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

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...

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Detalles Bibliográficos
Autores principales: Dalinger, A. I., Baev, D. S., Yarovaya, O. I., Chirkova, V. Yu., Sharlaeva, E. A., Belenkaya, S. V., Shcherbakov, D. N., Salakhutdinov, N. F., Vatsadze, S. Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926410/
https://www.ncbi.nlm.nih.gov/pubmed/36817558
http://dx.doi.org/10.1007/s11172-023-3729-x
Descripción
Sumario: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.

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