Discovery of HCV NS5B thumb site I inhibitors: core-refining from benzimidazole to indole scaffold.
Identifieur interne : 001329 ( Main/Exploration ); précédent : 001328; suivant : 001330Discovery of HCV NS5B thumb site I inhibitors: core-refining from benzimidazole to indole scaffold.
Auteurs : Fabao Zhao [République populaire de Chine] ; Na Liu [République populaire de Chine] ; Peng Zhan [République populaire de Chine] ; Xuemei Jiang [République populaire de Chine] ; Xinyong Liu [République populaire de Chine]Source :
- European journal of medicinal chemistry [ 1768-3254 ] ; 2015.
Descripteurs français
- KwdFr :
- MESH :
- antagonistes et inhibiteurs : Protéines virales non structurales.
- métabolisme : Protéines virales non structurales.
- pharmacologie : Antiviraux.
- Antiviraux, Benzimidazoles, Cristallographie aux rayons X, Indoles, Protéines virales non structurales, Relation structure-activité.
English descriptors
- KwdEn :
- Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Benzimidazoles (chemistry), Crystallography, X-Ray, Indoles (chemistry), Structure-Activity Relationship, Viral Nonstructural Proteins (antagonists & inhibitors), Viral Nonstructural Proteins (chemistry), Viral Nonstructural Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Viral Nonstructural Proteins.
- chemical , chemistry : Antiviral Agents, Benzimidazoles, Indoles, Viral Nonstructural Proteins.
- chemical , metabolism : Viral Nonstructural Proteins.
- chemical , pharmacology : Antiviral Agents.
- Crystallography, X-Ray, Structure-Activity Relationship.
Abstract
Hepatitis C virus (HCV) NS5B RNA-depended-RNA-polymerase (RdRp) is an essential enzyme in HCV viral replication and has no functional equivalent in mammalian cells. Several classes of nucleoside and non-nucleoside inhibitors, targeting the different allosteric sites, have demonstrated efficacy in clinical trials. Compared to other allosteric sites, thumb site I is a more compelling allosteric target with a significant number of inhibitors in clinical trials. Among them, indole analogues are the most important series of NS5B thumb site I inhibitors with considerable antiviral activity. This review focuses on the discovery and development of indole inhibitors targeting on NS5B thumb site I. Five fundamental principles, the general structure-activity relationships (SARs) model of indole scaffold, were summarized, which could pave the way for further structural optimization of indole-based anti-HCV agents.
DOI: 10.1016/j.ejmech.2015.03.012
PubMed: 25768704
Affiliations:
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Several classes of nucleoside and non-nucleoside inhibitors, targeting the different allosteric sites, have demonstrated efficacy in clinical trials. Compared to other allosteric sites, thumb site I is a more compelling allosteric target with a significant number of inhibitors in clinical trials. Among them, indole analogues are the most important series of NS5B thumb site I inhibitors with considerable antiviral activity. This review focuses on the discovery and development of indole inhibitors targeting on NS5B thumb site I. Five fundamental principles, the general structure-activity relationships (SARs) model of indole scaffold, were summarized, which could pave the way for further structural optimization of indole-based anti-HCV agents. </div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Zhao, Fabao" sort="Zhao, Fabao" uniqKey="Zhao F" first="Fabao" last="Zhao">Fabao Zhao</name></noRegion><name sortKey="Jiang, Xuemei" sort="Jiang, Xuemei" uniqKey="Jiang X" first="Xuemei" last="Jiang">Xuemei Jiang</name><name sortKey="Liu, Na" sort="Liu, Na" uniqKey="Liu N" first="Na" last="Liu">Na Liu</name><name sortKey="Liu, Xinyong" sort="Liu, Xinyong" uniqKey="Liu X" first="Xinyong" last="Liu">Xinyong Liu</name><name sortKey="Zhan, Peng" sort="Zhan, Peng" uniqKey="Zhan P" first="Peng" last="Zhan">Peng Zhan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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