Synthesis, physical-chemical properties and research of acute toxicity of 1,2,4-triazole derivatives containing thiophene core

• Main Author: V. A. Salionov
• Format: Article
• Language: English
• Published: Zaporozhye State Medical University 2015-12-01
• Series: Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki
• Subjects: 1 2 4-triazole; Thiophene; Esthers; Acute Toxicity Tests
• Online Access: http://pharmed.zsmu.edu.ua/article/view/52616/49791

The aim of research. Modern drugs must have certain characteristics, such as low toxicity and high efficiency. Special attention should be given to esthers of 2-(1,2,4-triazoles-3-iltio)acetic acids. It has been found that compounds of this class are able to show analgesic, neuroleptic, diuretic, anti-inflammatory, mild antimicrobial and other biological activities and also can be intermediates for the synthesis of amides, hydrazides, ilidenhidrazides and bicyclic structures. Therefore, we synthesized a series of esthers of 2-(4-R-5- (thiophene-2-yl)-4H-1,2,4-triazoles-3-iltio)acetic acids, to explore their physical and chemical properties, to explore the acute toxicity of the obtained compounds, to identify the nature and severity of their damaging effects on the body of experimental animals. Materials and methods. Esthers of 2-((4-R-5-(thiophene-2-yl)-4H-1,2,4-triazol-3-yl)thio)acetic acids have been obtained by the etherification of the corresponding 2-((4-R-5-(thiophene-2-yl)-4H-1,2,4-triazol-3-yl)thio)acetic acids with methyl, ethyl, isopropyl and butyl alcohols in the presence of the catalytic amount of concentrated sulfuric acid. The tabular rapid method of V. B. Prozorovskiy which was used in a number of scientists practical research, has been selected for the acute toxicity study. Test compounds were introduced intraperitoneally in doses from the logarithmic scale. Results. 16 new derivatives of 2-((4-R-5-(thiophene-2-yl)-4H-1,2,4-triazoles-3-yl)thio)acetic acids have been synthesized. Physical-chemical constants have been checked for all synthesized compounds and their structure has been confirmed by using elemental analysis, 1H NMR- and IR-spectroscopy. The indicators of acute toxicity have been studied for all synthesized compounds. The acute toxicity study of the esters of 2-((4-R-5-(thiophene-2-yl)-4H-1,2,4-triazoles-3-yl)thio)acetic acid shows that all compounds belong to the 4th or 5th grade of toxicity, they are practically non-toxic and low-toxic and their LD50 is in the range of 525±51 mg/kg to 2250±200 mg/kg.