Abstract
A series of benzyl pyridazinones were evaluated as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Several members of this series showed good activity against the wild-type virus and NNRTI-resistant viruses. The binding of inhibitor 5a to HIV-RT was analyzed by surface plasmon resonance spectroscopy. Pharmacokinetic studies of 5a in rat and dog demonstrated that this compound has good oral bioavailability in animal species. The crystal structure of a complex between HIV-RT and inhibitor 4c is also described.
MeSH terms
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Animals
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Dogs
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Drug Resistance, Viral / drug effects
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HIV Reverse Transcriptase / antagonists & inhibitors*
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Inhibitory Concentration 50
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Molecular Structure
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Pyridazines* / chemical synthesis
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Pyridazines* / chemistry
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Pyridazines* / pharmacology
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Rats
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Reverse Transcriptase Inhibitors* / chemical synthesis
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Reverse Transcriptase Inhibitors* / chemistry
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Reverse Transcriptase Inhibitors* / pharmacology
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Structure-Activity Relationship
Substances
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Pyridazines
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Reverse Transcriptase Inhibitors
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reverse transcriptase, Human immunodeficiency virus 1
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HIV Reverse Transcriptase