Discovering novel 7-azaindole-based series as potent AXL kinase inhibitors

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• 作者：Clé ; mence Feneyrolles ; Lé ; a Guiet ; Mathilde Singer ; Nathalie Van Hijfte ; Bé ; né ; dicte Daydé ; -Cazals ; Bé ; né ; dicte Fauvel ; Gwé ; naë ; l Chevé ; Abdelaziz Yasri ; ^{ayasri@oribase-pharma.com}
• 关键词：AXL ; 7-Azaindole ; Receptor tyrosine kinase ; Kinase inhibitor ; Modeling study ; Medicinal chemistry
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：27
• 期：4
• 页码：862-866
• 全文大小：1609 K
• 卷排序：27

文摘

AXL is a receptor tyrosine kinase that plays a key role in tumor growth and proliferation. The scientific community has validated AXL as therapeutic target in the treatment of cancers for several years now, and several AXL inhibitors have been developed but none of them are approved. In this context, we started to design new kinase inhibitors targeting AXL from the 7-azaindole scaffold well known to interact with the ATP binding site of the kinase. Focused screening and chemical diversification around 7-azaindole scaffold were developed, based on modeling studies and medicinal chemistry rational, leading to the discovery of a new family of hits with potent inhibitory activity against AXL.