Submission Details
Molecule(s):
O=c1[nH]cc(-c2cc(-c3cc(Cl)cc(OCc4ccccc4)c3)c(=O)n(-c3cccnc3)c2)c(=O)[nH]1
O=c1[nH]cc(-c2cc(-c3cc(Cl)cc(OCc4ccccc4F)c3)c(=O)n(-c3cccnc3)c2)c(=O)[nH]1
O=c1[nH]cc(-c2cc(-c3cc(Cl)cc(OCc4ccccc4Cl)c3)c(=O)n(-c3cccnc3)c2)c(=O)[nH]1
O=c1[nH]cc(-c2cc(-c3cc(Cl)c(F)c(OCc4ccccc4Cl)c3)c(=O)n(-c3cccnc3)c2)c(=O)[nH]1
Design Rationale:
Noncovalent compounds 14, 18, 21 and 23 by Jorgensen lab reported in fluorescence inhibition assay as IC50 of 128, 24, 18 and 20 nM, respectively.
Other Notes:
Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV‐2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations Chun-Hui Zhang,# Elizabeth A. Stone,# Maya Deshmukh,# Joseph A. Ippolito,# Mohammad M. Ghahremanpour, Julian Tirado-Rives, Krasimir A. Spasov, Shuo Zhang, Yuka Takeo, Shalley N. Kudalkar, Zhuobin Liang, Farren Isaacs, Brett Lindenbach, Scott J. Miller, Karen S. Anderson,* and William L. Jorgensen*. DOI: https://dx.doi.org/10.1021/acscentsci.1c00039