Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: structure-activity relationship study.
Identifieur interne : 001199 ( PubMed/Checkpoint ); précédent : 001198; suivant : 001200Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: structure-activity relationship study.
Auteurs : Pillaiyar Thanigaimalai [Japon] ; Sho Konno ; Takehito Yamamoto ; Yuji Koiwai ; Akihiro Taguchi ; Kentaro Takayama ; Fumika Yakushiji ; Kenichi Akaji ; Yoshiaki Kiso ; Yuko Kawasaki ; Shen-En Chen ; Aurash Naser-Tavakolian ; Arne Schön ; Ernesto Freire ; Yoshio HayashiSource :
- European journal of medicinal chemistry [ 1768-3254 ] ; 2013.
Descripteurs français
- KwdFr :
- Conception de médicament, Conformation moléculaire, Cysteine endopeptidases (métabolisme), Dipeptides (), Dipeptides (pharmacologie), Dipeptides (synthèse chimique), Humains, Inhibiteurs de la cystéine protéinase (), Inhibiteurs de la cystéine protéinase (pharmacologie), Inhibiteurs de la cystéine protéinase (synthèse chimique), Masse moléculaire, Modèles moléculaires, Protéines virales (antagonistes et inhibiteurs), Protéines virales (métabolisme), Relation dose-effet des médicaments, Relation structure-activité, Virus du SRAS (), Virus du SRAS (enzymologie).
- MESH :
- antagonistes et inhibiteurs : Protéines virales.
- enzymologie : Virus du SRAS.
- métabolisme : Cysteine endopeptidases, Protéines virales.
- pharmacologie : Dipeptides, Inhibiteurs de la cystéine protéinase.
- synthèse chimique : Dipeptides, Inhibiteurs de la cystéine protéinase.
- Conception de médicament, Conformation moléculaire, Dipeptides, Humains, Inhibiteurs de la cystéine protéinase, Masse moléculaire, Modèles moléculaires, Relation dose-effet des médicaments, Relation structure-activité, Virus du SRAS.
English descriptors
- KwdEn :
- Cysteine Endopeptidases (metabolism), Cysteine Proteinase Inhibitors (chemical synthesis), Cysteine Proteinase Inhibitors (chemistry), Cysteine Proteinase Inhibitors (pharmacology), Dipeptides (chemical synthesis), Dipeptides (chemistry), Dipeptides (pharmacology), Dose-Response Relationship, Drug, Drug Design, Humans, Models, Molecular, Molecular Conformation, Molecular Weight, SARS Virus (drug effects), SARS Virus (enzymology), Structure-Activity Relationship, Viral Proteins (antagonists & inhibitors), Viral Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemical synthesis : Cysteine Proteinase Inhibitors, Dipeptides.
- chemical , chemistry : Cysteine Proteinase Inhibitors, Dipeptides.
- chemical , metabolism : Cysteine Endopeptidases, Viral Proteins.
- chemical , pharmacology : Cysteine Proteinase Inhibitors, Dipeptides.
- drug effects : SARS Virus.
- enzymology : SARS Virus.
- Dose-Response Relationship, Drug, Drug Design, Humans, Models, Molecular, Molecular Conformation, Molecular Weight, Structure-Activity Relationship.
Abstract
This work describes the design, synthesis, and evaluation of low-molecular weight peptidic SARS-CoV 3CL protease inhibitors. The inhibitors were designed based on the potent tripeptidic Z-Val-Leu-Ala(pyrrolidone-3-yl)-2-benzothiazole (8; Ki = 4.1 nM), in which the P3 valine unit was substituted with a variety of distinct moieties. The resulting series of dipeptide-type inhibitors displayed moderate to good inhibitory activities against 3CL(pro). In particular, compounds 26m and 26n exhibited good inhibitory activities with Ki values of 0.39 and 0.33 μM, respectively. These low-molecular weight compounds are attractive leads for the further development of potent peptidomimetic inhibitors with pharmaceutical profiles. Docking studies were performed to model the binding interaction of the compound 26m with the SARS-CoV 3CL protease. The preliminary SAR study of the peptidomimetic compounds with potent inhibitory activities revealed several structural features that boosted the inhibitory activity: (i) a benzothiazole warhead at the S1' position, (ii) a γ-lactam unit at the S1-position, (iii) an appropriately hydrophobic leucine moiety at the S2-position, and (iv) a hydrogen bond between the N-arylglycine unit and a backbone hydrogen bond donor at the S3-position.
