Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators

被引：82

作者：

Bemis, Jean E. ^{[1
]}

Vu, Chi B. ^{[1
]}

Xie, Roger ^{[1
]}

Nunes, Joseph J. ^{[1
]}

Ng, Pui Yee ^{[1
]}

Disch, Jeremy S. ^{[1
]}

Milne, Jill C. ^{[1
]}

Carney, David P. ^{[1
]}

Lynch, Amy V. ^{[1
]}

Jin, Lei ^{[1
]}

Smith, Jesse J. ^{[1
]}

Lavu, Siva ^{[1
]}

Iffland, Andre ^{[1
]}

Jirousek, Michael R. ^{[1
]}

Perni, Robert B. ^{[1
]}

机构：

[1] A GSK Co, Sirtris, Cambridge, MA 01239 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 08期

关键词：

Sirtuins; SIRT1; activator; CALORIE RESTRICTION;

D O I：

10.1016/j.bmcl.2008.11.106

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：2350 / 2353

页数：4

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