Medicinal Chemistry of Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)
Medicinal Chemistry of Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)
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DOI：
10.1021/jm4014746
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发表时间：
2014-06-12
影响因子：
7.3
通讯作者：
Turnbull, Andrew V.
中科院分区：
文献类型：
--
作者：
Scott, James S.;Goldberg, Frederick W.;Turnbull, Andrew V.
11 β-羟基类固醇脱氢酶1型（11 β-HSD 1）是主要负责调节细胞内皮质醇水平的酶。抑制11 β-HSD 1是治疗肥胖症和代谢综合征其他要素的一种有吸引力的机制。新兴文献还支持在治疗其他未满足的医疗需求中的潜在作用，包括阿尔茨海默病，血管炎症，心血管疾病和青光眼。本文的目的是回顾药物化学文献围绕小分子方法开发11 β-HSD 1的合成抑制剂，并强调工业和学术团体的努力所产生的关键化合物。总结了已进入临床的11种β-HSD 1抑制剂的报告数据，然后从作者的角度进行了总结。
11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) is the enzyme primarily responsible for the regulation of intracellular cortisol levels. Inhibition of 11 beta-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. Emerging literature also supports a potential role in the treatment of other unmet medical needs including Alzheimer's disease, vascular inflammation, cardiovascular disease, and glaucoma. The aim of this article is to review the medicinal chemistry literature around small molecule approaches to developing synthetic inhibitors of 11 beta-HSD1 and to highlight key compounds that have resulted from the efforts of both industrial and academic groups. The reported data from 11 beta-HSD1 inhibitors that have progressed into the clinic are summarized followed by a perspective from the authors.