Study On Synthesis And Biological Activities 5,6,7,8-tetrahydor-1,6-naphthyridin-2(1H)-one Derivatives

Nitrogenous heterocyclic compounds which have various structural properties and biological activities are significant sources of lead compounds in pharmaceutical research.As an important member of nitrogenous heterocyclic compounds,naphthyridine derivatives possess unique structures and attract many attentions.Pyridone compounds also have extensive biological activities,such as antibacterial and antitumor activities.Piperidine derivatives are used in pesticides and pharmaceutical intermediates.Owing to containing above three structures,the 5,6,7,8-tetrahydro-1,6-naphthyridin-2?1H?-one which was studied in this thesis has the potential to be a lead compound for new drugs.The content of this paper mainly includes the following three parts:1.Synthesis of 1,5,6,7,8-tetrahydro-1,6-naphthyridin-2?1H?-one derivativesA series of 5,6,7,8-tetrahydro-1,6-naphthyridin-2?1H?-one derivatives hydrochloride were obtained using 4-piperidone monohydrate hydrochloride as raw material undergoing amidation,substitution,acylation,ring formation,deprotection reaction and so on.The synthetic method has the advantages of concise,high yield and good purity.The newly synthesized compounds and their derivatives were characterized by ¹H NMR,¹³C NMR,and high-resolution mass spectrometry.2.Study on Antibacterial Activity of 2,5,6,7,8-Tetrahydro-1,6-naphthyridin-2?1H?-one derivatives The determination of minimum inhibitory concentration of some of the synthesized 5,6,7,8-tetrahydro-1,6-naphthyridin-2?1H?-one derivatives were tested by micro-diluted dilution method to resist the Staphylococcus aureus and Escherichia coli.The results showed that the compounds 10b,10c,10f and 10g had potential antibacterial activity against Escherichia coli,and 10a and 10j had potential antibacterial activity against Staphylococcus aureus.Preliminary identification of quorum sensing inhibitors using real-time quantitative PCR techniques was also tested.The test results showed that compound 10j may be a novel quorum sensing inhibitor.3.Antitumor activity of 5,6,7,8-tetrahydro-1,6-naphthyridin-2?1H?-one derivativesIn order to understand the anti-tumor activity of the target compounds,docking of the target compounds with farnesyltransferase was carried out using Schrodinger software and the results showed that5,6,7,8-tetrahydro-1,6-naphthyridin-2?1H?-one derivative has potential inhibitory activity against farnesyl transferase.Anti-tumor activity of the intermediate 6 and ten 5,6,7,8-tetrahydro-1,6-naphthyridin-2?1H?-one derivatives were tested by MTT method for A549?human lung cancer cells?,MDA-MB-435?human breast ductal carcinoma cells?,HepG2?human liver cancer cells?and MOLM-13?human acute myeloid leukemia cells?cancer cells.The target compounds with a primary screening inhibition rate greater than 20%were selected to test their antiproliferative activity against HepG2,MDA-MB-435 and MOLM-13 cell lines.The results showed that the tested compounds had a certain inhibitory effect on these three tumor cells,and the inhibitory activity of 10l on MOLM-13 was 76.2?M,indicating that the compounds have further research value.