The discovery of novel cyclohexylamide CCR2 antagonists

被引：8

作者：

Lanter, James C. ^{[1
]}

Markotan, Thomas P. ^{[1
]}

Zhang, Xuqing ^{[1
]}

Subasinghe, Nalin ^{[1
]}

Kang, Fu-An ^{[1
]}

Hou, Cuifen ^{[1
]}

Singer, Monica ^{[1
]}

Opas, Evan ^{[1
]}

McKenney, Sandra ^{[1
]}

Crysler, Carl ^{[1
]}

Johnson, Dana ^{[1
]}

Molloy, Christopher J. ^{[1
]}

Sui, Zhihua ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev, Spring House, PA 19002 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 24期

关键词：

CCR2; Antagonist; MCP-1; hERG; CHEMOKINE RECEPTORS;

D O I：

10.1016/j.bmcl.2011.09.113

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

As a result of further SAR studies on a piperidinyl piperidine scaffold, we report the discovery of compound 44, a potent, orally bioavailable CCR2 antagonist. While having some in vitro hERG activity, this molecule was clean in an in vivo model of QT prolongation. In addition, it showed excellent efficacy when dosed orally in a transgenic murine model of acute inflammation. (C) 2011 Published by Elsevier Ltd.

引用

页码：7496 / 7501

页数：6

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