Synthesis and physical-chemical properties of 3-aryl-(aralkyl)-8-hydrazinemethylxanthines and their N-substituted derivatives

Abstract

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.

Keywords

• xanthines
• organic synthesis
• NMR-spectroscopy