Abstract
The discovery of a class of diheteroaromatic amines based on LY2835219 as cyclin-dependent kinase (CDK1/4/6) inhibitors was described. The series was found to have much more improved CDK1 inhibition and potent in vitro anti-proliferative effects against cancer cell lines. The synthesis and structure-activity relationship studies of these compounds were reported. One promising compound was selected to evaluate as a novel lead compound after in vitro and in vivo profiling.
Keywords:
CDK inhibitor; Cyclin-dependent kinase; In vitro and in vivo profiling; Structure-activity relationship.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Amines / administration & dosage
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Amines / chemistry
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Amines / pharmacology*
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Animals
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Biological Availability
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CDC2 Protein Kinase / antagonists & inhibitors*
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CDC2 Protein Kinase / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
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Cyclin-Dependent Kinase 4 / metabolism
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Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
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Cyclin-Dependent Kinase 6 / metabolism
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Dose-Response Relationship, Drug
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Drug Discovery
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Drug Screening Assays, Antitumor
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Humans
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Male
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Mice
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Mice, Inbred ICR
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Molecular Docking Simulation
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Molecular Structure
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Structure-Activity Relationship
Substances
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Amines
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Antineoplastic Agents
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Protein Kinase Inhibitors
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CDC2 Protein Kinase
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CDK1 protein, human
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CDK4 protein, human
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CDK6 protein, human
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase 6