Identification and structure-based optimization of novel dihydropyrones as potent HCV RNA polymerase inhibitors.
Identifieur interne : 003E67 ( Main/Exploration ); précédent : 003E66; suivant : 003E68Identification and structure-based optimization of novel dihydropyrones as potent HCV RNA polymerase inhibitors.
Auteurs : Hui Li [États-Unis] ; John Tatlock ; Angelica Linton ; Javier Gonzalez ; Allen Borchardt ; Peter Dragovich ; Tanya Jewell ; Tom Prins ; Ru Zhou ; Julie Blazel ; Hans Parge ; Robert Love ; Michael Hickey ; Chau Doan ; Stephanie Shi ; Rohit Duggal ; Cristina Lewis ; Shella FuhrmanSource :
- Bioorganic & medicinal chemistry letters [ 0960-894X ] ; 2006.
Descripteurs français
- KwdFr :
- Concentration inhibitrice 50, Cristallographie aux rayons X, DNA-directed RNA polymerases (), DNA-directed RNA polymerases (antagonistes et inhibiteurs), DNA-directed RNA polymerases (métabolisme), Hepacivirus (), Hepacivirus (enzymologie), Hydrogène (), Modèles moléculaires, Protéines virales non structurales (), Pyrones (), Pyrones (pharmacologie), Pyrones (synthèse chimique), RNA replicase (), RNA replicase (antagonistes et inhibiteurs), Relation structure-activité, Structure moléculaire.
- MESH :
- antagonistes et inhibiteurs : DNA-directed RNA polymerases, RNA replicase.
- enzymologie : Hepacivirus.
- métabolisme : DNA-directed RNA polymerases.
- pharmacologie : Pyrones.
- synthèse chimique : Pyrones.
- Concentration inhibitrice 50, Cristallographie aux rayons X, DNA-directed RNA polymerases, Hepacivirus, Hydrogène, Modèles moléculaires, Protéines virales non structurales, Pyrones, RNA replicase, Relation structure-activité, Structure moléculaire.
English descriptors
- KwdEn :
- Crystallography, X-Ray, DNA-Directed RNA Polymerases (antagonists & inhibitors), DNA-Directed RNA Polymerases (chemistry), DNA-Directed RNA Polymerases (metabolism), Hepacivirus (drug effects), Hepacivirus (enzymology), Hydrogen (chemistry), Inhibitory Concentration 50, Models, Molecular, Molecular Structure, Pyrones (chemical synthesis), Pyrones (chemistry), Pyrones (pharmacology), RNA Replicase (antagonists & inhibitors), RNA Replicase (chemistry), Structure-Activity Relationship, Viral Nonstructural Proteins (chemistry).
- MESH :
- chemical , antagonists & inhibitors : DNA-Directed RNA Polymerases, RNA Replicase.
- chemical , chemical synthesis : Pyrones.
- chemical , chemistry : DNA-Directed RNA Polymerases, Hydrogen, Pyrones, RNA Replicase, Viral Nonstructural Proteins.
- chemical , metabolism : DNA-Directed RNA Polymerases.
- drug effects : Hepacivirus.
- enzymology : Hepacivirus.
- chemical , pharmacology : Pyrones.
- Crystallography, X-Ray, Inhibitory Concentration 50, Models, Molecular, Molecular Structure, Structure-Activity Relationship.
Abstract
A novel class of non-nucleoside HCV NS5B polymerase inhibitors has been identified from screening. A co-crystal structure revealed an allosteric binding site in the protein that required a unique conformational change to accommodate inhibitor binding. Herein we report the structure-activity relationships (SARs) of this novel class of dihydropyrone-containing compounds that show potent inhibitory activities against the HCV RNA polymerase in biochemical assays.
DOI: 10.1016/j.bmcl.2006.06.065
PubMed: 16824756
Affiliations:
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Le document en format XML
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sort="Tatlock, John" uniqKey="Tatlock J" first="John" last="Tatlock">John Tatlock</name></author><author><name sortKey="Linton, Angelica" sort="Linton, Angelica" uniqKey="Linton A" first="Angelica" last="Linton">Angelica Linton</name></author><author><name sortKey="Gonzalez, Javier" sort="Gonzalez, Javier" uniqKey="Gonzalez J" first="Javier" last="Gonzalez">Javier Gonzalez</name></author><author><name sortKey="Borchardt, Allen" sort="Borchardt, Allen" uniqKey="Borchardt A" first="Allen" last="Borchardt">Allen Borchardt</name></author><author><name sortKey="Dragovich, Peter" sort="Dragovich, Peter" uniqKey="Dragovich P" first="Peter" last="Dragovich">Peter Dragovich</name></author><author><name sortKey="Jewell, Tanya" sort="Jewell, Tanya" uniqKey="Jewell T" first="Tanya" last="Jewell">Tanya Jewell</name></author><author><name sortKey="Prins, Tom" sort="Prins, Tom" uniqKey="Prins T" first="Tom" last="Prins">Tom Prins</name></author><author><name sortKey="Zhou, Ru" sort="Zhou, Ru" 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sortKey="Lewis, Cristina" sort="Lewis, Cristina" uniqKey="Lewis C" first="Cristina" last="Lewis">Cristina Lewis</name></author><author><name sortKey="Fuhrman, Shella" sort="Fuhrman, Shella" uniqKey="Fuhrman S" first="Shella" last="Fuhrman">Shella Fuhrman</name></author></analytic><series><title level="j">Bioorganic & medicinal chemistry letters</title><idno type="ISSN">0960-894X</idno><imprint><date when="2006" type="published">2006</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Crystallography, X-Ray</term><term>DNA-Directed RNA Polymerases (antagonists & inhibitors)</term><term>DNA-Directed RNA Polymerases (chemistry)</term><term>DNA-Directed RNA Polymerases (metabolism)</term><term>Hepacivirus (drug effects)</term><term>Hepacivirus (enzymology)</term><term>Hydrogen (chemistry)</term><term>Inhibitory Concentration 50</term><term>Models, Molecular</term><term>Molecular Structure</term><term>Pyrones (chemical