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• 作者：Longbin Liu ; Aaron Siegmund ; Ning Xi ; Paula Kaplan-Lefko ; Karen Rex ; April Chen ; Jasmine Lin ; Jodi Moriguchi ; Loren Berry ; Liyue Huang ; Yohannes Teffera ; Yajing Yang ; Yihong Zhang ; Steven F. Bellon ; M
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：July 10, 2008
• 年：2008
• 卷：51
• 期：13
• 页码：3688 - 3691
• 全文大小：569K
• 年卷期：v.51,no.13(July 10, 2008)
• ISSN：1520-4804

文摘

Deregulation of the receptor tyrosine kinase c-Met has been implicated in human cancers. Pyrazolones with N-1 bearing a pendent hydroxyalkyl side chain showed selective inhibition of c-Met over VEGFR2. However, studies revealed the generation of active, nonselective metabolites. Blocking this metabolic hot spot led to the discovery of 17 (AMG 458). When dosed orally, 17 significantly inhibited tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models with no adverse effect on body weight.