Discovery of Imidazo[1,2-b]thiazole Derivatives as Novel SIRT1 Activators
| العنوان: | Discovery of Imidazo[1,2-b]thiazole Derivatives as Novel SIRT1 Activators |
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| المؤلفون: | Philip D. Lambert, David J. Gagne, Joseph J. Nunes, Jerrold M. Olefsky, Jean Bemis, Chi B. Vu, Jill C. Milne, Amy V. Lynch, J. Joshua Smith, David P. Carney, Michael R. Jirousek, Robert B. Perni, Pui Yee Ng, Jeremy S. Disch, Simon Schenk, Siva Lavu |
| المصدر: | Journal of Medicinal Chemistry. 52:1275-1283 |
| بيانات النشر: | American Chemical Society (ACS), 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | medicine.drug_class, Stereochemistry, Enzyme Activators, Carboxamide, Chemical synthesis, Diabetes Mellitus, Experimental, Mice, Structure-Activity Relationship, Enzyme activator, chemistry.chemical_compound, Sirtuin 1, Quinoxalines, Amide, Drug Discovery, medicine, Animals, Hypoglycemic Agents, Structure–activity relationship, Thiazole, Bicyclic molecule, Imidazoles, Rats, Rats, Zucker, Thiazoles, Diabetes Mellitus, Type 2, chemistry, Molecular Medicine, NAD+ kinase |
| الوصف: | A series of imidazo[1,2-b]thiazole derivatives is shown to activate the NAD(+)-dependent deacetylase SIRT1, a potential new therapeutic target to treat various metabolic disorders. This series of compounds was derived from a high throughput screening hit bearing an oxazolopyridine core. Water-solubilizing groups could be installed conveniently at either the C-2 or C-3 position of the imidazo[1,2-b]thiazole ring. The SIRT1 enzyme activity could be adjusted by modifying the amide portion of these imidazo[1,2-b]thiazole derivatives. The most potent analogue within this series, namely, compound 29, has demonstrated oral antidiabetic activity in the ob/ob mouse model, the diet-induced obesity (DIO) mouse model, and the Zucker fa/fa rat model. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f7c6857bfb9e2c4e77d9cfa1518e2e0 https://doi.org/10.1021/jm8012954 |
| رقم الأكسشن: | edsair.doi.dedup.....1f7c6857bfb9e2c4e77d9cfa1518e2e0 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
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