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QSAR and 3D QSAR of inhibitors of the epidermal growth factor receptor
Author(s) -
PintoBazurco Mariano,
Tsakovska Ivanka,
Pajeva Ilza
Publication year - 2005
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.20901
Subject(s) - quantitative structure–activity relationship , chemistry , steric effects , stereochemistry , computational chemistry
This article reports quantitative structure–activity relationships (QSAR) and 3D QSAR models of 134 structurally diverse inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase. Free–Wilson analysis was used to derive the QSAR model. It identified the substituents in aniline, the polycyclic system, and the substituents at the 6‐ and 7‐positions of the polycyclic system as the most important structural features. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used in the 3D QSAR modeling. The steric and electrostatic interactions proved the most important for the inhibitory effect. Both QSAR and 3D QSAR models led to consistent results. On the basis of the statistically significant models, new structures were proposed and their inhibitory activities were predicted. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006