DOI: 10.1016/j.ejmech.2013.05.005
PubMed: 23747811
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:23747811Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: structure-activity relationship study.</title>
<author><name sortKey="Thanigaimalai, Pillaiyar" sort="Thanigaimalai, Pillaiyar" uniqKey="Thanigaimalai P" first="Pillaiyar" last="Thanigaimalai">Pillaiyar Thanigaimalai</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Konno, Sho" sort="Konno, Sho" uniqKey="Konno S" first="Sho" last="Konno">Sho Konno</name>
</author>
<author><name sortKey="Yamamoto, Takehito" sort="Yamamoto, Takehito" uniqKey="Yamamoto T" first="Takehito" last="Yamamoto">Takehito Yamamoto</name>
</author>
<author><name sortKey="Koiwai, Yuji" sort="Koiwai, Yuji" uniqKey="Koiwai Y" first="Yuji" last="Koiwai">Yuji Koiwai</name>
</author>
<author><name sortKey="Taguchi, Akihiro" sort="Taguchi, Akihiro" uniqKey="Taguchi A" first="Akihiro" last="Taguchi">Akihiro Taguchi</name>
</author>
<author><name sortKey="Takayama, Kentaro" sort="Takayama, Kentaro" uniqKey="Takayama K" first="Kentaro" last="Takayama">Kentaro Takayama</name>
</author>
<author><name sortKey="Yakushiji, Fumika" sort="Yakushiji, Fumika" uniqKey="Yakushiji F" first="Fumika" last="Yakushiji">Fumika Yakushiji</name>
</author>
<author><name sortKey="Akaji, Kenichi" sort="Akaji, Kenichi" uniqKey="Akaji K" first="Kenichi" last="Akaji">Kenichi Akaji</name>
</author>
<author><name sortKey="Kiso, Yoshiaki" sort="Kiso, Yoshiaki" uniqKey="Kiso Y" first="Yoshiaki" last="Kiso">Yoshiaki Kiso</name>
</author>
<author><name sortKey="Kawasaki, Yuko" sort="Kawasaki, Yuko" uniqKey="Kawasaki Y" first="Yuko" last="Kawasaki">Yuko Kawasaki</name>
</author>
<author><name sortKey="Chen, Shen En" sort="Chen, Shen En" uniqKey="Chen S" first="Shen-En" last="Chen">Shen-En Chen</name>
</author>
<author><name sortKey="Naser Tavakolian, Aurash" sort="Naser Tavakolian, Aurash" uniqKey="Naser Tavakolian A" first="Aurash" last="Naser-Tavakolian">Aurash Naser-Tavakolian</name>
</author>
<author><name sortKey="Schon, Arne" sort="Schon, Arne" uniqKey="Schon A" first="Arne" last="Schön">Arne Schön</name>
</author>
<author><name sortKey="Freire, Ernesto" sort="Freire, Ernesto" uniqKey="Freire E" first="Ernesto" last="Freire">Ernesto Freire</name>
</author>
<author><name sortKey="Hayashi, Yoshio" sort="Hayashi, Yoshio" uniqKey="Hayashi Y" first="Yoshio" last="Hayashi">Yoshio Hayashi</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2013">2013</date>
<idno type="RBID">pubmed:23747811</idno>
<idno type="pmid">23747811</idno>
<idno type="doi">10.1016/j.ejmech.2013.05.005</idno>
<idno type="wicri:Area/PubMed/Corpus">001183</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001183</idno>
<idno type="wicri:Area/PubMed/Curation">001183</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001183</idno>
<idno type="wicri:Area/PubMed/Checkpoint">001199</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001199</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: structure-activity relationship study.</title>
<author><name sortKey="Thanigaimalai, Pillaiyar" sort="Thanigaimalai, Pillaiyar" uniqKey="Thanigaimalai P" first="Pillaiyar" last="Thanigaimalai">Pillaiyar Thanigaimalai</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.</nlm:affiliation>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392</wicri:regionArea>
<placeName><settlement type="city">Tokyo</settlement>
<region type="région">Région de Kantō</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Konno, Sho" sort="Konno, Sho" uniqKey="Konno S" first="Sho" last="Konno">Sho Konno</name>
</author>
<author><name sortKey="Yamamoto, Takehito" sort="Yamamoto, Takehito" uniqKey="Yamamoto T" first="Takehito" last="Yamamoto">Takehito Yamamoto</name>
</author>
<author><name sortKey="Koiwai, Yuji" sort="Koiwai, Yuji" uniqKey="Koiwai Y" first="Yuji" last="Koiwai">Yuji Koiwai</name>
</author>
<author><name sortKey="Taguchi, Akihiro" sort="Taguchi, Akihiro" uniqKey="Taguchi A" first="Akihiro" last="Taguchi">Akihiro Taguchi</name>
</author>
