Discovery of a novel series of 6-azauracil-based thyroid hormone receptor ligands:: Potent, TRβ subtype-selective thyromimetics
Discovery of a novel series of 6-azauracil-based thyroid hormone receptor ligands:: Potent, TRβ subtype-selective thyromimetics
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DOI：
10.1016/s0960-894x(02)00947-2
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发表时间：
2003-02-10
影响因子：
2.7
通讯作者：
DaSilva-Jardine, P
中科院分区：
文献类型：
--
作者：
Dow, RL;Schneider, SR;DaSilva-Jardine, P
在这篇通讯中，我们希望描述一系列新的基于6-氮卓拉西林的甲状腺拟态化合物的发现，该系列化合物对甲状腺受体家族的β(1)-亚型的结合和功能激活具有高达100倍的选择性。3，5-和3‘-位的构效关系研究为化合物提供了增强的TRbeta亲和力和选择性。通过X-射线结晶学分析确定了6-氮杂环己烷部分与受体之间的关键结合作用。(C)2002爱思唯尔科学有限公司。保留所有权利。
In this communication, we wish to describe the discovery of a novel series of 6-azauracil-based thyromimetics that possess up to 100-fold selectivities for binding and functional activation of the beta(1)-isoform of the thyroid receptor family. Structure-activity relationship studies on the 3,5- and 3'-positions provided compounds with enhanced TRbeta affinity and selectivity. Key binding interactions between the 6-azauracil moiety and the receptor have been determined through of X-ray crystallographic analysis. (C) 2002 Elsevier Science Ltd. All rights reserved.