8-羟基-[1,6]萘啶的设计与合成：体外及感染细胞中新型HIV-1整合酶抑制剂的研究
Design and synthesis of 8-hydroxy-[1,6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells.
作者信息
Zhuang Linghang, Wai John S, Embrey Mark W, Fisher Thorsten E, Egbertson Melissa S, Payne Linda S, Guare James P, Vacca Joseph P, Hazuda Daria J, Felock Peter J, Wolfe Abigail L, Stillmock Kara A, Witmer Marc V, Moyer Gregory, Schleif William A, Gabryelski Lori J, Leonard Yvonne M, Lynch Joseph J, Michelson Stuart R, Young Steven D
机构信息
Departments of Medicinal Chemistry, Antiviral Research, and Pharmacology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
出版信息
J Med Chem. 2003 Feb 13;46(4):453-6. doi: 10.1021/jm025553u.
Naphthyridine 7 inhibits the strand transfer of the integration process catalyzed by integrase with an IC50 of 10 nM and inhibits 95% of the spread of HIV-1 infection in cell culture at 0.39 microM. It does not exhibit cytotoxicity in cell culture at < or =12.5 microM and shows a good pharmacokinetic profile when dosed orally to rats. The antiviral activity of 7 and its effect on integration were confirmed using viruses with specific integrase mutations.
萘啶 7 抑制整合酶催化的整合过程中的链转移，IC50 为 10 nM，在 0.39 microM 时可抑制细胞培养中 95% 的 HIV-1 感染传播。在细胞培养中，当浓度≤12.5 microM 时，它不表现出细胞毒性，口服给药至大鼠时显示出良好的药代动力学特征。使用具有特定整合酶突变的病毒证实了 7 的抗病毒活性及其对整合的影响。
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