Research On The Design,Synthesis,Anti-Dengue Virus Activity,Fluorescence Characteristics And Applications Of Pyrimidine Derivatives

Pyrimidine derivatives are a kind of aza-heterocyclic compounds with many biological activities or fluorescent properties,and they are used in many fields(such as medicines,pesticides and photolectric materials).Here,two novel pyrimidine derivatives were designed and synthesized through MCR developed by our group,and the structure-activity relationship(SAR)as novel anti-dengue virus(anti-DENV)inhibitors and new aggregation-induced emission(AIE)materials were studied in detail,respectively.In addition,the application of the new type of AIE compound as a titration indicator for critical micelle concentration(CMC)of surfactants was also studied.The content is divided into the following three parts:The first part is design,synthesis and SAR of octahydroquinazoline-5-ones(OHQs)as new anti-DENV inhibitors.DENV,belongs to the mosquito-borne Flavivirus,which may lead to death but without inhibitors were entered into clinical.OHQs,the products of new five-component reaction(5CR)that reported by our group,are novel pyrimidine derivatives,and we found these compounds have certain anti-DENV activity in the biological screening.Finally,52 OHQs were designed and synthesized,and the SAR of OHQs as anti-DENV inhibitors were studied in detail.The results showed that,about R3 group,the activity of aromatic substituted is significantly better than that aliphatic,and the substituted aryl groups is better than that unsubstituted;about R2 group,the activity of aromatic substituted is significantly better than that aliphatic,and the para-substituted aryl groups show best activity;the R1 group(optimal activity when R1=phenyl)have a greater effect on the activity of OHQs.In addition,we found OHQ-2 and OHQ-4 with good activity(EC50=1.31/1.33μM)and low toxicity(CC50>20 μM).The research results have a certain promotion and guidance for the further study of OHQs as a novel anti-DENV inhibitor.The second part is the SAR between molecular structure/molecular packing mode and optical properties of tetrahydropyrimidines(THPs).THPs,the products of five-component reaction which reported by our group,are novel pyrimidine derivatives and have a wide range of applications.In this thesis,we have designed and synthesized 66 THPs to study molecular structural effects on optical properties,and prepared 22 polymorphs to understand molecular structural effects on heteroenantiomeric self-assembly.Researches indicate that substituents and stacking modes have a great influence on the fluorescence properties of THPs(the slight changes in the substituents can make a significant effect on the optical properties of THPs).The research results can be a guidance and promotion for the further design and synthesis of novel racemic THPs.The third part is a study on the THP-54 as a CMC titration fluorescent probe.Surfactants have a wide range of applications,the CMC value is an important parameter and needs to be determined firstly in the practical application.Titration method is simple and fast,it has broad application prospects to develop an indicator that can be used for titration CMC value of various surfactants.We have investigated THP-54 as a probe for CMC titration of different kinds of surfactants.Through our research,we found that THP-54 is an excellent probe for fast and simple CMC titration of different kinds of surfactants,and the concentration of THP-54 in titrated solutions at titration end point(at CMC)is about 1 μM for zwitterionic surfantant and 2.5 μM for other kinds of surfactants.Therefore,THP-54 has a good application prospect as a titration indicator for fast and simple determining the CMC value of the surfactants.