Abstract
A novel class of HCV NS5B RNA dependent RNA polymerase inhibitors containing 2,3,4,9-tetrahydro-1H-carbazole and 1,2,3,4-tetrahydro-cyclopenta[b]indole scaffolds were designed and synthesized. Optimization of the aromatic region showed preference for 5,8-disubstitution pattern in both the scaffolds examined while favoring the n-propyl moiety for the C-1 position. 1,2,3,4-tetrahydro-cyclopenta[b]indole scaffold was slightly more potent than the corresponding 2,3,4,9-tetrahydro-1H-carbazole and analogue 36 displayed an IC50 of 550 nM against HCV NS5B enzyme.
MeSH terms
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Antiviral Agents / chemical synthesis*
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology
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Carbazoles* / chemical synthesis
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Carbazoles* / chemistry
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Carbazoles* / pharmacology
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Cyclopentanes* / chemical synthesis
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Cyclopentanes* / chemistry
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Cyclopentanes* / pharmacology
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Drug Design
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Indoles* / chemical synthesis
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Indoles* / chemistry
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Indoles* / pharmacology
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Microbial Sensitivity Tests
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Molecular Structure
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RNA-Dependent RNA Polymerase / antagonists & inhibitors*
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Reverse Transcriptase Inhibitors / chemical synthesis*
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Reverse Transcriptase Inhibitors / chemistry
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Reverse Transcriptase Inhibitors / pharmacology
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Structure-Activity Relationship
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Viral Nonstructural Proteins / drug effects*
Substances
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1,2,3,4-tetrahydro-cyclopenta(b)indole
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2,3,4,9-tetrahydro-1H-carbazole
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Antiviral Agents
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Carbazoles
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Cyclopentanes
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Indoles
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Reverse Transcriptase Inhibitors
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Viral Nonstructural Proteins
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NS-5 protein, hepatitis C virus
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RNA-Dependent RNA Polymerase