Design and efficient synthesis of novel arylthiourea derivatives as potent hepatitis C virus inhibitors.
Identifieur interne : 002006 ( Ncbi/Curation ); précédent : 002005; suivant : 002007Design and efficient synthesis of novel arylthiourea derivatives as potent hepatitis C virus inhibitors.
Auteurs : Iou-Jiun Kang [République populaire de Chine] ; Li-Wen Wang ; Sheng-Ju Hsu ; Chung-Chi Lee ; Yen-Chun Lee ; Yen-Shian Wu ; Andrew Yueh ; Jing-Chyi Wang ; Tsu-An Hsu ; Yu-Sheng Chao ; Jyh-Haur ChernSource :
- Bioorganic & medicinal chemistry letters [ 1464-3405 ] ; 2009.
Descripteurs français
- KwdFr :
- Antiviraux (), Antiviraux (synthèse chimique), Antiviraux (toxicité), Carbazoles (), Carbazoles (pharmacologie), Carbazoles (synthèse chimique), Conception de médicament, Hepacivirus (), Humains, Lignée cellulaire tumorale, Relation structure-activité, Réplication virale (), Thiourée (), Thiourée (analogues et dérivés), Thiourée (pharmacologie), Thiourée (synthèse chimique), Thiourée (toxicité).
- MESH :
- analogues et dérivés : Thiourée.
- pharmacologie : Carbazoles, Thiourée.
- synthèse chimique : Antiviraux, Carbazoles, Thiourée.
- toxicité : Antiviraux, Thiourée.
- Antiviraux, Carbazoles, Conception de médicament, Hepacivirus, Humains, Lignée cellulaire tumorale, Relation structure-activité, Réplication virale, Thiourée.
English descriptors
- KwdEn :
- Antiviral Agents (chemical synthesis), Antiviral Agents (chemistry), Antiviral Agents (toxicity), Carbazoles (chemical synthesis), Carbazoles (chemistry), Carbazoles (pharmacology), Cell Line, Tumor, Drug Design, Hepacivirus (drug effects), Humans, Structure-Activity Relationship, Thiourea (analogs & derivatives), Thiourea (chemical synthesis), Thiourea (chemistry), Thiourea (pharmacology), Thiourea (toxicity), Virus Replication (drug effects).
- MESH :
- chemical , analogs & derivatives : Thiourea.
- chemical , chemical synthesis : Antiviral Agents, Carbazoles, Thiourea.
- chemical , chemistry : Antiviral Agents, Carbazoles, Thiourea.
- chemical , pharmacology : Carbazoles, Thiourea.
- chemical , toxicity : Antiviral Agents, Thiourea.
- drug effects : Hepacivirus, Virus Replication.
- Cell Line, Tumor, Drug Design, Humans, Structure-Activity Relationship.
Abstract
A novel class of arylthiourea HCV inhibitors bearing various functionalities, such as cyclic urea, cyclic thiourea, urea, and thiourea, on the alkyl linker were designed and synthesized. Herein we report the synthesis and structure-activity relationships (SARs) of this novel class of arylthiourea derivatives that showed potent inhibitory activities against HCV in the cell-based subgenomic HCV replicon assay. Among compounds tested, the new carbazole derivative 64, which has an eight-carbon linkage between the phenyl and carbazole rings and a tolyl group at the N-9 position of carbazole, was found to possess strong anti-HCV activity (EC50=0.031 microM), lower cytotoxicity (CC50 >50 microM), and higher selectivity index (SI >1612) compared to its derivatives.
DOI: 10.1016/j.bmcl.2009.09.037
PubMed: 19796940
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pubmed:19796940Le document en format XML
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Chao</name></author><author><name sortKey="Chern, Jyh Haur" sort="Chern, Jyh Haur" uniqKey="Chern J" first="Jyh-Haur" last="Chern">Jyh-Haur Chern</name></author></analytic><series><title level="j">Bioorganic & medicinal chemistry letters</title><idno type="eISSN">1464-3405</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (chemical synthesis)</term><term>Antiviral Agents (chemistry)</term><term>Antiviral Agents (toxicity)</term><term>Carbazoles (chemical synthesis)</term><term>Carbazoles (chemistry)</term><term>Carbazoles (pharmacology)</term><term>Cell Line, Tumor</term><term>Drug Design</term><term>Hepacivirus (drug effects)</term><term>Humans</term><term>Structure-Activity Relationship</term><term>Thiourea (analogs & derivatives)</term><term>Thiourea (chemical synthesis)</term><term>Thiourea (chemistry)</term><term>Thiourea 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Agents</term><term>Carbazoles</term><term>Thiourea</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term><term>Carbazoles</term><term>Thiourea</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Carbazoles</term><term>Thiourea</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Antiviral Agents</term><term>Thiourea</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Thiourée</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Hepacivirus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Carbazoles</term><term>Thiourée</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Antiviraux</term><term>Carbazoles</term><term>Thiourée</term></keywords><keywords scheme="MESH" qualifier="toxicité" xml:lang="fr"><term>Antiviraux</term><term>Thiourée</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Drug Design</term><term>Humans</term><term>Structure-Activity Relationship</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Antiviraux</term><term>Carbazoles</term><term>Conception de médicament</term><term>Hepacivirus</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Relation structure-activité</term><term>Réplication virale</term><term>Thiourée</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A novel class of arylthiourea HCV inhibitors bearing various functionalities, such as cyclic urea, cyclic thiourea, urea, and thiourea, on the alkyl linker were designed and synthesized. Herein we report the synthesis and structure-activity relationships (SARs) of this novel class of arylthiourea derivatives that showed potent inhibitory activities against HCV in the cell-based subgenomic HCV replicon assay. Among compounds tested, the new carbazole derivative 64, which has an eight-carbon linkage between the phenyl and carbazole rings and a tolyl group at the N-9 position of carbazole, was found to possess strong anti-HCV activity (EC50=0.031 microM), lower cytotoxicity (CC50 >50 microM), and higher selectivity index (SI >1612) compared to its derivatives.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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