Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors.
Identifieur interne : 002358 ( PubMed/Curation ); précédent : 002357; suivant : 002359Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors.
Auteurs : Han-Zhong Zhang [États-Unis] ; Hong Zhang ; William Kemnitzer ; Ben Tseng ; Jindrich Cinatl ; Martin Michaelis ; Hans Wilhelm Doerr ; Sui Xiong CaiSource :
- Journal of medicinal chemistry [ 0022-2623 ] ; 2006.
Descripteurs français
- KwdFr :
- MESH :
- pharmacologie : Antiviraux, Dipeptides.
- synthèse chimique : Antiviraux, Dipeptides.
- Animaux, Antiviraux, Cellules Caco-2, Cellules Vero, Conception de médicament, Dipeptides, Humains, Mort cellulaire, Réplication virale, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (chemical synthesis), Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Caco-2 Cells, Cell Death (drug effects), Chlorocebus aethiops, Dipeptides (chemical synthesis), Dipeptides (chemistry), Dipeptides (pharmacology), Drug Design, Humans, SARS Virus (drug effects), Vero Cells, Virus Replication.
- MESH :
- chemical , chemical synthesis : Antiviral Agents, Dipeptides.
- chemical , chemistry : Antiviral Agents, Dipeptides.
- chemical , pharmacology : Antiviral Agents, Dipeptides.
- drug effects : Cell Death, SARS Virus.
- Animals, Caco-2 Cells, Chlorocebus aethiops, Drug Design, Humans, Vero Cells, Virus Replication.
Abstract
This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of >40.
DOI: 10.1021/jm0507678
PubMed: 16451084
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uniqKey="Tseng B" first="Ben" last="Tseng">Ben Tseng</name></author><author><name sortKey="Cinatl, Jindrich" sort="Cinatl, Jindrich" uniqKey="Cinatl J" first="Jindrich" last="Cinatl">Jindrich Cinatl</name></author><author><name sortKey="Michaelis, Martin" sort="Michaelis, Martin" uniqKey="Michaelis M" first="Martin" last="Michaelis">Martin Michaelis</name></author><author><name sortKey="Doerr, Hans Wilhelm" sort="Doerr, Hans Wilhelm" uniqKey="Doerr H" first="Hans Wilhelm" last="Doerr">Hans Wilhelm Doerr</name></author><author><name sortKey="Cai, Sui Xiong" sort="Cai, Sui Xiong" uniqKey="Cai S" first="Sui Xiong" last="Cai">Sui Xiong Cai</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2006">2006</date><idno type="RBID">pubmed:16451084</idno><idno type="pmid">16451084</idno><idno type="doi">10.1021/jm0507678</idno><idno type="wicri:Area/PubMed/Corpus">002358</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" 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(synthèse chimique)</term><term>Humains</term><term>Mort cellulaire ()</term><term>Réplication virale</term><term>Virus du SRAS ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Antiviral Agents</term><term>Dipeptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term><term>Dipeptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Dipeptides</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Death</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term><term>Dipeptides</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Antiviraux</term><term>Dipeptides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Caco-2 Cells</term><term>Chlorocebus aethiops</term><term>Drug Design</term><term>Humans</term><term>Vero Cells</term><term>Virus Replication</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Antiviraux</term><term>Cellules Caco-2</term><term>Cellules Vero</term><term>Conception de médicament</term><term>Dipeptides</term><term>Humains</term><term>Mort cellulaire</term><term>Réplication virale</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of >40.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16451084</PMID><DateCompleted><Year>2006</Year><Month>03</Month><Day>29</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>10</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-2623</ISSN><JournalIssue CitedMedium="Print"><Volume>49</Volume><Issue>3</Issue><PubDate><Year>2006</Year><Month>Feb</Month><Day>09</Day></PubDate></JournalIssue><Title>Journal of medicinal chemistry</Title><ISOAbbreviation>J. Med. Chem.</ISOAbbreviation></Journal><ArticleTitle>Design and synthesis of dipeptidyl glutaminyl fluoromethyl ketones as potent severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors.</ArticleTitle><Pagination><MedlinePgn>1198-201</MedlinePgn></Pagination><Abstract><AbstractText>This paper describes the design and synthesis of dipeptidyl N,N-dimethyl glutaminyl fluoromethyl ketones (fmk) as severe acute respiratory syndrome coronovirus (SARS-CoV) inhibitors. The compounds were tested against SARS-CoV-induced cell death in Vero or CaCo2 cells as a measurement of the inhibiting effects of the compounds on the replication of the virus. Z-Leu-Gln(NMe(2))-fmk (6a) was found to be a potent inhibitor with low toxicity in cells, protecting cells with an EC(50) value of 2.5 microM and exhibiting a selectivity index of >40.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Han-Zhong</ForeName><Initials>HZ</Initials><AffiliationInfo><Affiliation>Maxim Pharmaceuticals, 6650 Nancy Ridge Drive, San Diego, CA 92121, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Hong</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Kemnitzer</LastName><ForeName>William</ForeName><Initials>W</Initials></Author><Author ValidYN="Y"><LastName>Tseng</LastName><ForeName>Ben</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Cinatl</LastName><ForeName>Jindrich</ForeName><Initials>J</Initials><Suffix>Jr</Suffix></Author><Author ValidYN="Y"><LastName>Michaelis</LastName><ForeName>Martin</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Doerr</LastName><ForeName>Hans Wilhelm</ForeName><Initials>HW</Initials></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Sui Xiong</ForeName><Initials>SX</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>N01 AI 30048</GrantID><Acronym>AI</Acronym><Agency>NIAID 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></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Med Chem</MedlineTA><NlmUniqueID>9716531</NlmUniqueID><ISSNLinking>0022-2623</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004151">Dipeptides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C509003">benzyloxycarbonyl-leucyl-N,N-dimethylglutamine fluoromethyl ketone</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000138" MajorTopicYN="Y">chemical synthesis</QualifierName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018938" MajorTopicYN="N">Caco-2 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016923" MajorTopicYN="N">Cell Death</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002522" MajorTopicYN="N">Chlorocebus aethiops</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004151" MajorTopicYN="N">Dipeptides</DescriptorName><QualifierName UI="Q000138" MajorTopicYN="Y">chemical synthesis</QualifierName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015195" MajorTopicYN="N">Drug Design</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014709" MajorTopicYN="N">Vero Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014779" MajorTopicYN="N">Virus Replication</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>2</Month><Day>3</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2006</Year><Month>3</Month><Day>30</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>2</Month><Day>3</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">16451084</ArticleId><ArticleId IdType="doi">10.1021/jm0507678</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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