Synthesis And Anti-tumor Activity Of Isoquinolinimine And Fluorine-containing Bicyclic Pyridone Compounds

Isoquinolin-1(2H)-imines exhibit biological activities such as inhibiting acetylcholinesterase(AChE),butyryl-cholinester-ase(BChE),antibacterial,anti-inflammatory.However,the efficient methods for the production of isoquinolin-1(2H)-imines are very rare being the imide group is unstable.Therefore,the development of effective methodologi es for constructing molecular libraries of isoquinolinimine with greatpotential for drug discovery would be desirable.For one thing,bicyclic pyridone compounds have various biological activities.For another thing,the fluorine atom has several effects which usually can increase biological activity.Therefore,we design and synthesize the bicyclic pyridine compounds.Based on the importance of Isoquinolin-1(2H)-imines and bicyclic pyridines,this dissertation has carried out the works as following.In the first chapter,the research progress of heterocyclic ketene amine,Isoquinolin-1(2H)-imines and fluorine-containing bicyclic pyridone compounds has been reviewed.In chapter two,17 Isoquinolin-1(2H)-imine compounds have been synthesized with 55?80%yields by the reaction of HKAs witho-fluoro benzyl cyanide in 1,4-dioxane at reflux and catalyzed by Et3N.These 17 compounds and another 20 compounds which synthesized by Chao Huang our have been studied their anti-tumor activity.The results show that ?-10r,?-10s,?-10t,?10u have excellent anti-tumor activity.In the third chapter,we developed the method of synthesis of two kinds of bicyclic pyridone compounds by the reaction of HKAs withmethyl 3,3-difluoro-2-(trifluoromethyl)acrylate or bis(1,1,1,3,3,3-hexafluoropropan-2-yl)2-methylenesucc-inate in 1,4-dioxane and the proper conditions in one-pot.As results,40 targets compounds have been obtained with 75?96%yields.All thestructures of Isoquinolin-1(2H)-imines and fluorine-containing bicyclic pyridines were confirmed by spectroscopy.Among of them,?-10i and ?-7d were confirmedthrough the X-Ray analysis.