Design,Synthesis And Antitumor Activity Of Novel Indole Small Molecule Compounds

From the 1940s to the present,the incidence and mortality rate of the second largest disease（cancer）in humans has been growing year by year.Faced with a superior situation,the world and China have to attach great importance to this disease,so it is urgent to develop good anticancer drugs and effective treatment methods.Traditional auxiliary radiotherapy and chemistry in medicine.The treatment of drugs has serious side effects for the treatment of cancer.In particular,medical treatment,many time will be counterproductive,causing secondary damage to the patient’s body.This has driven us to work harder to improve anti-tumor drugs with good effects,low toxicity and few side effects.With the further development of medical science,the research of small molecule drug inhibitors plays an essential role in the development of anticancer drugs.The number of small molecule drug inhibitors has been increasing continuously in recent years.Some small molecule targeting inhibitors have been fully applied to the clinic,and some advantages such as obvious effects and minor side effects have also emerged.Indole derivatives are a class of important heterocyclic compounds that are closely linked to life activities.Among them,both sunitinib and oxymeridine are listed on the market.In 2008,sunitinib was successfully approved for the treatment of gastrointestinal stromal tumors and renal cell carcinoma,which is effective for multi-target receptor tyrosine kinases for platelet-derived growth factor receptor and vascular endothelial growth factor receptor.Inhibitor.The third-generation inhibitor of the receptor in the mutant（T790M）epidermal growth factor（EGFR）is oxymerinide.In 2015,AstraZeneca was granted marketing approval for its sale of T790 M mutation-positive NSCLC.In the study of this paper,we successfully synthesized a new type of small molecule drug inhibitor containing an indole skeleton.Indole derivatives were synthesized in the paper,the substituted phenylhydrazine hydrochloride as the starting material.Firstly,methyl 2-（1,2,5-trimethyl-1H-indole-3-yl）acetate is obtained by Fischer synthesis method,and then methylates the methyl group on the indole ring to introduce a methyl group,and then passes through the alkali.And then hydrolyzed under alkaline conditions to obtain vital the intermediate N-substituted2-（1,2,5–trimethyl-1H-indole-3-yl）acetic acid.The amide target compound（4a-d）is obtained by a peptide bond condensing agent method,and the target compound（4e-4i）containing an ester group is obtained by an esterification method.The target product was characterized by ¹H NMR,¹³C NMR,FT-IR and MS.The synthetic route of the indole derivatives was designed in the paper has the advantages of simple operation and low cost of reagents.The in vitro antitumor activities of five target compounds（4a,4b,4c,4d,4e）against SMMC-7721,Hela,MCF-7 and HepG2 cancer cells were tested by MTS assay.The in vitro activity results indicated that some compounds selectively acted on a cell and showed moderately weak inhibition of tumor cell proliferation,which deserves further study.