CoMFA and CoMSIA studies on 6,7- disubstituted-4-phenoxyquinoline derivatives as c-Met kinase inhibitors and anticancer agents

Abstract

c-Met kinase is a recognized target for the development of small-molecule inhibitors for the treatment of cancer. In this study, a diverse set of 74 c-Met kinase inhibitors consisted of 6,7-disubstituted-4-phenoxyquinoline derivatives were used for CoMFA and CoMSIA (3D QSAR). 3D QSAR models were obtained using rigid body (Distill) alignment of training and test set molecules. CoMFA and CoMSIA models were found statistically significant with leave-one-out correlation coefficients (q2) of 0.626 and 0.556, respectively, cross-validated coefficients (rcv 2 ) of 0.532 and 0.501, respectively, and conventional coefficients (r2) of 0.907 and 0.940, respectively. QSAR models were validated by a test set of 23 compounds giving satisfactory predicted correlation coefficients (rpred 2 ) of 0.456 and 0.701 for CoMFA and CoMSIA models, respectively. This study will provide clues to design new compounds as c-Met kinase inhibitors.