Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode

作者：Gummadi Venkateshwar Rao; Rajagopalan Sujatha; Looi Chung Yeng; Paydar Mohammadjavad; Renukappa Girish Aggunda; Ainan Bharathi Raja; Krishnamurthy Narasimha Rao; Panigrahi Sunil Kumar; Mahasweta Kumari; Raghuramachandran Sangeetha; Rajappa Manoj; Ramanathan Anuradha; Lakshminarasimhan Anirudha; Ramachandra Murali; Wong Pooi Fong; Mustafa Mohammad Rais; Nanduri Srinivas; Hosahalli Subramanya^*

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(17): 4911-4918.

DOI：10.1016/j.bmcl.2013.06.071

• Anaplastic lymphoma kinase (ALK)
• 7-Azaindole
• Anaplastic large cell lymphoma (ALCL)
• Cancer
• Karpas299

We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7h, 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.

• 出版日期2013-9-1