非对称-苄基双吡啶醇酰胺的合成及其对SARS-CoV-2病毒主要蛋白酶的抑制活性研究
Synthesis of non-symmetric -benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus.
作者信息
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
机构信息
Lomonosov Moscow State University, Build. 3, 1 Leninskie Gory, 119991 Moscow, Russian Federation.
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Acad. Lavrentieva, 630090 Novosibirsk, Russian Federation.
出版信息
Russ Chem Bull. 2023;72(1):239-247. doi: 10.1007/s11172-023-3729-x. Epub 2023 Feb 14.
Based on the data obtained by molecular modeling of the non-covalent interaction of non-symmetric -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 = 1.56±0.55 µmol L). It was found that only compound containing the 1,4-dihydroindeno[1,2-]pyrazole fragment showed moderate activity (IC = 100±5.7µmol L) and was characterized by the highest calculated binding energy among the studied bispidine derivatives according to molecular docking data.
基于对非对称苄基双吡啶-9-醇酰胺与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒主要蛋白酶3CLpro活性位点非共价相互作用进行分子建模所获得的数据，合成了一系列化合物，并研究了它们对3CLpro的抑制活性，并与已知抑制剂ML188（IC = 1.56±0.55 µmol/L）的抑制活性进行了比较。结果发现，只有含有1,4-二氢茚并[1,2-b]吡唑片段的化合物表现出中等活性（IC = 100±5.7µmol/L），并且根据分子对接数据，在所研究的双吡啶衍生物中，该化合物具有最高的计算结合能。
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