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.

Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches.

Identifieur interne : 001317 ( Main/Exploration ); précédent : 001316; suivant : 001318

Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches.

Auteurs : Boshi Huang [République populaire de Chine] ; Cuicui Li [République populaire de Chine] ; Wenmin Chen [République populaire de Chine] ; Tao Liu [République populaire de Chine] ; Mingyan Yu [République populaire de Chine] ; Lu Fu [République populaire de Chine] ; Yueyue Sun [République populaire de Chine] ; Huiqing Liu [République populaire de Chine] ; Erik De Clercq [Belgique] ; Christophe Pannecouque [Belgique] ; Jan Balzarini [Belgique] ; Peng Zhan [République populaire de Chine] ; Xinyong Liu [République populaire de Chine]

Source :

RBID : pubmed:25626145

Descripteurs français

English descriptors

Abstract

In our arduous efforts to develop new potent HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs), novel piperidine-linked [1,2,4]triazolo[1,5-a]pyrimidine derivatives were designed, synthesized and evaluated for their antiviral activities in MT-4 cell cultures. Biological results showed that all of the title compounds displayed moderate to excellent activities against wild-type (wt) HIV-1 strain (IIIB) with EC50 values ranging from 8.1 nM to 2284 nM in a cell-based assay. Among them, the most promising analog 7d possessed an EC50 value of 8.1 nM against wt HIV-1, which was much more potent than the reference drugs DDI, 3 TC, NVP and DLV. Additionally, 7d demonstrated weak activity against the double mutant HIV-1 strain (K103N + Y181C), and was more efficient than NVP in a RT inhibition assay. Besides, some measured and calculated physicochemical properties of 7d, like log P and water solubility, as well as the structure-activity relationships (SARs) analysis have been discussed in detail. Furthermore, the binding mode of the active compound 7d was rationalized by molecular simulation studies.

DOI: 10.1016/j.ejmech.2015.01.042
PubMed: 25626145


Affiliations:


