Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities.
Identifieur interne : 000554 ( Main/Merge ); précédent : 000553; suivant : 000555Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities.
Auteurs : Ting Xiao [République populaire de Chine] ; Jia-Fan Tang [République populaire de Chine] ; Ge Meng [République populaire de Chine] ; Christophe Pannecouque [Belgique] ; Yuan-Yuan Zhu [République populaire de Chine] ; Gen-Yan Liu [République populaire de Chine] ; Zhi-Qiang Xu [République populaire de Chine] ; Feng-Shou Wu [République populaire de Chine] ; Shuang-Xi Gu [République populaire de Chine] ; Fen-Er Chen [République populaire de Chine]Source :
- European journal of medicinal chemistry [ 1768-3254 ] ; 2020.
Descripteurs français
- KwdFr :
- Agents antiVIH (), Agents antiVIH (pharmacologie), Agents antiVIH (synthèse chimique), Conception de médicament, Humains, Indazoles (), Indazoles (pharmacologie), Inhibiteurs de la transcriptase inverse (), Inhibiteurs de la transcriptase inverse (pharmacologie), Inhibiteurs de la transcriptase inverse (synthèse chimique), Pipéridines (), Pipéridines (pharmacologie), Pipéridines (synthèse chimique), Pyrimidines (), Pyrimidines (pharmacologie), Pyrimidines (synthèse chimique), Relation dose-effet des médicaments, Relation structure-activité, Structure moléculaire, Tests de sensibilité microbienne, Transcriptase inverse du VIH (antagonistes et inhibiteurs), Transcriptase inverse du VIH (métabolisme), VIH (Virus de l'Immunodéficience Humaine) ().
- MESH :
- antagonistes et inhibiteurs : Transcriptase inverse du VIH.
- métabolisme : Transcriptase inverse du VIH.
- pharmacologie : Agents antiVIH, Indazoles, Inhibiteurs de la transcriptase inverse, Pipéridines, Pyrimidines.
- synthèse chimique : Agents antiVIH, Inhibiteurs de la transcriptase inverse, Pipéridines, Pyrimidines.
- Agents antiVIH, Conception de médicament, Humains, Indazoles, Inhibiteurs de la transcriptase inverse, Pipéridines, Pyrimidines, Relation dose-effet des médicaments, Relation structure-activité, Structure moléculaire, Tests de sensibilité microbienne, VIH (Virus de l'Immunodéficience Humaine).
English descriptors
- KwdEn :
- Anti-HIV Agents (chemical synthesis), Anti-HIV Agents (chemistry), Anti-HIV Agents (pharmacology), Dose-Response Relationship, Drug, Drug Design, HIV (drug effects), HIV Reverse Transcriptase (antagonists & inhibitors), HIV Reverse Transcriptase (metabolism), Humans, Indazoles (chemistry), Indazoles (pharmacology), Microbial Sensitivity Tests, Molecular Structure, Piperidines (chemical synthesis), Piperidines (chemistry), Piperidines (pharmacology), Pyrimidines (chemical synthesis), Pyrimidines (chemistry), Pyrimidines (pharmacology), Reverse Transcriptase Inhibitors (chemical synthesis), Reverse Transcriptase Inhibitors (chemistry), Reverse Transcriptase Inhibitors (pharmacology), Structure-Activity Relationship.
- MESH :
- chemical , antagonists & inhibitors : HIV Reverse Transcriptase.
- chemical , chemical synthesis : Anti-HIV Agents, Piperidines, Pyrimidines, Reverse Transcriptase Inhibitors.
- chemical , chemistry : Anti-HIV Agents, Indazoles, Piperidines, Pyrimidines, Reverse Transcriptase Inhibitors.
- chemical , metabolism : HIV Reverse Transcriptase.
- chemical , pharmacology : Anti-HIV Agents, Indazoles, Piperidines, Pyrimidines, Reverse Transcriptase Inhibitors.
- drug effects : HIV.
- Dose-Response Relationship, Drug, Drug Design, Humans, Microbial Sensitivity Tests, Molecular Structure, Structure-Activity Relationship.
Abstract
A series of indazolyl-substituted piperidin-4-yl-aminopyrimidines (IPAPYs) were designed from two potent HIV-1 NNRTIs piperidin-4-yl-aminopyrimidine 3c and diaryl ether 4 as the lead compounds by molecular hybridization strategy. The target molecules 5a-q were synthesized and evaluated for their anti-HIV activities and cytotoxicities in MT-4 cells. 5a-q displayed moderate to excellent activities against wild-type (WT) HIV-1 with EC50 values ranging from 1.5 to 0.0064 μM. Among them, 5q was regarded as the most excellent compound against WT HIV-1 (EC50 = 6.4 nM, SI = 2500). And also, it displayed potent activities against K103 N (EC50 = 0.077 μM), Y181C (EC50 = 0.11 μM), E138K (EC50 = 0.057 μM), and moderate activity against double mutants RES056 (EC50 = 8.7 μM). Moreover, the structure-activity relationships (SARs) were summarized, and the molecular docking was performed to investigate the binding mode of IPAPYs and HIV-1 reverse transcriptase.
