Synthesis and physical-chemical properties of 3-aryl-(aralkyl)-8-hydrazinemethylxanthines and their N-substituted derivatives
DOI:
https://doi.org/10.14739/2409-2932.2016.2.70906Keywords:
xanthines, organic synthesis, NMR-spectroscopyAbstract
Introduction. Analysis of last years’ literature shows, that the most wide spread drugs are those, which contain in their structures heterocyclic fragment. Such trend could be explained by the fact that, heterocycle containing compounds are the part of the number of substances, which play an important role in the metabolic processes. It should be noted, that most of these drugs have unpleasant side effects and some of them are rather toxic. Xanthine derivatives are low toxic natural compounds with wide spectrum of pronounced pharmacological properties (antioxidant, diuretic, antibacterial, anti-inflammatory etc.) and high variability of chemical modification, that make these compounds handy objects for pharmaceutical research. Thus, synthesis of novel less toxic biologically active compounds – potential medicines – by chemical modification of well-known natural substances, is one of the most important tasks of modern pharmaceutical science.
Aim of our research was the development of method of 3-aryl(aralkyl)-8-hydrazinemethylxanthines and their N-substituted derivatives synthesis and studying their physical-chemical properties.
Materials and methods. Melting points were determined using capillary method on DMP (M). 1Н NMR-spectra were recorded by Varian Mercury VX-200 device (company «Varian» – USA) solvent – (DMSO-d6), internal standard – ТМS. Elemental analysis of obtained compounds was produced on device Elementar Vario L cube.
Results and discussion. We selected 3-aryl(aralkyl)-8-chloromethylxanthines as initial compounds for our study. By their interaction with hydrazine hydrate we obtained respective 8-hydrazinemethylxanthines. The next stage of our research was further chemical modification of obtained 8-hydrazinemethylxanthines using the high ability of hydrazine residue for nucleophilic addition reactions. So, we studied the interaction of
3-aryl(aralkyl)-8-hydrazinemethylxanthines with phenylisothiocyanate and carbonyl compounds and synthesized number of N-substituted 8-hydrazinemethylxanthines. The structures of all obtained compounds were proved by the elemental analysis and 1H NMR-spectroscopy.
Conclusions. Obtained results of our work can be used for further search of biological active compounds among xanthine derivatives with hydrazine residue.
References
Saini, M. S., Kumar, A. Dwivedi, J., & Singh, R. (2013) A Review: Biological significances of heterocyclic compounds. International Journal of Pharma Sciences and Research, 3(4), 66–77.
Joule, J. A., & Mills, K. (2010) Heterocycles in Nature. Heterocyclic Chemistry at a Glance. Chichester: John Wiley & Sons, Ltd., (P. 158–166).
Joule, J. A., & Mills, K. (2010) Heterocycles in Medicine. Heterocyclic Chemistry at a Glance. Chichester: John Wiley & Sons, Ltd. (P. 167–179).
Müller, C. E., Sandoval-Ramírez, J., Schobert, U., Geis, U., Frobenius, W., & Klotz, K. N. (1998) 8-(Sulfostyryl)xanthines: water-soluble A2A-selective adenosine receptor antagonists. Bioorganic & Medicinal Chemistry, 6, 707–719.
Taran, A. V., Kornienko, V. I., Samura B. A., et al. (2010) Issledovanie diureticheskoj aktivnosti ammonievykh solej 7,8-dizameschennykh proizvodnykh 3-metilksantina [Research of diuretic activity of ammonium salts of 7,8-disubstituted 3-methylxanhtine derivatives]. Ukrainskyi biofarmatsevtychnyi zhurnal, 3, 14–17. [in Ukrainian].
Kornienko, V. I., Samura B. A., Litarov V. E., Nikolaev, V. A., Romanenko, N. I., Evseeva, L. V., & Ivanchenko, D. G. (2008) Issledovanie ostroj toksichnosti i diureticheskoj aktivnosti ammonijnykh solej 1,7-dizameschennykh 3-metilksantinil-8-tiouksusnoj kisloty [Research of acute toxicity and diuretic activity of ammonium salts of 1,7-disubstituted 3-methylxanthinyl-8-thioacetic acid]. Zaporozhskij medicinskij zhurnal, 5, 128–130. [in Ukrainian].
Kall, R. V., Elzein, E., Perry, T., Li, X., Palle, V., Varkhedkar, V., et al. (2006) Novel 1,3-disubstituted 8-(1-benzyl-1H-pyrazol-4-yl)xanthines: high affinity and selective A2B adenosine receptor antagonists. J. Med. Chem., 49, 3682–3692.
Romanenko, N. I., Nazarenko, M. V., Ivanchenko, D. G., Pakhomova, O. O., & Sharapova, T. A. (2015) The study of reactions of 7-substituted 8-hydrazino-3-methylxanthine with β-dicarbonyl compounds. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, 2(18), 4–8. [in Ukrainian].
Ivanchenko, D. G. (2015) Synthesis, physical-chemical and biological properties of 1,8-disubstituted of theobromine. V. 8-Benzylidenhydrazino-1-p-methylbenzyltheobromines. Zaporozhskij medicinskij zhurnal, 5(92), 89–92. [in Ukrainian]. doi: 10.14739/2310-1210.2015.5.53768.
Ivanchenko, D. H., Romanenko, M. I., Sharapova, T. A., Aleksandrova, K. V., Kamyshny, A. M., & Polishchuk, N. M. (2015) Syntez i protymikrobni vlastyvosti 8-benzylidenhidrazyno-1-n-propilteobrominiv [Synthesis and antibacterial properties of 8-beznylidenhydrazine-1-propyltheobromines]. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, 1(17), 51–55. [in Ukrainian].
Aleksandrova, K. V., Levich, S.V., Shkoda, A. S. et al. (2011) Syntez ta fizyko-khimichni vlastyvosti 3-fenil(benzyl)-ksantynil-8-metyltioatsetatnykh kyslot ta yikh vodorozchynnykh solei [Synthesis and physicochemical properties of 3-phenyl(benzyl)xanthinyl-8-methylthioacetic acids and their water-soluble salts. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, 2, 104–108. [in Ukrainian].
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- 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.
- 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.
- 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)
