Synthesis and physico-chemical properties of some derivatives of 7-((3-thio-4R-4H-1,2,4-triazole-5-yl)methyl)theophylline

  • A. S. Gotsulya Zaporizhzhia State Medical University
  • O. I. Panasenko Zaporizhzhia State Medical University
  • Ye. G. Knysh Zaporizhzhia State Medical University
  • A. O. Pryimenko Municipal Enterprise «Pharmacy», Zaporizhia
  • B. O. Varynskyi Zaporizhzhia State Medical University
Keywords: 1,2,4-triazole, theophylline, synthesis, IR-spectroscopy, mass- and chromato-mass-spectrometry

Abstract

Biologically active agents based on naturally occurring xanthines are used widely in medicine. Compounds containing in their structure the 1,2,4-triazole nucleus are slightly toxic or non-toxic substances with high biological activity, have antimicrobial, neurotropic, antioxidant, anti-inflammatory, antifungal, hypolipidemic activity. The synthesis of compounds which contain in their structure a fragment of theophylline and 1,2,4-triazole nucleus is important.

The aim of the work is new derivatives of 7-((3-thio-4-R-4H-1,2,4-triazole-5-yl)methyl)theophylline synthesis and research of their physical and chemical properties.

Sodium salt of theophylline was used as the initial substance to obtain a new series of this compounds. The 7-((3-thio-4-R-4H-1,2,4-triazole-5-yl)methyl)-theophyllines were obtained through a series of consecutive stages. The obtained compounds were useful initial semi-products, which in its structure had CH- and SH-acidic centers. A number of not described in the literature substances that represents a certain interest in terms of biologically active compounds investigation were synthesized.

The structure of the synthesized compounds was confirmed by elemental analysis methods, IR-spectroscopy, chromato-mass and mass-spectrometry. The  protonation of 7-((3-thio-4-R-4H-1,2,4-triazole-5-yl)methyl)theophylline using quantum-chemical calculations was determined. The reactivity was determined on the basis of quantum-chemical calculations ability of 7-((3-thio-4-R-4H-1,2,4-triazole-5-yl)methyl)theophylline. The chromatography-mass and mass-spectrometric research or the synthesized compounds was conducted.

References

1. Mashkovskij M. D. Lekarstvennye sredstva. 16-e izd. – M.: «Novaya volna», 2012. – 1216 s.
2. Samura I. B., Prijmenko B. A. Antiaritmicheskie svojstva di- i triciklicheskih zameshennyh ksantina // Zaporozh. med. zhurn. – 2002. – № 4. – S. 69–72.
3. Samura I. B., Prijmenko B. A., Dunaev V. V. Nejrotropnaya aktivnost zameshennyh 7-acilalkil-8-galogen-3-metilksantina // Tam zhe. – 2002. – № 6. – S. 81–83.
4. Romanenko N. I., Prijmenko B. A., Yakushev V. S. i dr. Sintez i gipolipidemicheskaya aktivnost 7,8-dizameshennyh 3-metilksantina // Tam zhe. – 2004. – № 3 – S. 127–129.
5. Romanenko N. I., Prijmenko B. A., Samura B. A. i dr. Sintez i izuchenie protivovospalitelnoj aktivnosti proizvodnyh triazino(3,4-f)ksantina // Tam zhe. – 2004. – № 5. – S. 141–143.
6. Evsyeyeva L. A., Romanenko M. I., Ivanchenko D. G. ta in. Sintez ta antioksidantna diya ilidengidrazinopohidnih 3-metil-7-p-ftorbenzilksantinu // Tam samo. – 2007. – № 4 (43). – S. 154–157.
7. Ivanchenko D. G., Romanenko M. I., Glushenko M. V. ta in. Sintez ta vivchennya antioksidantnoyi diyi 8-arilidengidrazino-1-p-hlorbenzilteobrominiv // Tam samo. – 2008. – № 1 (46). – S. 114–117.
8. Panasenko O. I. Gostra toksichnist deyakih benzipidenpohidnih 4-amino- ta 3,5-dimetil-4-amino-1,2,4-triazolu // Med. himiya. – 2003. – Vip. 5. – S. 94–96.
9. Parchenko V. V., Panasenko A. I., Knysh E. G. Sintez i biologicheskaya aktivnost nekotoryh alkilproizvodnyh 5-(furan-2-il)-4-fenil-2,4-digidro-1,2,4-triazol-3-tionov // Akt. pitannya farmac. med. nauki ta praktiki. – 2005. – Vip. XVI. – S. 263–266.
10. Pruglo Ye. G., Bilaj I. M., Parchenko V. V. Gipo-b-lipoproteyidemichni vlastivosti novih zamishenih 1,2,4-triazolu // Ukr. naukovo-medichnij molodizhnij zhurn. – 2009 – Vip. 3. – S. 19–21.
11. Goculya A. S., Mikolasyuk O. O., Panasenko O. I. ta in. Sintez i doslidzhennya fiziko-himichnih vlastivostej solej 2-(5-((teofilin-7’-il)metil)-4-fenil-4N-1,2,4-triazlol-3-ilitio)acetatnoyi kisloti // Zaporozh. med. zhurn. – 2014. – № 1 (82). – S. 91–94.
12. Jiang B., Huang X., Yao H. et al. Discovery of potential anti-inflammatory drugs: diaryl-1,2,4-triazoles bearing N-hydroxyurea moiety as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase // Org. Biomol. Chem. – 2014. – N 12 (13). – R. 2114–2127.
13. Pattan S., Gadhave P., Tambe V. et al. Synthesis and evaluation of some novel 1,2,4-triazole derivatives for antimicrobial, antitubercular and anti-inflamatory activities // Indian J. Chem. – 2012. – V. 51B. – P. 297–301.
14. Kazicyna L. A. Primenenie UF-, IK- i YaMR-spektroskopii v organicheskoj himii. – M.: Vysshaya shkola, 1971. – 264 s.
Published
2019-02-12
How to Cite
Gotsulya, A. S., Panasenko, O. I., Knysh, Y. G., Pryimenko, A. O., & Varynskyi, B. O. (2019). Synthesis and physico-chemical properties of some derivatives of 7-((3-thio-4R-4H-1,2,4-triazole-5-yl)methyl)theophylline. Farmatsevtychnyi Zhurnal, (6), 43-52. Retrieved from https://pharmj.org.ua/index.php/journal/article/view/272
Section
Synthesis and analysis of biologically active compounds

Most read articles by the same author(s)