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


Le document en format XML

<record>
<TEI>
<teiHeader>
<fileDesc>
<titleStmt>
<title xml:lang="en">Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches.</title>
<author>
<name sortKey="Huang, Boshi" sort="Huang, Boshi" uniqKey="Huang B" first="Boshi" last="Huang">Boshi Huang</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Li, Cuicui" sort="Li, Cuicui" uniqKey="Li C" first="Cuicui" last="Li">Cuicui Li</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chen, Wenmin" sort="Chen, Wenmin" uniqKey="Chen W" first="Wenmin" last="Chen">Wenmin Chen</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Liu, Tao" sort="Liu, Tao" uniqKey="Liu T" first="Tao" last="Liu">Tao Liu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yu, Mingyan" sort="Yu, Mingyan" uniqKey="Yu M" first="Mingyan" last="Yu">Mingyan Yu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Shandong Institute for Food and Drug Control, 2749 Xinluo Street, 250101 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shandong Institute for Food and Drug Control, 2749 Xinluo Street, 250101 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Fu, Lu" sort="Fu, Lu" uniqKey="Fu L" first="Lu" last="Fu">Lu Fu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Sun, Yueyue" sort="Sun, Yueyue" uniqKey="Sun Y" first="Yueyue" last="Sun">Yueyue Sun</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Liu, Huiqing" sort="Liu, Huiqing" uniqKey="Liu H" first="Huiqing" last="Liu">Huiqing Liu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Institute of Pharmacology, School of Medicine, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Pharmacology, School of Medicine, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="De Clercq, Erik" sort="De Clercq, Erik" uniqKey="De Clercq E" first="Erik" last="De Clercq">Erik De Clercq</name>
<affiliation wicri:level="1">
<nlm:affiliation>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven</wicri:regionArea>
<wicri:noRegion>B-3000 Leuven</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Pannecouque, Christophe" sort="Pannecouque, Christophe" uniqKey="Pannecouque C" first="Christophe" last="Pannecouque">Christophe Pannecouque</name>
<affiliation wicri:level="1">
<nlm:affiliation>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven</wicri:regionArea>
<wicri:noRegion>B-3000 Leuven</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Balzarini, Jan" sort="Balzarini, Jan" uniqKey="Balzarini J" first="Jan" last="Balzarini">Jan Balzarini</name>
<affiliation wicri:level="1">
<nlm:affiliation>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven</wicri:regionArea>
<wicri:noRegion>B-3000 Leuven</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Zhan, Peng" sort="Zhan, Peng" uniqKey="Zhan P" first="Peng" last="Zhan">Peng Zhan</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China. Electronic address: zhanpeng1982@sdu.edu.cn.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Liu, Xinyong" sort="Liu, Xinyong" uniqKey="Liu X" first="Xinyong" last="Liu">Xinyong Liu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China. Electronic address: xinyongl@sdu.edu.cn.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt>
<idno type="wicri:source">PubMed</idno>
<date when="2015">2015</date>
<idno type="RBID">pubmed:25626145</idno>
<idno type="pmid">25626145</idno>
<idno type="doi">10.1016/j.ejmech.2015.01.042</idno>
<idno type="wicri:Area/PubMed/Corpus">000E69</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000E69</idno>
<idno type="wicri:Area/PubMed/Curation">000E69</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000E69</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000E20</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000E20</idno>
<idno type="wicri:Area/Ncbi/Merge">002A21</idno>
<idno type="wicri:Area/Ncbi/Curation">002A21</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">002A21</idno>
<idno type="wicri:Area/Main/Merge">001319</idno>
<idno type="wicri:Area/Main/Curation">001317</idno>
<idno type="wicri:Area/Main/Exploration">001317</idno>
</publicationStmt>
<sourceDesc>
<biblStruct>
<analytic>
<title xml:lang="en">Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches.</title>
<author>
<name sortKey="Huang, Boshi" sort="Huang, Boshi" uniqKey="Huang B" first="Boshi" last="Huang">Boshi Huang</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Li, Cuicui" sort="Li, Cuicui" uniqKey="Li C" first="Cuicui" last="Li">Cuicui Li</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chen, Wenmin" sort="Chen, Wenmin" uniqKey="Chen W" first="Wenmin" last="Chen">Wenmin Chen</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Liu, Tao" sort="Liu, Tao" uniqKey="Liu T" first="Tao" last="Liu">Tao Liu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yu, Mingyan" sort="Yu, Mingyan" uniqKey="Yu M" first="Mingyan" last="Yu">Mingyan Yu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Shandong Institute for Food and Drug Control, 2749 Xinluo Street, 250101 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shandong Institute for Food and Drug Control, 2749 Xinluo Street, 250101 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Fu, Lu" sort="Fu, Lu" uniqKey="Fu L" first="Lu" last="Fu">Lu Fu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Sun, Yueyue" sort="Sun, Yueyue" uniqKey="Sun Y" first="Yueyue" last="Sun">Yueyue Sun</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Liu, Huiqing" sort="Liu, Huiqing" uniqKey="Liu H" first="Huiqing" last="Liu">Huiqing Liu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Institute of Pharmacology, School of Medicine, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Institute of Pharmacology, School of Medicine, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="De Clercq, Erik" sort="De Clercq, Erik" uniqKey="De Clercq E" first="Erik" last="De Clercq">Erik De Clercq</name>
