SrasV1, Main, Exploration, bibRecord, 000A86

Synthesis and biological evaluation of dihydroquinazoline-2-amines as potent non-nucleoside reverse transcriptase inhibitors of wild-type and mutant HIV-1 strains.

Identifieur interne : 000A86 ( Main/Exploration ); précédent : 000A85; suivant : 000A87

Synthesis and biological evaluation of dihydroquinazoline-2-amines as potent non-nucleoside reverse transcriptase inhibitors of wild-type and mutant HIV-1 strains.

Auteurs : Kaijun Jin [République populaire de Chine] ; Yali Sang [République populaire de Chine] ; Sheng Han [République populaire de Chine] ; Erik De Clercq [Belgique] ; Christophe Pannecouque [Belgique] ; Ge Meng [République populaire de Chine] ; Fener Chen [République populaire de Chine]

Source :

European journal of medicinal chemistry [ 1768-3254 ] ; 2019.

RBID : pubmed:31091477

Descripteurs français

English descriptors

KwdEn :
- Amines (chemical synthesis), Amines (metabolism), Amines (pharmacology), Amines (toxicity), Anti-HIV Agents (chemical synthesis), Anti-HIV Agents (metabolism), Anti-HIV Agents (pharmacology), Anti-HIV Agents (toxicity), Binding Sites, Cell Line, Tumor, HIV Reverse Transcriptase (antagonists & inhibitors), HIV Reverse Transcriptase (chemistry), HIV Reverse Transcriptase (metabolism), HIV-1 (enzymology), Humans, Molecular Docking Simulation, Molecular Structure, Protein Binding, Quinazolines (chemical synthesis), Quinazolines (metabolism), Quinazolines (pharmacology), Quinazolines (toxicity), Reverse Transcriptase Inhibitors (chemical synthesis), Reverse Transcriptase Inhibitors (metabolism), Reverse Transcriptase Inhibitors (pharmacology), Reverse Transcriptase Inhibitors (toxicity), Structure-Activity Relationship.
MESH :
- chemical , antagonists & inhibitors : HIV Reverse Transcriptase.
- chemical , chemical synthesis : Amines, Anti-HIV Agents, Quinazolines, Reverse Transcriptase Inhibitors.
- chemical , chemistry : HIV Reverse Transcriptase.
- chemical , metabolism : Amines, Anti-HIV Agents, HIV Reverse Transcriptase, Quinazolines, Reverse Transcriptase Inhibitors.
- chemical , pharmacology : Amines, Anti-HIV Agents, Quinazolines, Reverse Transcriptase Inhibitors.
- chemical , toxicity : Amines, Anti-HIV Agents, Quinazolines, Reverse Transcriptase Inhibitors.
- enzymology : HIV-1.
- Binding Sites, Cell Line, Tumor, Humans, Molecular Docking Simulation, Molecular Structure, Protein Binding, Structure-Activity Relationship.

Abstract

A novel series of dihydroquinazolin-2-amine derivatives were synthesized and evaluated for their anti-HIV-1 activity in MT-4 cell cultures. All of the molecules were active against wild-type HIV-1 with EC₅₀ values ranging from 0.61 μM to 0.84 nM. The most potent inhibitor, compound 4b, had an EC₅₀ value of 0.84 nM against HIV-1 strain IIIB, and thus was more active than the reference drugs efavirenz and etravirine. Moreover, most of the compounds maintained high activity (low-micromolar EC₅₀ values) against strains bearing the reverse transcriptase (RT) E138K mutation. Compound 4b had EC₅₀ values of 3.5 nM and 66 nM against non-nucleoside reverse transcriptase inhibitor-resistant strains bearing the RT E138K and RES056 mutations. In enzyme activity assays, compound 4b exhibited an IC₅₀ value of 10 nM against HIV-1 RT. Preliminary SARs and molecular docking studies provide valuable insights for further optimization.

DOI: 10.1016/j.ejmech.2019.05.011
PubMed: 31091477

Affiliations:

