Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki (Dec 2017)
Acute toxicity of 3-(2-, 3-fluorophenyl)-6-(aryl-, hetaryl)-[1,2,4]triazole[3,4-b][1,3,4]thiadiazoles
Abstract
Nowadays an attempt to create a number of new biologically active compounds by many scientific groups is being one of the topical issues in the domestic pharmaceutical industry. In our opinion an interesting and promising direction is the direction of synthetic research. Scientific publications and practical implementations have undoubtedly proved the relevance of this process. Particular attention deserves a heterocyclic system of 1,2,4-triazole due to its unique properties (low toxicity, high reactivity, biological activity). A vivid example of diverse 1,2,4-triazole derivatives is the registration of new domestic original medicines and fertilizers (“Trifuzol”, “Avesstim”, “Fortis Combi”). The aim was to study the acute toxicity of 3-(2-, 3-fluorophenyl)-6-(aryl-, hetaryl)-[1,2,4]triazole[3,4-b][1,3,4]thiadiazoles, to determine some regularities between the structure of compounds and their toxicity as well as the effects of various fragments of the corresponding 1,2,4-triazole[3,4-b][1,3,4]thiadiazoles on the indicated parameters. Materials and methods. Newly synthesized derivatives of 3-(2-, 3-fluorophenyl)-6-(aryl-, hetaryl)-[1,2,4]triazole[3,4-b][1,3,4]thiadiazoles were used in the study of acute toxicity. Parameters of acute toxicity were evaluated on white rats weighing 170-220 g which were administered intraperitoneally with the investigational compounds once. Rats were obtained from the seed plot of the Institute of Pharmacology and Toxicology of The Academy of Medical Sciences of Ukraine. Results. Analyzing the results of the acute toxicity study of 3-(2-, 3-fluorophenyl)-6-(aryl-, hetaryl)-[1,2,4]triazole[3,4-b][1,3,4]thiadiazoles it was found that the compound 2g, LD50 of which is 250 mg/kg, is the most toxic compound among the corresponding 1,2,4-triazole[3,4-b][1,3,4]thiadiazoles and belongs to the IV Class of toxicity. Perhaps this is due to the presence of nitrophenyl substituent. The smallest indicator of acute toxicity was found in compound 1b, LD50 of which is 1430 mg/kg. Conclusions. The acute toxicity of 3-(2-, 3-fluorophenyl)-6-(aryl-, hetaryl)-[1,2,4]triazole[3,4-b][1,3,4]thiadiazoles was studied for the first time. Parameters of acute toxicity are in the range from 250 mg/kg to 1430 mg/kg, which indicate the affiliation of compounds to IV-V classes of toxicity. Some regularities of "structure-action" were set for individual classes of 3-(2-, 3-fluorophenyl)-6-(aryl)-[1,2,4]triazole[3,4-b][1,3,4]thiadiazoles and 3-(2-, 3-fluorophenyl)-6-(hetaryl)-[1,2,4]triazole[3,4-b][1,3,4]thiadiazoles. The compounds with the smallest and the highest rates of toxicity by the known scale were found. In some cases a number of typical pharmacophores have been established which may affect on acute toxicity parameters.
Keywords