<author><name sortKey="Takayama, Kentaro" sort="Takayama, Kentaro" uniqKey="Takayama K" first="Kentaro" last="Takayama">Kentaro Takayama</name>
</author>
<author><name sortKey="Yakushiji, Fumika" sort="Yakushiji, Fumika" uniqKey="Yakushiji F" first="Fumika" last="Yakushiji">Fumika Yakushiji</name>
</author>
<author><name sortKey="Akaji, Kenichi" sort="Akaji, Kenichi" uniqKey="Akaji K" first="Kenichi" last="Akaji">Kenichi Akaji</name>
</author>
<author><name sortKey="Kiso, Yoshiaki" sort="Kiso, Yoshiaki" uniqKey="Kiso Y" first="Yoshiaki" last="Kiso">Yoshiaki Kiso</name>
</author>
<author><name sortKey="Kawasaki, Yuko" sort="Kawasaki, Yuko" uniqKey="Kawasaki Y" first="Yuko" last="Kawasaki">Yuko Kawasaki</name>
</author>
<author><name sortKey="Chen, Shen En" sort="Chen, Shen En" uniqKey="Chen S" first="Shen-En" last="Chen">Shen-En Chen</name>
</author>
<author><name sortKey="Naser Tavakolian, Aurash" sort="Naser Tavakolian, Aurash" uniqKey="Naser Tavakolian A" first="Aurash" last="Naser-Tavakolian">Aurash Naser-Tavakolian</name>
</author>
<author><name sortKey="Schon, Arne" sort="Schon, Arne" uniqKey="Schon A" first="Arne" last="Schön">Arne Schön</name>
</author>
<author><name sortKey="Freire, Ernesto" sort="Freire, Ernesto" uniqKey="Freire E" first="Ernesto" last="Freire">Ernesto Freire</name>
</author>
<author><name sortKey="Hayashi, Yoshio" sort="Hayashi, Yoshio" uniqKey="Hayashi Y" first="Yoshio" last="Hayashi">Yoshio Hayashi</name>
</author>
</analytic>
<series><title level="j">European journal of medicinal chemistry</title>
<idno type="eISSN">1768-3254</idno>
<imprint><date when="2013" type="published">2013</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cysteine Endopeptidases (metabolism)</term>
<term>Cysteine Proteinase Inhibitors (chemical synthesis)</term>
<term>Cysteine Proteinase Inhibitors (chemistry)</term>
<term>Cysteine Proteinase Inhibitors (pharmacology)</term>
<term>Dipeptides (chemical synthesis)</term>
<term>Dipeptides (chemistry)</term>
<term>Dipeptides (pharmacology)</term>
<term>Dose-Response Relationship, Drug</term>
<term>Drug Design</term>
<term>Humans</term>
<term>Models, Molecular</term>
<term>Molecular Conformation</term>
<term>Molecular Weight</term>
<term>SARS Virus (drug effects)</term>
<term>SARS Virus (enzymology)</term>
<term>Structure-Activity Relationship</term>
<term>Viral Proteins (antagonists & inhibitors)</term>
<term>Viral Proteins (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Conception de médicament</term>
<term>Conformation moléculaire</term>
<term>Cysteine endopeptidases (métabolisme)</term>
<term>Dipeptides ()</term>
<term>Dipeptides (pharmacologie)</term>
<term>Dipeptides (synthèse chimique)</term>
<term>Humains</term>
<term>Inhibiteurs de la cystéine protéinase ()</term>
<term>Inhibiteurs de la cystéine protéinase (pharmacologie)</term>
<term>Inhibiteurs de la cystéine protéinase (synthèse chimique)</term>
<term>Masse moléculaire</term>
<term>Modèles moléculaires</term>
<term>Protéines virales (antagonistes et inhibiteurs)</term>
<term>Protéines virales (métabolisme)</term>
<term>Relation dose-effet des médicaments</term>
<term>Relation structure-activité</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (enzymologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Cysteine Proteinase Inhibitors</term>
<term>Dipeptides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Cysteine Proteinase Inhibitors</term>
<term>Dipeptides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cysteine Endopeptidases</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Cysteine Proteinase Inhibitors</term>
<term>Dipeptides</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cysteine endopeptidases</term>
<term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Dipeptides</term>
<term>Inhibiteurs de la cystéine protéinase</term>
</keywords>
<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Dipeptides</term>
<term>Inhibiteurs de la cystéine protéinase</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Dose-Response Relationship, Drug</term>