Belgique, République populaire de Chine

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Synthesis and biological evaluation of dihydroquinazoline-2-amines as potent non-nucleoside reverse transcriptase inhibitors of wild-type and mutant HIV-1 strains.</title>
<author><name sortKey="Jin, Kaijun" sort="Jin, Kaijun" uniqKey="Jin K" first="Kaijun" last="Jin">Kaijun Jin</name>
<affiliation wicri:level="1"><nlm:affiliation>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433</wicri:regionArea>
<wicri:noRegion>200433</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sang, Yali" sort="Sang, Yali" uniqKey="Sang Y" first="Yali" last="Sang">Yali Sang</name>
<affiliation wicri:level="1"><nlm:affiliation>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433</wicri:regionArea>
<wicri:noRegion>200433</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Han, Sheng" sort="Han, Sheng" uniqKey="Han S" first="Sheng" last="Han">Sheng Han</name>
<affiliation wicri:level="1"><nlm:affiliation>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433</wicri:regionArea>
<wicri:noRegion>200433</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, Herestraat 49, B-3000, Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000, Leuven</wicri:regionArea>
<wicri:noRegion>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, Herestraat 49, B-3000, Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</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>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433</wicri:regionArea>
<wicri:noRegion>200433</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chen, Fener" sort="Chen, Fener" uniqKey="Chen F" first="Fener" last="Chen">Fener Chen</name>
<affiliation wicri:level="1"><nlm:affiliation>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, PR China. Electronic address: rfchen@fudan.edu.cn.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433</wicri:regionArea>
<wicri:noRegion>200433</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2019">2019</date>
<idno type="RBID">pubmed:31091477</idno>
<idno type="pmid">31091477</idno>
<idno type="doi">10.1016/j.ejmech.2019.05.011</idno>
<idno type="wicri:Area/PubMed/Corpus">000905</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000905</idno>
<idno type="wicri:Area/PubMed/Curation">000905</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000905</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000854</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000854</idno>
<idno type="wicri:Area/Ncbi/Merge">003047</idno>
<idno type="wicri:Area/Ncbi/Curation">003047</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">003047</idno>
<idno type="wicri:Area/Main/Merge">000A87</idno>
<idno type="wicri:Area/Main/Curation">000A86</idno>
<idno type="wicri:Area/Main/Exploration">000A86</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Synthesis and biological evaluation of dihydroquinazoline-2-amines as potent non-nucleoside reverse transcriptase inhibitors of wild-type and mutant HIV-1 strains.</title>
<author><name sortKey="Jin, Kaijun" sort="Jin, Kaijun" uniqKey="Jin K" first="Kaijun" last="Jin">Kaijun Jin</name>
<affiliation wicri:level="1"><nlm:affiliation>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433</wicri:regionArea>
<wicri:noRegion>200433</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sang, Yali" sort="Sang, Yali" uniqKey="Sang Y" first="Yali" last="Sang">Yali Sang</name>
<affiliation wicri:level="1"><nlm:affiliation>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433</wicri:regionArea>
<wicri:noRegion>200433</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Han, Sheng" sort="Han, Sheng" uniqKey="Han S" first="Sheng" last="Han">Sheng Han</name>
<affiliation wicri:level="1"><nlm:affiliation>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433</wicri:regionArea>
<wicri:noRegion>200433</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, Herestraat 49, B-3000, Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000, Leuven</wicri:regionArea>
<wicri:noRegion>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, Herestraat 49, B-3000, Leuven, Belgium.</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</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>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, PR China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433</wicri:regionArea>
<wicri:noRegion>200433</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chen, Fener" sort="Chen, Fener" uniqKey="Chen F" first="Fener" last="Chen">Fener Chen</name>
<affiliation wicri:level="1"><nlm:affiliation>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai, 200433, PR China. Electronic address: rfchen@fudan.edu.cn.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Engineering Center ofCatalysis and SynthesisforChiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433, PR China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, 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="2019" type="published">2019</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amines (chemical synthesis)</term>
<term>Amines (metabolism)</term>
<term>Amines (pharmacology)</term>
<term>Amines (toxicity)</term>
<term>Anti-HIV Agents (chemical synthesis)</term>
<term>Anti-HIV Agents (metabolism)</term>
<term>Anti-HIV Agents (pharmacology)</term>
<term>Anti-HIV Agents (toxicity)</term>
<term>Binding Sites</term>
<term>Cell Line, Tumor</term>
<term>HIV Reverse Transcriptase (antagonists & inhibitors)</term>
<term>HIV Reverse Transcriptase (chemistry)</term>
<term>HIV Reverse Transcriptase (metabolism)</term>
<term>HIV-1 (enzymology)</term>
<term>Humans</term>
<term>Molecular Docking Simulation</term>
<term>Molecular Structure</term>
<term>Protein Binding</term>
<term>Quinazolines (chemical synthesis)</term>
<term>Quinazolines (metabolism)</term>
<term>Quinazolines (pharmacology)</term>
<term>Quinazolines (toxicity)</term>
<term>Reverse Transcriptase Inhibitors (chemical synthesis)</term>
<term>Reverse Transcriptase Inhibitors (metabolism)</term>
<term>Reverse Transcriptase Inhibitors (pharmacology)</term>
