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Discovery and optimization of pyridazinone non-nucleoside inhibitors of HIV-1 reverse transcriptase.
Bioorg Med Chem Lett
; 18(15): 4352-4, 2008 Aug 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-18632268
RESUMEN
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.