Synthesis Of Small Molecule Quaternary Heterocyclic Compounds And Structural Modification Of Dacitinib

This thesis is mainly focused on the synthesis of oxa/azepine/thia-4 membered ring molecules, including monocyclic and spiro system, which display good water solubility. These modulars were not covered by most of the commercial drugs. Through rational drug design, we expect to improve molecular solubility and metabolic stability by docking those 4-membered ring molecules into the launched drug intermediates.To verify our speculation, a series of dasatinib intermediate-based 4-membered heterocyclic ring derivatives are synthesized. At the same time, we hope to get a series of totally new chemical entities with better water solubility and metabolic stability on the basis of maintaining the original drug activity, which will break the barriers of the original drug patent.This thesis includes three parts. The first part mainly focuses on the improvement and the process optimization of the synthetic route of some four-membered heterocyclic molecules; in second part, a series of small molecules modules are docked with dasatinib intermediates and related bioassays are undertaken; finally, computer-acid simulation and SAR studies are managed on those synthesized compounds.