<term>Reverse Transcriptase Inhibitors (toxicity)</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Agents antiVIH (métabolisme)</term>
<term>Agents antiVIH (pharmacologie)</term>
<term>Agents antiVIH (synthèse chimique)</term>
<term>Agents antiVIH (toxicité)</term>
<term>Amines (métabolisme)</term>
<term>Amines (pharmacologie)</term>
<term>Amines (synthèse chimique)</term>
<term>Amines (toxicité)</term>
<term>Humains</term>
<term>Inhibiteurs de la transcriptase inverse (métabolisme)</term>
<term>Inhibiteurs de la transcriptase inverse (pharmacologie)</term>
<term>Inhibiteurs de la transcriptase inverse (synthèse chimique)</term>
<term>Inhibiteurs de la transcriptase inverse (toxicité)</term>
<term>Liaison aux protéines</term>
<term>Lignée cellulaire tumorale</term>
<term>Quinazolines (métabolisme)</term>
<term>Quinazolines (pharmacologie)</term>
<term>Quinazolines (synthèse chimique)</term>
<term>Quinazolines (toxicité)</term>
<term>Relation structure-activité</term>
<term>Simulation de docking moléculaire</term>
<term>Sites de fixation</term>
<term>Structure moléculaire</term>
<term>Transcriptase inverse du VIH ()</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) (enzymologie)</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>Amines</term>
<term>Anti-HIV Agents</term>
<term>Quinazolines</term>
<term>Reverse Transcriptase Inhibitors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>HIV Reverse Transcriptase</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Amines</term>
<term>Anti-HIV Agents</term>
<term>HIV Reverse Transcriptase</term>
<term>Quinazolines</term>
<term>Reverse Transcriptase Inhibitors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Amines</term>
<term>Anti-HIV Agents</term>
<term>Quinazolines</term>
<term>Reverse Transcriptase Inhibitors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Amines</term>
<term>Anti-HIV Agents</term>
<term>Quinazolines</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="enzymologie" xml:lang="fr"><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>HIV-1</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Agents antiVIH</term>
<term>Amines</term>
<term>Inhibiteurs de la transcriptase inverse</term>
<term>Quinazolines</term>
<term>Transcriptase inverse du VIH</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Agents antiVIH</term>
<term>Amines</term>
<term>Inhibiteurs de la transcriptase inverse</term>
<term>Quinazolines</term>
</keywords>
<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Agents antiVIH</term>
<term>Amines</term>
<term>Inhibiteurs de la transcriptase inverse</term>
<term>Quinazolines</term>
</keywords>
<keywords scheme="MESH" qualifier="toxicité" xml:lang="fr"><term>Agents antiVIH</term>
<term>Amines</term>
<term>Inhibiteurs de la transcriptase inverse</term>
<term>Quinazolines</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term>
<term>Cell Line, Tumor</term>
<term>Humans</term>
<term>Molecular Docking Simulation</term>
<term>Molecular Structure</term>
<term>Protein Binding</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Humains</term>
<term>Liaison aux protéines</term>
<term>Lignée cellulaire tumorale</term>
<term>Relation structure-activité</term>
<term>Simulation de docking moléculaire</term>
<term>Sites de fixation</term>
<term>Structure moléculaire</term>
<term>Transcriptase inverse du VIH</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">A novel series of dihydroquinazolin-2-amine derivatives were synthesized and evaluated for their anti-HIV-1 activity in MT-4 cell cultures. All of the molecules were active against wild-type HIV-1 with EC<sub>50</sub>
 values ranging from 0.61 μM to 0.84 nM. The most potent inhibitor, compound 4b, had an EC<sub>50</sub>
 value of 0.84 nM against HIV-1 strain IIIB, and thus was more active than the reference drugs efavirenz and etravirine. Moreover, most of the compounds maintained high activity (low-micromolar EC<sub>50</sub>
 values) against strains bearing the reverse transcriptase (RT) E138K mutation. Compound 4b had EC<sub>50</sub>
 values of 3.5 nM and 66 nM against non-nucleoside reverse transcriptase inhibitor-resistant strains bearing the RT E138K and RES056 mutations. In enzyme activity assays, compound 4b exhibited an IC<sub>50</sub>
 value of 10 nM against HIV-1 RT. Preliminary SARs and molecular docking studies provide valuable insights for further optimization.</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="Jin, Kaijun" sort="Jin, Kaijun" uniqKey="Jin K" first="Kaijun" last="Jin">Kaijun Jin</name>
</noRegion>
<name sortKey="Chen, Fener" sort="Chen, Fener" uniqKey="Chen F" first="Fener" last="Chen">Fener Chen</name>
<name sortKey="Han, Sheng" sort="Han, Sheng" uniqKey="Han S" first="Sheng" last="Han">Sheng Han</name>
<name sortKey="Meng, Ge" sort="Meng, Ge" uniqKey="Meng G" first="Ge" last="Meng">Ge Meng</name>
<name sortKey="Sang, Yali" sort="Sang, Yali" uniqKey="Sang Y" first="Yali" last="Sang">Yali Sang</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="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 000A86 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000A86 | 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:31091477
   |texte=   Synthesis and biological evaluation of dihydroquinazoline-2-amines as potent non-nucleoside reverse transcriptase inhibitors of wild-type and mutant HIV-1 strains.
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:31091477" \
       | 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

Synthesis and biological evaluation of dihydroquinazoline-2-amines as potent non-nucleoside reverse transcriptase inhibitors of wild-type and mutant HIV-1 strains.

Synthesis and biological evaluation of dihydroquinazoline-2-amines as potent non-nucleoside reverse transcriptase inhibitors of wild-type and mutant HIV-1 strains.

Source :

Descripteurs français

English descriptors

Abstract

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

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

	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.