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ID: ALA2375296

Journal: Bioorg Med Chem Lett

Title: BCR-ABL tyrosine kinase inhibitor pharmacophore model derived from a series of phenylaminopyrimidine-based (PAP) derivatives.

Authors: Cui J, Fu R, Zhou LH, Chen SP, Li GW, Qian SX, Liu S.

Abstract: To reveal novel insights into the inhibition of BCR-ABL tyrosine kinase, pharmacophore mapping studies were performed for a series of phenylaminopyrimidine-based (PAP) derivatives, including imatinib (Gleevec). A seven-point pharmacophore model with one hydrophobic group (H), two hydrogen bond donors (D) and four aromatic rings (R) was developed using phase (pharmacophore alignment & scoring engine). The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of 0.886 and a survival score of 4.97 for training set molecules. The model showed excellent predictive power, with a correlation coefficient of Q(2)=0.768 for an external test set of ten molecules. The results obtained from our studies provide a valuable tool for designing new lead molecules with potent activity.

CiteXplore: 23473682

DOI: 10.1016/j.bmcl.2013.01.113