Abstract
New non-nucleoside reverse transcriptase inhibitors (NNRTI), which are similar in structure to earlier described di(arylamino)pyrimidines but featuring a 2,6-di(arylamino)-3-fluoropyridine, 2,4-di(arylamino)-5-fluoropyrimidine, or 1,3-di(arylamino)-4-fluorobenzene moiety instead of a 2,4-disubstituted pyrimidine moiety, are reported. The short and practical synthesis of novel NNRTI relies on two sequential Pd-catalyzed aminations as the key steps. It is demonstrated through direct comparison with reference compounds that the presence of a fluorine atom increases the in vitro anti-HIV activity, both against the wild type virus and drug-resistant mutant strains.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Aniline Compounds / chemistry
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Aniline Compounds / pharmacology*
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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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Dose-Response Relationship, Drug
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Fluorobenzenes / chemical synthesis
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Fluorobenzenes / chemistry
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Fluorobenzenes / pharmacology
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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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Pyridines / chemical synthesis
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Pyridines / chemistry
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Pyridines / pharmacology*
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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
Substances
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Aniline Compounds
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Anti-HIV Agents
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Fluorobenzenes
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Pyridines
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Reverse Transcriptase Inhibitors
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HIV Reverse Transcriptase