3D-QSAR Studies on Chemical Features of 3-(benzo[d]oxazol-2-yl)pyridine-2-amines in the External Region of c-Met Active Site
Joo Yun Lee, Kwang Ho Lee, Hyoung Rae Kim, Chong Hak Chae · Bulletin of the Korean Chemical Society · 2013
The three dimensional-quantitative structure activity relationship (3D-QSAR) studies on chemical features of pyridine-2-amines in the external region of c-Met active site (ER chemical features of pyridine-2-amines) were conducted by docking, comparative molecular field analysis (CoMFA), and topomer CoMFA methods. The CoMFA model obtained the partial least-squares (PLS) statistical results, cross-validated correlation coefficient (q 2 ) of 0.703, non cross-validated correlation coefficient (r 2 ) of 0.947 with standard error of estimate (SEE) of 0.23 and the topomer CoMFA obtained q 2 of 0.803, r 2 of 0.940, and SEE of 0.24. Further, the test set was applied to validate predictive abilities of models, where the predictive r 2 (r 2 pred) for CoMFA and topomer CoMFA models were 0.746 and 0.608, respectively. Each contribution of ER chemical features of pyridine-2amines to the inhibitory potency showed correlation coefficients, r 2 of 0.670 and 0.913 for two core parts, 3(benzo[d]oxazol-2-yl)pyridine-2-amine and 3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy) pyridine-2-amine, respectively, with corresponding experimental pIC50.