Sweeney Zachary K, Acharya Sahaja, Briggs Andrew, Dunn James P, Elworthy Todd R, Fretland Jennifer, Giannetti Anthony M, Heilek Gabrielle, Li Yu, Kaiser Ann C, Martin Michael, Saito Y David, Smith Mark, Suh Judy M, Swallow Steven, Wu Jeffrey, Hang Julie Q, Zhou Amy S, Klumpp Klaus
Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA.
Bioorg Med Chem Lett. 2008 Aug 1;18(15):4348-51. doi: 10.1016/j.bmcl.2008.06.080. Epub 2008 Jun 28.
Novel non-nucleoside inhibitors of HIV-RT that contain pyridazinone isosteres were prepared, and a series of triazolinones were found to be potent inhibitors of HIV replication. These compounds were active against several NNRTI-resistant virus strains. Pharmacokinetic studies indicated that inhibitor 7e has good bioavailability in rats. Several fragments of inhibitor 7c were prepared, and the binding of these compounds to HIV-RT was analyzed by surface plasmon resonance spectroscopy.
制备了含有哒嗪酮电子等排体的新型HIV逆转录酶非核苷抑制剂，发现一系列三唑啉酮是HIV复制的有效抑制剂。这些化合物对几种耐非核苷逆转录酶抑制剂的病毒株具有活性。药代动力学研究表明抑制剂7e在大鼠中具有良好的生物利用度。制备了抑制剂7c的几个片段，并通过表面等离子体共振光谱分析了这些化合物与HIV逆转录酶的结合情况。
