Abstract：
: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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Vu CB,Bemis JE,Disch JS,Ng PY,Nunes JJ,Milne JC,Carney DP,Lynch AV,Smith JJ,Lavu S,Lambert PD,Gagne DJ,Jirousek MR,Schenk S,Olefsky JM,Perni RBdoi
10.1021/jm8012954subject
Has Abstractpub_date
2009-03-12 00:00:00pages
1275-83issue
5eissn
0022-2623issn
1520-4804pii
10.1021/jm8012954journal_volume
52pub_type
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