Abstract
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.
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