<term>Drug Design</term>
<term>Humans</term>
<term>Models, Molecular</term>
<term>Molecular Conformation</term>
<term>Molecular Weight</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Conception de médicament</term>
<term>Conformation moléculaire</term>
<term>Dipeptides</term>
<term>Humains</term>
<term>Inhibiteurs de la cystéine protéinase</term>
<term>Masse moléculaire</term>
<term>Modèles moléculaires</term>
<term>Relation dose-effet des médicaments</term>
<term>Relation structure-activité</term>
<term>Virus du SRAS</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">This work describes the design, synthesis, and evaluation of low-molecular weight peptidic SARS-CoV 3CL protease inhibitors. The inhibitors were designed based on the potent tripeptidic Z-Val-Leu-Ala(pyrrolidone-3-yl)-2-benzothiazole (8; Ki = 4.1 nM), in which the P3 valine unit was substituted with a variety of distinct moieties. The resulting series of dipeptide-type inhibitors displayed moderate to good inhibitory activities against 3CL(pro). In particular, compounds 26m and 26n exhibited good inhibitory activities with Ki values of 0.39 and 0.33 μM, respectively. These low-molecular weight compounds are attractive leads for the further development of potent peptidomimetic inhibitors with pharmaceutical profiles. Docking studies were performed to model the binding interaction of the compound 26m with the SARS-CoV 3CL protease. The preliminary SAR study of the peptidomimetic compounds with potent inhibitory activities revealed several structural features that boosted the inhibitory activity: (i) a benzothiazole warhead at the S1' position, (ii) a γ-lactam unit at the S1-position, (iii) an appropriately hydrophobic leucine moiety at the S2-position, and (iv) a hydrogen bond between the N-arylglycine unit and a backbone hydrogen bond donor at the S3-position.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23747811</PMID>
<DateCompleted><Year>2014</Year>
<Month>02</Month>
<Day>19</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>04</Month>
<Day>07</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1768-3254</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>65</Volume>
<PubDate><Year>2013</Year>
<Month>Jul</Month>
</PubDate>
</JournalIssue>
<Title>European journal of medicinal chemistry</Title>
<ISOAbbreviation>Eur J Med Chem</ISOAbbreviation>
</Journal>
<ArticleTitle>Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: structure-activity relationship study.</ArticleTitle>
<Pagination><MedlinePgn>436-47</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ejmech.2013.05.005</ELocationID>
<ELocationID EIdType="pii" ValidYN="Y">S0223-5234(13)00305-X</ELocationID>
<Abstract><AbstractText>This work describes the design, synthesis, and evaluation of low-molecular weight peptidic SARS-CoV 3CL protease inhibitors. The inhibitors were designed based on the potent tripeptidic Z-Val-Leu-Ala(pyrrolidone-3-yl)-2-benzothiazole (8; Ki = 4.1 nM), in which the P3 valine unit was substituted with a variety of distinct moieties. The resulting series of dipeptide-type inhibitors displayed moderate to good inhibitory activities against 3CL(pro). In particular, compounds 26m and 26n exhibited good inhibitory activities with Ki values of 0.39 and 0.33 μM, respectively. These low-molecular weight compounds are attractive leads for the further development of potent peptidomimetic inhibitors with pharmaceutical profiles. Docking studies were performed to model the binding interaction of the compound 26m with the SARS-CoV 3CL protease. The preliminary SAR study of the peptidomimetic compounds with potent inhibitory activities revealed several structural features that boosted the inhibitory activity: (i) a benzothiazole warhead at the S1' position, (ii) a γ-lactam unit at the S1-position, (iii) an appropriately hydrophobic leucine moiety at the S2-position, and (iv) a hydrogen bond between the N-arylglycine unit and a backbone hydrogen bond donor at the S3-position.</AbstractText>
