Synthesis and physical-chemical properties of 8-bromo-3-methyl-7-α-methylbenzylxanthine derivatives
The level of modern pharmaceutical science development is determined by the introduction in medical practice of new effective and non-toxic drugs. The problem of new drugs search depends on the presence in the arsenal of pharmacologists significant amount of original and promising bioactive compounds. In this aspect a special role is given to synthetic compounds of natural origin, which are successfully used in medical practice. Recent researches of national and foreign scientists suggest significant perspective synthetic xanthine derivatives in the creation of new drugs with various effects.
The aim of this paper is synthesis of 8-bromo-3-methyl-7-α-methylbenzylxanthine derivatives, unspecified in scientific papers earlier, and to study their physical and chemical properties.
The melting point has been determined by open capillary method on the device PTP (M). Elemental analysis has been performed on the device Elementar Vario L cube. NMR spectra have been taken using spectrometer Bruker SF-200.
Synthesis of 8-bromo-3-methyl-7-α-methylbenzylxanthine was performed through boiling of 8-bromo-3-methylxanthine together with α-methylbenzylchloride. Having applied the reaction of the latter with an excess of a primary or secondary heterocyclic amine in the methoxyethanol environment, a range of corresponding 8-aminosubstituted 3-methylxanthine has been obtained. The heating of initial syntone with an excess of hydrazine hydrate in aqueous dioxane environment leads to the formation of 8-hydrazinoxanthine. Corresponding 8-(indolon-2-ylidene-3)-hydrazinoxanthines have been obtained through short-time heating up 8-hydrazinoxanthine with N-substituted isatin in aqueous dioxane environment. Structure of synthesized compounds has been definitely proved by NMR-spectroscopy.
Simple laboratory method has been elaborated to synthesize 8-bromo-3-methyl-7-α-methylbenzylxanthine, which is initial compound for further chemical modification of xanthine molecule. Reactions of 8-bromo-3-methyl-7-α-methylbenzylxanthine with N-containing nucleophiles have been investigated. This allowed to obtain the previously undescribed 8-amino- and 8-hydrazinosubstituted 3-methyl-7-α-methylbenzylxanthine. Physical and chemical properties of new synthesized compounds have been studied. A synthetic perspective of the obtained substances has been shown.
2. Belenichev I.F., Aleksandrov KV, Nosach S. G. et al. New xanthine derivative B-YR-2 as antioxidant modulator of post-stroke damage of sensorimotor cortex neurons in rats // Elixir Pharmacy. - 2014 - V. 76. - P. 28286-28292.
3. Aleksandrova KV, Levich SV, Belenichev I. F., Shkoda A. S. Research of energotropic properties of 3-benzylxanthine derivative - prospective neuroprotector // Inter. J. Pharmacy. - 2015 - V. 5, N 17. - P. 1-4.
4. Bilai I. M., Alexandrova K. V., Levich S. V. and others. Investigation of hypoglycemic activity of derivatives of 3-benzyl-8-methylxanthine // Ac. pit farm honey. science and practice. - 2015. - No. 1 (17). - P. 89-92.
5. Mak G., Hanania N.A. New Bronchodilators // Curr. Op Pharmacol - 2012. - N. 12. - P. 238-245.
6. Song B., Xiao T., Qi X. Design and synthesis of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors // Bioorg. Med. Chem Let it be. - 2012. - V. 22, Is. 4. - R. 1739-1742.
7. Mohamed T., Osman W., Tin G., Rao P. N. Selective Inhibition of Human Acetylcholinesterase by Xanthine Derivatives: In vitro Inhibition and Molecular Modeling Investigations // Ibid. - 2013. - N 23. - P. 4336-4341.
8. Priimenko B. A., Romanenko N. I., Garmash SN, etc. Preparation of 3-methyl-8-bromoxanthine and its alkylation // Ukr. chem journ - 1985. - Vol. 51, No. 6. - P. 660-663.
9. Romanenko N. I., Pekhtereva T. M., Cervinsky A. Yu., Etc. Synthesis and PMR-spectroscopic study of 8-acetylhydrazinoxanthines // Ibid. - 1988. - Vol. 54, No. 12. - P. 1305-1309.
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