Abstract
Cyclic ureas containing 3-aminoindazole P2/P2' groups are extremely potent inhibitors of HIV protease. The parent 3-aminoindazole 6 showed a Ki < 0.01 nM but poor translation of enzyme activity to antiviral activity was observed. A series of 3-alkylaminoindazoles revealed that translation improved with increasing lipophilicity. An X-ray crystal structure of 6 bound to HIV protease was obtained.
MeSH terms
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Crystallography, X-Ray
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Drug Design
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HIV Protease / chemistry
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HIV Protease / metabolism*
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HIV Protease Inhibitors / chemical synthesis
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HIV Protease Inhibitors / chemistry*
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HIV Protease Inhibitors / pharmacology
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Indazoles / chemistry*
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Indazoles / pharmacology
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Indicators and Reagents
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Models, Molecular
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Molecular Structure
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Structure-Activity Relationship
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Urea / analogs & derivatives*
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Urea / chemistry
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Urea / pharmacology
Substances
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HIV Protease Inhibitors
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Indazoles
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Indicators and Reagents
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Urea
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HIV Protease