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

被引：35

作者：

Johnson, Ted W. ^{[1
]}

Tanis, Steven P. ^{[1
]}

Butler, Scott L. ^{[1
]}

Dalvie, Deepak ^{[1
]}

DeLisle, Dorothy M. ^{[1
]}

Dress, Klaus R. ^{[1
]}

Flahive, Erik J. ^{[1
]}

Hu, Qiyue ^{[1
]}

Kuehler, Jon E. ^{[1
]}

Kuki, Atsuo ^{[1
]}

Liu, Wen ^{[1
]}

McClellan, Guy A. ^{[1
]}

Peng, Qinghai ^{[1
]}

Plewe, Michael B. ^{[1
]}

Richardson, Paul F. ^{[1
]}

Smith, Graham L. ^{[1
]}

Solowiej, Jim ^{[1
]}

Tran, Khanh T. ^{[1
]}

Wang, Hai ^{[1
]}

Yu, Xiaoming ^{[1
]}

Zhang, Junhu ^{[1
]}

Zhu, Huichun ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, La Jolla Labs, San Diego, CA 92121 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 09期

关键词：

VIRUS TYPE-1 INTEGRASE; REVERSE-TRANSCRIPTASE; RALTEGRAVIR; DISCOVERY; LIGAND;

D O I：

10.1021/jm200208d

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：3393 / 3417

页数：25

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