Wai John S, Kim Boyoung, Fisher Thorsten E, Zhuang Linghang, Embrey Mark W, Williams Peter D, Staas Donnette D, Culberson Chris, Lyle Terry A, Vacca Joseph P, Hazuda Daria J, Felock Peter J, Schleif William A, Gabryelski Lori J, Jin Lixia, Chen I-Wu, Ellis Joan D, Mallai Rama, Young Steven D
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
Bioorg Med Chem Lett. 2007 Oct 15;17(20):5595-9. doi: 10.1016/j.bmcl.2007.07.092. Epub 2007 Aug 22.
A series of potent novel dihydroxypyridopyrazine-1,6-dione HIV-1 integrase inhibitors was identified. These compounds inhibited the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 6 is active against replication of HIV with a CIC(95) of 0.31 microM and exhibits no shift in potency in the presence of 50% normal human serum. It displays a good pharmacokinetic profile when dosed in rats and no covalent binding with microsomal proteins in both in vitro and in vivo models.
鉴定出了一系列强效的新型二羟基吡啶并吡嗪 -1,6- 二酮HIV-1整合酶抑制剂。这些化合物抑制HIV-1整合酶的链转移过程以及细胞中的病毒复制。化合物6对HIV复制具有活性，CIC(95)为0.31微摩尔，并且在存在50%正常人血清的情况下效力没有变化。在大鼠给药时它显示出良好的药代动力学特征，并且在体外和体内模型中均不与微粒体蛋白发生共价结合。
