Synthesis, physical and chemical research of alkyl-, heterylderivatives of 7'-((4-ethyl-5-thio-4H-1,2,4-triazoles-3-yl)methyl)theophylline

Authors

  • A. S. Gotsulya Zaporizhzhia State Medical University,

DOI:

https://doi.org/10.14739/2409-2932.2016.2.71080

Keywords:

1, 2, 4-triazoles, theophylline, synthesis, IR-spectrometry, 1H NMR spectrometry

Abstract

Aim. To analyze the alkyl-, heterylderivatives of 7'-((4-ethyl-5-thio-4H-1,2,4-triazoles-3-yl)methyl)theophylline their mother substance has been synthesized and its interaction with halogenalkane and halogenheteryle has been carried out.

Methods and results. The physical and chemical properties of the obtained compounds have been studied and their structures have been confirmed by elemental analysis, infrared spectrometry, 1H NMR spectrometry, UV spectrophotometry and gas chromatography mass spectrometry. Preliminary computer study of acute toxicity and biological activity has been also carried out.

Results and their discussion. Theophylline was used as starting substance from which through series successive stages of transformation (electrophilic substitution reaction, hydrazinolysis, etherification and intramolecular alkaline heterocyclisation) starting thiol and alkyl derivatives were obtained. Alkyl derivatives were obtained in propanol-1 with heating. Synthesized substances were crystallized from methanol.

Signals of methyl groups of theophylline, N7-CH2-groups, thioalkyl fragments are fixed in 1H NMR spectrum of obtained compound. Protons of the S-alkyl fragments resonate in a strong field as a multiplet in area 1.53–1.01 ppm. Protons of N-C2H5 fragment are fixed also as a multiplet at 1.74–1.62 ppm. CH2-group is presented by protons signals as a singlet at 5.71 ppm. Protons of CH3-group of the xanthine sinton resonate at 2.95 and at 3.25 ppm.

Personality of the compounds has been established using chromato-mass spectrometry.

Conclusion. 13 New compounds have been obtained and their structure has been confirmed.

Indicators of computer evaluation of synthesized compounds using the PASS program have been researched. By means of prediction, results identified the most perspective compounds for testing the biological activity in vitro. During the analysis of obtained results, it was able to establish that obtained compounds possess different types of biological activity. Diuretic and analeptic activities dominate among the most likely types of that predicted activities for all 13 compounds.

References

Hotsulya, A. S., Mіkоlаsiuk, 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. [in Ukrainian].

Hotsulia, A. S., Panasenko, O. І., & Knysh, Ye. H. (2015). UF-spektrofotometrychne doslіdzhennya 7-((3-tіo-4-R-1,2,4-trіazol-3-іl)metyl)-teofіlіnіv [UV-spectrophotometric study of the 7-((3-thio-4-R-1,2,4-triazole-3-yl)methyl)-theophyllines]. Farmatsevtychnyj zhurnal, 4, 65–70. [in Ukrainian].

Hotsulia, A. S., Panasenko, O. I., Knysh, Ye. H., & Varynskyi, B. O. (2014). Syntez ta fizyko-khimichni vlastyvosti deiakykh pokhidnykh 7-((3-tio-4-R-4H-1,2,4-triazol-5-il)metyl)teofilinu [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, 43–53. [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 physic-chemical properties derivatives of 8-sustituted 3-benzylxanthines as perspective compounds for search of biologically active substances]. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, 1(11), 54–58. [in Ukrainian].

Yurchenko, D. M., Aleksandrova, K. V., Romanenko, M. І., Samura, B. A., & Taran, А. V. (patentee) (2011). Patent Ukrainy 61715, MPK (2011.01), S07D 473/00. Amіd 4-fenіl-5-(3'-metylksantynіl-7')metyl-1,2,4-trіazolіl-3-tіoacetatnoyі kysloty, yakyy vyіavlіaye dіuretychnuу, protyzapalnu ta analhetychnu dіyі. [Ukraine Patent 61715, IPC (2011.01) S07D 473/00. 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].

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]. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, XXIV (3), 104–108. [in Ukrainian].

Aleksandrova, K. V., Yurchenko, D. M., Romanenko, M. І., & Martyniuk, О. О. (2010). Syntez ta fizyko-khimichni vlastyvosti esteriv ksantynil-7-otstovoi kysloty [Synthesis and physic-chemical properties ester of xanthinyl-7-acetic acid]. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, XXІІІ, (1), 7–10. [in Ukrainian].

Kazunin, M. S., Prіjmenko, А. О., Vasil′ev, D. А., & Prіjmenko, B. А. (2010). Sintez, fiziko-khimycheskie 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. [in Ukrainian].

Gotsulya, A. S., Panasenko, O. I., Knysh, Ye. G., & Knyazevich, P. S. (2015). Synthesis and physical-chemical research of 7-((3-thio-4-R-4H-1,2,4-triazole-5-yl)methyl)theophylline carbonyl derivatives. Zaporozhskij medicinskij zhurnal, 90, 103.

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.

Downloads

How to Cite

1.
Gotsulya AS. Synthesis, physical and chemical research of alkyl-, heterylderivatives of 7’-((4-ethyl-5-thio-4H-1,2,4-triazoles-3-yl)methyl)theophylline. Current issues in pharmacy and medicine: science and practice [Internet]. 2016Jun.10 [cited 2024Apr.26];(2). Available from: http://pharmed.zsmu.edu.ua/article/view/71080

Issue

No. 2 (2016)

Section

Synthesis of the biologically active compounds

License

Authors who publish with this journal agree to the following terms:

    1. 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.     Лицензия Creative Commons
    2. 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.
    3. 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)