Synthesis And Biological Activity Of Quinoline Derivatives With Different Chain Lengths Of Tertiary Amine Groups

Alzheimer's disease(AD)is a fatal neurodegenerative disease characterized by reduced cognitive and memory abilities.With the development of society and the acceleration of aging,the prevalence of AD has gradually increased.Studies have shown that people over 65 years old are at a high risk of AD.As aging is getting worse,there will be 1 billion AD patients in the world.It is estimated that there will be 1 billion AD patients worldwide by 2030.In the early stage of AD,AChE plays a leading role in the hydrolysis of Ach,and by enhancing the inhibitory effect of AChE activity to weakens the hydrolysis of acetylcholine to prevent the development of AD.In the later stage of AD,inhibiting BChE activity has also become particularly important.Therefore,the inhibitory balance between AChE and BChE is more important for the treatment of AD.Based on this,research of the laboratory's preliminary tasks,continue to use the quinoline ring as the mother nucleus,and explore the biological activity of the target compound by changing the number of carbon chains of the tertiary amine group at the7-position of the quinoline ring.A series of quinoline derivatives with different chain lengths of tertiary amine groups.The target product was characterized by HR-ESI-MS,¹H-NMR,¹³C-NMR and other detection methods,and then this was determined by Ellman method.The inhibitory performance of acetylcholinesterase and butyrylcholinesterase of series of compounds.The DPPH activity,ABTS activity,and metal chelating ability of the products were also evaluated,and their medicinal properties were also predicted.Through the activity test results,it can be seen that most of the compounds have good AChE inhibitory performance,and some of them have certain BChE inhibitory performance.Among them,compound 10F(ee AChE IC₅₀=6.89?M,eq BChE IC₅₀=25.10?M),10N(ee AChE IC₅₀=8.70?M,eq BChE IC₅₀=36.60?M)has dual inhibitory performance on acetylcholinesterase and butyrylcholinesterase,and it was also found that The introduction of tertiary amine groups with different chain lengths changes the inhibitory performance of the compounds on cholinesterase.Most compounds with n=2 have better inhibitory performance on cholinesterase than when n=3.The inhibitory performance.From the results of the antioxidant test,it can be seen that most of the compounds have good ABTS free radical scavenging ability.Among them,compounds 10B,10E,and 10G have the best scavenging rate,and the scavenging rate is as high as 98% when the concentration is 1 mg/m L,and the scavenging rate of the reference Trolox is very similar,while the compound's scavenging ability to DPPH free radicals is relatively weak.Among them,the compounds 10K and 10L show good scavenging rates(78%).In addition,it was found from the metal chelation test that some compounds Interactions with different metal ions,among which the 4-N aniline group has a para-substituted and the tertiary amine group carbon chain number at the 7-position is 2 when the compound has a more obvious chelating effect with metal ions.It passes through the blood-brain barrier.It is predicted that all compounds have good lipophilicity,conform to the Lipinksi principle and have the possibility of penetrating the BBB.The activity tests and evaluations,it is shown that quinine substituted by tertiary amine groups with different chain lengths The morpholine derivatives have the scientific value of in-depth research and also provide new ideas and directions for the research of AD drugs.