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 Научная публикация

Журнал

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

Вых. Данные

Год: 2023, Том: 79, Страницы: 129080 Страниц : 1 DOI: 10.1016/j.bmcl.2022.129080

Ключевые слова

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

Авторы

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

Организации

1	Российский химико-технологический университет имени Д. И. Менделеева
2	Новосибирский институт органической химии им. Н.Н. Ворожцова СО РАН
3	Федеральное бюджетное учреждение науки Государственный научный центр вирусологии и биотехнологии Вектор

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

Поступила в редакцию:	13 окт. 2022 г.
Принята к публикации:	16 нояб. 2022 г.
Опубликована online:	19 нояб. 2022 г.

Web of science	WOS:000904529600004
РИНЦ	54610071
OpenAlex	W4309580618