomyelinase is an emerging drug target, especially for inflammatory lung diseases. Presently, there are no directly-acting potent inhibitors available for cell-based studies. The potent inhibitor phosphatidylinositol-3,5-bisphosphate (PtdIns3,5P2) is not only unsuited for cell culture studies, but also does not provide hints for further structural improvements. In the SAR study described here, we replaced the inositolphosphate moiety by a carbohydrate derivative and the phosphatidic acid residue by an alkylsulfone ester. The resulting compound is more active than its parent compound and offers new means for further structural modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Carbohydrates / chemical synthesis
  • Carbohydrates / chemistry
  • Carbohydrates / pharmacology*
  • Cell Line
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Conformation
  • Rats
  • Sphingomyelin Phosphodiesterase / antagonists & inhibitors*
  • Sphingomyelin Phosphodiesterase / isolation & purification
  • Stereoisomerism
  • Structure-Activity Relationship


  • Carbohydrates
  • Enzyme Inhibitors
  • Sphingomyelin Phosphodiesterase