Synthesis And Biological Activity Of Indolone Derivatives Containing 1,3,4-thiadiazole

Isatin is a small,general,and widely used in molecular pharmacology.Although its structure is relatively simple,but it is a useful chemical scaffold,can be used for a variety of chemical conversion.These characteristics make them and their derivatives as chemical and pharmacological research resources have attracted many research groups.Isatin,as a potential electrophilic and nucleophilic material,is an indispensable part in organic synthesis.Isatin has many biological and pharmacological properties,such as antimicrobial,anticancer,antimalaria and anti HIV activity.The biological significance of a variety of heterocyclic structures can be synthesized from isatin as substrate,and now it is an important nucleus structure of isatin synthesis of potential drugs and the core component of many drugs.1,3,4-Thiadiazole is a prevalent and important five-membered heterocyclic system.A large number of 1,3,4-Thiadiazole derivatives have different pharmacological properties,such as antiviral,antiparasitic,anticonvulsant,analgesic and antidepressant activities.In this paper,14 kinds of Indole derivatives containing 1,3,4-Thiadiazole ring were designed and synthesized based on the principle of drug superposition.IR,¹H NMR,¹³C NMR,HRMS and other modern characterization methods are applied to analysis the structures,the inhibitory activities of?-glucosidase of these compounds are screened.The main findings of this paper are described as follows:At first,under the alkaline condition with potassium carbonate,isatin and different substituted benzyl chloride were treated as the raw materials,reaction for nucleophilic substitution is made.The 13 kinds of intermediate products,N-substituted-2,3-indolinedione are obtained.Then,under the catalysis of glacial acetic acid,the intermediate product N-substituted-2,3-indolinedione are reacted with thiocarbazide.14 kinds of intermediates,N-substituted-indole-2,3-indolinedione thiocarbazone were synthesized,and the synthesis conditions were optimized,the optimum reaction conditions is found.The optimum reaction conditions are:absolute ethyl alcohol as solvent,volume ratio of matter is 1:1.2,the amount of acetic acid added to the catalyst is 1:0.05,the reaction time is 5 hours and the reaction temperature is 70?.Furthermore,the target product N-substituted-3-?1,3,4-thiadiazole-2-yl?hydrazono-indolin-2-one is get by the reaction between the intermediate product,N-substituted-indole-2,3-indolinedione thiocarbazone and triethyl orthoformate cyclization,and the synthesis conditions were optimized,the optimum reaction conditions is obtained.The optimum reaction conditions are Triethyl orthoformate as both reactant and solvent,reaction temperature is 120?and reaction time is 2hours.In the end,some of the inhibitory activities of?-glucosidase of the target compounds synthesis of N-substituted-3-?1,3,4-thiadiazole-2-yl?hydrazono-indolin-2-one were screened.It was found that the compounds containing chlorine atoms had better inhibitory activity of?-glucosidase,and they are superior to resveratrol.In addition,the N-?p-chlorobenzyl?-3-?1,3,4-thiadiazole-2-yl?hydrazono-indolin-2-one has excellent inhibitory activity of?-glucosidase,IC50=3.12?M.