Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives as novel small molecule chaperone amplifiers

被引：12

作者：

Zhou, Yuefen ^{[1
]}

Wei, Linyi ^{[1
]}

Brady, Thomas P. ^{[1
]}

Redddy, P. S. Murali Mohan ^{[1
]}

Nguyen, Tram ^{[1
]}

Chen, Jinhua ^{[1
]}

Au, Qingyan ^{[2
]}

Yoon, Il Sang ^{[2
]}

Yip, Gary ^{[2
]}

Zhang, Bin ^{[2
]}

Barber, Jack R. ^{[1
,2
]}

Ng, Shi Chung ^{[1
,2
]}

机构：

[1] CytRx Corp, Dept Chem, San Diego, CA 92109 USA

[2] CytRx Corp, Dept Biol, San Diego, CA 92109 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 15期

关键词：

Small molecule chaperone amplifiers; Protein misfolding; HSF1; Heat shock proteins ( HSPs); Stress granule; Rotenone stress; OGD; Neurodegenerative diseases; Cytoprotection; Pyrimidotriazinedione derivatives; HEAT-SHOCK; PARKINSONS-DISEASE; NEURODEGENERATION; ROTENONE; AGGREGATION; BRAIN; CELLS; MODEL;

D O I：

10.1016/j.bmcl.2009.05.073

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pyrimido[5,4-e][1,2,4] triazine-5,7(1H, 6H)-dione derivatives were investigated as novel small molecule amplifiers of heat shock factor 1 transcriptional activity. Lead optimization led to the discovery of compound 4A-13, which displayed potent HSF1 activity under mild heat stress (EC(50) = 2.5 mu M) and significant cytoprotection in both rotenone (EC(50) = 0.23 mu M) and oxygen-glucose deprivation cell toxicity models (80% protection at 2.5 mu M). (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：4303 / 4307

页数：5

共 18 条

[1] Protein misfolding in neurodegenerative diseases [J].