Synthesis And Biological Activity Of 2,4-disubstituted Selenoquinazoline Derivatives

As a nitrogen-containing heterocyclic compound,quinazoline has good biological activity.Such compounds are mainly used in the fields of medicine,pesticides,etc.The research on quinazoline derivatives mainly includes the following two aspects.One is the study of its synthesis method,and the other is the introduction of the quinazoline ring to cancer cells and bacteria.Groups that have inhibitory effects,and then pass the activity test to screen out compounds with more excellent activity.As an essential trace element for the human body,selenium-containing foods and selenium-containing heterocyclic drugs have good therapeutic effects on certain diseases,so it is widely used in the field of medicine.Combining the uniqueness of selenium,the following research was done by introducing different functional groups on the quinazoline ring in combination with organic selenium compounds.This article summarizes the application of quinazoline in medicine,designs and synthesizes a series of seleno-substituted quinazoline compounds.Firstly,the quinazoline ring which can be substituted at the 2,4 position is used as the starting module,and then through the analysis of a variety of organic study of the mechanism of selenium compounds,combined with the research of this subject,compares the 4-substituted selenoquinazoline derivatives to have a significant inhibitory effect on cancer cells,and then screens out compounds that can be used in clinical applications through the activity test.In this thesis,a series of seleno-substituted quinazoline compounds were designed and synthesized,and the target products were identified by ¹H NMR,¹³C NMR and HRMS.The synthesis of intermediates was optimized:（1）The quinazoline ring-closing solvent was selected;（2）The best chlorinating reagent was screened out through the study of comparative yield.The synthetic route of the final product was explored:（1）The synthesis of the product was explored by the grignard reagent method;（2）The quinazoline substituted by the 2,4-diselenyl group was used as the target product.Substitute hydrocarbons undergo nucleophilic substitution reaction and select the optimal synthesis route to synthesize the final compound.In addition,a method of synthesizing2-alkoxy-4-substituted selenoquinazoline was discovered during the experimental investigation.Through the screening of routes,a method of substituting quinazoline derivatives with seleno groups was successfully developed.2,4-Dichloroquinazoline reacts with sodium diselenide,then sodium borohydride is added,and nucleophilic substitution with halogenated hydrocarbons.Under neutral reaction conditions,a number of unreported disubstituted selenoquine can be synthesized oxazoline.Under basic reaction conditions,a number of unreported 2-alkoxy-4-substituted selenoquinazolines can be synthesized,and fifteen new substituted selenoquinazolines have been synthesized by this method,which shows that the method has a certain tolerance to functional groups.