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 : 002F04 ( Main/Exploration ); précédent : 002F03; suivant : 002F05Synthesis 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 [République populaire de Chine] ; Erik De Clercq [Belgique] ; Jan Balzarini [Belgique] ; Christophe Pannecouque [Belgique]Source :
- European journal of medicinal chemistry [ 0223-5234 ] ; 2009.
Descripteurs français
- Pascal (Inist)
- Synthèse chimique, In vitro, Composé non nucléoside, Virus HIV1, Inhibiteur reverse transcriptase, Antiviral, Activité biologique, Virus HIV2, RNA-directed DNA polymerase, Inhibiteur enzyme, Anti hiv, S-DABO, Pyrimidin-4-one(6-[3,5-diméthylbenzyl]-5-éthyl-2-[4-méthoxybenzylsulfanyl]), Pyrimidin-4-one(alkylsulfanyl benzyl).
English descriptors
- KwdEn :
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 IC50 range from 6.67 μM to 0.12 μM. Among them, 6-(3,5-dimethylbenzyl) analogue 5q exhibited the most potent anti-HIV-1 activity (IC50 = 0.12 μM, 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.
Affiliations:
- Belgique, République populaire de Chine
- Province du Brabant flamand
- Louvain
- Katholieke Universiteit Leuven
Links toward previous steps (curation, corpus...)
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- to stream PascalFrancis, to step Curation: 000768
- to stream PascalFrancis, to step Checkpoint: 000181
- to stream Main, to step Merge: 002F58
- to stream Main, to step Curation: 002F04
Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral</term>
<term>Biological activity</term>
<term>Chemical synthesis</term>
<term>Enzyme inhibitor</term>
<term>HIV-1 virus</term>
<term>HIV-2 virus</term>
<term>In vitro</term>
<term>Non nucleoside compound</term>
<term>RNA-directed DNA polymerase</term>
<term>Reverse transcriptase inhibitor</term>
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<keywords scheme="Pascal" xml:lang="fr"><term>Synthèse chimique</term>
<term>In vitro</term>
<term>Composé non nucléoside</term>
<term>Virus HIV1</term>
<term>Inhibiteur reverse transcriptase</term>
<term>Antiviral</term>
<term>Activité biologique</term>
<term>Virus HIV2</term>
<term>RNA-directed DNA polymerase</term>
<term>Inhibiteur enzyme</term>
<term>Anti hiv</term>
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<term>Pyrimidin-4-one(6-[3,5-diméthylbenzyl]-5-éthyl-2-[4-méthoxybenzylsulfanyl])</term>
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<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<sub>50</sub>
range from 6.67 μM to 0.12 μM. Among them, 6-(3,5-dimethylbenzyl) analogue 5q exhibited the most potent anti-HIV-1 activity (IC<sub>50</sub>
= 0.12 μM, 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>
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