Int. J. Mol. Sci. 2012, 13(2), 2387-2404; doi:10.3390/ijms13022387
Article

Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies

School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
* Authors to whom correspondence should be addressed.
Received: 21 December 2011; in revised form: 13 February 2012 / Accepted: 16 February 2012 / Published: 22 February 2012
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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 q2 of 0.542 and 0.552, non-cross-validated correlation coefficients r2 of 0.912 and 0.955, and predicted correction coefficients r2pred 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.
Keywords: CoMFA; CoMSIA; KDR inhibitor; pyrrolo[3,2-d]pyrimidine derivatives; Surflex-Dock

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MDPI and ACS Style

Wu, X.-Y.; Chen, W.-H.; Wu, S.-G.; Tian, Y.-X.; Zhang, J.-J. Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies. Int. J. Mol. Sci. 2012, 13, 2387-2404.

AMA Style

Wu X-Y, Chen W-H, Wu S-G, Tian Y-X, Zhang J-J. Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies. International Journal of Molecular Sciences. 2012; 13(2):2387-2404.

Chicago/Turabian Style

Wu, Xiao-Yun; Chen, Wen-Hua; Wu, Shu-Guang; Tian, Yuan-Xin; Zhang, Jia-Jie. 2012. "Pyrrolo[3,2-d]pyrimidine Derivatives as Type II Kinase Insert Domain Receptor (KDR) Inhibitors: CoMFA and CoMSIA Studies." Int. J. Mol. Sci. 13, no. 2: 2387-2404.

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