Discovery of novel phosphorus-containing steroids as selective glucocorticoid receptor antagonist

被引：19

作者：

Jiang, Weiqin ^{[1
]}

Fiordeliso, James J. ^{[1
]}

Allan, George ^{[1
]}

Linton, Olivia ^{[1
]}

Tannenbaum, Pamela ^{[1
]}

Xu, Jun ^{[1
]}

Zhu, Peifang ^{[1
]}

Gunnet, Joseph ^{[1
]}

Demarest, Keith ^{[1
]}

Lundeen, Scott ^{[1
]}

Sui, Zhihua ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Drug Discovery, Raritan, NJ 08869 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 05期

关键词：

phosphorus-containing steroids; selective glucocorticoid receptor antagonist;

D O I：

10.1016/j.bmcl.2006.10.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Mifepristone is a non-selective antagonist of 3-oxosteroid receptors with both abortifacient and anti-diabetic activities. For glucocorticoid receptor (GR) program, we sought an unexplored, synthetically accessible phosphorus-containing steroidal mimetic of mifepristone, suitable for parallel synthesis of analogues. One compound 4a, with high oral bioavailability (59%) in rat, exhibited functional antagonism of GR in oral glucose tolerance test (OGTT). Thus this series of compounds might be potentially useful for the treatment of type 11 diabetes. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1471 / 1474

页数：4

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