ArticleJournal of medicinal chemistry2013
Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL protease.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.
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Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 206 citations in OpenAlex.
- Drug targets for corona virus: A systematic review.Indian journal of pharmacologyPooled it
- Article
- Ugi-Tetrazole-Derived α‑Aminomethyl Scaffolds Reveal Unexpected Binding Modes in SARS-CoV‑2 3CLpro.ACS medicinal chemistry letters · 2026Article
- Biphenyl as a Privileged Structure in Medicinal Chemistry: Advances in Anti-Infective Drug Discovery.Molecules (Basel, Switzerland) · 2026Review
- Ugi multicomponent reactions of optically active aldehydes and chiral aminoindanols: diastereoselective synthesis of bisamides relevant to SARS-CoV-2 Mpro inhibitors.Organic & biomolecular chemistry · 2026Article
- Antiviral drug discovery and development: challenges and future directions.Signal transduction and targeted therapy · 2026Review
- From nicotine to SARS-CoV-2 antivirals with potent in vivo efficacy and a broad anti-coronavirus spectrum.Nature communications · 2026Article
- Leak Proof PDBBind: A Reorganized Data Set of Protein-Ligand Complexes for More Generalizable Binding Affinity Prediction.The journal of physical chemistry. B · 2026Article
- Discovery of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 Main Protease through Computer-Aided Drug Design.Journal of medicinal chemistry · 2025Article
- Molecular Dynamics Simulation of SARS-CoV-2 E Ion Channel: The Study of Lone Protein and its Conformational Changes in Complex with Potential Cage Inhibitors.Current computer-aided drug design · 2025Article
- Advances in the Search for SARS-CoV-2 MPathogens (Basel, Switzerland) · 2024Review
- 3-chymotrypsin-like protease in SARS-CoV-2.Bioscience reports · 2024Review
- Review
- Design, Synthesis, X-ray Crystallography, and Biological Activities of Covalent, Non-Peptidic Inhibitors of SARS-CoV-2 Main Protease.ACS infectious diseases · 2024Article
- On the origins of SARS-CoV-2 main protease inhibitors.RSC medicinal chemistry · 2024Review
- Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review.European journal of medicinal chemistry · 2023Review
- Exploring diverse reactive warheads for the design of SARS-CoV-2 main protease inhibitors.European journal of medicinal chemistry · 2023Article
- Large library docking for novel SARS-CoV-2 main protease non-covalent and covalent inhibitors.Protein science : a publication of the Protein Society · 2023Article
- A Tale of Two Proteases: MPharmaceuticals (Basel, Switzerland) · 2023Review
- Discovery of 3CLpro inhibitor of SARS-CoV-2 main protease.Future science OA · 2023Article
68 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
A high-throughput screen of the NIH molecular libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (16-(R), (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844). Unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, 16-(R) is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure-activity relationships within S(1'), S(1), and S(2) enzyme binding pockets. The X-ray structure of SARS-CoV 3CLpro bound with 16-(R) was instrumental in guiding subsequent rounds of chemistry optimization. 16-(R) provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.