1347756-70-0Relevant articles and documents
Rapid development of piperidine carboxamides as potent and selective anaplastic lymphoma kinase inhibitors
Bryan, Marian C.,Whittington, Douglas A.,Doherty, Elizabeth M.,Falsey, James R.,Cheng, Alan C.,Emkey, Renee,Brake, Rachael L.,Lewis, Richard T.
, p. 1698 - 1705 (2012/05/04)
Piperidine carboxamide 1 was identified as a novel inhibitor of anaplastic lymphoma kinase (ALK enzyme assay IC50 = 0.174 μM) during high throughput screening, with selectivity over the related kinase insulin-like growth factor-1 (IGF1R). The X-ray cocrystal structure of 1 with the ALK kinase domain revealed an unusual DFG-shifted conformation, allowing access to an extended hydrophobic pocket. Structure-activity relationship (SAR) studies were focused on the rapid parallel optimization of both the right- and left-hand side of the molecule, culminating in molecules with improved potency and selectivity over IGF1R.