<affiliation wicri:level="1">
<nlm:affiliation>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven</wicri:regionArea>
<wicri:noRegion>B-3000 Leuven</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Pannecouque, Christophe" sort="Pannecouque, Christophe" uniqKey="Pannecouque C" first="Christophe" last="Pannecouque">Christophe Pannecouque</name>
<affiliation wicri:level="1">
<nlm:affiliation>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven</wicri:regionArea>
<wicri:noRegion>B-3000 Leuven</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Balzarini, Jan" sort="Balzarini, Jan" uniqKey="Balzarini J" first="Jan" last="Balzarini">Jan Balzarini</name>
<affiliation wicri:level="1">
<nlm:affiliation>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Rega Institute for Medical Research, KU Leuven Minderbroedersstraat 10, B-3000 Leuven</wicri:regionArea>
<wicri:noRegion>B-3000 Leuven</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Zhan, Peng" sort="Zhan, Peng" uniqKey="Zhan P" first="Peng" last="Zhan">Peng Zhan</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China. Electronic address: zhanpeng1982@sdu.edu.cn.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Liu, Xinyong" sort="Liu, Xinyong" uniqKey="Liu X" first="Xinyong" last="Liu">Xinyong Liu</name>
<affiliation wicri:level="1">
<nlm:affiliation>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong, PR China. Electronic address: xinyongl@sdu.edu.cn.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012 Ji'nan, Shandong</wicri:regionArea>
<wicri:noRegion>Shandong</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">European journal of medicinal chemistry</title>
<idno type="eISSN">1768-3254</idno>
<imprint>
<date when="2015" type="published">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Anti-HIV Agents (chemical synthesis)</term>
<term>Anti-HIV Agents (chemistry)</term>
<term>Anti-HIV Agents (pharmacology)</term>
<term>Cell Line, Tumor</term>
<term>Dose-Response Relationship, Drug</term>
<term>HIV Reverse Transcriptase (antagonists & inhibitors)</term>
<term>HIV Reverse Transcriptase (metabolism)</term>
<term>HIV-1 (drug effects)</term>
<term>Heterocyclic Compounds (chemical synthesis)</term>
<term>Heterocyclic Compounds (chemistry)</term>
<term>Heterocyclic Compounds (pharmacology)</term>
<term>Heterocyclic Compounds, 2-Ring (chemical synthesis)</term>
<term>Heterocyclic Compounds, 2-Ring (chemistry)</term>
<term>Heterocyclic Compounds, 2-Ring (pharmacology)</term>
<term>Humans</term>
<term>Microbial Sensitivity Tests</term>
<term>Models, Molecular</term>
<term>Molecular Structure</term>
<term>Nitrogen (chemistry)</term>
<term>Reverse Transcriptase Inhibitors (chemical synthesis)</term>
<term>Reverse Transcriptase Inhibitors (chemistry)</term>
<term>Reverse Transcriptase Inhibitors (pharmacology)</term>
<term>Solubility</term>
<term>Structure-Activity Relationship</term>
<term>Sulfones (chemical synthesis)</term>
<term>Sulfones (chemistry)</term>
<term>Sulfones (pharmacology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Agents antiVIH ()</term>
<term>Agents antiVIH (pharmacologie)</term>
<term>Agents antiVIH (synthèse chimique)</term>
<term>Azote ()</term>
<term>Composés hétérobicycliques ()</term>
<term>Composés hétérobicycliques (pharmacologie)</term>
<term>Composés hétérobicycliques (synthèse chimique)</term>
<term>Composés hétérocycliques ()</term>
<term>Composés hétérocycliques (pharmacologie)</term>
<term>Composés hétérocycliques (synthèse chimique)</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 tumorale</term>
<term>Modèles moléculaires</term>
<term>Relation dose-effet des médicaments</term>
<term>Relation structure-activité</term>
<term>Solubilité</term>
<term>Structure moléculaire</term>
<term>Sulfones ()</term>
<term>Sulfones (pharmacologie)</term>
<term>Sulfones (synthèse chimique)</term>
<term>Tests de sensibilité microbienne</term>
<term>Transcriptase inverse du VIH (antagonistes et inhibiteurs)</term>
<term>Transcriptase inverse du VIH (métabolisme)</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>Anti-HIV Agents</term>
<term>Heterocyclic Compounds</term>
<term>Heterocyclic Compounds, 2-Ring</term>
<term>Reverse Transcriptase Inhibitors</term>
<term>Sulfones</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en">
<term>Anti-HIV Agents</term>
<term>Heterocyclic Compounds</term>
