Abstract
A series of potent novel dihydroxypyridopyrazine-1,6-dione HIV-1 integrase inhibitors was identified. These compounds inhibited the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 6 is active against replication of HIV with a CIC(95) of 0.31 microM and exhibits no shift in potency in the presence of 50% normal human serum. It displays a good pharmacokinetic profile when dosed in rats and no covalent binding with microsomal proteins in both in vitro and in vivo models.
MeSH terms
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Animals
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Benzene / chemistry
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Cell Line
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HIV / drug effects
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HIV / enzymology
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HIV / physiology
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HIV Integrase Inhibitors / chemical synthesis
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HIV Integrase Inhibitors / chemistry*
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HIV Integrase Inhibitors / pharmacokinetics
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HIV Integrase Inhibitors / pharmacology*
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Humans
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Microsomes, Liver / drug effects
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Models, Molecular
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Molecular Structure
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Pyrazines / chemical synthesis
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Pyrazines / chemistry*
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Pyrazines / pharmacokinetics
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Pyrazines / pharmacology*
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Rats
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Structure-Activity Relationship
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Virus Replication / drug effects
Substances
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HIV Integrase Inhibitors
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Pyrazines
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Benzene