Synthesis, structure, and antiviral properties of novel 2-adamantyl-5-aryl-2 H-tetrazoles

Olga V Mikolaichuk; Vladimir V Zarubaev; Anna А Muryleva; Yana L Esaulkova; Daria V Spasibenko; Alina А Batyrenko; Ilya V Kornyakov; Rostislav Е Trifonov

doi:10.1007/s10593-021-02931-5

Synthesis, structure, and antiviral properties of novel 2-adamantyl-5-aryl-2 H-tetrazoles

Chem Heterocycl Compd (N Y). 2021;57(4):442-447. doi: 10.1007/s10593-021-02931-5. Epub 2021 May 26.

Authors

Olga V Mikolaichuk¹, Vladimir V Zarubaev², Anna А Muryleva², Yana L Esaulkova², Daria V Spasibenko³, Alina А Batyrenko³, Ilya V Kornyakov^{1

4}, Rostislav Е Trifonov³

Affiliations

¹ Saint Petersburg State University, 7/9 University Embankment, Saint Petersburg, 199034 Russia.
² Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology, 14 Mira St, Saint Petersburg, 197101 Russia.
³ Saint Petersburg State Institute of Technology (Technical University), 26 Moskovsky Ave, Saint Petersburg, 190013 Russia.
⁴ Kola Science Center, Russian Academy of Sciences, 14 Fersmana St., Apatity, 184209 Murmansk Oblast, Russia.

Abstract

The reaction of 5-aryl-NH-tetrazoles with adamantan-1-ol in concentrated sulfuric acid proceeds regioselectively with the formation of the corresponding 2-adamantyl-5-aryl-2H-tetrazoles. Nitration of these compounds leads to 2-(adamantan-1-yl)-5-(3-nitroaryl)-2Htetrazoles. The structures and composition of the obtained novel 2-adamantyl-5-aryltetrazoles were proven by IR spectroscopy, ¹H and ¹³C NMR spectroscopy, high-resolution mass spectrometry, and also by X-ray structural analysis. According to the simultaneous thermal analysis data, the obtained compounds are thermally stable up to a temperature of about 150°C. In vitro studies have shown that some of the 2-adamantyl-5-aryltetrazoles exhibit moderate inhibitory activity against influenza A (H1N1) virus. The antiviral selectivity index (SI) of 2-[2-(adamantan-1-yl)-2H-tetrazol-5-yl]-6-bromo-4-nitroaniline is significantly higher (SI 11) than that of the reference drug rimantadine (SI 5).

Supplementary information: The online version contains supplementary material available at 10.1007/s10593-021-02931-5.

Keywords: 2-(adamantan-1-yl)-5-aryl-2H-tetrazoles; X-ray structural analysis; adamantylation; anti-influenza activity; nitration.