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10.1016/j.ejmech.2021.113622 http://scihub22266oqcxt.onion/10.1016/j.ejmech.2021.113622 34147744!8191315!34147744     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=34147744&cmd=llinks): Failed to open stream: HTTP request failed! 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Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetamides as novel SARS-CoV-2 RdRp inhibitors |pdf=|usr=}}{{34147744}} gab.com Text Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetamides as novel SARS-CoV-2 RdRp inhibitors JO: Eur J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=34147744 #FOAvip The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global pandemic coronavirus disease (COVID-19), but no specific antiviral drug has been proven effective for controlling this pandemic to date. In this study, several 2-((indol-3-yl)thio)-N-benzyl-acetamides were identified as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors. After a two-round optimization, a new series of 2-((indol-3-yl)thio)-N-benzyl-acetamides was designed, synthesized, and evaluated for SARS-CoV-2 RdRp inhibitory effect. Compounds 6b2, 6b5, 6c9, 6d2, and 6d5 were identified as potent inhibitors with IC(50) values of 3.35 +/- 0.21 muM, 4.55 +/- 0.2 muM, 1.65 +/- 0.05 muM, 3.76 +/- 0.79 muM, and 1.11 +/- 0.05 muM, respectively; the IC(50) of remdesivir (control) was measured as 1.19 +/- 0.36 muM. All of the compounds inhibited RNA synthesis by SARS-CoV-2 RdRp. The most potent compound 6d5, which showed a stronger inhibitory activity against the human coronavirus HCoV-OC43 than remdesivir, is a promising candidate for further investigation. Twit Text FOAVip Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetamides as novel SARS-CoV-2 RdRp inhibitors ????Eur J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=34147744 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34147744 #FOAvip English Wikipedia <ref>{{Cite pmid|34147744}}</ref> Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetamides as novel SARS-CoV-2 RdRp inhibitors #MMPMID34147744 Zhang GN; Zhao J; Li Q; Wang M; Zhu M; Wang J; Cen S; Wang Y Eur J Med Chem 2021[Nov]; 223 (ä): 113622 PMID34147744show ga The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global pandemic coronavirus disease (COVID-19), but no specific antiviral drug has been proven effective for controlling this pandemic to date. In this study, several 2-((indol-3-yl)thio)-N-benzyl-acetamides were identified as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors. After a two-round optimization, a new series of 2-((indol-3-yl)thio)-N-benzyl-acetamides was designed, synthesized, and evaluated for SARS-CoV-2 RdRp inhibitory effect. Compounds 6b2, 6b5, 6c9, 6d2, and 6d5 were identified as potent inhibitors with IC(50) values of 3.35 +/- 0.21 muM, 4.55 +/- 0.2 muM, 1.65 +/- 0.05 muM, 3.76 +/- 0.79 muM, and 1.11 +/- 0.05 muM, respectively; the IC(50) of remdesivir (control) was measured as 1.19 +/- 0.36 muM. All of the compounds inhibited RNA synthesis by SARS-CoV-2 RdRp. The most potent compound 6d5, which showed a stronger inhibitory activity against the human coronavirus HCoV-OC43 than remdesivir, is a promising candidate for further investigation. |*COVID-19 Drug Treatment[MESH] |Acetamides/*chemical synthesis/pharmacology[MESH] |Adenosine Monophosphate/analogs & derivatives/pharmacology/standards[MESH] |Alanine/analogs & derivatives/pharmacology/standards[MESH] |Antiviral Agents/*chemical synthesis/pharmacology[MESH] |Drug Evaluation, Preclinical[MESH] |Enzyme Inhibitors/*chemical synthesis/pharmacology[MESH] |Humans[MESH] |Inhibitory Concentration 50[MESH] |Molecular Docking Simulation[MESH] |Molecular Structure[MESH] |Protein Binding[MESH] |RNA, Viral/*antagonists & inhibitors[MESH] |RNA-Dependent RNA Polymerase/*antagonists & inhibitors[MESH] |SARS-CoV-2/*drug effects/genetics[MESH]Discovery and optimization of 2-((1H-indol-3-yl)thio)-N-benzyl-acetami(epmc).pdf DeepDyve Pubget Overpricing