Steroidal C-21 heteroaryl thioethers (Part 2): Discovery of orally bioavailable selective glucocorticoid receptor modulators (dissociated steroids)

被引：6

作者：

Biju, Purakkattle ^{[1
]}

McCormick, Kevin ^{[1
]}

Aslanian, Robert ^{[1
]}

Berlin, Michael ^{[1
]}

Solomon, Daniel ^{[1
]}

Wang, Hongwu ^{[1
]}

Lee, Yoon Joo ^{[1
]}

Bitar, Rema ^{[1
]}

Prelusky, Daniel ^{[1
]}

Mcleod, Robbie ^{[1
]}

Jia, Yanlin ^{[1
]}

Fernandez, Xiomora ^{[1
]}

Eckel, Stephen ^{[1
]}

House, Aileen ^{[1
]}

Lieber, Gissela ^{[1
]}

Jimenez, Johanna ^{[1
]}

Kelly, George ^{[1
]}

Chapman, Richard ^{[1
]}

Phillips, Jonathan ^{[1
]}

Anthes, John ^{[1
]}

机构：

[1] Merck Res Labs, Kenilworth, NJ 07033 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 02期

关键词：

Selective glucocorticoid receptor modulators; Dissociated steroids; Prednisolone; Transactivation; Transrepression; Asthma; PHARMACOKINETICS; MECHANISMS; THERAPY;

D O I：

10.1016/j.bmcl.2011.11.120

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The prednisolone C-21 heteroaryl thioethers have been synthesized and evaluated in cell based transrepression and transactivation assays. Most of the compounds demonstrated weak transactivational activity in both human and rat tyrosineaminotransferase functional assay while keeping potent antiinflammatory activity. The benzimidazole thioether 7 exhibited comparable anti-inflammatory activity and improved safety profile compared to the classical oral steroid prednisolone. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1086 / 1090

页数：5

共 23 条

[1]

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