DEVELOPMENT OF METHODS FOR DETERMINING THE AUTHENTICITY OF 2-[1-ISOBUTYL-3-METHYL-7-(1,1-DIOXOTHIETANYL-3)XANTHINYL-8- THIO]ACETIC ACID

The well-known drugs pentoxifylline, aminophylline, linagliptin and isradephylline have been created on the basis of natural methylxanthines by chemical modification. It has been identified that some synthetic derivatives of xanthine including thietane containing xanthines exhibit anti-inflammatory, analgesic, antidepressant, antidiabetic and antioxidant activity. We have synthesized 2- [1-isobutyl-3-methyl-7-(1,1-dioxothietanyl-3)xanthynyl-8-thio]acetic acid (I) which exhibits high antioxidant activity in the model system of generation of reactive oxygen species by blood phagocytes. Further pharmacological studies of compound I require the development of methods for determining the authenticity which is an integral part of the standardization of pharmaceutical substances.The aim of this research is to study the chemical and physicochemical properties of 2-[1-isobutyl-3-methyl-7-(1,1- dioxothietanyl-3)xanthynyl-8-thio]acetic acid to develop methods for determining its authenticity.Material and methods. Objects of research are 5 experimental batches of 2-[1-isobutyl-3-methyl-7-(1,1-dioxothietanyl-3)xanthynyl-8-thio]acetic acid. Solubility has been determined in water and various organic solvents. 1H, 13C NMR spectra were recorded on a Bruker AV-500 instrument. IR spectra were taken on a spectrophotometer «Infralum FT-02», UV spectra - on a«Shimadzu UV-1800» device. As a reaction for determining the authenticity a murexide test and a characteristic reaction with a solution of iron (III) chloride 3% were carried out. The melting point was measured by the capillary method on an SMP 30 device.Weight loss on drying was determined according to Method 1. Results. All synthesized batches of 2-[1-isobutyl-3-methyl-7-(1,1-dioxothietanyl-3)xanthynyl-8-thio]acetic acid are odorless white crystalline powders with different solubility in water and organic solvents. The structure of acid I is confirmed by the 1H NMR spectrum which shows the presence of proton signals of isobutyl substituent, methyl group of xanthine, thiethane dioxide ring and thioglycolic acid residue. The structure of acid I is also confirmed by 13C NMR spectrum which besides characteristic carbon signals of xanthine, alkyl substituents and thiethane dioxide cycle contains carbon signals of thioglycolic acid residue. Determination of the authenticity of acid I was carried out by IR and UV spectra. Intense absorption bands of stretching vibrations of SO2 bonds of thiethane dioxide groups and C=O, C=N bonds of xanthine as well as a wide absorption band of stretching vibrations of the O-H bond of thioglycolic acid residue were found in IR spectra. UV spectra are characterized by the presence of two absorption maxima at 219,8 nm, 294,7 nm and one absorption minimum at 259,4 nm in the wavelength range from 210 nm to 350 nm. When carrying out a murexid test for acid I a red-violet coloration was observed. As a result of a characteristic reaction with a solution of iron (III) chloride 3% a light brick precipitate is formed. The range of values of the melting point was 234,6-235,5 °C. Weight loss on drying makes up no more than 0.2%.Conclusions. The description and solubility of 2-[1-isobutyl-3-methyl-7-(1,1-dioxothietanyl-3)xanthynyl-8-thio]acetic acid have been determined. Chemical and physicochemical methods for determining the authenticity of acid I have been studied. According to obtained results IR spectroscopy, UV spectroscopy, murexide test, reaction with a solution of iron (III) chloride 3% and measurement of the melting point have been proposed to determine the authenticity. Weight loss on drying was determined.

xanthines, thietanes, authenticity, infrared spectroscopy, ultraviolet spectroscopy

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