Send to

Choose Destination
J Med Chem. 2012 Feb 23;55(4):1698-705. doi: 10.1021/jm201565s. Epub 2012 Feb 9.

Rapid development of piperidine carboxamides as potent and selective anaplastic lymphoma kinase inhibitors.

Author information

Medicinal Chemistry Research Technologies, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, United States.


Piperidine carboxamide 1 was identified as a novel inhibitor of anaplastic lymphoma kinase (ALK enzyme assay IC(50) = 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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center