Novel inhibitors of 17β-hydroxysteroid dehydrogenase type 1: Templates for design

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• 作者：Gillian M. Allan ; Nigel Vicker ; Harshani R. Lawrence ; Helena J. Tutill ; Joanna M. Day ; Marion Huchet ; Eric Ferr ; is ; Michael J. Reed ; Atul Purohit ; Barry V.L. Potter
• 关键词：Hydroxysteroid dehydrogenase ; 17β ; -HSD1 ; 17β ; -HSD2 ; Breast cancer
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：15 April 2008
• 年：2008
• 卷：16
• 期：8
• 页码：4438-4456
• 全文大小：364 K

文摘

The 17β-hydroxysteroid dehydrogenases (17β-HSDs) catalyze the interconversion between the oxidized and reduced forms of androgens and estrogens at the 17 position. The 17β-HSD type 1 enzyme (17β-HSD1) catalyzes the reduction of estrone (E1) to estradiol and is expressed in malignant breast cells. Inhibitors of this enzyme thus have potential as treatments for hormone dependent breast cancer. Syntheses and biological evaluation of novel non-steroidal inhibitors designed to mimic the E1 template are reported using information from potent steroidal inhibitors. Of the templates investigated biphenyl ethanone was promising and led to inhibitors with IC₅₀ values in the low micromolar range.