Medicinal Chemistry of Inhibitors of 11尾-Hydroxysteroid Dehydrogenase Type 1 (11尾-HSD1)

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• 作者：James S. Scott ; Frederick W. Goldberg ; Andrew V. Turnbull
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：June 12, 2014
• 年：2014
• 卷：57
• 期：11
• 页码：4466-4486
• 全文大小：898K
• 年卷期：v.57,no.11(June 12, 2014)
• ISSN：1520-4804

文摘

11尾-Hydroxysteroid dehydrogenase type 1 (11尾-HSD1) is the enzyme primarily responsible for the regulation of intracellular cortisol levels. Inhibition of 11尾-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鈥檚 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尾-HSD1 and to highlight key compounds that have resulted from the efforts of both industrial and academic groups. The reported data from 11尾-HSD1 inhibitors that have progressed into the clinic are summarized followed by a perspective from the authors.