example 100 [WO2022043374]   Click here for help

GtoPdb Ligand ID: 11952

Compound class: Synthetic organic
Comment: This compound is a coronavirus 3CL proteinase (3CLpro, Mpro) inhibitor from Hoffman La Roche's patent WO2022043374 [1]. It exhibits potent inhibitory activity at 3CLpro enzymes from a range of human coronaviruses (hCoV-229E, MERS-CoV, hCoV-OC43, SARS-CoV and SARS-CoV-2) in vitro. We present this as one of the most potent broad-range inhibitors from this patent. Extensive experimental work (in suitable cell lines, virus infection models etc.) would be required to determine which example (if any) is suitable for preclinical evaluation.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 3
Rotatable bonds 13
Topological polar surface area 133.64
Molecular weight 493.13
XLogP 1.71
No. Lipinski's rules broken 0
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Canonical SMILES F[C@@H](C(=O)N(NC(=O)[C@H](CC1(C)CC1)NC(=O)c1noc(c1)C(F)F)C[C@@H]1CCNC1=O)Cl
Isomeric SMILES CC1(C[C@H](NC(=O)c2noc(c2)C(F)F)C(=O)NN(C[C@@H]2CCNC2=O)C(=O)[C@H](F)Cl)CC1
InChI InChI=1S/C19H23ClF3N5O5/c1-19(3-4-19)7-11(25-16(30)10-6-12(14(22)23)33-27-10)17(31)26-28(18(32)13(20)21)8-9-2-5-24-15(9)29/h6,9,11,13-14H,2-5,7-8H2,1H3,(H,24,29)(H,25,30)(H,26,31)/t9-,11-,13-/m0/s1
Bioactivity Comments
Inhibitory constants using recombinant 3CLpro enzymes from human coronaviruses in addition to the two SARS viruses were determined in in vitro assays [1]:
hCoV-229E IC50 28 nM
MERS-CoV IC50 94 nM
hCoV-OC43 IC50 17 nM
Selectivity at other protein targets
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
CoV 3C-like (main) protease SARS-CoV-2 Inhibitor Inhibition 7.6 pIC50 - 1
pIC50 7.6 (IC50 2.4x10-8 M) [1]
CoV 3C-like (main) protease SARS-CoV Inhibitor Inhibition 7.5 pIC50 - 1
pIC50 7.5 (IC50 3.1x10-8 M) [1]