Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-jun NH2-terminal kinase inhibitors

被引：68

作者：

Zhao, Hongyu ^{[1
]}

Serby, Michael D. ^{[1
]}

Xin, Zhili ^{[1
]}

Szczepankiewicz, Bruce G. ^{[1
]}

Liu, Mei ^{[1
]}

Kosogof, Christi ^{[1
]}

Liu, Bo ^{[1
]}

Nelson, Lissa T. J. ^{[1
]}

Johnson, Eric F. ^{[1
]}

Wang, Sanyi ^{[1
]}

Pederson, Terry ^{[1
]}

Gum, Rebecca J. ^{[1
]}

Clampit, Jill E. ^{[1
]}

Haasch, Deanna L. ^{[1
]}

Abad-Zapatero, Cele ^{[1
]}

Fry, Elizabeth H. ^{[1
]}

Rondinone, Cristina ^{[1
]}

Trevillyan, James M. ^{[1
]}

Sham, Hing L. ^{[1
]}

Liu, Gang ^{[1
]}

机构：

[1] Abbott Labs, Metab Dis Res, Global Pharmaceut Res & Dev, Abbott Pk, IL 60064 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 15期

关键词：

D O I：

10.1021/jm060465l

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

C-Jun NH2 terminal kinases (JNKs) are important cell signaling enzymes. JNK1 plays a central role in linking obesity and insulin resistance. JNK2 and JNK3 may be involved in inflammatory and neurological disorders, respectively. Small-molecule JNK inhibitors could be valuable tools to study the therapeutic benefits of inhibiting these enzymes and as leads for potential drugs targeting JNKs. In this report, we disclose a series of potent and highly selective JNK inhibitors with good pharmacokinetic profiles.

引用

页码：4455 / 4458

页数：4