3,5-diarylazoles as novel and selective inhibitors of protein kinase D

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1447-51. doi: 10.1016/j.bmcl.2011.01.014. Epub 2011 Jan 11.

Abstract

The synthesis and preliminary studies of the SAR of novel 3,5-diarylazole inhibitors of Protein Kinase D (PKD) are reported. Notably, optimized compounds in this class have been found to be active in cellular assays of phosphorylation-dependant HDAC5 nuclear export, orally bioavailable, and highly selective versus a panel of additional putative histone deacetylase (HDAC) kinases. Therefore these compounds could provide attractive tools for the further study of PKD/HDAC5 signaling.

MeSH terms

  • Administration, Oral
  • Animals
  • Azoles / chemical synthesis
  • Azoles / chemistry
  • Azoles / pharmacokinetics
  • Azoles / pharmacology*
  • Biological Availability
  • Histone Deacetylases / metabolism
  • Inhibitory Concentration 50
  • Molecular Structure
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C / metabolism
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Azoles
  • Protein Kinase Inhibitors
  • protein kinase D
  • Protein Kinase C
  • Hdac5 protein, rat
  • Histone Deacetylases