Solid-phase analogue synthesis of caspase-3 inhibitors via palladium-catalyzed amination of 3-bromopyrazinones

Caspase-3 is a cysteinyl protease that mediates apoptotic cell death. Its inhibition may have an important impact on the treatment of several degenerative diseases. Here we report the synthesis of reversible inhibitors via a solid-support palladium-catalyzed amination of 3-bromopyrazinones and the d...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2007-03, Vol.17 (6), p.1671-1674
Main Authors: Isabel, Elise, Aspiotis, Renee, Black, W. Cameron, Colucci, John, Fortin, Réjean, Giroux, André, Grimm, Erich L., Han, Yongxin, Mellon, Christophe, Nicholson, Donald W., Rasper, Dita M., Renaud, Johanne, Roy, Sophie, Tam, John, Tawa, Paul, Vaillancourt, John P., Xanthoudakis, Steven, Zamboni, Robert J.
Format: Article
Language:English
Subjects:
Amination
Biological and medical sciences
Caspase
Caspase Inhibitors
Catalysis
Cell Line
Chromatography, High Pressure Liquid
Humans
Indicators and Reagents
Mass Spectrometry
Medical sciences
Miscellaneous
Palladium - chemistry
Palladium-catalyzed amination
Pharmacology. Drug treatments
Protease Inhibitors - chemical synthesis
Protease Inhibitors - pharmacology
Pyrazines - chemical synthesis
Pyrazines - pharmacology
Pyrazinone
Recombinant Proteins - chemistry
Structure-Activity Relationship
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Summary:Caspase-3 is a cysteinyl protease that mediates apoptotic cell death. Its inhibition may have an important impact on the treatment of several degenerative diseases. Here we report the synthesis of reversible inhibitors via a solid-support palladium-catalyzed amination of 3-bromopyrazinones and the discovery of a pan-caspase reversible inhibitor.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.12.110