Back to Search
Start Over
Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2.
- Source :
-
ChemMedChem [ChemMedChem] 2021 Jan 19; Vol. 16 (2), pp. 340-354. Date of Electronic Publication: 2020 Oct 16. - Publication Year :
- 2021
-
Abstract
- Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL <superscript>pro</superscript> ) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL <superscript>pro</superscript> . Moreover, we report the discovery of isoindolines as a new class of potent PL <superscript>pro</superscript> inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL <superscript>pro</superscript> are valuable starting points for the development of new pan-coronaviral inhibitors.<br /> (© 2020 The Authors. Published by Wiley-VCH GmbH.)
- Subjects :
- Animals
Antiviral Agents chemical synthesis
Antiviral Agents metabolism
Benzamides chemical synthesis
Benzamides metabolism
Catalytic Domain
Chlorocebus aethiops
Coronavirus 3C Proteases chemistry
Crystallography, X-Ray
Cysteine Proteinase Inhibitors chemical synthesis
Cysteine Proteinase Inhibitors metabolism
Isoindoles chemical synthesis
Isoindoles metabolism
Molecular Docking Simulation
Molecular Structure
Protein Binding
Structure-Activity Relationship
Vero Cells
Virus Replication drug effects
Antiviral Agents pharmacology
Benzamides pharmacology
Coronavirus 3C Proteases metabolism
Cysteine Proteinase Inhibitors pharmacology
Isoindoles pharmacology
SARS-CoV-2 drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1860-7187
- Volume :
- 16
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- ChemMedChem
- Publication Type :
- Academic Journal
- Accession number :
- 32930481
- Full Text :
- https://doi.org/10.1002/cmdc.202000548