Abstract
C-6 Biarylmethylamino purine derivatives of roscovitine (1) inhibit cyclin dependent kinases and demonstrate potent antiproliferative activity. Replacement of the aryl rings of the C-6 biarylmethylamino group with heterobiaryl rings has provided compounds with significantly improved activity. In particular, derivatives 18 g and 9 c demonstrated 1000-fold and 1250-fold improvements, respectively, in the growth inhibition of HeLa cells compared to roscovitine (1).
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Cell Proliferation / drug effects
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Cyclin-Dependent Kinases / antagonists & inhibitors*
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Drug Design
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Drug Screening Assays, Antitumor
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HeLa Cells
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Humans
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Molecular Structure
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Purines / chemical synthesis
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Purines / chemistry
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Purines / pharmacology*
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Roscovitine
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Purines
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Roscovitine
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Cyclin-Dependent Kinases