Substituted tetrahydroquinolines as potent allosteric inhibitors of reverse transcriptase and its key mutants
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- 作者：Dai-Shi Su ; John J. Lim ; Elizabeth Tinney ; Bang-Lin Wan ; Mary Beth Young ; Kenneth D. Anderson ; Deanne Rudd ; V ; na Munshi ; Carolyn Bahnck ; Peter J. Felock ; Meiqing Lu ; Ming-Tain Lai ; Sinoeun Touch ; Greg
- 关键词：Non-nucleoside reverse transcriptase inhibitor (NNRTI) ; SAR ; Molecular modeling ; Crystal structure ; Mutant virus ; Tetrahydroquinoline
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2009
- 出版时间：1 September 2009
- 年：2009
- 卷：19
- 期：17
- 页码：5119-5123
- 全文大小：449 K
文摘
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are key elements of multidrug regimens, called HAART (Highly Active Antiretroviral Therapy), that are used to treat HIV-1 infections. Elucidation of the structure–activity relationships of the thiocarbamate moiety of the previous published lead compound 2 provided a series of novel tetrahydroquinoline derivatives as potent inhibitors of HIV-1 RT with nanomolar intrinsic activity on the WT and key mutant enzymes and potent antiviral activity in infected cells. The SAR optimization, mutation profiles, preparation of compounds, and pharmacokinetic profile of compounds are described.