Discovery of orally active pyrrolopyridine- and aminopyridine-based Met kinase inhibitors

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• 作者：Zhen-Wei Cai ; Donna Wei ; Gretchen M. Schroeder ; Lyndon A.M. Cornelius ; Kyoung Kim ; Xiao-Tao Chen ; Robert J. Schmidt ; David K. Williams ; John S. Tokarski ; Yongmi An ; John S. Sack ; Veeraswamy Manne ; Amr
• 关键词：Met ; Receptor tyrosine kinase ; Protein kinase inhibitors
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2008
• 出版时间：1 June 2008
• 年：2008
• 卷：18
• 期：11
• 页码：3224-3229
• 全文大小：275 K

文摘

A series of acylurea analogs derived from pyrrolopyridine and aminopyridine scaffolds were identified as potent inhibitors of Met kinase activity. The SAR at various positions of the two kinase scaffolds was investigated. These studies led to the discovery of compounds 3b and 20b, which demonstrated favorable pharmacokinetic properties in mice and significant antitumor activity in a human gastric carcinoma xenograft model.