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

Bioorganic & Medicinal Chemistry Letters
2013.0

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.

DOI： 10.1016/j.bmcl.2013.01.113

Knowledge Graph

Similar Paper

BCR-ABL tyrosine kinase inhibitor pharmacophore model derived from a series of phenylaminopyrimidine-based (PAP) derivatives
Bioorganic & Medicinal Chemistry Letters 2013.0
Potent and selective inhibitors of the Abl-kinase: phenylamino-pyrimidine (PAP) derivatives
Bioorganic & Medicinal Chemistry Letters 1997.0
Design, synthesis, and biological activity of phenyl-pyrazole derivatives as BCR–ABL kinase inhibitors
Bioorganic & Medicinal Chemistry 2015.0
Design, synthesis, and biological activity of 4-(imidazo[1,2- b ]pyridazin-3-yl)-1 H -pyrazol-1-yl-phenylbenzamide derivatives as BCR–ABL kinase inhibitors
Bioorganic & Medicinal Chemistry Letters 2016.0
Synthesis and docking study of 2-phenylaminopyrimidine Abl tyrosine kinase inhibitors
Bioorganic & Medicinal Chemistry Letters 2011.0
Pharmacophore modeling study based on known Spleen tyrosine kinase inhibitors together with virtual screening for identifying novel inhibitors
Bioorganic & Medicinal Chemistry Letters 2009.0
Identification of novel inhibitors of BCR-ABL tyrosine kinase via virtual screening
Bioorganic & Medicinal Chemistry Letters 2003.0
Structure-based analysis and biological characterization of imatinib derivatives reveal insights towards the inhibition of wild-type BCR-ABL and its mutants
Bioorganic & Medicinal Chemistry Letters 2019.0
Pharmacophore identification of Raf-1 kinase inhibitors
Bioorganic & Medicinal Chemistry Letters 2008.0
Rational design, synthesis, and structure–activity relationships of 5-amino-1H-pyrazole-4-carboxylic acid derivatives as protein tyrosine phosphatase 1B inhibitors
Bioorganic & Medicinal Chemistry 2017.0