新型环己基酰胺 CCR2 拮抗剂的发现。
The discovery of novel cyclohexylamide CCR2 antagonists.
机构信息
Johnson & Johnson Pharmaceutical Research and Development, Welsh & McKean Roads, Spring House, PA 19002, USA.
出版信息
Bioorg Med Chem Lett. 2011 Dec 15;21(24):7496-501. doi: 10.1016/j.bmcl.2011.09.113. Epub 2011 Oct 8.
PMID:22061641
Abstract
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.
摘要
基于对哌啶基哌啶骨架的进一步 SAR 研究，我们发现了化合物 44，这是一种强效、可口服的 CCR2 拮抗剂。虽然该分子在体外具有一定的 hERG 活性，但在体内 QT 延长模型中表现出良好的安全性。此外，它在急性炎症的转基因小鼠模型中口服给药时显示出优异的疗效。
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