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

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.

Keywords

• 4-triazoles
• theophylline
• synthesis
• IR-spectrometry
• 1H NMR spectrometry