Establishment of diuretic activity indicators for (3-thio-4-R-4-H-1,2,4-triazole-5-yl)(phenyl)methanols and their derivatives
Keywords:1, 2, 4-triazole, synthesis, diuretics
Diuretic drugs are drugs that, by blocking the transport systems of the renal tubules, promote the removal of excess electrolytes and water from the body, normalization of the internal environment. They eliminate edema, reduce the fluid content in the body cavity. Diuretic drugs differ in their chemical structure, the mechanism of action on the urinary tract function of the kidneys and on the mechanisms of regulation of this function. It should be noted that the use of the above mentioned agents can lead to undesirable side effects, such as nausea, vomiting, unpleasant sensations in the stomach, headache, facial hyperemia.
To date, there is evidence that 5-R-1,2,4-triazole derivatives have diuretic activity. The advantage of synthetic triazole derivatives is that, along with the expressed pharmacological action of the compound, there are relatively low rates of acute and chronic toxicity, but almost no side effects.
Therefore, it is important to create new low-toxic substances of derivatives (3-thio-4-R-4-H-1,2,4-triazole-3-yl)(phenyl)methanols and study their diuretic properties.
The purpose of the work is the purposeful search for new low-toxic and highly effective diuretic compounds among the derivatives of (3-thio-4-R-4-H-1,2,4-triazole-5-yl)(phenyl)methanols.
Materials and methods. To establish the influence of compounds, which have been synthesized at the Physical and Chemical Chemistry Department of ZSMU, the method of E. B. Berchin was used on the excretory function of kidneys. Experiments on diuretic activity were conducted at the Department of Clinical Pharmacy, Pharmacotherapy and MFE of FPE, Zaporizhzhia State Medical University.
Results. The diuretic activity of derivatives (3-thio-4-R-4H-1,2,4-triazole-5-yl)(phenyl)methanols was investigated. The study and analysis of the obtained experimental data were compared with the reference diuretic hypothiazide. Regularities "structure – activity" were established. The studies indicate that (3-thio-4-R-4H-1,2,4-triazoles-3-yl)(phenyl)methanol are not able to exceed hypothiazide diuretic effect, but 4-(5-hydroxy(phenyl)methyl-4-phenyl-4H-1,2,4-triazolе-3-ylthiomethyl)benzonitrile showed the results closer to the reference drug.
Conclusion. By the method of E.B. Berchin the diuretic activity of derivatives (3-thio-4-R-4H-1,2,4-triazol-5-yl)(phenyl)methanols was investigated. Derivatives (3-thio-4-R-4H-1,2,4-triazole-3-yl)(phenyl)methanols do not excee the diuretic action of hypothiazide. Patterns "structure – action" were established. The most active compound was 4-(5-hydroxy(phenyl)methyl-4-phenyl-4H-1,2,4-triazolе-3-ylthiomethyl)benzonitrile.
Kaplaushenko, A. H., Sameluk, Yu G., Parchenko, V. V., et al. (2016) Praktychne znachennia ta zastosuvannia pokhіdnykh 1,2,4-trіazolu [Practical value and application of derivatives of 1,2,4-triazole]. Zaporizhzhia. [in Ukrainian].
Berkhin, E. B. (1977) Metody izucheniya dejstviya novykh khimicheskikh soedinenij na funkciyu pochek [Methods for studying the effect of new chemical compounds on renal function]. Khimiko-pharmacevticheskij jurnal, 11(5), 3–11. [in Russian].
Rud, A. M., Kaplaushenko, A. H., Kucheriavyi, Yu. M., et al. (patentee) (2015) Patent 99044 Ukrainy na korusnu model, C07D 249/00, A61K 31/41. (4-amino-3-(detsyltio)-1,2,4-tryazol-5-il)(fenil)metanol, shcho vyiavliaie diuretychnu aktyvnist [(4-amino-3- (decylthio)-1,2,4-triazole-5-yl)(phenyl)methanol, which exhibits diuretic activity]. Biuleten, 9. [in Ukrainian].
Rud, A. M., Kucheriavyi, Yu. M., Kaplaushenko, A. H., Sameliuk, Yu. H., et al. (patentee) (2016) Patent Ukrainy na vynakhid 112830 Ukrainа, C07D 249/00, A61K 31/4196, A61Р 7/10 4-(((5-(hidroksy(fenil)metyl)-4-fenil-4N-1,2,4-tryazol-3-il)tio)metyl)benzonitryl, shcho vyiavliaie diuretychnu aktyvnist [4-(((5-(hydroxy(phenyl)methyl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)methyl)benzonitrile, which exhibits diuretic activity]. Biuleten, 20. [in Ukrainian].
Rud, A.M., Kaplaushenko, A. H., Kucheriavyi, Yu. M. (2015) Vstanovlennia pokaznykiv diuretychnoi aktyvnosti riadu (4-amino-5-(alkiltio)-1,2,4-triazol-3-il)(fenil)metanoliv [Establishment of indices of diuretic activity of a number of (4-amino-5-(alkylthio)-1,2,4-triazole-3-yl)(phenyl)methanol]. Suchasni aspekty medytsyny i farmatsii – 2015, (P. 16). Zaporizhzhia. [in Ukrainian].
How to Cite
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)