Design,synthesis,Biological Evaluation Of 2-Methylquinolin-4-amine Derivation

Currently,the most widely discussed approach to eliminating this reservoir involves reactivating latent HIV-1 in patients on HAART,induce the expression of the latent HIV-1 and eliminate virus and host cells with anti-retroviral drugs or immune system.In this paper,we reviewed the potential HIV-1 reactivators in various clinical trials and briefly introduced a series of HIV latent activator and its clinical application.We do some research on HIV-1 reacticators as follows:(1)Design and synthesis of 2-methyquinolin-4-amine derivatives:Design a series of unreported 2-methylquinolin-4-amine derivatives with AV6 as the lead compound.56 compounds were synthesized after the synthetic route optimized,then identificate structure by 1H-NMR,13C-NMR,MS and other methods.Searching with SciFinder or other references,48 compounds were certified as new compounds.(2)Activity screening:In this study,we determine the latent HIV reactivation activity of synthesized 2-methylquinolin-4-amine derivatives with luciferase assay,and test the anti-proliferative activity of these compounds.The result showed that compound 5k and 51 was better than SAHA on the activity of latent HIV reactivation which reactivation rates were over 80%at the concentration of 10 ?M.In addition,the half inhibitory concentration(IC50)of compound 5k and 51 was 0.320±0.008 ?mol and 0.460±0.010 ?mol.(3)Research on the structure-activity relationship:The effects of the substituent groups and their positions on the activation of latent HIV-1 virus.