Synthesis and PKCtheta inhibitory activity of a series of 4-(indol-5-ylamino)thieno[2,3-b]pyridine-5-carbonitriles

Diane H Boschelli; Biqi Wu; Ana Carolina Barrios Sosa; Joan Chen; Magda Asselin; Derek C Cole; Julie Lee; Xiaoke Yang; Divya Chaudhary

doi:10.1016/j.bmcl.2008.03.077

Synthesis and PKCtheta inhibitory activity of a series of 4-(indol-5-ylamino)thieno[2,3-b]pyridine-5-carbonitriles

Bioorg Med Chem Lett. 2008 May 1;18(9):2850-3. doi: 10.1016/j.bmcl.2008.03.077. Epub 2008 Apr 8.

Authors

Diane H Boschelli¹, Biqi Wu, Ana Carolina Barrios Sosa, Joan Chen, Magda Asselin, Derek C Cole, Julie Lee, Xiaoke Yang, Divya Chaudhary

Affiliation

¹ Wyeth Research, Chemical and Screening Sciences, 401 N. Middletown Road, Pearl River, NY 10965, USA. bosched@wyeth.com

PMID: 18434148
DOI: 10.1016/j.bmcl.2008.03.077

Abstract

The thieno[2,3-b]pyridine-5-carbonitrile with a 5-indolylamine at C-4 and a phenyl group at C-2 had a moderate activity against PKCtheta. Optimization of the groups at C-4 and C-2 led to analog 29, which has an IC(50) value of 7.5nM for the inhibition of PKCtheta.

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Cell Line, Tumor / drug effects
Cell Line, Tumor / pathology
Inhibitory Concentration 50
Isoenzymes / antagonists & inhibitors*
Mice
Mice, Knockout
Models, Chemical
Nitriles / chemical synthesis
Nitriles / pharmacology*
Protein Kinase C / antagonists & inhibitors*
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / pharmacology*
Pyridines / chemical synthesis
Pyridines / pharmacology*
Rats
Structure-Activity Relationship
Thiophenes / chemical synthesis
Thiophenes / pharmacology*

Substances

Antineoplastic Agents
Isoenzymes
Nitriles
Protein Kinase Inhibitors
Pyridines
Thiophenes
Protein Kinase C