Discovery of liver selective non-steroidal glucocorticoid receptor antagonist as novel antidiabetic agents

被引：5

作者：

Shah, Kiran ^{[1
,2
]}

Patel, Dipam ^{[1
]}

Jadav, Pradip ^{[1
]}

Sheikh, Mubeen ^{[1
]}

Sairam, Kalapatapu V. V. M. ^{[1
]}

Joharapurkar, Amit ^{[1
]}

Jain, Mukul R. ^{[1
]}

Bahekar, Rajesh ^{[1
]}

机构：

[1] Zydus Res Ctr, Ahmadabad 382210, Gujarat, India

[2] Maharaja Sayajirao Univ Baroda, Fac Sci, Dept Chem, Vadodara 380002, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 18期

关键词：

Glucocorticoid; Diabetes; Antagonist; Non-steroidal; Liver Selective; STEROID-HORMONE RECEPTORS; LIGAND-BINDING DOMAIN; LONG-TERM TREATMENT; PROGESTERONE; HYPERGLYCEMIA;

D O I：

10.1016/j.bmcl.2012.07.078

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Series of benzyl-phenoxybenzyl amino-phenyl acid derivatives (8a-q) are reported as non-steroidal GR antagonist. Compound 8g showed excellent h-GR binding and potent antagonistic activity (in vitro). The lead compound 8g exhibited significant oral antidiabetic and antihyperlipidemic effects (in vivo), along with liver selectivity. These preliminary results confirm discovery of potent and liver selective passive GR antagonist for the treatment of T2DM. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：5857 / 5862

页数：6

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