SrasV1, Main, Exploration, bibRecord, 000554

Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities.

Identifieur interne : 000554 ( Main/Exploration ); précédent : 000553; suivant : 000555

Indazolyl-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.

RBID : pubmed:31767136

Descripteurs français

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

Affiliations:

Belgique, République populaire de Chine

Le document en format XML

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<term>Conception de médicament</term>
<term>Humains</term>
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<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>
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<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>
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<name sortKey="Liu, Gen Yan" sort="Liu, Gen Yan" uniqKey="Liu G" first="Gen-Yan" last="Liu">Gen-Yan Liu</name>
<name sortKey="Meng, Ge" sort="Meng, Ge" uniqKey="Meng G" first="Ge" last="Meng">Ge Meng</name>
<name sortKey="Tang, Jia Fan" sort="Tang, Jia Fan" uniqKey="Tang J" first="Jia-Fan" last="Tang">Jia-Fan Tang</name>
<name sortKey="Wu, Feng Shou" sort="Wu, Feng Shou" uniqKey="Wu F" first="Feng-Shou" last="Wu">Feng-Shou Wu</name>
<name sortKey="Xu, Zhi Qiang" sort="Xu, Zhi Qiang" uniqKey="Xu Z" first="Zhi-Qiang" last="Xu">Zhi-Qiang Xu</name>
<name sortKey="Zhu, Yuan Yuan" sort="Zhu, Yuan Yuan" uniqKey="Zhu Y" first="Yuan-Yuan" last="Zhu">Yuan-Yuan Zhu</name>
</country>
<country name="Belgique"><noRegion><name sortKey="Pannecouque, Christophe" sort="Pannecouque, Christophe" uniqKey="Pannecouque C" first="Christophe" last="Pannecouque">Christophe Pannecouque</name>
</noRegion>
</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 000554 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/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=   Exploration
   |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/Exploration/RBID.i   -Sk "pubmed:31767136" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/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

Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities.

Indazolyl-substituted piperidin-4-yl-aminopyrimidines as HIV-1 NNRTIs: Design, synthesis and biological activities.

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Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	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.