Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators
Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators
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DOI：
10.1016/j.bmcl.2008.11.106
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发表时间：
2009-04-15
影响因子：
2.7
通讯作者：
Perni, Robert B.
中科院分区：
文献类型：
--
作者：
Bemis, Jean E.;Vu, Chi B.;Perni, Robert B.
SIRT1 是一种 NAD(+) 依赖性蛋白脱乙酰酶，似乎对葡萄糖和胰岛素稳态等代谢参数产生有益的影响。白藜芦醇 (1) 激活 SIRT1 已被证明可以调节胰岛素抵抗、增加线粒体含量并延长低等生物和高脂肪饮食小鼠的存活时间。在此，我们描述了一系列作为 SIRT1 新型小分子激活剂的恶唑并[4,5-b]吡啶的鉴定和 SAR，其在结构上与白藜芦醇无关且比白藜芦醇更有效。 (C) 2009 年，爱思唯尔有限公司出版。
SIRT1 is an NAD(+)-dependent protein deacetylase that appears to produce beneficial effects on metabolic parameters such as glucose and insulin homeostasis. Activation of SIRT1 by resveratrol ( 1) has been shown to modulate insulin resistance, increase mitochondrial content and prolong survival in lower organisms and in mice on a high fat diet. Herein, we describe the identification and SAR of a series of oxazolo[4,5-b]pyridines as novel small molecule activators of SIRT1 which are structurally unrelated to and more potent than resveratrol. (C) 2009 Published by Elsevier Ltd.