Design of EGFR kinase inhibitors: a ligand-based approach and its confirmation with structure-based studies

Vema, Aparna ; Panigrahi, Sunil K. ; Rambabu, G. ; Gopalakrishnan, B. ; Sarma, J. A. R. P. ; Desiraju, Gautam R. (2003) Design of EGFR kinase inhibitors: a ligand-based approach and its confirmation with structure-based studies Bioorganic & Medicinal Chemistry, 11 (21). pp. 4643-4653. ISSN 0968-0896

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Official URL: http://linkinghub.elsevier.com/retrieve/pii/S09680...

Related URL: http://dx.doi.org/10.1016/S0968-0896(03)00482-6

Abstract

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 100 anilinoquinazolines, inhibiting epidermal growth factor receptor (EGFR) kinase. The studies included molecular field analysis (MFA) and receptor surface analysis (RSA). The cross-validated r2 (r2cv) values are 0.81 and 0.79 for MFA and RSA, respectively. The predictive ability of these models was validated by 28 test set molecules. The results of the best QSAR model were further compared with structure-based investigations using docking studies with the crystal structure of EGFR kinase domain. The results helped to understand the nature of substituents at the 6- and 7-positions, thereby providing new guidelines for the design of novel inhibitors.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
ID Code:10893
Deposited On:09 Nov 2010 04:34
Last Modified:30 May 2011 09:35

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