Study On Synthesis And Biological Activity Of Novel Isatin Containing Spiro Derivatives

Isatin derivatives are kinds of heterocyclic compounds containing nitrogen structure. Many drug molecules which present good bioactivity include isatin structure. These compounds have a widespread range of biological activities, such as antitumor, antidepression, antiseizure, antifungal, anti HIV and antiinflammatory.According to the drug design mosaic and active principle of superposition, a series of new spiro isatin derivatives were synthesized, then IR, MS, 1H NMR and 13 C NMR were applied to characterize the structure of derivatives, what's more, we preliminarily discussed the structure-activity relationship, and evaluated the activity inhibition effect to antitumor. The main results are shown as follows:1. We adopt better method for the synthesis of intermediates 5-substituted-4-amino-3-thiol-1,2,4-triazole. These compounds were synthesized from carboxylic acid via activating carboxyl by using benzotriazole, hydrazinolysis, cyclization. Compared with the conventional procedures, this method becomes more moderate and higher yield.2. 4-amino of 5-substituted-3-thiol-4-amino-1,2,4-triazole mercaptan reacted with isatin to gain 3-((3-mercapto-5-methyl-4H-1,2,4-triazol-4-yl)imino)indolin-2-one schiff base, The best conditions for the reaction of the schiff base was obtained: ethanol as solvent, the molar ratio of reactants being 1:1.2, the amount of toluene sulfonic acid being 2%, reaction temperature being 80?, reaction time being 6 h.3. 3-((3-mercapto-5-methyl-4H-1,2,4-triazol-4-yl)imino)indolin-2-one was reacted with 2-bromo-4'-substituted-phenylethanone to get 3,7-substituted-spiro[[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-6,3'-indolin]-2'-one. What's more, the reaction conditions were optimized to obtain the target product. such as: methanolas as solvent, the reaction temperature was 65?, the molar ratio of intermediates 2, 2-bromo-4'-substitutedphenylethanone and triethylamine were 1:1.2:0.2.4. The antitumor activity of 12 target compounds was studied, and preliminary result showed: party of these compounds can inhibited antitum. Among them, 7-benzoyl-3-(4-methylbenzoyl)-spiro[[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-6,3'-indoline]-2'-one 3d effection is best on antitumor activity inhibition.