synthesis)</term><term>Pyrones (chemistry)</term><term>Pyrones (pharmacology)</term><term>RNA Replicase (antagonists & inhibitors)</term><term>RNA Replicase (chemistry)</term><term>Structure-Activity Relationship</term><term>Viral Nonstructural Proteins (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Concentration inhibitrice 50</term><term>Cristallographie aux rayons X</term><term>DNA-directed RNA polymerases ()</term><term>DNA-directed RNA polymerases (antagonistes et inhibiteurs)</term><term>DNA-directed RNA polymerases (métabolisme)</term><term>Hepacivirus ()</term><term>Hepacivirus (enzymologie)</term><term>Hydrogène ()</term><term>Modèles moléculaires</term><term>Protéines virales non structurales ()</term><term>Pyrones ()</term><term>Pyrones (pharmacologie)</term><term>Pyrones (synthèse chimique)</term><term>RNA replicase ()</term><term>RNA replicase (antagonistes et inhibiteurs)</term><term>Relation structure-activité</term><term>Structure moléculaire</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>DNA-Directed RNA Polymerases</term><term>RNA Replicase</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Pyrones</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>DNA-Directed RNA Polymerases</term><term>Hydrogen</term><term>Pyrones</term><term>RNA Replicase</term><term>Viral Nonstructural Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA-Directed RNA Polymerases</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>DNA-directed RNA polymerases</term><term>RNA replicase</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Hepacivirus</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Hepacivirus</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Hepacivirus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>DNA-directed RNA polymerases</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Pyrones</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Pyrones</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Pyrones</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Crystallography, X-Ray</term><term>Inhibitory Concentration 50</term><term>Models, Molecular</term><term>Molecular Structure</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Concentration inhibitrice 50</term><term>Cristallographie aux rayons X</term><term>DNA-directed RNA polymerases</term><term>Hepacivirus</term><term>Hydrogène</term><term>Modèles moléculaires</term><term>Protéines virales non structurales</term><term>Pyrones</term><term>RNA replicase</term><term>Relation structure-activité</term><term>Structure moléculaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A novel class of non-nucleoside HCV NS5B polymerase inhibitors has been identified from screening. A co-crystal structure revealed an allosteric binding site in the protein that required a unique conformational change to accommodate inhibitor binding. Herein we report the structure-activity relationships (SARs) of this novel class of dihydropyrone-containing compounds that show potent inhibitory activities against the HCV RNA polymerase in biochemical assays.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><noCountry><name sortKey="Blazel, Julie" sort="Blazel, Julie" uniqKey="Blazel J" first="Julie" last="Blazel">Julie Blazel</name><name sortKey="Borchardt, Allen" sort="Borchardt, Allen" uniqKey="Borchardt A" first="Allen" last="Borchardt">Allen Borchardt</name><name sortKey="Doan, Chau" sort="Doan, Chau" uniqKey="Doan C" first="Chau" last="Doan">Chau Doan</name><name sortKey="Dragovich, Peter" sort="Dragovich, Peter" uniqKey="Dragovich P" first="Peter" last="Dragovich">Peter Dragovich</name><name sortKey="Duggal, Rohit" sort="Duggal, Rohit" uniqKey="Duggal R" first="Rohit" last="Duggal">Rohit Duggal</name><name sortKey="Fuhrman, Shella" sort="Fuhrman, Shella" uniqKey="Fuhrman S" first="Shella" last="Fuhrman">Shella Fuhrman</name><name sortKey="Gonzalez, Javier" sort="Gonzalez, Javier" uniqKey="Gonzalez J" first="Javier" last="Gonzalez">Javier Gonzalez</name><name sortKey="Hickey, Michael" sort="Hickey, Michael" uniqKey="Hickey M" first="Michael" last="Hickey">Michael Hickey</name><name sortKey="Jewell, Tanya" sort="Jewell, Tanya" uniqKey="Jewell T" first="Tanya" last="Jewell">Tanya Jewell</name><name sortKey="Lewis, Cristina" sort="Lewis, Cristina" uniqKey="Lewis C" first="Cristina" last="Lewis">Cristina Lewis</name><name sortKey="Linton, Angelica" sort="Linton, Angelica" uniqKey="Linton A" first="Angelica" last="Linton">Angelica Linton</name><name sortKey="Love, Robert" sort="Love, Robert" uniqKey="Love R" first="Robert" last="Love">Robert Love</name><name sortKey="Parge, Hans" sort="Parge, Hans" uniqKey="Parge H" first="Hans" last="Parge">Hans Parge</name><name sortKey="Prins, Tom" sort="Prins, Tom" uniqKey="Prins T" first="Tom" last="Prins">Tom Prins</name><name sortKey="Shi, Stephanie" sort="Shi, Stephanie" uniqKey="Shi S" first="Stephanie" last="Shi">Stephanie Shi</name><name sortKey="Tatlock, John" sort="Tatlock, John" uniqKey="Tatlock J" first="John" last="Tatlock">John Tatlock</name><name sortKey="Zhou, Ru" sort="Zhou, Ru" uniqKey="Zhou R" first="Ru" last="Zhou">Ru Zhou</name></noCountry><country name="États-Unis"><region name="Californie"><name sortKey="Li, Hui" sort="Li, Hui" uniqKey="Li H" first="Hui" last="Li">Hui Li</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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