Zaporožskij Medicinskij Žurnal (Jun 2018)
The search for new 4-amino-5-methyl-4H-1,2,4-triasole-3-thion derivatives with diuretic activity
Abstract
1,2,4-Triazole derivatives have been widely used in medical practice due to their wide spectrum of biological activities and low toxicity, as they have 1,2,4-triazole cycle in their structure. That makes 1,2,4-triazole derivatives a very promising and attractive class of organic compounds in research of their physical and chemical properties, and biological activity determining. In order to find new substances with potential biological activity 20 new compounds of 4-amino-5-methyl-4H-1,2,4-tiazole-3-thion derivatives were synthesized, which have never been described in literature before. The objective of this study was the research of bioactivity of 4-amino-5-methyl-4H-1,2,4-tiazole-3-thion derivatives. Materials and methods. Compounds of research were synthesized in Department of Toxicological and Inorganic Chemistry of ZSMU. Berchin method was used in order to estimate the effect of compounds on excretory function of kidneys. Results. Diuretic activities of 4-amino-5-methyl-4H-1,2,4-tiazole-3-thion derivatives were studied. The compounds exhibit both diuretic and antidiuretic effects. It is worth noting that 4-((R-idene)amino)-5-methyl-4H-1,2,4-triazole-3-thion derivatives demonstrated both moderate and high diuretic activity. In such way, introduction of 3,4-methoxybenzyl, 3,5-methoxybenzyl and 2-chloro-6-fluorobenzyl substituents into the structure of 4-((R-idene)amino)-5-methyl-4H-1,2,4-triazole-3-thion slightly increased diuretic effect. Reduction of compounds 4-((4-bromobenzylidene)amino)-5-methyl-4H-1,2,4-triazole-3-thion, 5-methyl-4-((thiophen-2-ylmethylene)amino)-4H-1,2,4-triazole-3-thion, 4-((2-chloro-6-fluorobenzylidene)amino)-5-methyl-4H-1,2,4-triazole-3-thion caused decline of diuretic activity. The most potent bioactivity was observed in 4-((4-methoxybenzyl)amino)-5-methyl-4H-1,2,4-triazole-3-thion. Conclusion. Derivatives of 4-amino-5-methyl-4H-1,2,4-tiazole-3-thion exhibit both diuretic and antidiuretic effects. “Structure – Effect” relation was shown. The most potent activity was observed in 4-((4-methoxybenzyl)amino)-5-methyl-4H-1,2,4-triazole-3-thion.
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