Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors
Identifieur interne : 003617 ( Main/Merge ); précédent : 003616; suivant : 003618Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors
Auteurs : Arun K. Ghosh [États-Unis] ; GANGLI GONG [États-Unis] ; Valerie Grum-Tokars [États-Unis] ; Debbie C. Mulhearn [États-Unis] ; Susan C. Baker [États-Unis] ; Melissa Coughlin [États-Unis] ; Bellur S. Prabhakar [États-Unis] ; Katrina Sleeman [États-Unis] ; Michael E. Johnson [États-Unis] ; Andrew D. Mesecar [États-Unis]Source :
- Bioorganic & medicinal chemistry letters : (Print) [ 0960-894X ] ; 2008.
Descripteurs français
- Pascal (Inist)
- Synthèse chimique, Antiviral, Relation structure activité, In vitro, Cysteine endopeptidases, Virus syndrome respiratoire aigu sévère, Hétérocycle azote, Composé bicyclique, Composé aromatique, Dérivé de la pyridine, Modèle moléculaire, Complexe enzyme inhibiteur, Modélisation, Inhibiteur enzyme, Indole-4-carboxylique acide ester 5-chloro-3-pyridyle.
English descriptors
- KwdEn :
Abstract
Design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. Position of the carboxylate functionality is critical to potency. Inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a SARS-CoV 3CLpro IC50 value of 30 nM and an antiviral EC50 value of 6.9 μM. Molecular docking studies have provided possible binding modes of these inhibitors.
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Purdue University, 560 Oval drive</s1><s2>West Lafayette, IN 47907</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Indiana</region></placeName></affiliation></author><author><name sortKey="Grum Tokars, Valerie" sort="Grum Tokars, Valerie" uniqKey="Grum Tokars V" first="Valerie" last="Grum-Tokars">Valerie Grum-Tokars</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Pharmaceutical Biotechnology, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S</s1><s2>Ashland, IL 60607</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Mulhearn, Debbie C" sort="Mulhearn, Debbie C" uniqKey="Mulhearn D" first="Debbie C." last="Mulhearn">Debbie C. Mulhearn</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Pharmaceutical Biotechnology, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S</s1><s2>Ashland, IL 60607</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Baker, Susan C" sort="Baker, Susan C" uniqKey="Baker S" first="Susan C." last="Baker">Susan C. Baker</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Microbiology and Immunology, Loyola University of Chicago, Stritch School of Medicine</s1><s2>Maywood, IL</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de Chicago</orgName></affiliation></author><author><name sortKey="Coughlin, Melissa" sort="Coughlin, Melissa" uniqKey="Coughlin M" first="Melissa" last="Coughlin">Melissa Coughlin</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Microbiology and Immunology, University of Illinois</s1><s2>Chicago, IL 60607</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Prabhakar, Bellur S" sort="Prabhakar, Bellur S" uniqKey="Prabhakar B" first="Bellur S." last="Prabhakar">Bellur S. Prabhakar</name><affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Microbiology and Immunology, University of Illinois</s1><s2>Chicago, IL 60607</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Sleeman, Katrina" sort="Sleeman, Katrina" uniqKey="Sleeman K" first="Katrina" last="Sleeman">Katrina Sleeman</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Microbiology and Immunology, Loyola University of Chicago, Stritch School of Medicine</s1><s2>Maywood, IL</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de Chicago</orgName></affiliation></author><author><name sortKey="Johnson, Michael E" sort="Johnson, Michael E" uniqKey="Johnson M" first="Michael E." last="Johnson">Michael E. Johnson</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Pharmaceutical Biotechnology, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S</s1><s2>Ashland, IL 60607</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author><author><name sortKey="Mesecar, Andrew D" sort="Mesecar, Andrew D" uniqKey="Mesecar A" first="Andrew D." last="Mesecar">Andrew