Abstract
The presence of a structural recognition motif for the nucleoside P2 transporter in a library of pyrimidine and triazine non-nucleoside HIV-1 reverse transcriptase inhibitors, prompted for the evaluation of antitrypanosomal activity. It was demonstrated that the structure-activity relationship for anti-HIV and antitrypanosomal activity was different. Optimization in the diaryl triazine series led to 6-(mesityloxy)-N2-phenyl-1,3,5-triazine-2,4-diamine (69), a compound with potent in vitro and moderate in vivo antitrypanosomal activity.
Keywords:
African trypanosomiasis; Antitrypanosomal activity; NNRTIs; Triazines; Trypanosoma brucei.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Cell Line
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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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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HIV-1 / enzymology
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Humans
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Microbial Sensitivity Tests
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Molecular Structure
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Parasitic Sensitivity Tests
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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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Trypanocidal Agents / chemical synthesis
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Trypanocidal Agents / chemistry
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Trypanocidal Agents / pharmacology*
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Trypanosoma brucei brucei / drug effects*
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Trypanosoma brucei rhodesiense / drug effects*
Substances
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Anti-HIV Agents
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Reverse Transcriptase Inhibitors
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Trypanocidal Agents
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HIV Reverse Transcriptase