DOI: 10.1016/j.ejmech.2019.111864
PubMed: 31767136
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000857
- to stream PubMed, to step Curation: 000857
- to stream PubMed, to step Checkpoint: 000441
- to stream Ncbi, to step Merge: 003106
- to stream Ncbi, to step Curation: 003106
- to stream Ncbi, to step Checkpoint: 003106
Links to Exploration step
pubmed:31767136Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities.</title>
<author><name sortKey="Xiao, Ting" sort="Xiao, Ting" uniqKey="Xiao T" first="Ting" last="Xiao">Ting Xiao</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tang, Jia Fan" sort="Tang, Jia Fan" uniqKey="Tang J" first="Jia-Fan" last="Tang">Jia-Fan Tang</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Meng, Ge" sort="Meng, Ge" uniqKey="Meng G" first="Ge" last="Meng">Ge Meng</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry, Fudan University, Shanghai, 200433, 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>200433</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>KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000, Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhu, Yuan Yuan" sort="Zhu, Yuan Yuan" uniqKey="Zhu Y" first="Yuan-Yuan" last="Zhu">Yuan-Yuan Zhu</name>
<affiliation wicri:level="1"><nlm:affiliation>School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Liu, Gen Yan" sort="Liu, Gen Yan" uniqKey="Liu G" first="Gen-Yan" last="Liu">Gen-Yan Liu</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Xu, Zhi Qiang" sort="Xu, Zhi Qiang" uniqKey="Xu Z" first="Zhi-Qiang" last="Xu">Zhi-Qiang Xu</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wu, Feng Shou" sort="Wu, Feng Shou" uniqKey="Wu F" first="Feng-Shou" last="Wu">Feng-Shou Wu</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gu, Shuang Xi" sort="Gu, Shuang Xi" uniqKey="Gu S" first="Shuang-Xi" last="Gu">Shuang-Xi Gu</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China. Electronic address: shuangxigu@163.com.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</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>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China; Department of Chemistry, Fudan University, Shanghai, 200433, China. Electronic address: rfchen@fudan.edu.cn.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China; Department of Chemistry, Fudan University, Shanghai, 200433</wicri:regionArea>
<wicri:noRegion>200433</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2020">2020</date>
<idno type="RBID">pubmed:31767136</idno>
<idno type="pmid">31767136</idno>
<idno type="doi">10.1016/j.ejmech.2019.111864</idno>
<idno type="wicri:Area/PubMed/Corpus">000857</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000857</idno>
<idno type="wicri:Area/PubMed/Curation">000857</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000857</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000441</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000441</idno>
<idno type="wicri:Area/Ncbi/Merge">003106</idno>
<idno type="wicri:Area/Ncbi/Curation">003106</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">003106</idno>
<idno type="wicri:Area/Main/Merge">000554</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities.</title>
<author><name sortKey="Xiao, Ting" sort="Xiao, Ting" uniqKey="Xiao T" first="Ting" last="Xiao">Ting Xiao</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tang, Jia Fan" sort="Tang, Jia Fan" uniqKey="Tang J" first="Jia-Fan" last="Tang">Jia-Fan Tang</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Meng, Ge" sort="Meng, Ge" uniqKey="Meng G" first="Ge" last="Meng">Ge Meng</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Chemistry, Fudan University, Shanghai, 200433, 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>200433</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>KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000, Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>KU Leuven, Department of Microbiology and Immunology, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhu, Yuan Yuan" sort="Zhu, Yuan Yuan" uniqKey="Zhu Y" first="Yuan-Yuan" last="Zhu">Yuan-Yuan Zhu</name>
<affiliation wicri:level="1"><nlm:affiliation>School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Liu, Gen Yan" sort="Liu, Gen Yan" uniqKey="Liu G" first="Gen-Yan" last="Liu">Gen-Yan Liu</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Xu, Zhi Qiang" sort="Xu, Zhi Qiang" uniqKey="Xu Z" first="Zhi-Qiang" last="Xu">Zhi-Qiang Xu</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wu, Feng Shou" sort="Wu, Feng Shou" uniqKey="Wu F" first="Feng-Shou" last="Wu">Feng-Shou Wu</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gu, Shuang Xi" sort="Gu, Shuang Xi" uniqKey="Gu S" first="Shuang-Xi" last="Gu">Shuang-Xi Gu</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China. Electronic address: shuangxigu@163.com.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205</wicri:regionArea>
<wicri:noRegion>430205</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>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China; Department of Chemistry, Fudan University, Shanghai, 200433, China. Electronic address: rfchen@fudan.edu.cn.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, 430205, China; Department of Chemistry, Fudan University, Shanghai, 200433</wicri:regionArea>
