The search for new 4-amino-5-methyl-4H-1,2,4-triasole-3-thion derivatives with diuretic activity
DOI:
https://doi.org/10.14739/2310-1210.2018.3.130548Keywords:
1, 2, 4-triazole, diuretic effect, derivatives of 4-amino-5-methyl-4H-1, 4-triazole-3-thionAbstract
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.
References
Pruglo Ye. S. (2015) Dіuretichna aktivnіst' 3-(5-bromfuran-2-іl)-4-R-(4N)-1,2,4-trіazol-5-tіonіv, їh S-pohіdnih ta 2-(5-bromfuran-2-іl)-5-R´-tіazolo[3,2-b][1,2,4]trіazol-6(5N)-onіv [Diuretic activity of 3-(5-bromofuran-2-yl)-4-R-(4N)-1,2,4-trіazole-5-thiones, their S-derivatives, and 2-(5-bromofuran-2-yl)-5-R´-thіazolo[3,2-b][1,2,4]trіazole-6(5N)-ons]. Aktualnі pytannіa farmacevtychnoi і medychnoi nauky ta praktyky, №3, 9-13. [in Ukrainian].
Kucheryavyi Yu. M., Kaplaushenko A. G., Pruhlo Ye. S. (2014) Synthesis and diuretic activity of 2-(5-(phenoxymethyl)-4-r1-1,2,4-triazole-3-ylthio)acetic acids and their salts. Zaporozhye medical zhurnal, 6 (87), 101–104.
Danilchenko D. M., Safonov A. A. (2017) Diuretic activity of 2-((4-amino-5-R-4H-1,2,4-triazole-3-yl)thio)acetohydrazides. Zaporozhye medical zhurnal. 19, 4(103). S. 517-519.
Britanova T.S., Pruglo Ye.S., Goculya A.S., Panasenko O.І., Knysh Ye.G. (2013) Vyvchennia dіuretychnoi aktyvnostі іlіdenpokhіdnyh halohenіdіv 3,5-R-4H-amіno-R1-1,2,4-trіazolu [Diuretic activity investigation of ilidene-derivatives of 3,5-R-4H-amіno-R1-1,2,4-trіazole halides]. Current issues in pharmacy and medicine: science and practice, №1 (11), S. 18-20. [in Ukrainian].
Shcherbyna R.O., Panasenko O.І., Knysh Ye. G., Bіlai І. M., Pruglo Ye. S., Mikhailiuk Ye. O. (2011) Vplyv pokhіdnykh 4-R-5-R1-1,2,4-trіzol-3-tіonu na vydіl'nu funktsіiu nyrok [Effect of 4-R-5-R1-1,2,4-trіzole-3-thіone derivatives on excretory function of kidneys]. Lіky-liudyny: materіaly XXVIII vseukrains'koi naukovo-praktychnoi konferentsіi z mіzhnarodnoiu uchastiu, Kharkіv, Ukraina. 15-16. [in Ukrainian].
Parchenko V.V. (2014) Syntez, peretvorennia, fіzyko-khіmіchnі ta bіolohіchnі vlastyvostі v riadі 5-furylzamіshchenykh 1,2,4-trіazol-3-tіonіv (Dis… dokt. farm. nauk). [Synthesis, transformation, physical, chemical and biological properties in the row of 1,2,4-trіazol-3-thione 5-furyl-derivatives. Dr. farm. sci. diss.]. Zaporіzhzhia, ZSMU. [in Ukrainian].
Panasenko O.І. (2005) Syntez, peretvorennia, fіzyko-khіmіchnі ta bіolohіchnі vlastyvostі amіno- і tіopokhіdnykh 1,2,4-trіazolu (Dis… dokt. farm. nauk). [Synthesis, transformation, physical, chemical and biological properties of amino- and thio-derivatives of 1,2,4-trіazoles. Dr. farm. sci. diss.]. Kyiv. 396. [in Ukrainian].
Safonov A.A. (2014) Syntez, fіzyko-khіmіchnі ta bіolohіchnі vlastyvostі pokhіdnykh 5-geteryl-4-R-amіno-1,2,4-trіazol-3-tіolіv (Dis… kand. farm. nauk). [Synthesis, physical, chemical and biological properties of 5-geteryl-4-R-amіno-1,2,4-trіazole-3-thiol derivatives] : Candidate’s thesis k.farm.n. Zaporіzhzhia, ZSMU, 195 s. [in Ukrainian].
Ermakova X.G., Shaulina L.P., Kuznetsova N.P. et al. (2012) Sorption Recovery of Noble Metal Ions with a Copolymer of l-Vinyl-l,2,4-triazole with Acrylonitrile. Rus. J. of Applied Chem. Vol. 85, №8, P. 1289–1295.
Salіonov V.O. (2016) Syntez, fіzyko-khіmіchnі ta bіolohіchnі vlastyvostі pokhіdnykh 5-tіenіl-4-(alkіl-, aril)-1,2,4-trіazol-3-tіonіv (Dis… kand. farm. nauk). [Synthesis, physical, chemical and biological properties of 5-thienyl-4-(alkyl-, aryl)-1,2,4-trіazole-3-thіone derivatives] : Candidate’s thesis k.farm.n. Zaporіzhzhia, 312. [in Ukrainian].
