2. Academic Validation
  3. 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

  • Bioorg Med Chem Lett. 2023 Jan 1:79:129080. doi: 10.1016/j.bmcl.2022.129080.
P A Nikitina 1,  E I Basanova 2,  E B Nikolaenkova 3,  I A Os'kina 3,  O A Serova 4,  N I Bormotov 4,  L N Shishkina 4,  V P Perevalov 2,  A Ya Tikhonov 3
Affiliations

Affiliations

  • 1 D.I. Mendeleev University of Chemical Technology of Russia, Miusskaya sq., 9, Moscow 125047, Russia. Electronic address: polinandrevna@yandex.ru.
  • 2 D.I. Mendeleev University of Chemical Technology of Russia, Miusskaya sq., 9, Moscow 125047, Russia.
  • 3 N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Avenue, 9, 630090 Novosibirsk, Russia.
  • 4 State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk Region, 630559, Russia.
PMID: 36414175 DOI: 10.1016/j.bmcl.2022.129080
Abstract

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).

Keywords

1-Hydroxyimidazole; Antiviral activity; Cytotoxicity; Orthopoxviruses; Vaccinia virus.

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