1037904-52-1Relevant articles and documents
Discovery and Mechanism of SARS-CoV-2 Main Protease Inhibitors
Bray, William,Carlin, Aaron F.,Clark, Alex E.,Endsley, Mark,Huante, Matthew B.,Huff, Sarah,Kummetha, Indrasena Reddy,Rana, Tariq M.,Smith, Davey,Tiwari, Shashi Kant,Wang, Shaobo
supporting information, (2021/10/20)
The emergence of a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an urgent public health crisis. Without available targeted therapies, treatment options remain limited for COVID-19 patients. Using medicinal chemistry and rational drug design strategies, we identify a 2-phenyl-1,2-benzoselenazol-3-one class of compounds targeting the SARS-CoV-2 main protease (Mpro). FRET-based screening against recombinant SARS-CoV-2 Mpro identified six compounds that inhibit proteolysis with nanomolar IC50 values. Preincubation dilution experiments and molecular docking determined that the inhibition of SARS-CoV-2 Mpro can occur by either covalent or noncovalent mechanisms, and lead E04 was determined to inhibit Mpro competitively. Lead E24 inhibited viral replication with a nanomolar EC50 value (844 nM) in SARS-CoV-2-infected Vero E6 cells and was further confirmed to impair SARS-CoV-2 replication in human lung epithelial cells and human-induced pluripotent stem cell-derived 3D lung organoids. Altogether, these studies provide a structural framework and mechanism of Mpro inhibition that should facilitate the design of future COVID-19 treatments.
Synthesis of (1H)-isochromen-1-imines by nickel-catalyzed reaction of 2-iodobenzamides with alkynes
Miura, Tomoya,Hiraga, Kentaro,Toyoshima, Takeharu,Yamauchi, Motoshi,Murakami, Masahiro
supporting information; experimental part, p. 798 - 800 (2012/09/07)
2-Iodobenzamides reacted with alkynes in the presence of a nickel(0)/P(4-ClC6H4)3 catalyst to produce substituted (1H)-isochromen-1-imines. The reaction proceeded through the formation of an oxanickelacycle, alkyne insertion, and reductive elimination.
