Synthesis of esters and amides of 2-aryl-1-hydroxy-4-methyl-1H-imidazole-5-carboxylic acids and study of their antiviral activity against orthopoxviruses

Synthesis of esters and amides of 2-aryl-1-hydroxy-4-methyl-1H-imidazole-5-carboxylic acids and study of their antiviral activity against orthopoxviruses Full article

Journal

Bioorganic and Medicinal Chemistry Letters
ISSN: 0960-894X , E-ISSN: 1464-3405

Output data

Year: 2023, Volume: 79, Pages: 129080 Pages count : 1 DOI: 10.1016/j.bmcl.2022.129080

Tags

1-Hydroxyimidazole, Vaccinia virus, Antiviral activity, Cytotoxicity, Orthopoxviruses

Authors

Nikitina P.A. ¹ , Basanova E.I. ¹ , Nikolaenkova E.B. ² , Os'kina I.A. ² , Serova O.A. ³ , Bormotov N.I. ³ , Shishkina L.N. ³ , Perevalov V.P. ¹ , Tikhonov A.Ya. ²

Affiliations

1	D. Mendeleyev University of Chemical Technology of Russia
2	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of Siberian Branch of Russian Academy of Sciences
3	State Research Center of Virology and Biotechnology VECTOR

Smallpox was eradicated >40 years ago but it is not a reason to forget forever about orthopoxviruses pathogenic to humans. Though in 1980 the decision of WHO to cease vaccination against smallpox had seemed logical, it led to the decrease of cross immunity against other infections caused by orthopoxviruses. As a result, in 2022 the multi-country monkeypox outbreak becomes a topic of great concern. In spite of existing FDA-approved drugs for the treatment of such diseases, the search for new small-molecule orthopoxvirus inhibitors continues. In the course of this search a series of novel 2-aryl-1-hydroxyimidazole derivatives containing ester or carboxamide moieties in position 5 of heterocycle has been synthesized and tested for activity against Vaccinia virus in Vero cell culture. Some of the compounds under consideration revealed a selectivity index higher than that of the reference drug Cidofovir. The highest selectivity index SI = 919 was exhibited by ethyl 1-hydroxy-4-methyl-2-[4- (trifluoromethyl)phenyl]-1H-imidazole-5-carboxylate 1f. The most active compound also demonstrated inhibitory activity against the cowpox virus (SI = 20) and the ectromelia virus (SI = 46).

Nikitina P.A. , Basanova E.I. , Nikolaenkova E.B. , Os'kina I.A. , Serova O.A. , Bormotov N.I. , Shishkina L.N. , Perevalov V.P. , Tikhonov A.Y.
Synthesis of esters and amides of 2-aryl-1-hydroxy-4-methyl-1H-imidazole-5-carboxylic acids and study of their antiviral activity against orthopoxviruses
Bioorganic and Medicinal Chemistry Letters. 2023. V.79. P.129080. DOI: 10.1016/j.bmcl.2022.129080 WOS РИНЦ

Submitted:	Oct 13, 2022
Accepted:	Nov 16, 2022
Published online:	Nov 19, 2022

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