Shcherbyna R. O., Panasenko O. І., Knysh Ye. G. (2016) Vyvchennia antyoksydantnoi aktyvnostі solei 2-((4-R-3-(morfolіnometylen)-4H-1,2,4-triazol-5-іl)tіo)acetatnykh kyslot [Antioxidant activity investigation of 2-((4-R-3-(morpholіnomethylene)-4H-1,2,4-triazole-5-yl)thіo)acetate salts]. Ukr. bіofarmats. zhurn. № 1, S. 37–40. [in Ukrainian].
Yanchenko V.O. (2005) Syntez ta vlastyvosti pokhidnykh 4-amino-3-merkapto-4N-1,2,4-tryazolu: dys. na zdobuttia naukovoho stupenia k. farm. n. [Synthesis and properties of 4-amino-3-mercapto-4H-1,2,4-triazole derivatives]. Kharkiv, 146 s. [in Ukrainian].
Kaplaushenko A. G. (2015) Khimichni vlastyvosti amino- i tiozamishchenykh 1,2,4-triazoliv [Chemical properties of amino- and thio-derivatives of 1,2,4-triazole]. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, №1 (17), S 101-106. [in Ukrainian].
Fizer M.M. (2016) Syntez kondensovanykh azaheterotsykliv na osnovi pokhidnykh 5-amino-1,2,4-tryazol-3-tionu [Synthesis of condensed azaheterocyclic compounds based on 5-amino-1,2,4-triazole-3-thione derivatives]: dys. na zdobuttia naukovoho stupenia k. khim. n. Uzhhorod, 144 s. [in Ukrainian].
Gotsulya A. S., Kamyshnyi O.M., Polishchuk N.M., Panasenko O.І., Knysh Ye.G. (2015) Issledovanie protivomikrobnoj i protivogribkovoj aktivnosti S-proizvodnyh 7-((3-tio-4-R-4N-1,2,4-triazol-3-il)metil)teofillina [Research of the antimicrobial and antifungal activity of 7-((3-thio-4-R-4N-1,2,4-triazoles-3-yl)methyl)theophylline S- derivatives]. Zaporozhye medical zhurnal, 4(91), 95–99. [in Russian].
Barmyn M.Y., Melnykov V.V. (2002) Novye amyno-1,2,4-tryazolyl i tetrazolyl alkany [New 1,2,4-triazolyl and tetrazolyl alkanes]. Sank-Peterburhskyi Hosudarstvennyi unyversytet tekhnolohyy i dyzaina, 213 s. [in Russian].
Berhin E. B. (1977) Metody izucheniya dejstviya novyh himicheskih soedinenij na funkciyu pochek [Approaches to determine effects of chemical compounds on kidney functions]. Him.-farmac. zhurn. 11, № 5, S. 3–11. [in Russian].
Bilay I.M., Pruglo Ye.S., Mihaylyuk E. O. (and al.) (2011) Vplyv pokhidnykh 4-R-5-R1-1,2,4-trsazol-3-tsonu na vydilnu funktsiiu nyrok [Effect of 4-R-5-R1-1,2,4-triazol-3-thione derivatives on excretory function of kidneys]. Materialy XXVIII vseukr. nauk.-prakt. konf. z mizhnar. uchastiu «Liky-liudyni», H., 2011, S. 15–16. [in Ukrainian].
Pruglo Ye. S., Bilay I. M., Scherbyna R. O. [ta in.] (2010) Vplyv S-pokhidnyk 4-R-5-R1-1,2,4-triazol-3-tionu na vydilnu funktsiiu nyrok pry eksperymentalnii hiperlipidemii [Effect of S-derivatives of 4-R-5-R1-1,2,4-triazol-3-thione on excretory function of kidneys during the experimental hyperlipidemia]. Farmats. zhurn. № 6, S. 62–67. [in Ukrainian].
Kucheryaviy Yu. M., Kaplaushenko A. G., Pruglo Ye. S (2015) Pat. 98923 Ukraina, C07D 249/00 A61K 31/41. 3-((2-hloretil)tio)-4-etil-5-(fenoksimetil)-4H-1,2,4-triazol, scho vyiavliaie diuretychnu aktyvnist [The 3-((2-chloroethyl)thio)-4-ethyl-5-(phenoxymethyl)-4H-1,2,4-triazole, which demonstrates diuretic activity]. № 98923 ; zaiavl. 05.12.14 ; opubl. 12.05.15, Byul. № 9. [in Ukrainian].
Kucheryaviy Yu. M., Kaplaushenko A. G., Pruglo Ye. S. (2015) Pat. 98919 Ukraina, C07D 249/00, A61K 31/41. 4-еtil-3-(fenoksymetil)-5-((2-((5-(fenoksimetil)-4-fenil-4H-1,2,4-triazol-3-il)tio)-etil)tio)-4H-1,2,4-triazol, scho vyiavliaie diuretychnu aktyvnist [4-ethyl-3-(phenoxymethyl)-5-((2-((5-(phenoxymethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)-ethyl)thio)-4H-1,2,4-triazole, which demonstrates diuretic activity]. № 98919 ; zaiavl. 05.12.14 ; opubl. 12.05.15, Byul. № 9. [in Ukrainian].
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