Abstract
A combinatorial library of 300HIV protease inhibitors has been synthesized. The library was screened against recombinant wild-type and mutant HIV-1 protease enzymes. The pharmacokinetics of the library was evaluated by dosing in dogs. Compounds that are notably more potent than indinavir and have favorable pharmacokinetic properties were identified.
MeSH terms
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Animals
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Area Under Curve
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Combinatorial Chemistry Techniques
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Dogs
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Drug Evaluation, Preclinical
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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-1 / drug effects
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HIV-1 / genetics
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HIV-1 / growth & development
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Humans
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Indinavir / analogs & derivatives*
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Indinavir / pharmacokinetics
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Indinavir / pharmacology
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Inhibitory Concentration 50
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Metabolic Clearance Rate
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Mutation
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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