Synthesis and Evaluation of Diarylthiazole Derivatives That Inhibit Activation of Sterol Regulatory Element-Binding Proteins
| Autor: | Kouhei Yamada, Motonari Uesugi, Lutfi Abu-Elheiga, Hiroki Shimogawa, Takashi Shirakawa, Shinji Kamisuki, Akira Kugimiya, Salih J. Wakil, Hea-Young Park Choo |
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| Rok vydání: | 2011 |
| Předmět: |
Blood Glucose
Male Pyridines Mice Obese CHO Cells Article Permeability Eating Mice Structure-Activity Relationship chemistry.chemical_compound Cricetulus Biosynthesis Cricetinae Drug Discovery polycyclic compounds Animals Structure–activity relationship Fatostatin Sterol Regulatory Element Binding Proteins Sulfonamides biology Chemistry Chinese hamster ovary cell Membranes Artificial biology.organism_classification Small molecule Sterol Sterol regulatory element-binding protein Thiazoles Solubility Biochemistry Hepatocytes Molecular Medicine lipids (amino acids peptides and proteins) |
| Zdroj: | Journal of Medicinal Chemistry. 54:4923-4927 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm200304y |
| Popis: | 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. The present study synthesized and evaluated a series of fatostatin derivatives. Our structure-activity relationships led to the identification of N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methanesulfonamide (24; FGH10019) as the most potent drug-like molecule among the analogs tested. Compound 24 has high aqueous solubility and membrane permeability, and may serve as a seed molecule for further development. |
| Databáze: | OpenAIRE |
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