Design And Synthesis Of Bridged Bis-1,4-dihydropyridine Derivatives And Their Antitumor Activities

1,4-dihydropyridine is a special cyclohexadiene structure containing two unsaturated double bonds with 6πelectrons and an N heteroatom,which is chemically very active and has been studied by many scholars because of its wide application in biomedicine,veterinary medicine,material chemistry,chemical industry and other fields,and its contribution in medicine is especially outstanding.1,4-dihydropyridine’s parent nucleus structure has anticancer effects,and researchers have In order to broaden the range of biological and pharmacological activities of 1,4-dihydropyridines,this paper will carry out the synthesis and activity testing of bridging bis-1,4-dihydropyridines derivatives.In this paper,we used Auto Dock Tools software to virtually dock the bridged bis-1,4-dihydropyridine compounds I and II with anti-cancer target proteins（FGFR-1 and VEGFR-2）,and the docking results showed that both compounds I and II docked with anti-cancer target proteins with better binding power than the original ligand docked with anti-cancer target proteins.Based on the docking results,we optimized the design of compoundⅠand compoundⅡto obtain class I series and class II series compounds,and docked them with the target proteins respectively,and the docking results showed that class I series and class II series compounds have potential antitumor activity,and synthesize it..Three routes were designed for the synthesis of the target compounds,and parallel experiments of the three routes were conducted for compounds I and II,respectively.The results of the parallel experiments for both target compounds showed that the third route had shorter reaction time and higher yield than the first two routes,therefore,the third synthetic route was determined to be the best synthetic route for the synthesis of the two series of compounds,and a total of 14 bis-1,4-dihydropyridines were synthesized A total of 14 bis-1,4-dihydropyridines derivatives were synthesized,and the correct structures were confirmed by ¹H NMR and ¹³C NMR,13 of which were not reported in the literature.The third route used hydrothermal reaction method has the advantage of good high temperature and high pressure containment compared with the traditional method,which can shorten the reaction time and improve the yield to some extent.Preliminary evaluation of the anti-tumor in vitro activity of some synthesized compounds using the CCK8 method showed weak anti-tumor activity...