pci-32765 and cinnoline

BTK inhibitors have been proved as an effective target for B-cell malignancies. Ibrutinib is the most advanced irreversible BTK inhibitor for treating mantle cell lymphoma/chronic lymphocytic leukaemia but with existing drug resistance and adverse effects. To design novel effective and safety reversible BTK inhibitors, 115 newly cinnoline analogues were selected to perform molecular docking and 3D-QSAR study because of the main scaffold similarity to Ibrutinib. Both established CoMFA and CoMSIA models obtained high predictive and satisfactory value. CoMFA/CoMSIA contour maps demonstrated that bulky substitutions are preferred at R

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Heterocyclic Compounds, 2-Ring; Humans; Hydrophobic and Hydrophilic Interactions; Molecular Docking Simulation; Piperidines; Protein Conformation; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines; Quantitative Structure-Activity Relationship; Reproducibility of Results; Static Electricity