2-Aryl-1-hydroxyimidazoles possessing antiviral activity against a wide range of orthopoxviruses, including the variola virus.

Autor: Basanova EI; Department of Fine Organic Synthesis and Chemistry of Dyes, D.I. Mendeleev University of Chemical Technology of Russia Miusskaya sq., 9 125047 Moscow Russia basanova.elizavetka@mail.ru polinandrevna@yandex.ru., Kulikova EA; Department of Fine Organic Synthesis and Chemistry of Dyes, D.I. Mendeleev University of Chemical Technology of Russia Miusskaya sq., 9 125047 Moscow Russia basanova.elizavetka@mail.ru polinandrevna@yandex.ru., Bormotov NI; State Research Center of Virology and Biotechnology VECTOR Rospotrebnadzor 630559 Koltsovo Russia., Serova OA; State Research Center of Virology and Biotechnology VECTOR Rospotrebnadzor 630559 Koltsovo Russia., Shishkina LN; State Research Center of Virology and Biotechnology VECTOR Rospotrebnadzor 630559 Koltsovo Russia., Ovchinnikova AS; State Research Center of Virology and Biotechnology VECTOR Rospotrebnadzor 630559 Koltsovo Russia., Odnoshevskiy DA; State Research Center of Virology and Biotechnology VECTOR Rospotrebnadzor 630559 Koltsovo Russia., Pyankov OV; State Research Center of Virology and Biotechnology VECTOR Rospotrebnadzor 630559 Koltsovo Russia., Agafonov AP; State Research Center of Virology and Biotechnology VECTOR Rospotrebnadzor 630559 Koltsovo Russia., Yarovaya OI; Department of Medicinal Chemistry, N.N. Vorozhtsov Institute of Organic Chemistry SB RAS Lavrentyev Ave., 9 630090 Novosibirsk Russia., Borisevich SS; SRF 'SKIF' 630559 Koltsovo Russia., Ilyina MG; SRF 'SKIF' 630559 Koltsovo Russia., Kolybalov DS; Scientific Educational Center 'Institute of Chemical Technology', Novosibirsk State University Pirogova str., 1 630090 Novosibirsk Russia., Arkhipov SG; Scientific Educational Center 'Institute of Chemical Technology', Novosibirsk State University Pirogova str., 1 630090 Novosibirsk Russia., Bogdanov NE; Scientific Educational Center 'Institute of Chemical Technology', Novosibirsk State University Pirogova str., 1 630090 Novosibirsk Russia.; V.S. Sobolev Institute of Geology and Mineralogy, Siberian Branch of Russian Academy of Sciences Koptyuga Ave., 3 630090 Novosibirsk Russia., Pavlova MA; Laboratory of Photoactive Supramolecular Systems, A.N. Nesmeyanov Institute of Organoelement Compounds RAS Vavilova str., 28 119991 Moscow Russia., Salakhutdinov NF; Department of Medicinal Chemistry, N.N. Vorozhtsov Institute of Organic Chemistry SB RAS Lavrentyev Ave., 9 630090 Novosibirsk Russia., Perevalov VP; Department of Fine Organic Synthesis and Chemistry of Dyes, D.I. Mendeleev University of Chemical Technology of Russia Miusskaya sq., 9 125047 Moscow Russia basanova.elizavetka@mail.ru polinandrevna@yandex.ru., Nikitina PA; Department of Fine Organic Synthesis and Chemistry of Dyes, D.I. Mendeleev University of Chemical Technology of Russia Miusskaya sq., 9 125047 Moscow Russia basanova.elizavetka@mail.ru polinandrevna@yandex.ru.
Jazyk: angličtina
Zdroj: RSC medicinal chemistry [RSC Med Chem] 2024 Jul 05. Date of Electronic Publication: 2024 Jul 05.
DOI: 10.1039/d4md00181h
Abstrakt: Scientific interest in orthopoxvirus infections and search for new highly effective compounds possessing antiviral activity against orthopoxviruses have significantly increased as a result of worldwide mpox outbreak in 2022. The present work deals with the synthesis of new 2-arylimidazoles exhibiting in vitro activity not only against the vaccinia virus, cowpox virus and ectromelia (mousepox) virus but also against the variola virus. Among the imidazole derivatives under consideration (1-hydroxyimidazoles, 1-methoxyimidazoles, 1-benzyloxyimidazoles, and imidazole N -oxides), the most promising antiviral activity is demonstrated by 1-hydroxyimidazoles, which may exist as two prototropic tautomers. Both of these tautomers may be manifested in different crystal structures of these compounds, according to single-crystal X-ray diffraction analysis, while predominantly one of them ( N -hydroxy-tautomeric form) is present in DMSO- d 6 solutions and in the gaseous state, as shown by NMR spectroscopy and quantum-chemical calculations. The leader compound 1-hydroxy-2-(4-nitrophenyl)imidazole 4a demonstrated the highest selectivity indices against the vaccinia virus (SI = 1072) and the variola virus (SI = 373).
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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