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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 series of new potent KDR inhibitors.

SUBMITTER: Wu XY

PROVIDER: S-EPMC3292029 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Wu Xiao-Yun XY Chen Wen-Hua WH Wu Shu-Guang SG Tian Yuan-Xin YX Zhang Jia-Jie JJ

International journal of molecular sciences 20120222 2

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-v ...[more]

PMID: 22408460

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