compound 58 [WO2021252491A1]   Click here for help

GtoPdb Ligand ID: 12043

Compound class: Synthetic organic
Comment: This compound is one of the SARS-CoV-2 main protease (Mpro) inhibitors claimed in patent WO2021252491A1 from Aligos Therapeutics and Katholieke Universiteit Leuven [2]. We selected this example (58) for its combination of potency against SARS-CoV-2 Mpro enzymatic activity, and its ability to inhibit SARS-CoV-2 infection with relatively low cytotoxicity against model cell lines in vitro. Aligos Therapeutics have declared ALG-097558 as their lead clinical candidate SARS-CoV-2 antiviral, but have not yet disclosed its chemical structure (June 2022). Aligos have also published in vitro data (inhibition of SARS-CoV-2 infection in the Syrian hamster model) for another Mpro inhibitor, ALG-097111 [1], but again no complete chemical structure was divulged.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 10
Hydrogen bond donors 5
Rotatable bonds 9
Topological polar surface area 177.28
Molecular weight 532.2
XLogP 0.3
No. Lipinski's rules broken 0
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Canonical SMILES O=C1NCCC[C@H]1C[C@@H](C(S(=O)(=O)O)O)NC(=O)[C@@H]1[C@H]2CCC[C@H]2CN1C(=O)c1cc2c([nH]1)cccc2
Isomeric SMILES [nH]1c(cc2ccccc12)C(=O)N1[C@@H]([C@@H]2[C@H](C1)CCC2)C(=O)N[C@H](C(S(=O)(=O)O)O)C[C@H]1C(=O)NCCC1
InChI InChI=1S/C25H32N4O7S/c30-22-15(7-4-10-26-22)12-20(25(33)37(34,35)36)28-23(31)21-17-8-3-6-16(17)13-29(21)24(32)19-11-14-5-1-2-9-18(14)27-19/h1-2,5,9,11,15-17,20-21,25,27,33H,3-4,6-8,10,12-13H2,(H,26,30)(H,28,31)(H,34,35,36)/t15-,16-,17-,20-,21-,25?/m0/s1
Bioactivity Comments
Compound 58 is a very low potency inhibitor of human cathepsin L protease activity, with a binned IC50 value of 1-10 μM [2].
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 >7.7 pIC50 - 2
pIC50 >7.7 (IC50 <2x10-8 M) [2]