2-Naphthylmethyl-Benzimidazole Substituted Triazolethiadiazine Derivatives Dynthesis, Characterization

In recent years, the triazolo-thiadiazines derivatives have made outstanding achievementsin the field of medicine, a large number of literature report that triazole-thiadiazinesderivatives possess diverse pharmacological activities such as anticancer, antibacterial,antiviral, antiinflammatory, analgesic, PDE4receptor inhibitor and so on. The anticancer andantibacterial activities of them are so excellent that some of the derivatives have higherinhibitory on leukemia, prostate cancer, lung cancer, and the antibacterial activity of manycompounds are significantly higher than the current clinical drugs such as chloramphenicol,ampicillin, fluconazole and ketoconazole. In addition, they are also widely used in agricultureand materials.2-Arylmethyl benzimidazol also have a wide range of applications inagriculture, materials and medicine, in which their biological activities of anticancer,antihypertension, antiviral, antibacterial are very important.In view of that the important biological activities of the triazolo-thiadiazine and2-Arylmethyl benzimidazol Pharmacophore, we design to combine triazolo-thiadiazine and2-naphthyl methyl-benzimidazole in the one molecule, and successfully prepare a series of6-aryl-3-[2-(1-naphthylmethyl)-benzimidazol-1-yl]methyl-7H-1,2,4-triazolo[3,4-b][1,3,4]thidiazines derivatives. The main contents and contributions are listed as follows:In this paper,2-(1-naphthylmethyl)-1H-benzimidazole (1) was synthesized by thereaction of o-phenylenediamine with1-naphthylacetic acid using a melting method. Theinfluences of the mole ratio of the reactants, the reaction time, the reaction temperature on theyield were investigated and optimum experimental conditions were found. The compound1after multi-step got compounds2,3and5, which had not been seen in literature. In the last,the intermediate compound5reacts with bromoacetophenone successful synthesize of ninetarget compounds6-aryl-3-[2-(1-naphthylmethyl)-benzimidazol-1-yl]methyl-7H-1,2,4-triazolo[3,4-b][1,3,4]thidiazines derivatives (6a~i). All the synthetic compounds werecharacterized by IR and1H NMR techniques. The target compounds6a~6i, intermediatecompounds2,3and5were tested for their biological activities. The preliminary resultsindicated all the tested compounds except6g,2and3showed excellent activity at theconcentration of5μg/mL, some of them showed the best biological activities with theinhibition of99.90%. In summary, the results in this paper were very important andsignificant to research further the synthesis, biological activity, drug designing anddevelopment containing condensed heterocyclic moieties.