CADD Studies On ALK Kinase Inhibitors

With the rapid development of computer technology, research and development of new drugs to treat lung cancer using computer-aided drug design (CADD) method can not only shorten the drug development cycle, but also save a lot of manpower and financial resources. Novartis grams azole imatinib in the treatment of non-small cell lung cancer have a significant effect, can prolong survival of patients. We refer grams azole imatinib basic structure, using computer-aided drug design method of compound 36 were 2-acyl amino benzimidazole derivatives and 492,4-aryl-aminopyridine like three-dimensional quantitative structure-activity relationship (3D-QSAR) studies and protein docking (Docking) research, mainly for the study of the following five parts:The first chapter, we conducted a protein kinase A more detailed exposition, through various studies have shown that protein kinase ALK mutations in a variety of major diseases plays a vital role in the study of great significance.Second chapter, a more detailed description of the method of computer-aided drug design, including three-dimensional quantitative structure-activity model (3D-QSAR) to establish and molecular docking (Docking), and summed up the conclusions of computer-aided drug design methods for ALK phosphorylation Research and design of novel inhibitors of kinase inhibitor molecule with landmark role.The third chapter introduces the study of ALK kinase with a simple three-dimensional QSAR and docking inhibitors. ALK kinase inhibitors for a variety of major diseases can play a good role, ALK has become a new target for drug research. This selection of newly released bioactive good 362-acyl amino benzimidazole derivatives as the research object, the application of three-dimensional quantitative structure-activity relationship models (3D a QSAR) methods and molecular docking (Docking) for ALK kinase inhibitor a systematic study of the interaction. Structure-activity relationship studies of compounds, the use of comparative molecular analysis standpoint (CoMFA) method and comparative molecular similarity indices analysis (CoMSIA) method to establish the two models, good and better analytical model for the ligand has a good predictability. Utilizing 3D contour plots and protein molecular docking (Docking) showed, different core ligands have different biological activities, different ligands may improve biological activity in accordance with the structure. Using the model results of the design of a new molecular design of compounds selective synthesis, screening and improve biological activity.The fourth chapter, the use of SYBYL X 2.0 software for 49 2,4-aryl amino pyridine analogue compounds dimensional quantitative structure-activity relationship (3D-QSAR) studies and protein molecular docking (Docking) study, using data elaborated model the reliability of the study follow-up is similar to ALK kinase inhibitors play a crucial role.The fifth chapter, the central idea of the article for a summary to clarify the method of computer-aided drug design is of great significance for the study of ALK kinase inhibitors.