Synthesis And Activity Determination Of Indole Carboxylic Acid Derivatives

With the improvement of people's living standard,the incidence of cancer is increasing.Vascular endothelial growth factor(VEGF)is an important vascular inducing factor.Studies show that it can bind specifically with the vascular endothelial growth factor receptor-2(VEGFR-2)tyrosine kinase to activate downstream signaling,leading to the proliferation of tumors.Therefore,VEGFR-2 tyrosine kinase inhibitors come into being,becoming the research focus of anticancer drugs.Indole carboxylic acid derivatives are potential VEGFR-2 tyrosine kinase inhibitors,which were obtained from de novo design and drug-like screening.This paper mainly studied on the synthesis and biological activity of indole carboxylic acid derivatives.The main contents of the paper are as follows:1 First,5-bromo indole and 5-nitro indole were synthesized by using indole as the raw material.Then synthesis technique of indole-3-carboxylic acid and its derivatives were available from indole and its derivatives in the presence of trifluoroacetic anhydride and N,N-dimethylformamide(DMF)which followed by hydrolysis reaction.2 2-hydroxymethyl benzimidazole and its derivatives were prepared from o-phenylenediamine and its derivatives in the presence of hydroxyacetic acid and concentrated phosphoric acid.With o-phenylenediamine and its derivatives as raw materials,benzimidazole-2-ethanol derivatives were synthesized in the presence of lactic acid and concentrated phosphoric acid followed by the reaction of nucleophilic substitution and dehydration cyclization.3 Benzothiazol-2-amine and its derivatives were prepared from phenylthiourea and its derivatives,which were achieved by reaction of aniline and its derivatives with ammonium thiocyanate in the presence of bromine.4 The benzofuran-2-carboxylic acid and its derivatives were synthesized by esterification,condensation,hydrolysis reaction with salicylic aldehyde and its derivatives and ethyl chloroacetate as raw materials.5 First,indole-3-carboxylic acid and its derivatives were esterified with 2-hydroxymethyl benzimidazole and its derivatives in the presence of 4-dimethylaminopyridine(DMAP)and N,N-dicyclohexylcarbodiimide(DCC)as dehydrants and catalysts to yield(1H-benzoimidazol-2-yl)methyl 1H-indole-3-carboxylate derivatives.Then N-(benzothiazol-2-yl)-1H-indole-3-carboxamide derivatives were obtained from indole-3-carboxylic acid and its derivatives and benzothiazol-2-amine and its derivatives by amidation.(1H-benzoimidazol-2-yl)methyl 1H-benzofuran-2-carboxylate were prepared from benzofuran-2-carboxylic acid and 2-hydroxymethyl benzimidazole by the esterification.6 The synthesized compounds were evaluated for their ability to inhibit VEGFR-2 tyrosine kinase and five kinds of tumor cells.