Basanova Elizaveta I, Kulikova Ekaterina A, Bormotov Nikolai I, Serova Olga A, Shishkina Larisa N, Ovchinnikova Alyona S, Odnoshevskiy Dmitry A, Pyankov Oleg V, Agafonov Alexander P, Yarovaya Olga I, Borisevich Sophia S, Ilyina Margarita G, Kolybalov Dmitry S, Arkhipov Sergey G, Bogdanov Nikita E, Pavlova Marina A, Salakhutdinov Nariman F, Perevalov Valery P, Nikitina Polina A
Department of Fine Organic Synthesis and Chemistry of Dyes, D.I. Mendeleev University of Chemical Technology of Russia Miusskaya sq., 9 125047 Moscow Russia
State Research Center of Virology and Biotechnology VECTOR Rospotrebnadzor 630559 Koltsovo Russia.
RSC Med Chem. 2024 Jul 5;15(9):3196-211. doi: 10.1039/d4md00181h.
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 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 -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 (-hydroxy-tautomeric form) is present in DMSO- 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).
由于2022年全球猴痘疫情的爆发，对正痘病毒感染的科学兴趣以及对具有抗正痘病毒活性的新型高效化合物的研究显著增加。目前的工作涉及新型2-芳基咪唑的合成，这些化合物不仅对痘苗病毒、牛痘病毒和埃可病毒（鼠痘病毒）有活性，而且对天花病毒也有活性。在所研究的咪唑衍生物（1-羟基咪唑、1-甲氧基咪唑、1-苄氧基咪唑和咪唑氧化物）中，1-羟基咪唑表现出最有前景的抗病毒活性，它可能以两种质子互变异构体的形式存在。根据单晶X射线衍射分析，这两种互变异构体可能在这些化合物的不同晶体结构中表现出来，而核磁共振光谱和量子化学计算表明，在二甲亚砜溶液和气态中，主要存在其中一种（α-羟基互变异构体）。先导化合物1-羟基-2-(4-硝基苯基)咪唑4a对痘苗病毒（SI = 1072）和天花病毒（SI = 373）表现出最高的选择性指数。
