Abstract
A series of N-phenyl-imidazo[4,5-b]pyridin-2-amines, 4-indazolyl-N-phenylpyrimidin-2-amines and N-phenyl-4-pyrazolo[3,4-b]pyridin-pyrimidin-2-amines have been synthesized. Their anti-proliferative activities were tested in HCT-116 human colon carcinoma and MCF-7 breast carcinoma cell lines. Many exhibited potent anti-proliferative and CDK9 inhibitory activities. A lead compound 18b demonstrated the ability to reduce the level of Mcl-1 anti-apoptotic protein, to activate caspase 3/7 and induce cancer cell apoptosis.
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Amines / chemical synthesis*
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Amines / pharmacology
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Caspase 3 / metabolism
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Caspase 7 / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cyclin-Dependent Kinase 9 / antagonists & inhibitors
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Cyclin-Dependent Kinase 9 / metabolism
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Drug Design
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Drug Discovery
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Enzyme Activation / drug effects
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Humans
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Myeloid Cell Leukemia Sequence 1 Protein
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Protein Kinase Inhibitors / chemical synthesis*
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Pyridines / chemical synthesis*
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Pyridines / pharmacology
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Pyrimidines / chemical synthesis*
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Pyrimidines / pharmacology
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Structure-Activity Relationship
Substances
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Amines
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Antineoplastic Agents
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Myeloid Cell Leukemia Sequence 1 Protein
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Protein Kinase Inhibitors
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Proto-Oncogene Proteins c-bcl-2
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Pyridines
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Pyrimidines
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CDK9 protein, human
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Cyclin-Dependent Kinase 9
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Caspase 3
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Caspase 7