Optimization and metabolic stabilization of a class of nonsteroidal glucocorticoid modulators

被引：10

作者：

Link, JT

Sorensen, BK

Patel, J

Arendsen, D

Li, GQ

Swanson, S

Nguyen, B

Emery, M

Grynfarb, M

Goos-Nilsson, A

机构：

[1] Abbott Labs, Metab Dis Res, Dept 4CB, Abbott Pk, IL 60064 USA

[2] Abbott Labs, Med Chem Technol, Dept 4CP, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 16期

关键词：

glucocorticoid modulator; antidiabetic;

D O I：

10.1016/j.bmcl.2004.06.023

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The optimization of a series of nonsteroidal glucocorticoid modulators is reported. Potent selective GR ligands that have improved metabolic stability were discovered typified by the subnanomolar acid 12 (GR binding IC50 = 0.6nM). (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4169 / 4172

页数：4

相关论文

共 7 条

[1] The pursuit of differentiated ligands for the glucocorticoid receptor [J].

Coghlan, MJ ;

Elmore, SW ;

Kym, PR ;

Kort, ME .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2003, 3 (14) :1617-1635

[2] Selective glucocorticold receptor modulators [J].

Coghlan, MJ ;

Elmore, SW ;

Kym, PR ;

Kort, ME .

ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 37, 2002, 37 :167-176

[3] Phosphoenolpyruvate carboxykinase (GTP) gene transcription and hyperglycemia are regulated by glucocorticoids in genetically obese db/db transgenic mice [J].

Friedman, JE ;

Sun, Y ;

Ishizuka, T ;

Farrell, CJ ;

McCormack, SE ;

Herron, LM ;

Hakimi, P ;

Lechner, P ;

Yun, JS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (50) :31475-31481

[4] Synthesis, activity, metabolic stability, and pharmacokinetics of glucocorticoid receptor modulator-statin hybrids [J].

Link, JT ;

Sorensen, BK ;

Lai, CQ ;

Wang, JH ;

Fung, S ;

Deng, D ;

Emery, M ;

Carroll, S ;

Grynfarb, M ;

Goos-Nilsson, A ;

von Geldern, T .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (16) :4173-4178

[5] Discovery of novel nonsteroidal glucocorticoid receptor modulators [J].

Link, JT ;

Sorensen, BK ;

Patel, J ;

Emery, M ;

Grynfarb, M ;

Goos-Nilsson, A .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (09) :2209-2212

[6] An evaluation of a C-glucuronide as a liver targeting group: Conjugate of a glucocorticoid antagonist [J].

Sorensen, BK ;

Link, JT ;

von Geldern, T ;

Emery, M ;

Wang, JH ;

Hickman, B ;

Grynfarb, M ;

Goos-Nilsson, A ;

Carroll, S .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (14) :2307-2310

[7] Bile acid conjugates of a nonsteroidal glucocorticoid receptor modulator [J].

Tu, N ;

Link, JT ;

Sorensen, BK ;

Emery, M ;

Grynfarb, M ;

Goos-Nilsson, A ;

Nguyen, B .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (16) :4179-4183