Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode
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- 作者：Venkateshwar Rao Gummadi ; Sujatha Rajagopalan ; Chung-Yeng Looi ; Mohammadjavad Paydar ; Girish Aggunda Renukappa ; Bharathi Raja Ainan ; Narasimha Rao Krishnamurthy ; Sunil Kumar Panigrahi ; Kumari Mahasweta ; Sangeetha Raghuramach ; ran ; Manoj Rajappa ; Anuradha Ramanathan ; Anirudha Lakshminarasimhan ; Murali Ramach ; ra ; Pooi-Fong Wong ; Mohammad Rais Mustafa ; Srinivas N ; uri ; Subramanya Hosahalli
- 关键词：PGSYBTKGCJXUAV-UHFFFAOYSA-N ; LRWNZUVVRSBHQU-UHFFFAOYSA-N ; JJYRLIVLBDHFEU-UHFFFAOYSA-N ; FADONZKXBUVWLH-UHFFFAOYSA-N ; ATZJNUYRMAFPBF-UHFFFAOYSA-N ; FPQUAATUWBOAGG-UHFFFAOYSA-N ; SDWMCZUOCJDBOJ-UHFFFAOYSA-N ; KNRKBZCJMLVHPB-UHFFFAOYSA-N ; ZHUGMFFQPPOJNL-UHFFFAOY
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：1 September, 2013
- 年：2013
- 卷：23
- 期：17
- 页码：4911-4918
- 全文大小：1852 K
文摘
We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7b, 7m and 7n demonstrate excellent potencies in biochemical and cellular assays. X-ray crystal structure of one of the compounds (7k) revealed a unique binding mode with the benzyl group occupying the back pocket, explaining its potency towards ALK and selectivity over tested kinases particularly Aurora-A. This binding mode is in contrast to that of known ALK inhibitors such as Crizotinib and NVP-TAE684 which occupy the ribose binding pocket, close to DFG motif.