Steroidal C-21 mercapto derivatives as dissociated steroids: Discovery of an inhaled dissociated steroid

被引：12

作者：

Biju, Purakkattle ^{[1
]}

McCormick, Kevin ^{[1
]}

Aslanian, Robert ^{[1
]}

Berlin, Michael ^{[1
]}

Solomon, Daniel ^{[1
]}

Chapman, Richard ^{[1
]}

McLeod, Robbie ^{[1
]}

Prelusky, Daniel ^{[1
]}

Eckel, Stephen ^{[1
]}

Kelly, George ^{[1
]}

Natiello, Michelle ^{[1
]}

House, Aileen ^{[1
]}

Fernandez, Xiomara ^{[1
]}

Bitar, Rema ^{[1
]}

Phillips, Jonathan ^{[1
]}

Anthes, John ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 21期

关键词：

Inhaled asthma; Hydrocortisone; C-21 mercapto derivatives; Dissociated Steroid; Transactivation and transrepression; GLUCOCORTICOID-RECEPTOR MODULATORS; A-RING MIMETICS; MECHANISMS; AGONISTS; PHARMACODYNAMICS; PHARMACOKINETICS; CORTICOSTEROIDS; EFFICACY; LIGANDS; PROFILE;

D O I：

10.1016/j.bmcl.2011.08.108

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of C-21 mercapto derivatives of hydrocortisone have been synthesized and evaluated in cell based transrepression and transactivation assays. The benzothiazole derivative, compound 6 not only showed a dissociated profile in vitro functional assays but also a pharmacological profile in a Brown-Norway rat therapeutic index model of asthma that dissociated side effects (thymolysis) while maintaining efficacy against pulmonary inflammation and lung function. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：6343 / 6347

页数：5

共 38 条

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