Abstract
A series of novel, azacyclic ureas which are highly potent inhibitors of the HIV-1 protease (IC50 = 4.1 to < 0.5 nM) were synthesized. Aqueous solubilities of this series of compounds were improved by incorporating polar functional groups at the P1' P2 and P2' positions. These compounds also possess good anti-viral activity by inhibition of the cytopathic effect of HIV-13B in MT-4 cells in vitro.
MeSH terms
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Amino Acid Sequence
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Animals
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Biological Availability
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Cell Line
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HIV Protease / genetics
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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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HIV-1 / enzymology*
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Humans
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Male
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Molecular Sequence Data
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Rats
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Rats, Sprague-Dawley
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / genetics
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Urea / analogs & derivatives*
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Urea / chemical synthesis
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Urea / pharmacokinetics
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Urea / pharmacology
Substances
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HIV Protease Inhibitors
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Recombinant Proteins
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Urea
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HIV Protease