N-1H-benzimidazol-5-ylbenzenesulfonamide derivatives as potent hPXR agonists.

Benod C; Subra G; Nahoum VMallavialle AGuichou JFMilhau JRobles SBourguet WPascussi JMBalaguer PChavanieu A

首页> 外文期刊>Bioorganic and medicinal chemistry >N-1H-benzimidazol-5-ylbenzenesulfonamide derivatives as potent hPXR agonists.

【24h】

N-1H-benzimidazol-5-ylbenzenesulfonamide derivatives as potent hPXR agonists.

机译：N-1H-benzimidazol-5-ylbenzenesulfonamide derivatives as potent hPXR agonists.

获取原文

获取原文并翻译 | 示例

获取外文期刊封面封底 >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

The Human Pregnane X Receptor (hPXR) is a nuclear receptor that regulates the expression of phase I and phase II drug-metabolizing enzymes, as well as that of drug transporters. Because this receptor plays a critical role in protecting tissues from potentially toxic endo- and xenobiotics, highly active agonists could represent novel therapeutic tools in treating several human diseases. Using an in vitro screening reporter system that allow to characterize hPXR activators and a first step of chemical modifications of an original agonist ligand (C2BA-4, 1-(2-chlorophenyl)-N-1-(1-phenylethyl)-1H-benzimidazol-5-ylmethanesulfonamide), we identified compounds with a N-1H-benzimidazol-5-ylbenzenesulfonamide scaffold as a potent family of hPXR agonists. Further chemical modifications allowed us to identify enhanced activators, notably N-(1-benzyl-1H-benzimidazol-5-yl)-2,3,4,5,6-pentamethylbenzenesulfonamide (6n) with an EC(50) value in the subnanomolar range. Accordingly to their potent EC(50), these compounds induced an efficient protection of hPXR against proteolytic digestion by trypsin even at very low ligand concentrations and were able to induce the expression of the main target genes of hPXR, CYP3A4 and CYP2B6, in primary cultures of human hepatocytes.

著录项

来源
《Bioorganic and medicinal chemistry》 |2008年第7期|3537-3549|共13页
作者
Benod C; Subra G; Nahoum VMallavialle AGuichou JFMilhau JRobles SBourguet WPascussi JMBalaguer PChavanieu A;
展开▼
作者单位

INSERM, U554, Montpellier, F-34090, Univ Montpellier 1 and 2, CNRS, UMR5048, Centre de Biochimie Structurale, Montpellier F-34090, France.;

ost.saga-med.ac.jp;

展开▼
收录信息
原文格式 PDF
正文语种英语
中图分类药学;生物化学;
关键词
Aryl Hydrocarbon Hydroxylases; Benzimidazoles; Cell Line; Cytochrome P-450 CYP3A; 芳基烃羟化酶类; 苯咪唑类; 细胞系; 基因表达调控; 模型; 分子; 分子结构; 氧化还原酶类; N-脱甲基;

N-1H-benzimidazol-5-ylbenzenesulfonamide derivatives as potent hPXR agonists.

摘要

著录项

相关主题

期刊订阅