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

共 50 条

[1] Synthesis and optimization of thiadiazole derivatives as a novel class of substrate competitive c-Jun N-terminal kinase inhibitors
De, Surya K.
Chen, Vida
Stebbins, John L.
Chen, Li-Hsing
Cellitti, Jason F.
Machleidt, Thomas
Barile, Elisa
Riel-Mehan, Megan
Dahl, Russell
Yang, Li
Emdadi, Aras
Murphy, Ria
Pellecchia, Maurizio
BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (02) : 590 - 596
[2] Design, synthesis, and structure-activity relationship studies of thiophene-3-carboxamide derivatives as dual inhibitors of the c-Jun N-terminal kinase
De, Surya K.
Barile, Elisa
Chen, Vida
Stebbins, John L.
Cellitti, Jason F.
Machleidt, Thomas
Carlson, Coby B.
Yang, Li
Dahl, Russell
Pellecchia, Maurizio
BIOORGANIC & MEDICINAL CHEMISTRY, 2011, 19 (08) : 2582 - 2588
[3] Recent Advances in c-Jun N-Terminal Kinase (JNK) Inhibitors
Li, Gang
Qi, Wenqing
Li, Xiaoxun
Zhao, Jinwu
Luo, Meihua
Chen, Jianjun
CURRENT MEDICINAL CHEMISTRY, 2021, 28 (03) : 607 - 627
[4] Synthesis and SAR of 2-Phenoxypyridines as novel c-Jun N-terminal kinase inhibitors
Song, Xinyi
Chen, Weimin
Lin, Li
Ruiz, Claudia H.
Cameron, Michael D.
Duckett, Derek R.
Kamenecka, Theodore M.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (23) : 7072 - 7075
[5] Pyrazole derivatives as potent inhibitors of c-Jun N-terminal kinase: Synthesis and SAR studies
Doma, Anuradha
Kulkarni, Ravindra
Palakodety, Radhakrishna
Sastry, G. Narahari
Sridhara, Janardhan
Garlapati, Achaiah
BIOORGANIC & MEDICINAL CHEMISTRY, 2014, 22 (21) : 6209 - 6219
[6] Synthesis and SAR of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors
Shin, Youseung
Chen, Weiming
Habel, Jeff
Duckett, Derek
Ling, Yuan Yuan
Koenig, Marcel
He, Yuanjun
Vojkovsky, Tomas
LoGrasso, Philip
Kamenecka, Theodore M.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (12) : 3344 - 3347
[7] Discovery of 2-(5-nitrothiazol-2-ylthio) benzo[d] thiazoles as novel c-Jun N-terminal kinase inhibitors
De, Surya K.
Chen, Li-Hsing
Stebbins, John L.
Machleidt, Thomas
Riel-Mehan, Megan
Dahl, Russell
Chen, Vida
Yuan, Hongbin
Barile, Elisa
Emdadi, Aras
Murphy, Ria
Pellecchia, Maurizio
BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (07) : 2712 - 2717
[8] c-Jun N-Terminal kinase signaling inhibitors under development
Han S.-Y.
Toxicological Research, 2008, 24 (2) : 93 - 100
[9] Structure Optimization of c-Jun N-terminal Kinase 1 Inhibitors for Treating Idiopathic Pulmonary Fibrosis
Huang, Yi
Liu, Fengling
Ren, Shuhua
Ding, Yuanqing
Chi, Man
Huang, Weiwei
Gu, Wenjing
Qian, Hewen
Yuan, Yaxia
Hou, Shurong
Chen, Xiabin
Ma, Lei
JOURNAL OF MEDICINAL CHEMISTRY, 2024, 67 (19) : 17713 - 17737
[10] c-Jun N-Terminal Kinase Phosphorylation Is a Biomarker of Plitidepsin Activity
Munoz-Alonso, Maria J.
Alvarez, Enrique
Jose Guillen-Navarro, Maria
Pollan, Marina
Aviles, Pablo
Galmarini, Carlos M.
Munoz, Alberto
MARINE DRUGS, 2013, 11 (05): : 1677 - 1692

← 1 2 3 4 5 →