Synthesis and antiexudative activityof pyrolin derivatives 2 - ((4-amino-5- (furan-2-yl)-1,2,4-triazol-4H-3-il)-sulfanil)-N-acetamides

Keywords: derivatives of 1,2,4-triazol-3-thion, synthesis, structure, physicochemical properties, antiexudative activity


The continuous research of new effective drugs is associated with a significant number of diseases, pathological conditions. Conventional treatment with existing drugs could be ineffective, or addictive, and have a large number of side effects. Therefore, the aim of modern pharmacy is to minimize the toxicity of drugs and create new modern domestic medicine that would be more effective in relation to their activity and relatively non-toxic.

Derivatives of 1,2,4-triazol have considerable synthetic, pharmacological potential. That’s why study of the synthetic methods of the new structures obtain, its physical, physico-chemical, biological properties may become the basic for their spector of the synthesized derivatives and biological activity widening.

The aim of the work: choice on the investigation ground in silico the basic structures 1,2,4-triazol-3-thione and the special purpose synthesis of the new potential biological active compounds, definition its structure and physic-chemical properties mark of antiexudative activity. The synthesis of pyroline derivatives of 2-((4-amino-5-(furan-2-il)-1,2,4-triazol-4H-3-il)-sulfanyl)-N-acetamides was accomplished by stages.

The article describes the synthesis of new pyrolin derivatives 2-((4-amino-5(furan-2-yl)-1,2,4-triazol-4H-3-il)-sulfanyl)-N-acetamide. Acetamides were obtained by alkylation of 2-((4-amino-5(furan-2-yl)-1,2,4-triazol-3-thione N-aryl-substituted α-chloroacetamides in the presence of KOH. Using Paal-Knorr condensation of the amino group at 4th position of the triazole ring modified into pyrolium fragment. Physical and chemical characteristics, chemical structure and anti-exudative activity of the obtained compounds were established.

Anti-exudative activity of compounds was investigated in the experiments on the white rats in the doses 10 mg/kg comparately with reference drug-diclophenac natrium in formalin edema modulation. The paw size was measured by pletismography before drugs introduction. For the first time 24 compounds have been synthesized: 4 pyroline derivatives 2-((4-amino-5-(furan-2-il)-1,2,4-triazol-4H-3-il)-sulfanyl)-N-acetamides. In 91% of the new synthesized derivatives the antiexudative properties have been found, 5 compounds (10.9, 10.10, 10.15, 10.21, 10.1) by anti-exudative activity have exceeded the reference drug. It is considered that the investigations of these compounds by presence or absence analgesics activities are perspective.


1. Pirogova V. I. Suchasni aspekty racionalnogo vyboru nesteroyidnyx protyzapalnyx preparativ: poglyad ginekologa (Klinichna lekciya) // Zdorove zhenshhyny. – 2017. – № 3 (119), S. 11–15.
2. Gladkyx F. V. Preventyvno-lechebnye strategyy farmakokorekcyy gastropatyy, ynducyrovannoj nesteroydnymy protyvovospalytelnymy preparatamy // Obzory po klynycheskoj farmkologyy y lekarstvennoj terapyy. – 2017. – Т. 15, № 4. – S. 14–23.
3. Yang M., Wang H. T., Zhao M. et al. Network Meta-Analysis Comparing Relatively Selective COX-2 Inhibitors Versus Coxibs for the Prevention of NSAID-Induced Gastrointestinal Injury // Medicine (Baltimore). ‒ 2015. ‒ V. 94 (40). – e1592. 0000000000001592
4. Karateev A. E., Nasonov E. L., Yakhno N. N. et al. Clinical guidelines «Rational use of nonsteroidal antiinflammatory drugs (NSAIDs) in clinical practice» // Sovr. Revmatologiya. – 2015. – Т. 9, № 1. – S. 4–23.
5. Karateev A. E. Lekarstvennye oslozhnenyya: kto vynovat y chto delat? // Sovr. revmatologyya. – 2018. – Т. 12, № 1. – S. 85–92.
6. Demetskaіa A. Nezhelatelnye lekarstvennye reakcіі: NPVP // Farmacevt praktik. – 2017. – № 2. – S. 28–29.
7. Bykkynyna G. M., Safuanov A. R. Nezhelatelnye lekarstvennыe reakcyy nesteroydnyx protyvovospaly`tel`nыx preparatov // Molodoj uchenyj. − 2015. − № 7. − S. 269–272.
8. Romanenko T. G., Sulymenko O. M., Zhaloba G. M. Efektyvnist oryginalnyx nesteroyidnyx protyzapalnyx preparativ ta yix analogiv (dzhenerykiv) pry likuvanni xronichnogo tazovogo bolyu // Akusherstvo. Gynekologiya. Genetyka. 2017. – Т. 3, № 1. – С. 32–37.
9. Asghar W., Jamali F. The effect of COX-2- selective meloxicam on the myocardial, vascular and renal risks: a systematic review // Inflammopharmacology. – 2015 – V. 23, N 1. – P. 1–16.
10. Ameri A., Khodarahmi G., Hassanzadeh F. et al. Novel aldimine-type Schiff bases of 4-amino-5-[(3,4,5-trimethoxyphenyl)methyl]-1,2,4-triazole-3-thione/thiol: Docking study, synthesis, biological evaluation, and anti-tubulin activity // Arch. Pharm. (Weinheim). 2016. – V. 349, N 8. – P. 662–681.
11. Thakkar S. S., Thakor P., Doshi H., Ray A. 1,2,4-Triazole and 1,3,4-oxadiazole analogues: Synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities // Bioorg. Med. Chem. – 2017. – V. 25, N 15. – P. 4064–4075.
12. . Ahmad A., Varshney H., Rauf A. et al. Synthesis and anticancer activity of longchain substituted 1,3,4-oxadiazol-2-thione, 1,2,4-triazol-3-thione and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine derivatives // Arabian J. Chem. – 2017. – V. 10, Suppl. 2. – P. 3347–3357.
13. Mahmoud M. R., Abou-Elmagd W. S. I., El-Shahawi M. M., Hekal M. H. Novel fused and spiro heterocyclic compounds derived from 4-(4-amino-5-mercapto-4h-1,2,4-triazol-3-yl)phthalazin-1(2h)-one // Eur. Chem. Bull. – 2014. – V. 3, N 7. – Р. 723–728.
14. Goghani D. R., Jogel A. A., Sanghani A. M., Mehta J. P. Synthesis and pharmacological screening of 1,2,4-triazole drivatives // Indian J. Chem. – 2015. – V. 54B. – P. 556–564.
15. Rybolovlev Ju. R., Rybolovlev R. S. Dozirovanie veshhestv dlja mlekopitajushhih po konstantam biologicheskoj aktivnosti // Doklady AN SSSR. – 1979. – № 6. – С. 1513–1516.
16. Stefanov O. V. Doklinični doslidžennja likarsʹkyx zasobiv: metod. rekomendaciji. – K.: Avicena, 2001. – S. 292–306.
17. Vukolov E. Fundamentals of statistical analysis. Workshop on statistical methods and operations research using STATISTICA and EXCEL packages: Uch. allowance. – M.: Forum, 2008. – 464 s.
How to Cite
Chalenko, N. M., Bezugly, P. A., Sirova, A. O., Chekman, I. S., & Demchenko, A. (2019). Synthesis and antiexudative activityof pyrolin derivatives 2 - ((4-amino-5- (furan-2-yl)-1,2,4-triazol-4H-3-il)-sulfanil)-N-acetamides. Farmatsevtychnyi Zhurnal, (5), 65-74.
Synthesis and analysis of biologically active compounds