Abstract
Fifteen new thieno[2,3-b ]- and thieno[3,4-b]pyrrolizines were synthesized and tested against two protein kinases, CDK1/cyclin B and GSK-3. Among these compounds, 3-(3-hydroxy-4-methoxyphenyl)-8H-thieno[2,3-b]pyrrolizin-8-one 4g was identified as a moderate inhibitor of these kinases. Its molecular modeling study brought to the fore the pivotal role of the 2-methoxyphenol grouping and the interest in replacing it by bioisosteric moieties in future pharmacomodulations.
MeSH terms
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Binding Sites / drug effects
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CDC2 Protein Kinase / antagonists & inhibitors*
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Cell Cycle / drug effects
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Crystallography, X-Ray
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Cyclin B / antagonists & inhibitors
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Glycogen Synthase Kinase 3 / antagonists & inhibitors*
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Humans
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Models, Molecular
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Molecular Structure
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Protein Conformation
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Protein Structure, Tertiary
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Pyrroles / chemical synthesis*
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Pyrroles / chemistry
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Pyrroles / pharmacology*
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Structure-Activity Relationship
Substances
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Cyclin B
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Enzyme Inhibitors
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Pyrroles
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CDC2 Protein Kinase
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Glycogen Synthase Kinase 3