Design, Synthesis, and Structure-Activity Relationship of Substrate Competitive, Selective, and in Vivo Active Triazole and Thiadiazole Inhibitors of the c-Jun N-Terminal Kinase

被引：77

作者：

De, Surya K. ^{[1
,2
]}

Stebbins, John L. ^{[1
,2
]}

Chen, Li-Hsing ^{[1
,2
]}

Riel-Mehan, Megan ^{[1
,2
]}

Machleidt, Thomas ^{[3
]}

Dahl, Russell ^{[1
,2
]}

Yuan, Hongbin ^{[1
,2
]}

Embadi, Aras ^{[1
,2
]}

Barile, Elisa ^{[1
,2
]}

Chen, Vida ^{[1
,2
]}

Murphy, Ria ^{[1
,2
]}

Pellecchia, Maurizio ^{[1
,2
]}

机构：

[1] Burnham Inst Med Res, Infect & Inflammatory Dis Ctr, La Jolla, CA 92037 USA

[2] Burnham Inst Med Res, Ctr Canc, La Jolla, CA 92037 USA

[3] Invitrogen Corp, Invitrogen Discovery Serv, Madison, WI 53719 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 07期

关键词：

JNK; PEPTIDE; POTENT; IDENTIFICATION; PATHWAYS; DOCKING;

D O I：

10.1021/jm801503n

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report comprehensive structure-activity relationship studies on a novel series of c-Jun N-terminal kinase (JNK) inhibitors. The compounds are substrate competitive inhibitors that bind to the docking site of the kinase. The reported medicinal chemistry and structure-based optimizations studies resulted in the discovery of selective and potent thiadiazole JNK inhibitors that display promising in vivo activity in mouse models of insulin insensitivity.

引用

页码：1943 / 1952

页数：10

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