Synthesis and biological analysis of benzazol-2-yl piperazine sulfonamides as 11¦Â-hydroxysteroid dehydrogenase 1 inhibitors

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• 作者：S ; ra Hofer ; Denise V. Kratschmar ; Brigitte Schernthanner ; Anna Vuorinen ; Daniela Schuster ; Alex Odermatt ; Johnny Easmon
• 关键词：11¦Â-Hydroxysteroid dehydrogenase ; 2-Benzazolylpiperazine ; Structure&ndash ; activity relationships (SAR) ; Metabolic diseases ; Molecular modeling
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 October, 2013
• 年：2013
• 卷：23
• 期：19
• 页码：5397-5400
• 全文大小：818 K

文摘

In the last decade the inhibition of the enzyme 11¦Â-hydroxysteroid dehydrogenase 1 (11¦Â-HSD1) emerged as a promising new strategy to treat diabetes and several metabolic syndrome phenotypes. Using a molecular modeling approach and classical bioisosteric studies, we discovered a new class of 11¦Â-HSD1 inhibitors bearing an arylsulfonylpiperazine scaffold. Optimization of the initial lead resulted in compound 11 that selectively inhibits 11¦Â-HSD1 (IC₅₀ = 0.7 ¦ÌM).