<CopyrightInformation>Copyright © 2013 Elsevier Masson SAS. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Thanigaimalai</LastName>
<ForeName>Pillaiyar</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Konno</LastName>
<ForeName>Sho</ForeName>
<Initials>S</Initials>
</Author>
<Author ValidYN="Y"><LastName>Yamamoto</LastName>
<ForeName>Takehito</ForeName>
<Initials>T</Initials>
</Author>
<Author ValidYN="Y"><LastName>Koiwai</LastName>
<ForeName>Yuji</ForeName>
<Initials>Y</Initials>
</Author>
<Author ValidYN="Y"><LastName>Taguchi</LastName>
<ForeName>Akihiro</ForeName>
<Initials>A</Initials>
</Author>
<Author ValidYN="Y"><LastName>Takayama</LastName>
<ForeName>Kentaro</ForeName>
<Initials>K</Initials>
</Author>
<Author ValidYN="Y"><LastName>Yakushiji</LastName>
<ForeName>Fumika</ForeName>
<Initials>F</Initials>
</Author>
<Author ValidYN="Y"><LastName>Akaji</LastName>
<ForeName>Kenichi</ForeName>
<Initials>K</Initials>
</Author>
<Author ValidYN="Y"><LastName>Kiso</LastName>
<ForeName>Yoshiaki</ForeName>
<Initials>Y</Initials>
</Author>
<Author ValidYN="Y"><LastName>Kawasaki</LastName>
<ForeName>Yuko</ForeName>
<Initials>Y</Initials>
</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Shen-En</ForeName>
<Initials>SE</Initials>
</Author>
<Author ValidYN="Y"><LastName>Naser-Tavakolian</LastName>
<ForeName>Aurash</ForeName>
<Initials>A</Initials>
</Author>
<Author ValidYN="Y"><LastName>Schön</LastName>
<ForeName>Arne</ForeName>
<Initials>A</Initials>
</Author>
<Author ValidYN="Y"><LastName>Freire</LastName>
<ForeName>Ernesto</ForeName>
<Initials>E</Initials>
</Author>
<Author ValidYN="Y"><LastName>Hayashi</LastName>
<ForeName>Yoshio</ForeName>
<Initials>Y</Initials>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R01 GM057144</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>GM57144</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2013</Year>
<Month>05</Month>
<Day>20</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>France</Country>
<MedlineTA>Eur J Med Chem</MedlineTA>
<NlmUniqueID>0420510</NlmUniqueID>
<ISSNLinking>0223-5234</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D015853">Cysteine Proteinase Inhibitors</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D004151">Dipeptides</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014764">Viral Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.22.-</RegistryNumber>
<NameOfSubstance UI="C099456">3C-like proteinase, Coronavirus</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.22.-</RegistryNumber>
<NameOfSubstance UI="D003546">Cysteine Endopeptidases</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D003546" MajorTopicYN="N">Cysteine Endopeptidases</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015853" MajorTopicYN="N">Cysteine Proteinase Inhibitors</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004151" MajorTopicYN="N">Dipeptides</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015195" MajorTopicYN="Y">Drug Design</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008958" MajorTopicYN="N">Models, Molecular</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008968" MajorTopicYN="N">Molecular Conformation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008970" MajorTopicYN="N">Molecular Weight</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014764" MajorTopicYN="N">Viral Proteins</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Cysteine protease inhibitors</Keyword>
<Keyword MajorTopicYN="N">Dipeptide</Keyword>
<Keyword MajorTopicYN="N">Docking study</Keyword>
<Keyword MajorTopicYN="N">Peptidomimetics</Keyword>
<Keyword MajorTopicYN="N">SARS</Keyword>
<Keyword MajorTopicYN="N">SARS-CoV 3CL protease</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2013</Year>
<Month>03</Month>
<Day>11</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2013</Year>
<Month>04</Month>
<Day>20</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2013</Year>
<Month>05</Month>
<Day>07</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2013</Year>
<Month>6</Month>
<Day>11</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2013</Year>
