Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1

…, J Hixon, T McDonagh, K Keavey, JF Pons…

文献索引：Napper, Andrew D.; Hixon, Jeffrey; McDonagh, Thomas; Keavey, Kenneth; Pons, Jean-Francois; Barker, Jonathan; Yau, Wei Tsung; Amouzegh, Patricia; Flegg, Adam; Hamelin, Estelle; Thomas, Russell J.; Kates, Michael; Jones, Stephen; Navia, Manuel A.; Saunders, Jeffrey O.; DiStefano, Peter S.; Curtis, Rory Journal of Medicinal Chemistry, 2005 , vol. 48, # 25 p. 8045 - 8054

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被引用次数: 312

摘要

High-throughput screening against the human sirtuin SIRT1 led to the discovery of a series of indoles as potent inhibitors that are selective for SIRT1 over other deacetylases and NAD- processing enzymes. The most potent compounds described herein inhibit SIRT1 with IC50 values of 60-100 nM, representing a 500-fold improvement over previously reported SIRT inhibitors. Preparation of enantiomerically pure indole derivatives allowed for their ...