Tokyo Medical and Dental University, Institute of Biomaterials and Bioengineering, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Expert Opin Ther Pat. 2010 Feb;20(2):213-28. doi: 10.1517/13543770903567069.
Thyroid hormones are produced by the thyroid gland and peripheral tissues, and control metabolic rate, including oxygen consumption, lipid metabolism and the cardiovascular system, mainly through binding to and activating thyroid hormone receptors (TRs). Abnormal elevation or lowering of circulating thyroid hormone induces various physiological disorders. As candidates for the treatment of such diseases, various thyromimetics, such as subtype- or tissue-selective TR agonists and antagonists, have been developed.
This review focuses on recent reports and patents covering thyromimetics, especially those published in the last 6 years.
In this review, we classify thyromimetics based on structure. The structures of most thyromimetic compounds are based on those of endogenous thyroid hormones, which consist of a biaryl ether skeleton substituted with iodine, alpha-alanine moiety and hydroxyl group at two benzene rings. Many thyromimetics have been developed by replacement of the polar group, changing the bridging oxygen, or introduction of heterocycles. This review provides an overview of the structure-activity relationship.
Some thyromimetics are subtype- or tissue-selective TR agonists and antagonists, and such compounds have the potential to become novel therapeutic agents, especially in the field of metabolic diseases.
甲状腺激素由甲状腺和外周组织产生，通过与甲状腺激素受体（TR）结合并激活 TR 来控制代谢率，包括耗氧量、脂代谢和心血管系统，主要作用。循环甲状腺激素的异常升高或降低会引起各种生理紊乱。作为治疗此类疾病的候选药物，已经开发出各种甲状腺刺激剂，如亚型或组织选择性 TR 激动剂和拮抗剂。
本综述重点介绍了涵盖甲状腺刺激剂的最新报告和专利，特别是过去 6 年发表的报告和专利。
在这篇综述中，我们根据结构对甲状腺刺激剂进行分类。大多数甲状腺刺激剂化合物的结构基于内源性甲状腺激素，其由碘取代的二芳基醚骨架、α-丙氨酸部分和两个苯环上的羟基组成。许多甲状腺刺激剂通过取代极性基团、改变桥接氧或引入杂环来开发。本综述提供了结构-活性关系的概述。
一些甲状腺刺激剂是亚型或组织选择性 TR 激动剂和拮抗剂，这些化合物有可能成为新型治疗药物，特别是在代谢疾病领域。