<wicri:noRegion>200433</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">European journal of medicinal chemistry</title>
<idno type="eISSN">1768-3254</idno>
<imprint><date when="2020" type="published">2020</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>Dose-Response Relationship, Drug</term>
<term>Drug Design</term>
<term>HIV (drug effects)</term>
<term>HIV Reverse Transcriptase (antagonists & inhibitors)</term>
<term>HIV Reverse Transcriptase (metabolism)</term>
<term>Humans</term>
<term>Indazoles (chemistry)</term>
<term>Indazoles (pharmacology)</term>
<term>Microbial Sensitivity Tests</term>
<term>Molecular Structure</term>
<term>Piperidines (chemical synthesis)</term>
<term>Piperidines (chemistry)</term>
<term>Piperidines (pharmacology)</term>
<term>Pyrimidines (chemical synthesis)</term>
<term>Pyrimidines (chemistry)</term>
<term>Pyrimidines (pharmacology)</term>
<term>Reverse Transcriptase Inhibitors (chemical synthesis)</term>
<term>Reverse Transcriptase Inhibitors (chemistry)</term>
<term>Reverse Transcriptase Inhibitors (pharmacology)</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Agents antiVIH ()</term>
<term>Agents antiVIH (pharmacologie)</term>
<term>Agents antiVIH (synthèse chimique)</term>
<term>Conception de médicament</term>
<term>Humains</term>
<term>Indazoles ()</term>
<term>Indazoles (pharmacologie)</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>Pipéridines ()</term>
<term>Pipéridines (pharmacologie)</term>
<term>Pipéridines (synthèse chimique)</term>
<term>Pyrimidines ()</term>
<term>Pyrimidines (pharmacologie)</term>
<term>Pyrimidines (synthèse chimique)</term>
<term>Relation dose-effet des médicaments</term>
<term>Relation structure-activité</term>
<term>Structure moléculaire</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 (Virus de l'Immunodéficience Humaine) ()</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>Piperidines</term>
<term>Pyrimidines</term>
<term>Reverse Transcriptase Inhibitors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Anti-HIV Agents</term>
<term>Indazoles</term>
<term>Piperidines</term>
<term>Pyrimidines</term>
<term>Reverse Transcriptase Inhibitors</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>Indazoles</term>
<term>Piperidines</term>
<term>Pyrimidines</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</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>Indazoles</term>
<term>Inhibiteurs de la transcriptase inverse</term>
<term>Pipéridines</term>
<term>Pyrimidines</term>
</keywords>
<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Agents antiVIH</term>
<term>Inhibiteurs de la transcriptase inverse</term>
<term>Pipéridines</term>
<term>Pyrimidines</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Dose-Response Relationship, Drug</term>
<term>Drug Design</term>
<term>Humans</term>
<term>Microbial Sensitivity Tests</term>
<term>Molecular Structure</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Agents antiVIH</term>
<term>Conception de médicament</term>
<term>Humains</term>
<term>Indazoles</term>
<term>Inhibiteurs de la transcriptase inverse</term>
<term>Pipéridines</term>
<term>Pyrimidines</term>
<term>Relation dose-effet des médicaments</term>
<term>Relation structure-activité</term>
<term>Structure moléculaire</term>
<term>Tests de sensibilité microbienne</term>
<term>VIH (Virus de l'Immunodéficience Humaine)</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">A series of indazolyl-substituted piperidin-4-yl-aminopyrimidines (IPAPYs) were designed from two potent HIV-1 NNRTIs piperidin-4-yl-aminopyrimidine 3c and diaryl ether 4 as the lead compounds by molecular hybridization strategy. The target molecules 5a-q were synthesized and evaluated for their anti-HIV activities and cytotoxicities in MT-4 cells. 5a-q displayed moderate to excellent activities against wild-type (WT) HIV-1 with EC<sub>50</sub>
values ranging from 1.5 to 0.0064 μM. Among them, 5q was regarded as the most excellent compound against WT HIV-1 (EC<sub>50</sub>
= 6.4 nM, SI = 2500). And also, it displayed potent activities against K103 N (EC<sub>50</sub>
= 0.077 μM), Y181C (EC<sub>50</sub>
= 0.11 μM), E138K (EC<sub>50</sub>
= 0.057 μM), and moderate activity against double mutants RES056 (EC<sub>50</sub>
= 8.7 μM). Moreover, the structure-activity relationships (SARs) were summarized, and the molecular docking was performed to investigate the binding mode of IPAPYs and HIV-1 reverse transcriptase.</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Main/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000554 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Merge/biblio.hfd -nk 000554 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= Main |étape= Merge |type= RBID |clé= pubmed:31767136 |texte= Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Merge/RBID.i -Sk "pubmed:31767136" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Merge/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
This area was generated with Dilib version V0.6.33. |