Abstract
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are key elements of multidrug regimens, called HAART (Highly Active Antiretroviral Therapy), that are used to treat HIV-1 infections. Elucidation of the structure-activity relationships of the thiocarbamate moiety of the previous published lead compound 2 provided a series of novel tetrahydroquinoline derivatives as potent inhibitors of HIV-1 RT with nanomolar intrinsic activity on the WT and key mutant enzymes and potent antiviral activity in infected cells. The SAR optimization, mutation profiles, preparation of compounds, and pharmacokinetic profile of compounds are described.
MeSH terms
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Allosteric Site
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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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Crystallography, X-Ray
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HIV Reverse Transcriptase / antagonists & inhibitors*
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HIV Reverse Transcriptase / metabolism
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Molecular Conformation
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Mutant Proteins / antagonists & inhibitors
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Mutant Proteins / metabolism
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Quinolines / chemical synthesis
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Quinolines / chemistry*
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Quinolines / 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
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Thiocarbamates / chemistry
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Thiocarbamates / pharmacology
Substances
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Anti-HIV Agents
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Mutant Proteins
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Quinolines
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Reverse Transcriptase Inhibitors
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Thiocarbamates
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reverse transcriptase, Human immunodeficiency virus 1
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HIV Reverse Transcriptase