Abstract
Substitution of the t-butylcarboxamide substituent in analogues of the HIV protease inhibitor (PI) Indinavir with a trifluoroethylamide moiety confers greater potency against both the wild-type (NL4-3) virus and PI-resistant HIV. The trifluoroethyl substituent also affords a slower clearance rate in vivo (dogs); however, this may be due to more potent inhibition of at least two P450 isoforms.
MeSH terms
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Animals
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Dogs
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Drug Resistance, Multiple*
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HIV / drug effects*
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HIV Protease / drug effects
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HIV Protease Inhibitors / administration & dosage
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HIV Protease Inhibitors / chemical synthesis*
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HIV Protease Inhibitors / pharmacokinetics
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HIV Protease Inhibitors / pharmacology
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Humans
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Indinavir / administration & dosage
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Indinavir / analogs & derivatives*
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Indinavir / pharmacokinetics
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Inhibitory Concentration 50
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Metabolic Clearance Rate
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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HIV Protease Inhibitors
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Indinavir
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HIV Protease