D. Mesecar</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Pharmaceutical Biotechnology, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S</s1><s2>Ashland, IL 60607</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Illinois</region><settlement type="city">Chicago</settlement></placeName><orgName type="university">Université de l'Illinois à Chicago</orgName></affiliation></author></analytic><series><title level="j" type="main">Bioorganic & medicinal chemistry letters : (Print)</title><title level="j" type="abbreviated">Bioorg. med. chem. lett. : (Print)</title><idno type="ISSN">0960-894X</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Bioorganic & medicinal chemistry letters : (Print)</title><title level="j" type="abbreviated">Bioorg. med. chem. lett. : (Print)</title><idno type="ISSN">0960-894X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral</term><term>Aromatic compound</term><term>Bicyclic compound</term><term>Chemical synthesis</term><term>Cysteine endopeptidases</term><term>Enzyme inhibitor</term><term>In vitro</term><term>Inhibitor enzyme complex</term><term>Modeling</term><term>Molecular model</term><term>Nitrogen heterocycle</term><term>Pyridine derivatives</term><term>Severe acute respiratory syndrome virus</term><term>Structure activity relation</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Synthèse chimique</term><term>Antiviral</term><term>Relation structure activité</term><term>In vitro</term><term>Cysteine endopeptidases</term><term>Virus syndrome respiratoire aigu sévère</term><term>Hétérocycle azote</term><term>Composé bicyclique</term><term>Composé aromatique</term><term>Dérivé de la pyridine</term><term>Modèle moléculaire</term><term>Complexe enzyme inhibiteur</term><term>Modélisation</term><term>Inhibiteur enzyme</term><term>Indole-4-carboxylique acide ester 5-chloro-3-pyridyle</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Design, synthesis and biological evaluation of a series of 5-chloropyridine ester-derived severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors is described. Position of the carboxylate functionality is critical to potency. Inhibitor 10 with a 5-chloropyridinyl ester at position 4 of the indole ring is the most potent inhibitor with a SARS-CoV 3CLpro IC<sub>50</sub> value of 30 nM and an antiviral EC<sub>50</sub> value of 6.9 μM. Molecular docking studies have provided possible binding modes of these inhibitors.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li><li>Indiana</li></region><settlement><li>Chicago</li></settlement><orgName><li>Université de Chicago</li><li>Université de l'Illinois à Chicago</li></orgName></list><tree><country name="États-Unis"><region name="Indiana"><name sortKey="Ghosh, Arun K" sort="Ghosh, Arun K" uniqKey="Ghosh A" first="Arun K." last="Ghosh">Arun K. Ghosh</name></region><name sortKey="Baker, Susan C" sort="Baker, Susan C" uniqKey="Baker S" first="Susan C." last="Baker">Susan C. Baker</name><name sortKey="Coughlin, Melissa" sort="Coughlin, Melissa" uniqKey="Coughlin M" first="Melissa" last="Coughlin">Melissa Coughlin</name><name sortKey="Gangli Gong" sort="Gangli Gong" uniqKey="Gangli Gong" last="Gangli Gong">GANGLI GONG</name><name sortKey="Grum Tokars, Valerie" sort="Grum Tokars, Valerie" uniqKey="Grum Tokars V" first="Valerie" last="Grum-Tokars">Valerie Grum-Tokars</name><name sortKey="Johnson, Michael E" sort="Johnson, Michael E" uniqKey="Johnson M" first="Michael E." last="Johnson">Michael E. Johnson</name><name sortKey="Mesecar, Andrew D" sort="Mesecar, Andrew D" uniqKey="Mesecar A" first="Andrew D." last="Mesecar">Andrew D. Mesecar</name><name sortKey="Mulhearn, Debbie C" sort="Mulhearn, Debbie C" uniqKey="Mulhearn D" first="Debbie C." last="Mulhearn">Debbie C. Mulhearn</name><name sortKey="Prabhakar, Bellur S" sort="Prabhakar, Bellur S" uniqKey="Prabhakar B" first="Bellur S." last="Prabhakar">Bellur S. Prabhakar</name><name sortKey="Sleeman, Katrina" sort="Sleeman, Katrina" uniqKey="Sleeman K" first="Katrina" last="Sleeman">Katrina Sleeman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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