3D-QSAR and docking studies of piperidine carboxamide derivatives as ALK inhibitors

Anaplastic lymphoma kinase (ALK) is an important and attractive target for the design of new anticancer drugs. In the present study, quantitative structure-activity relationship (QSAR) models of piperidine carboxamide derivatives against ALK were developed by CoMFA and CoMSIA approaches. Both the CoMFA and CoMSIA models yielded significant statistical results. The results of the QSAR model indicated the importance of steric, electrostatic, and hydrophobic properties in the potent ALK inhibitors. Furthermore, molecular docking of the most active compound 25 with the active site of ALK was also investigated. The outcomes of this study may result in a better understanding of the inhibition mechanism of ALK and aided in the development of new and more potent anticancer drugs.