Allosteric inhibitors of hepatitis C polymerase: Discovery of potent and orally bioavailable carbon-linked dihydropyrones

被引：36

作者：

Li, Hui ^{[1
]}

Linton, Angelica ^{[1
]}

Tatlock, John ^{[1
]}

Gonzalez, Javier ^{[1
]}

Borchardt, Allen ^{[1
]}

Abreo, Mel ^{[1
]}

Jewell, Tanya ^{[1
]}

Patel, Leena ^{[1
]}

Drowns, Matthew ^{[1
]}

Ludlum, Sarah ^{[1
]}

Goble, Mike ^{[1
]}

Yang, Michele ^{[1
]}

Blazel, Julie ^{[1
]}

Rahavendran, Ravi ^{[1
]}

Skor, Heather ^{[1
]}

Shi, Stephanie ^{[1
]}

Lewis, Cristina ^{[1
]}

Fuhrman, Shella ^{[1
]}

机构：

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 17期

关键词：

D O I：

10.1021/jm0704447

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery and optimization of a novel class of carbon-linked dihydropyrones as allosteric HCV NS5B polymerase inhibitors are presented. Replacement of the sulfur linker atom with carbon reduced compound acidity and greatly increased cell permeation. Further structure-activity relationship (SAR) studies led to the identification of compounds, exemplified by 23 and 24, with significantly improved antiviral activities in the cell-based replicon assay and favorable pharmacokinetic profiles.

引用

页码：3969 / 3972

页数：4

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