Research On The Synthesis And Biological Activities Of Quinoline Derivatives And Arylamides

Quinoline and arylamide derivatives are two kinds of very important compounds.They possess a wide range of biological activities and have important applications in medicine and pesticides.In this paper,we studied the synthetic methodologies for two types of quinoline derivatives(alkenylquinolines and quinazolines),and the anti-tumor activity of quinazolines was tested.We also synthesized a series of N-(2-benzoylphenyl)arylamides and researched the structure-activity relationship of against type 2 diabetes.The content of the research is divided into the following three parts:The first part is the synthesis of(E)-alkenylquinolines.As an important part of quinoline family,alkenylquinolines have significant biological and medicinal utilities.However,all reported methods have some drewbacks,such as poor atomic economy,use of metal catalysis and high reaction temperature.Here,we reported a direct alkenylation of 2-methylquinolines with aldehydes through synergistic catalysis of 1,3-dimethylbarbituric acid and HOAc.The transformations provided 43 compounds and the yield reached up to 97%,which offerred a new approach for further studying the biological activity and other application of this kind of compounds.The second part is focused on the synthetic methodology of quinazoline derivatives Quinazoline derivatives prossess various biological activities such as anti-tumor,anti-bacteria,etc.Neverthless,the developed transformations required the use of strong oxidants,which made the reaction conditions harsh and substrate scope poor.Herein,31 polysubstituted quinazolines were synthesized by using copper salt as catalyst,oxygen as green oxidant,and acid as additive.The yield was up to 88%.A simple and efficient synthetic method was provided for further research on the application of polysubstituted quinazolines.6 compounds screened by MTT have significant anti-tumor activity,among which the compounds 3-3am,3-3ai,and 3-3fa have very significant inhibitory effects on tested the tumor cells,which is stronger than the positive control drug 5-fluorouracil.The third part is the synthesis and structure activity relationship(SAR)of N-(2-benzoylphenyl)arylamides as lead compounds against type 2 diabetes.Impaired glucose-stimulated insulin secretion(GSIS)and pancreatic β-cells’ death are two typical dysfunctions of pancreatic β-cells in diabetic patients.Therefore,developing a reagent able to overcome these two dysfunctions is of importance research value and practical significance.N-(2-benzoylphenyl)-5-bromo-2-thiophene carboxamide(BBT)reported by our cooperator is a small organic molecule that selectively promotes insulin secretion.In this part,31 compounds were synthesized based on the structure of BBT.Moreover,SAR studies were performed by using BBT as a positive control.Inspiringly,the EC50 values of the two compounds with the highest activity are 5.28μM and 4.52 μM,and the amount of insulin secretion are 2.50 and 3.12 folds of BBT,respectively.