Abstract
A series of novel 2-phenylaminopyrimidine (PAP) derivatives structurally related to STI-571 were designed and synthesized. The abilities of these compounds to inhibit proliferation were tested in human chronic myeloid leukemia K562 cells. (E)-3-(2-bromophenyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]acrylamide(12d) was the most effective cell growth inhibitor and was 3-fold more potent than STI-571.
MeSH terms
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Acrylamides / chemical synthesis
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Acrylamides / chemistry*
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Acrylamides / pharmacology
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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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Benzamides
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Drug Design*
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Fusion Proteins, bcr-abl / antagonists & inhibitors
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Fusion Proteins, bcr-abl / metabolism
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Humans
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Imatinib Mesylate
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Piperazines / chemical synthesis
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Piperazines / chemistry*
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Piperazines / pharmacology
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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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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry*
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Pyrimidines / pharmacology
Substances
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(E)-3-(2-bromophenyl)-N-(4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl)acrylamide
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Acrylamides
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Antineoplastic Agents
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Benzamides
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Piperazines
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Protein Kinase Inhibitors
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Pyrimidines
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Imatinib Mesylate
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Protein-Tyrosine Kinases
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Fusion Proteins, bcr-abl