Polysubstituted Pyrimidine, Fluorine-containing The Bicyclic The Pyridine Class Heterocyclic Compounds Synthesized And Sensitivity Test

Nitrogen containing heterocyclic compounds is a type of very important compounds due to their many characteristics of structural changes and extensive pharmaceutical activities. Pyrimidine compounds possess excellent biological activities such as anti HIV-1 reverse transcriptase enzyme, dihydrofolate reductase, anti-tumor, protein kinase, bacteria, fungus and so on. Bicyclic pyridones frequently found in the pharmacophores such as camptothecin and huperzine, and played an important role in drug discovery. They had been attracted considerable attention in the field of pharmaceutical chemistry and used as anticancer, analgestic, antiphlogistic agents. Their pharmaceutical activity will be increased when the active fluorine atom was introduced. The main contents and results of this thesis as follows:In Chapter 1, An one-pot strategy which was a concise efficient synthesis method was established in the synthesis of multisubstituted pyrimidine derivatives. Firstly,β-bromovinyl aldehydes 2 (2a-2d) were synthesized by readily available reagents DMF, phosphorous tribromide, acetophenone derivatives or ketone 1. Thenβ-bromovinyl aldehydes 2 were reacted with amidine hydrochlorides 3 in "one-pot" reaction which catalyzed by triethylamine under reflux to get multisubstituted pyrimidine derivatives 4 (4a-4v, among them,4a,4g,4h,4j,4m,4n,4p,4r,4s,4u and 4v have not seen in the literatures) with potential drug activity. This method had many advantages such as concise synthetic route, simple operation, high efficiency and environment friendly, etc.In Chapter 2, on the basis of our previous work, trifluoro ethyl acetoacetate, heterocyclic ketene aminals (HKAs) and aromatic aldhydes were refluxed in dioxane and catalyzed by triethylamine in "one-pot" reaction to obtain twenty-five novel bicyclic pyridines 11 (11a-11y). which were synthesized with the three-component and one-pot synthesis method. The protocol also had the advantage of environmental friendliness, high yields, short reaction times and convenient operation, etc.The two type structures of heterocyclic compounds and intermediates were characterized by 1H NMR,13C NMR, MS spectra and IR, the 11o was analyzed and characterized by single crystal X-ray diffraction analysis.In Chapter 3, we have screened the antibacterial activities of nearly 200 compounds by drug susceptibility test, and get some compounds with high antibiotic sensitivity.