Syntheses Of 3-tertiary Amine Quaternary Carbon Oxindole Compounds And Their Evaluations Of Anti-tumor Activity

Due to their special skeleton structure,3,3-disubstituted oxindole compounds,determined that their have wide range of biological activities,the most prominent of these is anti-tumor activity.The quaternary carbon oxindole compounds of the3-tertiary amine atom are an important class of derivatives of the 3,3-disubstituted oxindole compounds,which are widely present in the natural product and in the drug molecule framework.In recent years,there have been limitations in the synthesis methods of the 3-tertiary amine quaternary carbon oxindole compounds that the methods are more complicated,the reaction conditions are harsh,etc.In this paper,aniline was used as the starting material,the synthesis route and antitumor activity evaluation of these compounds were studied.During this period,we mainly did two parts.The first part of the work,syntheses and anti-tumor activity evaluations of 3-tertiary amine quaternary carbon oxindole of 3-position connected nitrogen containing fatty group:This section through the optimization and innovation of synthetic methods,The basic skeleton structure of 3-tertiary amine quaternary carbon oxindole compounds with 3-position nitrogen-containing aliphatic groups ware constructed by N-alkylation reaction.Pyrrolidine,piperidine,morpholine and thiomorpholine were respectively used as nitrogen donors.24 target compounds were successfully synthesized.And using the MTT method,using human chronic myeloid leukemia cells（K562）as a subject,the antitumor activity of representative compounds in each class of compounds was preliminary studied.The results showed that the IC₅₀0 of compound3aa was 64.6,IC₅₀0 of 3ab was 88.7,the IC₅₀0 of compound 3ec and compound 3bd is greater than 100.The second part of the work,syntheses and anti-tumor activity evaluations of3-quaternary carbonl oxindoles of 3-position connected nitrogen-containing aromatic group:This section through the optimization and innovation of synthetic methods,The basic skeletal structure of 3-quaternary carbon oxindole compounds with3-nitroaryl aromatic groups was constructed by substitution reaction.34,15 and 7target compounds were successfully synthesized using terpenoids,pyrrole compounds,and benzylamine compounds as nitrogen donors,and a total of 56 target compounds were synthesized.Using MTT assay,human chronic myeloid leukemia cells（K562）were studied as subjects,and the antitumor activity of representative compounds in each class of target compounds was preliminary studied.The results showed that the IC₅₀0 of compound 5qa was found to be 98.9,the IC₅₀0 of 5dc was 15.4,the IC₅₀0 of 6ja was 75.1,the IC₅₀0 of 7da was 35.5.