Abstract
The iterative process for the discovery of a series of pyrazinone mono-amides as potent, selective and reversible non-peptide caspase-3 inhibitors (e.g., M826 and M867) is reported. These compounds display potent anti apoptotic activities in a number of cell based systems in vitro as well as in several animal models in vivo.
MeSH terms
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Amides / chemical synthesis*
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Amides / pharmacology
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Animals
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Apoptosis / drug effects
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Caspase 3
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Caspase Inhibitors*
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Drug Design
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Humans
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Inhibitory Concentration 50
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Leukocytes / drug effects
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Mice
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Neurons / drug effects
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Pyrazines / chemical synthesis
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Pyrazines / pharmacology
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Rats
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Structure-Activity Relationship
Substances
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Amides
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Caspase Inhibitors
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Enzyme Inhibitors
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Pyrazines
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CASP3 protein, human
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Casp3 protein, mouse
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Casp3 protein, rat
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Caspase 3