3D-QSAR Studies of Various Diaryl Urea Derivatives of Multi-targeted Receptor Tyrosine Kinase Inhibitors: Molecular Field Analysis Approach

Abstract

3D-QSAR analysis has been performed on a series of diaryl urea derivatives of multi-targeted receptor tyrosine kinase inhibitors. Models were developed using the most widely used computational approach molecular field analysis (MFA) from our dataset for the KDR, cKit and FLT3 inhibitors using genetic partial least square (G/PLS) method. These models showed excellent internal predictability and consistency and validation using test set compounds yielded a good predictive power for the activity values of three set of inhibitors. These models would offer utility in guiding the rational design of multi-targeted KDR, cKit and FLT3 receptor tyrosine kinase inhibitors for therapeutic applications. Keywords: QSAR, Receptor tyrosine kinase, MFA, Molecular field analysis, Genetic partial least squares (G/PLS) method