Abstract
Two new series of potent and selective dual EGFR/ErbB-2 kinase inhibitors derived from novel thienopyrimidine cores have been identified. Isomeric thienopyrimidine cores were evaluated as isosteres for a 4-anilinoquinazoline core and several analogs containing the thieno[3,2-d]pyrimidine core showed anti-proliferative activity with IC(50) values less than 1 microM against human tumor cells in vitro.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Cell Proliferation
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Drug Screening Assays, Antitumor
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Enzyme Inhibitors / pharmacology
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ErbB Receptors / chemistry*
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Humans
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Inhibitory Concentration 50
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Lapatinib
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Models, Chemical
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Molecular Conformation
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Pyrimidines / chemistry*
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Quinazolines / pharmacology
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Receptor, ErbB-2 / antagonists & inhibitors*
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Pyrimidines
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Quinazolines
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thienopyrimidine
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Lapatinib
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ErbB Receptors
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Receptor, ErbB-2