<term>Heterocyclic Compounds, 2-Ring</term>
<term>Nitrogen</term>
<term>Reverse Transcriptase Inhibitors</term>
<term>Sulfones</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>HIV Reverse Transcriptase</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Anti-HIV Agents</term>
<term>Heterocyclic Compounds</term>
<term>Heterocyclic Compounds, 2-Ring</term>
<term>Reverse Transcriptase Inhibitors</term>
<term>Sulfones</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="métabolisme" xml:lang="fr">
<term>Transcriptase inverse du VIH</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr">
<term>Agents antiVIH</term>
<term>Composés hétérobicycliques</term>
<term>Composés hétérocycliques</term>
<term>Inhibiteurs de la transcriptase inverse</term>
<term>Sulfones</term>
</keywords>
<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr">
<term>Agents antiVIH</term>
<term>Composés hétérobicycliques</term>
<term>Composés hétérocycliques</term>
<term>Inhibiteurs de la transcriptase inverse</term>
<term>Sulfones</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Cell Line, Tumor</term>
<term>Dose-Response Relationship, Drug</term>
<term>Humans</term>
<term>Microbial Sensitivity Tests</term>
<term>Models, Molecular</term>
<term>Molecular Structure</term>
<term>Solubility</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Agents antiVIH</term>
<term>Azote</term>
<term>Composés hétérobicycliques</term>
<term>Composés hétérocycliques</term>
<term>Humains</term>
<term>Inhibiteurs de la transcriptase inverse</term>
<term>Lignée cellulaire tumorale</term>
<term>Modèles moléculaires</term>
<term>Relation dose-effet des médicaments</term>
<term>Relation structure-activité</term>
<term>Solubilité</term>
<term>Structure moléculaire</term>
<term>Sulfones</term>
<term>Tests de sensibilité microbienne</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">In our arduous efforts to develop new potent HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs), novel piperidine-linked [1,2,4]triazolo[1,5-a]pyrimidine derivatives were designed, synthesized and evaluated for their antiviral activities in MT-4 cell cultures. Biological results showed that all of the title compounds displayed moderate to excellent activities against wild-type (wt) HIV-1 strain (IIIB) with EC50 values ranging from 8.1 nM to 2284 nM in a cell-based assay. Among them, the most promising analog 7d possessed an EC50 value of 8.1 nM against wt HIV-1, which was much more potent than the reference drugs DDI, 3 TC, NVP and DLV. Additionally, 7d demonstrated weak activity against the double mutant HIV-1 strain (K103N + Y181C), and was more efficient than NVP in a RT inhibition assay. Besides, some measured and calculated physicochemical properties of 7d, like log P and water solubility, as well as the structure-activity relationships (SARs) analysis have been discussed in detail. Furthermore, the binding mode of the active compound 7d was rationalized by molecular simulation studies. </div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Belgique</li>
<li>République populaire de Chine</li>
</country>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Huang, Boshi" sort="Huang, Boshi" uniqKey="Huang B" first="Boshi" last="Huang">Boshi Huang</name>
</noRegion>
<name sortKey="Chen, Wenmin" sort="Chen, Wenmin" uniqKey="Chen W" first="Wenmin" last="Chen">Wenmin Chen</name>
<name sortKey="Fu, Lu" sort="Fu, Lu" uniqKey="Fu L" first="Lu" last="Fu">Lu Fu</name>
<name sortKey="Li, Cuicui" sort="Li, Cuicui" uniqKey="Li C" first="Cuicui" last="Li">Cuicui Li</name>
<name sortKey="Liu, Huiqing" sort="Liu, Huiqing" uniqKey="Liu H" first="Huiqing" last="Liu">Huiqing Liu</name>
<name sortKey="Liu, Tao" sort="Liu, Tao" uniqKey="Liu T" first="Tao" last="Liu">Tao Liu</name>
<name sortKey="Liu, Xinyong" sort="Liu, Xinyong" uniqKey="Liu X" first="Xinyong" last="Liu">Xinyong Liu</name>
<name sortKey="Sun, Yueyue" sort="Sun, Yueyue" uniqKey="Sun Y" first="Yueyue" last="Sun">Yueyue Sun</name>
<name sortKey="Yu, Mingyan" sort="Yu, Mingyan" uniqKey="Yu M" first="Mingyan" last="Yu">Mingyan Yu</name>
<name sortKey="Zhan, Peng" sort="Zhan, Peng" uniqKey="Zhan P" first="Peng" last="Zhan">Peng Zhan</name>
</country>
<country name="Belgique">
<noRegion>
<name sortKey="De Clercq, Erik" sort="De Clercq, Erik" uniqKey="De Clercq E" first="Erik" last="De Clercq">Erik De Clercq</name>
</noRegion>
<name sortKey="Balzarini, Jan" sort="Balzarini, Jan" uniqKey="Balzarini J" first="Jan" last="Balzarini">Jan Balzarini</name>
<name sortKey="Pannecouque, Christophe" sort="Pannecouque, Christophe" uniqKey="Pannecouque C" first="Christophe" last="Pannecouque">Christophe Pannecouque</name>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001317 | SxmlIndent | more

Ou

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001317 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    SrasV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:25626145
   |texte=   Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:25626145" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a SrasV1 

Wicri

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