Thyroid receptor ligands. Part 7: Indirect antagonists of the thyroid hormone receptor with improved affinity

被引：11
作者：
Malm, Johan [1 ]
Gordon, Sandra [1 ]
Brandt, Peter [1 ]
Carlsson, Bo [1 ]
Agback, Peter [1 ]
Saeidi, Anna Backbro [1 ]
Sandberg, Johnny [1 ]
机构：
[1] Karo Bio AB, S-14157 Huddinge, Sweden
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 07期
关键词：
thyroid hormone receptor; thyroid hormone antagonist; indirect antagonism; benzyloxyphenyl derivatives; thyroid hormone agonist; thyrotoxicosis; hyperthyroidism;
D O I：
10.1016/j.bmcl.2007.01.009
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Based on the concept of 'indirect antagonism' of nuclear receptors, a series of thyroid hormone receptor (TR) antagonists were prepared with improved affinity compared with what was previously described. The results of a binding assay for the human TR and reporter cell assay revealed, within this series, that an m-bromobenzoyl substituent (11f) was optimal in terms of affinity and antagonist activity. Compared with already reported TR antagonists, their affinities are within the same range, thus potentially representing useful approach to novel and high-affinity TR-antagonists. (c) 2007 Elsevier Ltd. All rights reserved.
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收藏
页码：2018 / 2021
页数：4
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