Synthesis of non-symmetric N -benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus.

Autor: Dalinger AI; Lomonosov Moscow State University, Build. 3, 1 Leninskie Gory, 119991 Moscow, Russian Federation., Baev DS; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Acad. Lavrentieva, 630090 Novosibirsk, Russian Federation., Yarovaya OI; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Acad. Lavrentieva, 630090 Novosibirsk, Russian Federation., Chirkova VY; Altai State University, 61 prosp. Lenina, 656049 Barnaul, Russian Federation., Sharlaeva EA; Altai State University, 61 prosp. Lenina, 656049 Barnaul, Russian Federation., Belenkaya SV; Novosibirsk State University, 2 ul. Pirogova, 630090 Novosibirsk, Russian Federation.; Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, State Research Center of Virology and Biotechnology VECTOR, 630559 Koltsovo, Novosibirsk region, Russian Federation., Shcherbakov DN; Altai State University, 61 prosp. Lenina, 656049 Barnaul, Russian Federation.; Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, State Research Center of Virology and Biotechnology VECTOR, 630559 Koltsovo, Novosibirsk region, Russian Federation., Salakhutdinov NF; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Acad. Lavrentieva, 630090 Novosibirsk, Russian Federation., Vatsadze SZ; N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991 Moscow, Russian Federation.
Jazyk: angličtina
Zdroj: Russian chemical bulletin = Izvestiia Akademii nauk. Seriia khimicheskaia [Russ Chem Bull] 2023; Vol. 72 (1), pp. 239-247. Date of Electronic Publication: 2023 Feb 14.
DOI: 10.1007/s11172-023-3729-x
Abstrakt: Based on the data obtained by molecular modeling of the non-covalent interaction of non-symmetric N -benzylbispidin-9-ol amides with the active site of the main protease 3CLpro of the SARS-CoV-2 virus, a series of compounds was synthesized, and their inhibitory activity against 3CLpro was studied and compared with that of the known inhibitor ML188 (IC 50 = 1.56±0.55 µmol L -1 ). It was found that only compound 1g containing the 1,4-dihydroindeno[1,2- c ]pyrazole fragment showed moderate activity (IC 50 = 100±5.7µmol L -1 ) and was characterized by the highest calculated binding energy among the studied bispidine derivatives according to molecular docking data.
(© Springer Science+Business Media LLC 2023.)
Databáze: MEDLINE
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