DEVELOPMENT OF METHODS FOR THE IDENTIFICATION OF 3-BROMO-1-(1,1-DIOXOTIETHAN-3-YL)- 4-NITRO-N-PHENYL-1H-PYRAZOL-5-AMINE

Pyrazole derivatives are widely used as anticoagulants, antitumor, psychotropic and anti-inflammatory agents. Among the thietane-containing pyrazoles, we have found compounds promising for further in-depth studies as antidepressants, one of which is 3-bromo-1-(1,1-dioxothiethane-3-yl)-4-nitro-N-phenyl-1H-pyrazole-5-amine (I).

The objective of the work is to study the physical, physicochemical properties and spectral characteristics of the promising 3-bromo-1-(1,1-dioxothiethane-3-yl)-4-nitro-N-phenyl-1H-pyrazole-5-amine substance for the development of methods for determining identification.

Material and methods. The object of the study was 3 experimental batches of 3-bromo-1-(1,1-dioxothiethane-3-yl)-4-nitro-N-phenyl-1H-pyrazole-5-amine (I). The solubility of the chemical compound was determined in water and various organic solvents. IR spectra were recorded on the Infralum FT-02 spectrophotometer, UV spectra were recorded on the Shimadzu UV-1800. To determine identification, a reaction with a 20% sodium hydroxide solution was carried out. The melting point was measured by the capillary method on the "SMP 30" device. Thin-layer chromatography was performed on "Sorbfil" PTSH-AF-A-UV plates. Chromato-mass spectra were recorded on a gas-liquid chromatograph with an Agilent MSD 5977B quadrupole mass-selective detector.

The main results. Methods for determining the identification of a promising biologically active substance of 3-bromo-1-(1,1-dioxothiethane-3-yl)-4-nitro-N-phenyl-1H-pyrazole-5-amine (I) have been studied for the first time. It was found that the substance is a reddish-brown crystalline powder, easily soluble in acetone and dimethylformamide, and practically insoluble in water and alcohol. The melting point of substance I is from 182.6 to 184.0 °C. The analysis of substance I by IR spectroscopy made it possible to identify the absorption bands belonging to the pyrazole and substituents. Two peaks at 457.17 nm and 277.50 nm and one absorption minimum at 364.78 nm are recorded in the UV spectrum. Thin-layer chromatography and gas chromatography with mass spectrometric detection are proposed to confirm identification. As a result of the reaction with a 10% sodium hydroxide solution, a bright red staining is formed.

Conclusions. Based on the results of the study of the physical, physicochemical properties and spectral characteristics of 3-bromo-1-(1,1-dioxothiethane-3-yl)-4-nitro-N-phenyl-1H-pyrazole-5-amine, methods for determining identification are proposed.

1. Wishart David S. [et al.], DrugBank: a comprehensive resource for in silico drug discovery and exploration // Nucleic Acids Research. 2006; 34(1): 668-672. (In English).

2. Apixaban // Reactions Weekly. 2021; 1843(1): 62. (In English).

3. Gordeeva O.O., Meshcheryakov A.A., Meshcheryakova N.A. Targeted therapy with crizotinib for non-small cell lung cancer with Alk translocation: Complete Tumor Regression // Russian Journal of Oncology. 2019; 24(1–2): 51-55. (In Russ).

4. Noguchi H. [et al.] Binding and neuropharmacological profile of zaleplon, a novel nonbenzodiazepine sedative/hypnotic // European Journal of Pharmacology. 2002; 434(1–2): 21-28. (In English).

5. Emery, P. [et al.] Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison // The Lancet. 1999; 354(9196): 2106-21112. (In English).

6. Patent of the Russian Federation No. RU 2785340. 1-(1,1-Dioxothietan-3-yl)-4-(2-oxo-2-phenylethyl)-1,2,4-triazol-4-im bromide, showing antidepressant activity / E.E. Klen, I. L. Nikitina, G. A. Rozit [et al.]. Appl. 15.03.2022. Published 06.12.2022. Bulletin No. 34. (In Russ).

7. Klen E.E. [et al.] Reactions of Thiiranes with NH Heterocycles: II. C-Bromo/Nitro-1-(thietan-3-yl)pyrazoles as Convenient Synthons for Substituted 1-(Thietan-3-yl)pyrazoles //Russ J Org Chem. 2022; 58(9): 1192–1199 (2022). https://doi.org/10.1134/S1070428022090020. (In Russ).

8. Khaliullin, F.A., Klen, E.E., Pavlov, V.N. [et al.] Synthesis and Biological Activity of 5-alkoxy- and 5-amino-substituted 3- bromo-4-nitro-1-(thietan-3-yl)-1H-pyrazoles. Pharm Chem J. 2022; 56(3): 316–320 https://doi.org/10.1007/s11094-022-02636-9. (In Russ).

9. Patent of the Russian Federation No. RU 2801039C1. 5-Amino-substituted thietane-containing 3-bromo-4-nitropyrazoles with antidepressant activity / E.E. Klen, I.L. Nikitina, S. O. Shepilova, E.A. Nikitina, V.N. Pavlov, A.V. Samorodov, F. A. Khaliullin. Appl. 24.11.2022. Published 01.08.2023. Bulletin No. 22. (In Russ).

10. Kovaleva, E.L. Standardization of pharmaceutical substances and preparations in the dosage form "Pills". Moscow: Grif i K, 2012. 288 p. (In Russ).

11. Gosudarstvennaya farmakopeya Rossiiskoi Federatsii 14 izd. Vol 1. Moscow, 2018. URL: URL: http://www.femb.ru (date of application: 10.07.23) (in Russ.).

12. Prech, E. Determination of the structure of organic compounds. Tables of Spectral Data / E. Prech, F. Bulmann, K. Affolter. – M. World:, 2006. (In Russ).

13. Shepilova S.O., Klen E.E., Khaliullin F.A. Study of the structure of 5-amino-substituted 3-bromo-4-nitro-1-(thietanyl-3)-1H-pyrazoles by IR spectroscopy // Bashkir Chemical Journal. 2022; 29 (3): 40-43 doi: 10.17122/bcj-2022-3-40-43. (In Russ).

14. Silverstein, R. Spectrometric identification of organic compounds / R. Silverstein, F. Webster, D. Kiml. - BINOM. Lab. knowledge, 2011. (In Russ).