<Month>6</Month>
<Day>12</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2014</Year>
<Month>2</Month>
<Day>20</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">23747811</ArticleId>
<ArticleId IdType="pii">S0223-5234(13)00305-X</ArticleId>
<ArticleId IdType="doi">10.1016/j.ejmech.2013.05.005</ArticleId>
<ArticleId IdType="pmc">PMC7115367</ArticleId>
</ArticleIdList>
<ReferenceList><Reference><Citation>Chem Biol Drug Des. 2008 Jul;72(1):34-49</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18611220</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Future Microbiol. 2011 Feb;6(2):153-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21366416</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Med Chem. 2005 Nov 3;48(22):6832-42</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16250642</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Bioorg Med Chem. 2008 Apr 15;16(8):4652-60</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18329272</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Bioorg Med Chem. 2008 Nov 1;16(21):9400-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18845442</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Science. 2003 Jun 13;300(5626):1763-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12746549</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13190-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">14585926</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Bioorg Med Chem Lett. 2009 May 15;19(10):2722-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19362479</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>PLoS Biol. 2005 Oct;3(10):e324</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16128623</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Bioorg Med Chem. 2008 Apr 1;16(7):4138-49</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18343121</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Mol Biol. 2005 Nov 11;353(5):1137-51</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16219322</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>N Engl J Med. 2003 May 15;348(20):1953-66</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12690092</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Bioorg Med Chem. 2013 Jan 15;21(2):412-24</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23245752</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>N Engl J Med. 2003 May 15;348(20):1986-94</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12682352</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Chem Biol. 2004 Oct;11(10):1445-53</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15489171</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>N Engl J Med. 2012 Nov 8;367(19):1814-20</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23075143</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Med Chem. 2011 Dec 8;54(23):7962-73</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22014094</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Chem Biol. 2006 Mar;13(3):261-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16638531</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Bioorg Med Chem. 2010 Nov 15;18(22):7849-54</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20947359</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>N Engl J Med. 2003 May 15;348(20):1967-76</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12690091</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Med Chem. 2006 Jun 15;49(12):3440-3</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16759084</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Med Chem. 2006 Aug 10;49(16):4971-80</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16884309</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Gen Virol. 2003 Sep;84(Pt 9):2305-2315</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12917450</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Biochemistry. 2006 Dec 19;45(50):14908-16</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17154528</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Science. 