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

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

Journal

Russian Chemical Bulletin
ISSN: 1573-9171 , E-ISSN: 1066-5285

Output data

Year: 2023, Volume: 72, Number: 1, Pages: 239-247 Pages count : 9 DOI: 10.1007/s11172-023-3729-x

Authors

Dalinger A.I. ¹ , Baev D.S. ² , Yarovaya O.I. ² , Chirkova V.Yu. ³ , Sharlaeva E.A. ³ , Belenkaya S.V. ^4,5 , Shcherbakov D.N. ^3,4 , Salakhutdinov N.F. ² , Vatsadze S.Z. ⁶

Affiliations

1	Lomonosov Moscow State University, Moscow, Russian Federation
2	N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation
3	Altai State University, Barnaul, Russian Federation
4	Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region, Russian Federation
5	Novosibirsk State University, Novosibirsk, Russian Federation
6	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation

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 (IC50 = 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 (IC50 = 100±5.7µmol L−1) and was characterized by the highest calculated binding energy among the studied bispidine derivatives according to molecular docking data.

Dalinger A.I. , Baev D.S. , Yarovaya O.I. , Chirkova V.Y. , Sharlaeva E.A. , Belenkaya S.V. , Shcherbakov D.N. , Salakhutdinov N.F. , Vatsadze S.Z.
Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus
Russian Chemical Bulletin. 2023. V.72. N1. P.239-247. DOI: 10.1007/s11172-023-3729-x WOS Scopus OpenAlex

Web of science:	WOS:000933481700019
Scopus:	2-s2.0-85148451003
OpenAlex:	W4320736067

DB	Citing
OpenAlex	6
Scopus	6
Web of science	6