Design and Synthesis of Novel N-Hydroxy-Dihydronaphthyridinones as Potent and Orally Bioavailable HIV-1 Integrase Inhibitors

作者：Ted W. Johnson, Steven P. Tanis, Scott L. Butler, Deepak Dalvie, Dorothy M. DeLisle, Klaus Dress, Erik J. Flahive, Qiyue Hu, Jon Kuehler, Atsuo Kuki, Wen Liu, Guy A. McClellan, Qinghai Peng, Michael Plewe, Paul Richardson, Graham L. Smith, Jim Solowiej, Khanh Tran, Hai Wang, Xiaoming Yu, Junhu Zhang, Huichun Zhu · 发表于：Journal of Medicinal Chemistry · 年份：2011 · DOI：10.1021/jm200208d · 被引用次数：43 · 研究领域：HIV/AIDS drug development and treatment、Biochemical and Molecular Research、HIV Research and Treatment

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.