Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding.
Identifieur interne : 002011 ( Main/Exploration ); précédent : 002010; suivant : 002012Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding.
Auteurs : Mark Turlington [États-Unis] ; Aspen Chun ; Sakshi Tomar ; Aimee Eggler ; Valerie Grum-Tokars ; Jon Jacobs ; J Scott Daniels ; Eric Dawson ; Adrian Saldanha ; Peter Chase ; Yahira M. Baez-Santos ; Craig W. Lindsley ; Peter Hodder ; Andrew D. Mesecar ; Shaun R. StaufferSource :
- Bioorganic & medicinal chemistry letters [ 1464-3405 ] ; 2013.
Descripteurs français
- KwdFr :
- Acétamides (), Acétamides (pharmacologie), Acétamides (synthèse chimique), Antiviraux (), Antiviraux (pharmacologie), Antiviraux (synthèse chimique), Humains, Modèles moléculaires, Relation structure-activité, Syndrome respiratoire aigu sévère (traitement médicamenteux), Syndrome respiratoire aigu sévère (virologie), Virus du SRAS ().
- MESH :
- pharmacologie : Acétamides, Antiviraux.
- synthèse chimique : Acétamides, Antiviraux.
- traitement médicamenteux : Syndrome respiratoire aigu sévère.
- virologie : Syndrome respiratoire aigu sévère.
- Acétamides, Antiviraux, Humains, Modèles moléculaires, Relation structure-activité, Virus du SRAS.
English descriptors
- KwdEn :
- Acetamides (chemical synthesis), Acetamides (chemistry), Acetamides (pharmacology), Antiviral Agents (chemical synthesis), Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Humans, Models, Molecular, SARS Virus (drug effects), Severe Acute Respiratory Syndrome (drug therapy), Severe Acute Respiratory Syndrome (virology), Structure-Activity Relationship.
- MESH :
- chemical , chemical synthesis : Acetamides, Antiviral Agents.
- chemical , chemistry : Acetamides, Antiviral Agents.
- chemical , pharmacology : Acetamides, Antiviral Agents.
- drug effects : SARS Virus.
- drug therapy : Severe Acute Respiratory Syndrome.
- virology : Severe Acute Respiratory Syndrome.
- Humans, Models, Molecular, Structure-Activity Relationship.
Abstract
Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S2-S4 binding pockets leading to the first sub-micromolar noncovalent 3CLpro inhibitors retaining a single amide bond.
DOI: 10.1016/j.bmcl.2013.08.112
PubMed: 24080461
Affiliations:
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Le document en format XML
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Stauffer</name></author></analytic><series><title level="j">Bioorganic & medicinal chemistry letters</title><idno type="eISSN">1464-3405</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acetamides (chemical synthesis)</term><term>Acetamides (chemistry)</term><term>Acetamides (pharmacology)</term><term>Antiviral Agents (chemical synthesis)</term><term>Antiviral Agents (chemistry)</term><term>Antiviral Agents (pharmacology)</term><term>Humans</term><term>Models, Molecular</term><term>SARS Virus (drug effects)</term><term>Severe Acute Respiratory Syndrome (drug therapy)</term><term>Severe Acute Respiratory Syndrome (virology)</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Acétamides ()</term><term>Acétamides (pharmacologie)</term><term>Acétamides (synthèse chimique)</term><term>Antiviraux ()</term><term>Antiviraux (pharmacologie)</term><term>Antiviraux (synthèse chimique)</term><term>Humains</term><term>Modèles moléculaires</term><term>Relation structure-activité</term><term>Syndrome respiratoire aigu sévère (traitement médicamenteux)</term><term>Syndrome respiratoire aigu sévère (virologie)</term><term>Virus du SRAS ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Acetamides</term><term>Antiviral Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Acetamides</term><term>Antiviral Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Acetamides</term><term>Antiviral Agents</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Acétamides</term><term>Antiviraux</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Acétamides</term><term>Antiviraux</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Severe Acute Respiratory Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Models, Molecular</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Acétamides</term><term>Antiviraux</term><term>Humains</term><term>Modèles moléculaires</term><term>Relation structure-activité</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S2-S4 binding pockets leading to the first sub-micromolar noncovalent 3CLpro inhibitors retaining a single amide bond. </div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Tennessee</li></region></list><tree><noCountry><name sortKey="Baez Santos, Yahira M" sort="Baez Santos, Yahira M" uniqKey="Baez Santos Y" first="Yahira M" last="Baez-Santos">Yahira M. Baez-Santos</name><name sortKey="Chase, Peter" sort="Chase, Peter" uniqKey="Chase P" first="Peter" last="Chase">Peter Chase</name><name sortKey="Chun, Aspen" sort="Chun, Aspen" uniqKey="Chun A" first="Aspen" last="Chun">Aspen Chun</name><name sortKey="Daniels, J Scott" sort="Daniels, J Scott" uniqKey="Daniels J" first="J Scott" last="Daniels">J Scott Daniels</name><name sortKey="Dawson, Eric" sort="Dawson, Eric" uniqKey="Dawson E" first="Eric" last="Dawson">Eric Dawson</name><name sortKey="Eggler, Aimee" sort="Eggler, Aimee" uniqKey="Eggler A" first="Aimee" last="Eggler">Aimee Eggler</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="Hodder, Peter" sort="Hodder, Peter" uniqKey="Hodder P" first="Peter" last="Hodder">Peter Hodder</name><name sortKey="Jacobs, Jon" sort="Jacobs, Jon" uniqKey="Jacobs J" first="Jon" last="Jacobs">Jon Jacobs</name><name sortKey="Lindsley, Craig W" sort="Lindsley, Craig W" uniqKey="Lindsley C" first="Craig W" last="Lindsley">Craig W. Lindsley</name><name sortKey="Mesecar, Andrew D" sort="Mesecar, Andrew D" uniqKey="Mesecar A" first="Andrew D" last="Mesecar">Andrew D. Mesecar</name><name sortKey="Saldanha, Adrian" sort="Saldanha, Adrian" uniqKey="Saldanha A" first="Adrian" last="Saldanha">Adrian Saldanha</name><name sortKey="Stauffer, Shaun R" sort="Stauffer, Shaun R" uniqKey="Stauffer S" first="Shaun R" last="Stauffer">Shaun R. Stauffer</name><name sortKey="Tomar, Sakshi" sort="Tomar, Sakshi" uniqKey="Tomar S" first="Sakshi" last="Tomar">Sakshi Tomar</name></noCountry><country name="États-Unis"><region name="Tennessee"><name sortKey="Turlington, Mark" sort="Turlington, Mark" uniqKey="Turlington M" first="Mark" last="Turlington">Mark Turlington</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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