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Synthesis and Antidepressant Activity of 5-Amine-Substituted 3-Bromo-1-(1,1-Dioxothietan-3-yl)-4-Nitro-1H-Pyrazoles

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Pharmaceutical Chemistry Journal Aims and scope

5-Amino-substituted 3-bromo-1-(1,1-dioxothietan-3-yl)-4-nitro-1H-pyrazoles were synthesized via the reactions of 3,5-dibromo-1-(1,1-dioxothietan-3-yl)-4-nitro-1H-pyrazole with aliphatic, aromatic, and heterocyclic amines. The structures of the synthesized compounds were confirmed by IR, PMR, and 13C NMR spectroscopy and mass spectrometry. According to in silico calculations, they were predicted to have no toxic risks (mutagenicity, tumorigenicity, reproductive effects, irritating effects), low toxicity (class IV-V), and acceptable oral bioavailability (based on the topological polar surface area indicator). All synthesized compounds, regardless of the amine structure, showed significant antidepressant activity after a single intraperitoneal injection to male mice in the forced swimming test that was comparable to that of amitriptyline, while 1-[3-bromo-1-(1,1-dioxothietan-3-yl)-4-nitro-1H-pyrazol-5-yl]-4-methylpiperazine (compound IIi) had a significant sedative effect in the open field test. The results of a comprehensive assessment of the biological activity of the synthesized compounds in vivo/in silico indicated that the class of 5-amino-substituted pyrazole derivatives was promising for further research.

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Authors and Affiliations

  1. Bashkir State Medical University, Ministry of Health of Russia, 3 Lenina St, Ufa, 450008, Russia

    E. E. Klen, I. L. Nikitina, F. A. Khaliullin, S. O. Shepilova, E. A. Nikitina, G. G. Gaisina, M. A. Urazbaev, A. V. Samorodov & V. N. Pavlov

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  1. E. E. Klen
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  2. I. L. Nikitina
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  3. F. A. Khaliullin
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  4. S. O. Shepilova
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  5. E. A. Nikitina
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  6. G. G. Gaisina
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  7. M. A. Urazbaev
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  8. A. V. Samorodov
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  9. V. N. Pavlov
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Correspondence to F. A. Khaliullin.

Additional information

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 57, No. 7, pp. 33 – 40, July, 2023.

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Klen, E.E., Nikitina, I.L., Khaliullin, F.A. et al. Synthesis and Antidepressant Activity of 5-Amine-Substituted 3-Bromo-1-(1,1-Dioxothietan-3-yl)-4-Nitro-1H-Pyrazoles. Pharm Chem J 57, 1202–1209 (2023). https://doi.org/10.1007/s11094-024-03027-y

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