2003 May 30;300(5624):1394-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12730500</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Med Chem. 2004 Dec 2;47(25):6113-6</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15566280</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Virol. 2007 Apr;81(7):3051-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17079323</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Biochem Biophys Res Commun. 2003 Aug 15;308(1):148-51</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12890493</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Science. 2003 May 30;300(5624):1399-404</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12730501</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Virol. 2005 Jun;79(11):7095-103</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15890949</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Bioorg Med Chem Lett. 2010 Jun 15;20(12):3569-72</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20494577</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Lancet. 2003 Apr 19;361(9366):1319-25</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12711465</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Japon</li>
</country>
<region><li>Région de Kantō</li>
</region>
<settlement><li>Tokyo</li>
</settlement>
</list>
<tree><noCountry><name sortKey="Akaji, Kenichi" sort="Akaji, Kenichi" uniqKey="Akaji K" first="Kenichi" last="Akaji">Kenichi Akaji</name>
<name sortKey="Chen, Shen En" sort="Chen, Shen En" uniqKey="Chen S" first="Shen-En" last="Chen">Shen-En Chen</name>
<name sortKey="Freire, Ernesto" sort="Freire, Ernesto" uniqKey="Freire E" first="Ernesto" last="Freire">Ernesto Freire</name>
<name sortKey="Hayashi, Yoshio" sort="Hayashi, Yoshio" uniqKey="Hayashi Y" first="Yoshio" last="Hayashi">Yoshio Hayashi</name>
<name sortKey="Kawasaki, Yuko" sort="Kawasaki, Yuko" uniqKey="Kawasaki Y" first="Yuko" last="Kawasaki">Yuko Kawasaki</name>
<name sortKey="Kiso, Yoshiaki" sort="Kiso, Yoshiaki" uniqKey="Kiso Y" first="Yoshiaki" last="Kiso">Yoshiaki Kiso</name>
<name sortKey="Koiwai, Yuji" sort="Koiwai, Yuji" uniqKey="Koiwai Y" first="Yuji" last="Koiwai">Yuji Koiwai</name>
<name sortKey="Konno, Sho" sort="Konno, Sho" uniqKey="Konno S" first="Sho" last="Konno">Sho Konno</name>
<name sortKey="Naser Tavakolian, Aurash" sort="Naser Tavakolian, Aurash" uniqKey="Naser Tavakolian A" first="Aurash" last="Naser-Tavakolian">Aurash Naser-Tavakolian</name>
<name sortKey="Schon, Arne" sort="Schon, Arne" uniqKey="Schon A" first="Arne" last="Schön">Arne Schön</name>
<name sortKey="Taguchi, Akihiro" sort="Taguchi, Akihiro" uniqKey="Taguchi A" first="Akihiro" last="Taguchi">Akihiro Taguchi</name>
<name sortKey="Takayama, Kentaro" sort="Takayama, Kentaro" uniqKey="Takayama K" first="Kentaro" last="Takayama">Kentaro Takayama</name>
<name sortKey="Yakushiji, Fumika" sort="Yakushiji, Fumika" uniqKey="Yakushiji F" first="Fumika" last="Yakushiji">Fumika Yakushiji</name>
<name sortKey="Yamamoto, Takehito" sort="Yamamoto, Takehito" uniqKey="Yamamoto T" first="Takehito" last="Yamamoto">Takehito Yamamoto</name>
</noCountry>
<country name="Japon"><region name="Région de Kantō"><name sortKey="Thanigaimalai, Pillaiyar" sort="Thanigaimalai, Pillaiyar" uniqKey="Thanigaimalai P" first="Pillaiyar" last="Thanigaimalai">Pillaiyar Thanigaimalai</name>
</region>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/PubMed/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001199 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd -nk 001199 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= PubMed |étape= Checkpoint |type= RBID |clé= pubmed:23747811 |texte= Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: structure-activity relationship study. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/RBID.i -Sk "pubmed:23747811" \ | HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
![]() | This area was generated with Dilib version V0.6.33. | ![]() |