Abstract
A novel synthetic route and anti-HIV activity evaluation of a new series of 2-(4-(2,4-dibromophenyl)-1,2,3-thiadiazol-5-ylthio)acetamide (TTA) derivatives are described. Bioactivity assay indicated that most of the title compounds showed good activities against HIV-1. In particular, compound 7c displayed the most potent anti-HIV-1 activity (EC(50)=36.4nM), inhibiting HIV-1 replication in MT-4 cells more effectively than NVP (by sevenfold) and DLV (by eightfold). The preliminary structure-activity relationships (SAR) of the newly synthesized congeners are discussed, and molecular modeling of compound 7c in complex with HIV-1 RT is described, allowing rationalization of some SAR conclusions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetamides / chemical synthesis*
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Acetamides / chemistry
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Acetamides / pharmacology
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Acquired Immunodeficiency Syndrome / drug therapy
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Anti-HIV Agents / chemical synthesis*
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Anti-HIV Agents / chemistry
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Anti-HIV Agents / pharmacology
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Binding Sites
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Cell Line
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Computer Simulation
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HIV Reverse Transcriptase / antagonists & inhibitors*
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HIV Reverse Transcriptase / metabolism
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HIV-1 / drug effects*
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Humans
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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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Thiadiazoles / chemical synthesis*
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Thiadiazoles / chemistry
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Thiadiazoles / pharmacology
Substances
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Acetamides
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Anti-HIV Agents
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N-(2-chloropyridin-3-yl)-2-(4-(2,4-dibromophenyl)-1,2,3-thiadiazol-5-ylthio)acetamide
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Reverse Transcriptase Inhibitors
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Thiadiazoles
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reverse transcriptase, Human immunodeficiency virus 1
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HIV Reverse Transcriptase