Rapid Development of Piperidine Carboxamides as Potent and Selective Anaplastic Lymphoma Kinase Inhibitors
Journal of Medicinal Chemistry2012Vol. 55(4), pp. 1698–1705
Citations Over TimeTop 10% of 2012 papers
Marian C. Bryan, Douglas A. Whittington, Elizabeth M. Doherty, James R. Falsey, Alan C. Cheng, Renee Emkey, Rachael Brake, Richard T. Lewis
Abstract
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.
Related Papers
- → ANTIOXIDANT POTENTIAL OF PIPERIDINE CONTAINING COMPOUNDS-A SHORT REVIEW(2018)20 cited
- → METABOLITES OF PIPERIDINE IN RAT URINE(1978)17 cited
- → An Efficient Synthesis of Aldohexose-Derived Piperidine Nitrones: Precursors of Piperidine Iminosugars(2013)4 cited
- → Synthesis of 1'-substituted 2-amino-spiro(4H-3,1-benzoxazine-4,4'-piperidine) derivatives.(1988)3 cited
- → Benzoyl Piperidine(2003)1 cited