SrasV1, Ncbi, Merge, bibRecord, 001D12

Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors.

Identifieur interne : 001D12 ( Ncbi/Merge ); précédent : 001D11; suivant : 001D13

Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors.

Auteurs : Yue-Ping Wang [République populaire de Chine] ; Fen-Er Chen ; Erik De Clercq ; Jan Balzarini ; Christophe Pannecouque

Source :

European journal of medicinal chemistry [ 1768-3254 ] ; 2009.

RBID : pubmed:18692274

Descripteurs français

English descriptors

KwdEn :
- Cell Line, Crystallography, X-Ray, HIV Reverse Transcriptase (antagonists & inhibitors), HIV-1 (drug effects), Humans, Magnetic Resonance Spectroscopy, Pyrimidinones (chemical synthesis), Pyrimidinones (chemistry), Pyrimidinones (pharmacology), Reverse Transcriptase Inhibitors (chemical synthesis), Reverse Transcriptase Inhibitors (chemistry), Reverse Transcriptase Inhibitors (pharmacology), Spectrometry, Mass, Electrospray Ionization, Spectroscopy, Fourier Transform Infrared, Structure-Activity Relationship.
MESH :
- chemical , antagonists & inhibitors : HIV Reverse Transcriptase.
- chemical , chemical synthesis : Pyrimidinones, Reverse Transcriptase Inhibitors.
- chemical , chemistry : Pyrimidinones, Reverse Transcriptase Inhibitors.
- drug effects : HIV-1.
- chemical , pharmacology : Pyrimidinones, Reverse Transcriptase Inhibitors.
- Cell Line, Crystallography, X-Ray, Humans, Magnetic Resonance Spectroscopy, Spectrometry, Mass, Electrospray Ionization, Spectroscopy, Fourier Transform Infrared, Structure-Activity Relationship.

Abstract

A series of new 5-alkyl-2-benzylsulfanylpyrimidin-4(3H)-ones (5a-y) bearing different substituted arylmethyl moieties at the C-6 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against HIV-1 and HIV-2 in MT-4 cell cultures. The majority of the title compounds showed moderate to good activities against HIV-1 with an IC(50) range from 6.67 microM to 0.12 microM. Among them, 6-(3,5-dimethylbenzyl) analogue 5q exhibited the most potent anti-HIV-1 activity (IC(50)=0.12 microM, SI>2642), which was about 40-fold more active than the reference compounds 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 2',3'-dideoxyinosine (DDI). The structure-activity relationships (SARs) of these new congeners were further discussed.

DOI: 10.1016/j.ejmech.2008.06.028
PubMed: 18692274

Links toward previous steps (curation, corpus...)

to stream PubMed, to step Corpus: 001A90
to stream PubMed, to step Curation: 001A90
to stream PubMed, to step Checkpoint: 001770

