Discovery and optimization of pyridazinone non-nucleoside inhibitors of HIV-1 reverse transcriptase
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- 作者：Zachary K. Sweeney ; James P. Dunn ; Yu Li ; Gabrielle Heilek ; Pete Dunten ; Todd R. Elworthy ; Xiaochun Han ; Seth F. Harris ; Donald R. Hirschfeld ; J. Heather Hogg ; Walter Huber ; Ann C. Kaiser ; Denis J. Ke
- 关键词：Human immunodeficiency virus ; HIV ; NNRTI ; Non-nucleoside ; Reverse transcriptase
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 出版时间：1 August 2008
- 年：2008
- 卷：18
- 期：15
- 页码：4352-4354
- 全文大小：268 K
文摘
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.