Abstract
An imidazole series of cyclin-dependent kinase (CDK) inhibitors has been developed. Protein inhibitor structure determination has provided an understanding of the emerging structure activity trends for the imidazole series. The introduction of a methyl sulfone at the aniline terminus led to a more orally bioavailable CDK inhibitor that was progressed into clinical development.
MeSH terms
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Aniline Compounds / chemistry
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Animals
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Cell Cycle Proteins / chemistry
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Chemistry, Pharmaceutical / methods
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Crystallography, X-Ray / methods
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Cyclin-Dependent Kinases / antagonists & inhibitors*
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Drug Design
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Humans
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Hydrogen Bonding
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Imidazoles / chemistry*
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Inhibitory Concentration 50
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Mice
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Models, Chemical
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Molecular Conformation
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Structure-Activity Relationship
Substances
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Aniline Compounds
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Cell Cycle Proteins
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Imidazoles
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Cyclin-Dependent Kinases
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aniline