Synthesis and Evaluation of Diarylthiazole Derivatives That Inhibit Activation of Sterol Regulatory Element-Binding Proteins

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• 作者：Shinji Kamisuki ; Takashi Shirakawa ; Akira Kugimiya ; Lutfi Abu-Elheiga ; Hea-Young Park Choo ; Kohei Yamada ; Hiroki Shimogawa ; Salih J. Wakil ; Motonari Uesugi
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：July 14, 2011
• 年：2011
• 卷：54
• 期：13
• 页码：4923-4927
• 全文大小：781K
• 年卷期：v.54,no.13(July 14, 2011)
• ISSN：1520-4804

文摘

Fatostatin, a recently discovered small molecule that inhibits activation of sterol regulatory element-binding protein (SREBP), blocks biosynthesis and accumulation of fat in obese mice. We synthesized and evaluated a series of fatostatin derivatives. Our structure鈥揳ctivity relationships led to the identification of N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methanesulfonamide (24, FGH10019) as the most potent druglike molecule among the analogues tested. Compound 24 has high aqueous solubility and membrane permeability and may serve as a seed molecule for further development.