The discovery of highly selective erbB2 (Her2) inhibitors for the treatment of cancer.
2007
Abstract The synthesis and biological evaluation of potent and selective inhibitors of the erbB2 kinase is presented. Based on the 4-anilinoquinazoline chemotype, the syntheses of several new series of erbB2 inhibitors are described with quinazoline and pyrido[4,3- d ]pyrimidine cores. The vast majority of these compounds are found to be >100× selective over the closely related EGFR kinase. Two lead compounds are further shown to have low clearance and moderate bioavailability in rat.
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