The synthesis and evaluation of indolylureas as PKCα inhibitors

Jane F Djung; Richard J Mears; Christian A G N Montalbetti; Thomas S Coulter; Adam Golebiowski; Andrew N Carr; Oliver Barker; Kenneth D Greis; Songtao Zhou; Elizabeth Dolan; Gregory F Davis

doi:10.1016/j.bmc.2011.02.036

The synthesis and evaluation of indolylureas as PKCα inhibitors

Bioorg Med Chem. 2011 Apr 15;19(8):2742-50. doi: 10.1016/j.bmc.2011.02.036. Epub 2011 Feb 26.

Authors

Jane F Djung¹, Richard J Mears, Christian A G N Montalbetti, Thomas S Coulter, Adam Golebiowski, Andrew N Carr, Oliver Barker, Kenneth D Greis, Songtao Zhou, Elizabeth Dolan, Gregory F Davis

Affiliation

¹ Procter & Gamble Pharmaceuticals Inc., Health Care Research Center, Mason, OH 45040-9462, USA.

PMID: 21435888
DOI: 10.1016/j.bmc.2011.02.036

Abstract

PKCα and PKA have crucial but opposing roles in the regulation of calcium handling within myocytes. Identification of compounds that inhibit PKCα, but not PKA, are potential therapeutic targets for the treatment of heart disease. The synthesis of indolylureas are described, and a compound displaying nanomolar inhibition towards PKCα with significant selectivity over PKA has been identified.

MeSH terms

Cyclic AMP-Dependent Protein Kinases
Heart Diseases / drug therapy
Humans
Protein Kinase C-alpha / antagonists & inhibitors*
Protein Kinase Inhibitors / chemical synthesis*
Urea / chemical synthesis*
Urea / chemistry
Urea / pharmacology*

Substances

Protein Kinase Inhibitors
Urea
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C-alpha