Ghosh, Arun K.; Takayama, Jun; Aubin, Yoann; Ratia, Kiira; Chaudhuri, Rima; Baez, Yahira; Sleeman, Katrina; Coughlin, Melissa; Nichols, Daniel B.; Mulhearn, Debbie C.; Prabhakar, Bellur S.; Baker, Susan C.; Johnson, Michael E.; Mesecar, Andrew D. published the artcile< Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease>, Quality Control of 103261-68-3, the main research area is SARS CoV Coronavirus severe acute respiratory syndrome; naphthalene derivative SAR preparation antiviral agent.
We describe here the design, synthesis, mol. modeling, and biol. evaluation of a series of small mol., nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chem. library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells. Upon the basis of the X-ray crystal structure of inhibitor (III)-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, (I) (enzyme IC50 = 0.46 μM; antiviral EC50 = 6 μM). Interestingly, its methylamine derivative, (II), displayed good enzyme inhibitory potency (IC50 = 1.3 μM) and the most potent SARS antiviral activity (EC50 = 5.2 μM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.
Journal of Medicinal Chemistry published new progress about Antiviral agents. 103261-68-3 belongs to class nitriles-buliding-blocks, and the molecular formula is C10H9NO2, Quality Control of 103261-68-3.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts