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

Aim. To analyze the alkyl-, heterylderivatives of 7'-((4-ethyl-5-thio-4 H -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, 1 H 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, N 7 -CH 2 -groups, thioalkyl fragments are fixed in 1 H 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-C 2 H 5 fragment are fixed also as a multiplet at 1.74–1.62 ppm. CH 2 -group is presented by protons signals as a singlet at 5.71 ppm. Protons of CH 3 -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.

1,2,4-Triazole fragment is a successful synton, used at medicines creation [10].Therefore, combining it with different nature radicals may be interesting for further research [3,9].Thus, increasing the probability of new pharmacological effects appearance and strengthening of existing is possible.The fact that of 1,2,4-triazole derivatives are often marked by low toxicity parameters simultaneously with high effi ciency is also important.Based on this fact, absolute value is studying the effect of different syntons in 1,2,4-triazole structure on different types of biological activity.Thus, research of derivatives of such heterocyclic system is actual and practically signifi cant.

Materials and methods
During the research process as initial material for synthesis of new series of compounds the theophylline has been chosen.It is important to note that considering the variety and strength of pharmacological effects, that occur, this structure takes its rightful place among the heterocyclic compounds [4][5][6][7].7'-((4-Ethyl-5-thio-4H-1,2,4-triazoles-3-yl)methyl) theophyllin has been received from theophylline through series of successive stages.

S R
In the IR-spectrum of synthesized alkyl derivatives we observe deformation vibrations of C-S-H fragment of alkyl groups in ranges from 630 to 1400 cm -1 and H-C-H fragment in a narrow area of frequency 1370-1500 cm -1 .For example, for CH 3 -group δ-vibrations occupied area at 1378-1380 cm -1 , and for C 4 H 9 -at 1390-1410 cm -1 .Valence vibrations of bonds of C-H alkyl groups form bands in area 2850-3100 cm -1 .780-840 cm -1 occupies a band of average intensity with a complex circuit that has several peaks (skeletal vibrations of C-C bonds).
By means of program PASS and GUSSAR products, prediction of the acute toxicity of synthesized compounds has been performed.It has been established that these compounds belong to low-toxic, which correlates with the known literature facts, and also help to open medical and biological potential of these compounds.

Conclusions
The optimal conditions for obtaining various derivatives of 7'-((4-ethyl-5-thio-4H-1,2,4-triazole-3-yl)methyl)-theophylline with halogenalkanes and halogen containing heteryle compounds have been established.Computer estimation indexes of synthesized compounds have been investigated using PASS program.The most promising compounds for in vitro testing have been determined.Diuretic and analeptic activities dominate in all 13 compounds.
Confl icts of Interest: аuthor have no confl ict of interest to declare.