Identification of dissociated non-steroidal glucocorticoid receptor agonists

被引：32
|
作者：
Kuzmich, Daniel
Kirrane, Tom
Proudfoot, John
Bekkali, Younes
Zindell, Renee
Beck, Laura
Nelson, Richard
Shih, Cheng-Kon
Kukulka, Alison J.
Paw, Zofia
Reilly, Patty
Deleon, Rodney
Cardozo, Mario
Nabozny, Gerald
Thomson, David
机构：
[1] Boehringer Ingelheim Pharmaceut Inc, Dept Med Chem, Ridgefield, CT 06877 USA
[2] Boehringer Ingelheim Pharmaceut Inc, Inflammat & Immunol Dept, Ridgefield, CT 06877 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 18期
关键词：
glucocorticoid receptor; glucocorticoid receptor agonist; anti-inflammatory; IL-6; aromatase;
D O I：
10.1016/j.bmcl.2007.07.031
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A new series of ligands for the glucocorticoid receptor (GR) is described. SAR development was guided by docking 3 into the GR active site and optimizing an trnsubstituted phenyl ring for key interactions found in the steroid A-ring binding pocket. To identify compounds with an improved side effect profile over marketed steroids the functional activity of compounds was evaluated in cell based assays for transactivation (aromatase) and transrepression (IL-6). Through this effort, 36 has been identified as a partial agonist with a dissociated profile in these cell based assays. (c) 2007 Elsevier Ltd. All riehts reserved.
引用
收藏
页码：5025 / 5031
页数：7
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