The synthesis and evaluation of indolylureas as PKCα inhibitors

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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2011-04, Vol.19 (8), p.2742-2750
Main Authors: Djung, Jane F., Mears, Richard. J., Montalbetti, Christian A.G.N., Coulter, Thomas S., Golebiowski, Adam, Carr, Andrew N., Barker, Oliver, Greis, Kenneth D., Zhou, Songtao, Dolan, Elizabeth, Davis, Gregory F.
Format: Article
Language:English
Subjects:
Biological and medical sciences
calcium
cAMP-dependent protein kinase
Cardiovascular system
chemistry
Cyclic AMP-Dependent Protein Kinases
Heart disease
heart diseases
Heart Diseases - drug therapy
Humans
Indolylurea
Kinase inhibitor
Medical sciences
Miscellaneous
myocytes
Pharmacology. Drug treatments
Protein kinase C alpha
Protein Kinase C-alpha - antagonists & inhibitors
Protein Kinase Inhibitors - chemical synthesis
Urea - chemical synthesis
Urea - chemistry
Urea - pharmacology
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Summary: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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2011.02.036