Synthesis and investigation of the physical-chemical properties of 2-(5-((theophylline-7'-yl)methyl)-4-methyl-4H-1,2,4-triazole-3-ylthio)acetic acid salts

Authors

  • A. S. Gotsulya Zaporizhzhia State Medical University,

DOI:

https://doi.org/10.14739/2409-2932.2016.3.77832

Keywords:

Theophylline, 1, 2, 4-triazole, Physical-Chemical Properties, Synthesis

Abstract

At this stage of modern science development scientists get a lot of questions in the field of medicine and pharmacy. The study and search of new ways for synthesis of high-performance and low-toxic substances is one of the most important questions among them. Special attention is paid to 1,2,4-triazole and xanthine. On their basis some medical drugs have been previously made and are widely used in nowadays medicine.

The aim of this work was the synthesis of salts of 2-(5-((theophylline-7'-yl)methyl)-4-methyl-4H-1,2,4-triazole-3-ylthio)acetic acid and the study of their properties.

Methods and results. Theophylline has been selected as starting material. Through a number of stages 7'-((3-thio-4-methyl-4H-1,2,4-triazole-5-yl)methyl)theophylline has been obtained.

Salts with organic and inorganic bases have been obtained by the neutralization reaction in aqueous medium. The structure of the compounds has been confirmed with elemental analysis on Elemental Vario EL cube (Elementar Analysensysteme, Germany), IR spectra (4000–400 cm-1) have been taken off the module ALPHA-T of Bruker ALPHA FT-IR spectrometer (Bruker optics, Germany). Gear Liquid Chromatography System with Mass spectrometric detector (Agilent Technologies, USA): Agilent 1260 Infinity HPLC System; single quadrupole mass spectrometer Agilent 6120 with electrospray ionization (ESI); Open LAB CDS Software. The formation of salts has been confirmed by the signals corresponding to protonated amines.

Conclusions. The optimal conditions of obtaining salts of 2-(5-((theophylline-7'-yl)methyl)-4-methyl-4H-1,2,4-triazole-3-ylthio)acetic acid with inorganic and organic bases have been determined. Corresponding carboxylic acid has been obtained by interaction of the resulting thiol with monochloroacetic acid in aqueous solution with double quantity of alkali and subsequent neutralization by hydrochloric acid.

It has been confirmed that the greatest outputs of the reaction products were observed while using water as the solvent and its further replacement of propan-1-ol or acetone.  The general physical-chemical properties of the obtained compounds have been studied and a preliminary study of biological activity has been done.

References

Gotsulia, A. S., Mikоlаsyuk, O. O., Panasenko, O. І., et al. (2014). Syntez і doslіdzhennia fіzyko-khіmіchnykh vlastyvostei solei 2-(5-((teofіlіn-7-іl)metyl)-4-fenіl-4Н-1,2,4-trіazlol-3-іlіtіo)atsetatnoi kysloty [Synthesis and investigation of the physico-chemical properties of 2-(5-((theophylline-7'-yl)methyl)-4-phenyl-4H-1,2,4-triazole-3-ylthio) acetic acid salts]. Zaporozhskij medicinskij zhurnal, 1(82), 91–94. [in Ukrainian].

Gunawardhana, L., Tsai, M., & Naik, H. (patentee) (2012) Methods for concomitant of theophylline and febuxostat. Patent US, no. 0065236, 2012.

Eckhardt, M., Himmelsbach, F., Langkopf, E., & Maier, R. (patentee) (2009) Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions. Patent US, no. 7560450, 2009.

Hatley, R. J. D., Mason, A. M., & Pinto, I. L. (patentee) (2010) Xanthine derivatives as selective HM74A agonists. Patent US, no. 0168122, 2010.

Kazunin, M. S., Prіjmenko, А. О., Vasil´ev, D. А., & Prіjmenko, D. А. (2010). Sintez, fiziko-khimicheskie svojstva 3-(3-metilksantinil-8)-propanovoj kisloty i nekotorykh eyo proizvodnykh [Synthesis, physic-chemical properties 3-(3-methylxanthinyl-8)-propanoic acid and some of its derivatives]. Zaporozhskij medicinskij zhurnal, 3(12), 103–107. [in Ukrainian].

Levіch, S. V., Shkoda, O. S., Aleksandrova, K. V. (2013). Syntez ta fizyko-khimichni vlastyvosti S-zamishchenykh pokhidnykh 3-benzyl-8-metyl-7-[(4-fenil-5-tio-4N-1,2,4-triazol-3-il)metyl]-ksantynu [Synthesis and physical-chemical properties of S-substituted derivatives of 3-benzyl-8-methyl-7-[(4-phenyl-5-thio-4H-1,2,4-triazole-3-yl)methyl]-xanthine]. Aktualnі pytannia farmatsevtychnoі і medychnoі nauky ta praktyky, 1(11), 54–58. [in Ukrainian].

Lupascu, F. G., Dragostin, O. M., Foia, L., Lupascu, D., & Profire, L. (2013). The synthesis and the biological evaluation of new thiazolidine-4-one derivatives containing a xanthine moiety. Molecules, 18, 9684–9703. doi:10.3390/molecules18089684.

Raafat, M. S. (2006). The chemistry of mercapto- and thionesubstituted 1,2,4-triazoles and their utility in heterocyclic synthesis. ARKIVOC, IX, 59–112. doi: http://dx.doi.org/10.3998/ark.5550190.0007.904.

Yurchenko, D. M., Aleksandrova, K. V., Romanenko, M. І., & Makoіd, O. B. (2011). Syntez, reaktsii ta fizyko-khimichni vlastyvosti pokhidnykh 8-tioksantynil-7-atsetatnykh kyslot [Synthesis, reaction and physic-chemical properties derivatives of 8-thioxanthinyl-7-acetic acid]. Aktualnі pytannia farmatsevtychnoi і medychnoi nauky ta praktyky, XXIV(3), 104–108. [in Ukrainian].

Yurchenko, D. M., Aleksandrova, K. V., Romanenko, M. І., Samura, B. A., Taran, А. V. (patentee) (2011). Patent Ukrainy 61715, МПК (2011.01), С07D 473/00. Amіd 4-fenіl-5-(3'-metylksantynіl-7')metyl-1,2,4-trіazolіl-3-tіoatsetatnoі kysloty, yakyi vyіavlіaie dіuretychnu, protyzapalnu ta analhetychnu dіі. [Amide of 4-phenyl-5-(3'-methylxanthinyl-7')methyl-1,2,4-triazolyl-3-thioacetic acid which exhibits a diuretic, anti-inflammatory and analgesic effect]. [in Ukrainian].

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How to Cite

1.
Gotsulya AS. Synthesis and investigation of the physical-chemical properties of 2-(5-((theophylline-7’-yl)methyl)-4-methyl-4H-1,2,4-triazole-3-ylthio)acetic acid salts. Current issues in pharmacy and medicine: science and practice [Internet]. 2016Sep.22 [cited 2024Dec.29];9(3). Available from: http://pharmed.zsmu.edu.ua/article/view/77832

Issue

No. 3 (2016)

Section

Synthesis of the biologically active compounds

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