Abstract
Starting from initial lead 1 containing a basic 5-substituent, optimisation of the glycolamide-derived neutral 5-substituent led to potent inhibitors of erbB2 with good pharmacokinetics. Representative compounds 19 and 21 inhibited phosphorylation of erbB2 in a mouse BT474C xenograft model after oral administration.
MeSH terms
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Administration, Oral
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Animals
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Cell Line
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Magnetic Resonance Spectroscopy
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Mice
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Neoplasm Transplantation
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Phosphorylation
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacokinetics
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Protein Kinase Inhibitors / pharmacology*
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Quinazolines / administration & dosage
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Quinazolines / chemistry
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Quinazolines / pharmacokinetics
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Quinazolines / pharmacology*
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Receptor, ErbB-2 / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Protein Kinase Inhibitors
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Quinazolines
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Receptor, ErbB-2