Gummadi V.R.,Aurigene Discovery Technologies Ltd. and 39 40 KIADB Indus. Area Electrical City Ph II Hosur Rd. |
Rajagopalan S.,Aurigene Discovery Technologies Ltd. and 39 40 KIADB Indus. Area Electrical City Ph II Hosur Rd. |
Looi C.-Y.,University of Malaya |
Paydar M.,University of Malaya |
And 14 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2013
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. © 2013 Elsevier Ltd. All rights reserved.