Second generation 4-(4-methyl-1H-indol-5-ylamino)-2-phenylthieno[2,3-b]pyridine-5-carbonitrile PKCtheta inhibitors

Bioorg Med Chem Lett. 2009 Feb 1;19(3):766-9. doi: 10.1016/j.bmcl.2008.12.021. Epub 2008 Dec 10.

Abstract

Thieno[2,3-b]pyridine-5-carbonitrile 16 with a 4-methyl-5-indolylamine at C-4 and a 5-methoxy-2-(dimethylamino)-methylphenyl group at C-2 had an IC(50) value of 16 nM for the inhibition of PKCtheta. While moderate inhibition of PKCdelta was also observed (IC(50)=130 nM), 16 had IC(50) values of greater than 5 microM against Lyn and other members of the Src kinase family.

MeSH terms

  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / pharmacology
  • Inhibitory Concentration 50
  • Isoenzymes / antagonists & inhibitors*
  • Models, Chemical
  • Nitriles / chemical synthesis
  • Nitriles / chemistry*
  • Nitriles / pharmacology
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C-theta
  • Pyridines / chemistry*
  • Structure-Activity Relationship
  • src-Family Kinases / antagonists & inhibitors

Substances

  • 4-(4-methyl-1H-indol-5-ylamino)-2-phenylthieno(2,3-b)pyridine-5-carbonitrile
  • Enzyme Inhibitors
  • Indoles
  • Isoenzymes
  • Nitriles
  • Pyridines
  • src-Family Kinases
  • PRKCQ protein, human
  • Protein Kinase C
  • Protein Kinase C-theta