The discovery of highly selective erbB2 (Her2) inhibitors for the treatment of cancer
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- 作者：Blaise Lippa ; Goss S. Kauffman ; Joel Arcari ; Tricia Kwan ; Jinshan Chen ; William Hungerford ; Samit Bhattacharya ; Xumiao Zhao ; Courtney Williams ; Jun Xiao ; et al.
- 关键词：erbB2 ; Her2 ; Anilinoquinazoline ; Kinase ; Cancer
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2007
- 出版时间：1 June 2007
- 年：2007
- 卷：17
- 期：11
- 页码：3081-3086
- 全文大小：161 K
文摘
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.