Pyrrolo[3,2-d]pyrimidine derivatives as type II kinase insert domain receptor (KDR) inhibitors: CoMFA and CoMSIA studies.

ABSTRACT: Kinase insert domain receptor (KDR) inhibitors have been proved to be very effective anticancer agents. Molecular docking, 3D-QSAR methods, CoMFA and CoMSIA were performed on pyrrolo[3,2-d]pyrimidine derivatives as non-ATP competitive KDR inhibitors (type II). The bioactive conformation was explored by docking one potent compound 20 into the active site of KDR in its DFG-out inactive conformation. The constructed CoMFA and CoMSIA models produced statistically significant results with the cross-validated correlation coefficients q(2) of 0.542 and 0.552, non-cross-validated correlation coefficients r(2) of 0.912 and 0.955, and predicted correction coefficients r(2) (pred) of 0.913 and 0.897, respectively. These results ensure the CoMFA and CoMSIA models as a tool to guide the design of a ser

SUBMITTER: Wu XY 

PROVIDER: S-EPMC3292029 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature