compound 5 [Zhang et al., 2021]   Click here for help

GtoPdb Ligand ID: 11443

PDB Ligand
Compound class: Synthetic organic
Comment: Compound 5 is a non-covalent SARS-CoV-2 Mpro (3CL-pro) inhibitor with in vitro antiviral activity [1]. It appears to provide synergistic antiviral activity with the viral polymerase inhibitor remdesivir in vitro, in a replicon assay that utilised a non-infectious SARS-CoV-2 clone. Structurally, 5 is a derivative of the anticonvulsant drug perampanel, and was designed to optimise perampanel's weak (IC50100-250 μM) Mpro inhibitory activity. Several nM potency inhibitors were identified in this study (e.g. 21, IC50 18 nM in an enzyme kinetic assay), but they did not deliver antiviral activity in the in vitro assays and/or were cytotoxic. Compound 26 with 1 μM antiviral activity and no cytotoxicity was highlighted as a significant lead structure. The crystal structure of 5 bound to SARS-CoV-2 Mpro has been resolved to 1.8 Å and was submitted to the Protein Data Bank with accession ID 7L11.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 2
Hydrogen bond donors 0
Rotatable bonds 6
Topological polar surface area 67.39
Molecular weight 441.12
XLogP 6.52
No. Lipinski's rules broken 1
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Canonical SMILES CCCOc1cc(Cl)cc(c1)c1cc(cn(c1=O)c1cccnc1)c1ccccc1C#N
Isomeric SMILES CCCOc1cc(Cl)cc(c1)c1cc(cn(c1=O)c1cccnc1)c1ccccc1C#N
InChI InChI=1S/C26H20ClN3O2/c1-2-10-32-23-12-19(11-21(27)14-23)25-13-20(24-8-4-3-6-18(24)15-28)17-30(26(25)31)22-7-5-9-29-16-22/h3-9,11-14,16-17H,2,10H2,1H3
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
2-(3-(3-Chloro-5-propoxyphenyl)-2-oxo-2H [1,3'-bipyridin]-5-yl)benzonitrile
Database Links Click here for help
GtoPdb PubChem SID 440816812
PubChem CID 155803729
Search Google for chemical match using the InChIKey KFGXONJZGIXSGH-UHFFFAOYSA-N
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UniChem Compound Search for chemical match using the InChIKey KFGXONJZGIXSGH-UHFFFAOYSA-N
UniChem Connectivity Search for chemical match using the InChIKey KFGXONJZGIXSGH-UHFFFAOYSA-N