Abstract
We herein describe the synthesis of novel dipyrrolo- and furopyrrolopyrazinones related to highly cytotoxic tripentones and to their oximes. The synthetic pathway involved in particular a Curtius rearrangement and a subsequent cyclisation into the title pyrazinones. The biological evaluation towards various cyclin-dependent kinases (CDKs1-5, GSK-3) highlighted a weak inhibitory activity for the oximes whose SAR was studied by a molecular modeling study.
MeSH terms
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Animals
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Cyclin-Dependent Kinases / antagonists & inhibitors*
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Cyclization
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Glycogen Synthase Kinase 3 / antagonists & inhibitors*
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Humans
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Ketones
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Models, Molecular
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Oximes
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / pharmacology
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Pyrazines / chemical synthesis*
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Pyrazines / pharmacology
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Structure-Activity Relationship
Substances
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Ketones
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Oximes
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Protein Kinase Inhibitors
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Pyrazines
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Cyclin-Dependent Kinases
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Glycogen Synthase Kinase 3