Design, synthesis and structure-activity relationship studies of novel sirtuin 2 (SIRT2) inhibitors with a benzamide skeleton

作者：Sakai Taki; Matsumoto Yotaro; Ishikawa Minoru^*; Sugita Kazuyuki; Hashimoto Yuichi; Wakai Nobuhiko; Kitao Akio; Morishita Era; Toyoshima Chikashi; Hayashi Tomoatsu; Akiyama Tetsu

来源：Bioorganic & Medicinal Chemistry, 2015, 23(2): 328-339.

DOI：10.1016/j.bmc.2014.11.027

• Sirtuin
• SIRT2

Human sirtuin 2 (SIRT2) is an attractive target molecule for development of drugs to treat neurodegenerative diseases and cancer, because SIRT2 inhibitors have a protective effect against neurodegeneration and an anti-proliferative effect on cancer stem cells. We designed and synthesized a series of benzamide derivatives as SIRT2 inhibitor candidates. Among them, compound 17k showed the most potent SIRT2-inhibitory activity (IC50 = 0.60 mu M), with more than 150-fold selectivity over SIRT1 and SIRT3 isoforms (IC50 > 100 mu M).

• 出版日期2015-1-15