Synthesis and PKCtheta inhibitory activity of a series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6575-7. doi: 10.1016/j.bmcl.2009.10.031. Epub 2009 Oct 13.

Abstract

A series of 5-vinyl phenyl sulfonamide-3-pyridinecarbonitriles were prepared and evaluated as PKCtheta inhibitors. Optimization resulted in the identification of compound 15 with an IC(50) value 0.44 nM for the inhibition of PKCtheta with 150-fold selectivity over PKCdelta.

MeSH terms

  • Drug Design
  • Isoenzymes / antagonists & inhibitors*
  • Molecular Structure
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Isoenzymes
  • Protein Kinase Inhibitors
  • Pyridines
  • Sulfonamides
  • Protein Kinase C