Links to Exploration step

pubmed:18692274

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors.</title>
<author><name sortKey="Wang, Yue Ping" sort="Wang, Yue Ping" uniqKey="Wang Y" first="Yue-Ping" last="Wang">Yue-Ping Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry, Fudan University, Shanghai 200433, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Chemistry, Fudan University, Shanghai 200433</wicri:regionArea>
<wicri:noRegion>Shanghai 200433</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chen, Fen Er" sort="Chen, Fen Er" uniqKey="Chen F" first="Fen-Er" last="Chen">Fen-Er Chen</name>
</author>
<author><name sortKey="De Clercq, Erik" sort="De Clercq, Erik" uniqKey="De Clercq E" first="Erik" last="De Clercq">Erik De Clercq</name>
</author>
<author><name sortKey="Balzarini, Jan" sort="Balzarini, Jan" uniqKey="Balzarini J" first="Jan" last="Balzarini">Jan Balzarini</name>
</author>
<author><name sortKey="Pannecouque, Christophe" sort="Pannecouque, Christophe" uniqKey="Pannecouque C" first="Christophe" last="Pannecouque">Christophe Pannecouque</name>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2009">2009</date>
<idno type="RBID">pubmed:18692274</idno>
<idno type="pmid">18692274</idno>
<idno type="doi">10.1016/j.ejmech.2008.06.028</idno>
<idno type="wicri:Area/PubMed/Corpus">001A90</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001A90</idno>
<idno type="wicri:Area/PubMed/Curation">001A90</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001A90</idno>
<idno type="wicri:Area/PubMed/Checkpoint">001770</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001770</idno>
<idno type="wicri:Area/Ncbi/Merge">001D12</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors.</title>
<author><name sortKey="Wang, Yue Ping" sort="Wang, Yue Ping" uniqKey="Wang Y" first="Yue-Ping" last="Wang">Yue-Ping Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry, Fudan University, Shanghai 200433, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Chemistry, Fudan University, Shanghai 200433</wicri:regionArea>
<wicri:noRegion>Shanghai 200433</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chen, Fen Er" sort="Chen, Fen Er" uniqKey="Chen F" first="Fen-Er" last="Chen">Fen-Er Chen</name>
</author>
<author><name sortKey="De Clercq, Erik" sort="De Clercq, Erik" uniqKey="De Clercq E" first="Erik" last="De Clercq">Erik De Clercq</name>
</author>
<author><name sortKey="Balzarini, Jan" sort="Balzarini, Jan" uniqKey="Balzarini J" first="Jan" last="Balzarini">Jan Balzarini</name>
</author>
<author><name sortKey="Pannecouque, Christophe" sort="Pannecouque, Christophe" uniqKey="Pannecouque C" first="Christophe" last="Pannecouque">Christophe Pannecouque</name>
</author>
</analytic>
<series><title level="j">European journal of medicinal chemistry</title>
<idno type="eISSN">1768-3254</idno>
<imprint><date when="2009" type="published">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cell Line</term>
<term>Crystallography, X-Ray</term>
<term>HIV Reverse Transcriptase (antagonists & inhibitors)</term>
<term>HIV-1 (drug effects)</term>
<term>Humans</term>
<term>Magnetic Resonance Spectroscopy</term>
<term>Pyrimidinones (chemical synthesis)</term>
<term>Pyrimidinones (chemistry)</term>
<term>Pyrimidinones (pharmacology)</term>
<term>Reverse Transcriptase Inhibitors (chemical synthesis)</term>
<term>Reverse Transcriptase Inhibitors (chemistry)</term>
<term>Reverse Transcriptase Inhibitors (pharmacology)</term>
<term>Spectrometry, Mass, Electrospray Ionization</term>
<term>Spectroscopy, Fourier Transform Infrared</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Cristallographie aux rayons X</term>
<term>Humains</term>
<term>Inhibiteurs de la transcriptase inverse ()</term>
<term>Inhibiteurs de la transcriptase inverse (pharmacologie)</term>
<term>Inhibiteurs de la transcriptase inverse (synthèse chimique)</term>
<term>Lignée cellulaire</term>
<term>Pyrimidinones ()</term>
<term>Pyrimidinones (pharmacologie)</term>
<term>Pyrimidinones (synthèse chimique)</term>
<term>Relation structure-activité</term>
<term>Spectrométrie de masse ESI</term>
<term>Spectroscopie infrarouge à transformée de Fourier</term>
<term>Spectroscopie par résonance magnétique</term>
<term>Transcriptase inverse du VIH (antagonistes et inhibiteurs)</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) ()</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>HIV Reverse Transcriptase</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Pyrimidinones</term>
<term>Reverse Transcriptase Inhibitors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Pyrimidinones</term>
<term>Reverse Transcriptase Inhibitors</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Transcriptase inverse du VIH</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>HIV-1</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Inhibiteurs de la transcriptase inverse</term>
<term>Pyrimidinones</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Pyrimidinones</term>
<term>Reverse Transcriptase Inhibitors</term>
</keywords>
<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Inhibiteurs de la transcriptase inverse</term>
<term>Pyrimidinones</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Cell Line</term>
<term>Crystallography, X-Ray</term>
<term>Humans</term>
<term>Magnetic Resonance Spectroscopy</term>
<term>Spectrometry, Mass, Electrospray Ionization</term>
<term>Spectroscopy, Fourier Transform Infrared</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Cristallographie aux rayons X</term>
<term>Humains</term>
<term>Inhibiteurs de la transcriptase inverse</term>
<term>Lignée cellulaire</term>
<term>Pyrimidinones</term>
<term>Relation structure-activité</term>
<term>Spectrométrie de masse ESI</term>
<term>Spectroscopie infrarouge à transformée de Fourier</term>
<term>Spectroscopie par résonance magnétique</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">A series of new 5-alkyl-2-benzylsulfanylpyrimidin-4(3H)-ones (5a-y) bearing different substituted arylmethyl moieties at the C-6 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against HIV-1 and HIV-2 in MT-4 cell cultures. The majority of the title compounds showed moderate to good activities against HIV-1 with an IC(50) range from 6.67 microM to 0.12 microM. Among them, 6-(3,5-dimethylbenzyl) analogue 5q exhibited the most potent anti-HIV-1 activity (IC(50)=0.12 microM, SI>2642), which was about 40-fold more active than the reference compounds 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 2',3'-dideoxyinosine (DDI). The structure-activity relationships (SARs) of these new congeners were further discussed.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">18692274</PMID>
