Pfizer Global Research and Development, La Jolla Laboratories, 10770 Science Center Drive, San Diego, California 92121, United States.
J Med Chem. 2011 May 12;54(9):3393-417. doi: 10.1021/jm200208d. Epub 2011 Apr 13.
HIV-1 integrase (IN) is one of three enzymes encoded by the HIV genome and is essential for viral replication, and HIV-1 IN inhibitors have emerged as a new promising class of therapeutics. Recently, we reported the synthesis of orally bioavailable azaindole hydroxamic acids that were potent inhibitors of the HIV-1 IN enzyme. Here we disclose the design and synthesis of novel tricyclic N-hydroxy-dihydronaphthyridinones as potent, orally bioavailable HIV-1 integrase inhibitors displaying excellent ligand and lipophilic efficiencies.
HIV-1 整合酶（IN）是 HIV 基因组编码的三种酶之一，是病毒复制所必需的，HIV-1 IN 抑制剂已成为一类有前途的新型治疗药物。最近，我们报道了具有口服生物利用度的氮杂吲哚羟肟酸的合成，它们是 HIV-1 IN 酶的有效抑制剂。在这里，我们公开了新型三环 N-羟基二氢萘啶酮的设计和合成，它们是有效的、具有口服生物利用度的 HIV-1 整合酶抑制剂，具有优异的配体和脂溶性效率。