<DateCompleted><Year>2009</Year>
<Month>06</Month>
<Day>11</Day>
</DateCompleted>
<DateRevised><Year>2009</Year>
<Month>03</Month>
<Day>02</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1768-3254</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>44</Volume>
<Issue>3</Issue>
<PubDate><Year>2009</Year>
<Month>Mar</Month>
</PubDate>
</JournalIssue>
<Title>European journal of medicinal chemistry</Title>
<ISOAbbreviation>Eur J Med Chem</ISOAbbreviation>
</Journal>
<ArticleTitle>Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors.</ArticleTitle>
<Pagination><MedlinePgn>1016-23</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.ejmech.2008.06.028</ELocationID>
<Abstract><AbstractText>A series of new 5-alkyl-2-benzylsulfanylpyrimidin-4(3H)-ones (5a-y) bearing different substituted arylmethyl moieties at the C-6 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against HIV-1 and HIV-2 in MT-4 cell cultures. The majority of the title compounds showed moderate to good activities against HIV-1 with an IC(50) range from 6.67 microM to 0.12 microM. Among them, 6-(3,5-dimethylbenzyl) analogue 5q exhibited the most potent anti-HIV-1 activity (IC(50)=0.12 microM, SI>2642), which was about 40-fold more active than the reference compounds 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 2',3'-dideoxyinosine (DDI). The structure-activity relationships (SARs) of these new congeners were further discussed.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Yue-Ping</ForeName>
<Initials>YP</Initials>
<AffiliationInfo><Affiliation>Department of Chemistry, Fudan University, Shanghai 200433, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Fen-Er</ForeName>
<Initials>FE</Initials>
</Author>
<Author ValidYN="Y"><LastName>De Clercq</LastName>
<ForeName>Erik</ForeName>
<Initials>E</Initials>
</Author>
<Author ValidYN="Y"><LastName>Balzarini</LastName>
<ForeName>Jan</ForeName>
<Initials>J</Initials>
</Author>
<Author ValidYN="Y"><LastName>Pannecouque</LastName>
<ForeName>Christophe</ForeName>
<Initials>C</Initials>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2008</Year>
<Month>07</Month>
<Day>04</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="D011744">Pyrimidinones</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D018894">Reverse Transcriptase Inhibitors</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.7.-</RegistryNumber>
<NameOfSubstance UI="C514824">reverse transcriptase, Human immunodeficiency virus 1</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.7.49</RegistryNumber>
<NameOfSubstance UI="D054303">HIV Reverse Transcriptase</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018360" MajorTopicYN="N">Crystallography, X-Ray</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054303" MajorTopicYN="N">HIV Reverse Transcriptase</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015497" MajorTopicYN="N">HIV-1</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009682" MajorTopicYN="N">Magnetic Resonance Spectroscopy</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011744" MajorTopicYN="N">Pyrimidinones</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="Y">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018894" MajorTopicYN="N">Reverse Transcriptase Inhibitors</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="Y">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D021241" MajorTopicYN="N">Spectrometry, Mass, Electrospray Ionization</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017550" MajorTopicYN="N">Spectroscopy, Fourier Transform Infrared</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2008</Year>
<Month>02</Month>
<Day>01</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2008</Year>
<Month>06</Month>
<Day>20</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2008</Year>
<Month>06</Month>
<Day>30</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2008</Year>
<Month>8</Month>
<Day>12</Day>
<Hour>9</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2009</Year>
<Month>6</Month>
<Day>12</Day>
<Hour>9</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2008</Year>
<Month>8</Month>
<Day>12</Day>
<Hour>9</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">18692274</ArticleId>
<ArticleId IdType="pii">S0223-5234(08)00326-7</ArticleId>
<ArticleId IdType="doi">10.1016/j.ejmech.2008.06.028</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>République populaire de Chine</li>
</country>
</list>
<tree><noCountry><name sortKey="Balzarini, Jan" sort="Balzarini, Jan" uniqKey="Balzarini J" first="Jan" last="Balzarini">Jan Balzarini</name>
<name sortKey="Chen, Fen Er" sort="Chen, Fen Er" uniqKey="Chen F" first="Fen-Er" last="Chen">Fen-Er Chen</name>
<name sortKey="De Clercq, Erik" sort="De Clercq, Erik" uniqKey="De Clercq E" first="Erik" last="De Clercq">Erik De Clercq</name>
<name sortKey="Pannecouque, Christophe" sort="Pannecouque, Christophe" uniqKey="Pannecouque C" first="Christophe" last="Pannecouque">Christophe Pannecouque</name>
</noCountry>
<country name="République populaire de Chine"><noRegion><name sortKey="Wang, Yue Ping" sort="Wang, Yue Ping" uniqKey="Wang Y" first="Yue-Ping" last="Wang">Yue-Ping Wang</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Ncbi/Merge

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001D12 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 001D12 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    SrasV1
   |flux=    Ncbi
   |étape=   Merge
   |type=    RBID
   |clé=     pubmed:18692274
   |texte=   Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i   -Sk "pubmed:18692274" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd   \
       | NlmPubMed2Wicri -a SrasV1

This area was generated with Dilib version V0.6.33.
Data generation: Tue Apr 28 14:49:16 2020. Site generation: Sat Mar 27 22:06:49 2021

	Serveur d'exploration SRAS
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration SRAS

Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors.

Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki