Benzoyl 2-methyl indoles as selective PPAR???? modulators

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• 作者：Acton ; John J. ; Black ; Regina M. ; Jones ; A. Brian ; Moller ; David E. ; Colwell ; Lawrence ; Doebber ; Thomas W. ; et. al.
• 关键词：PPAR ; Indole ; Selective PPAR modulator
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2005
• 出版时间：January 17, 2005
• 年：2005
• 卷：15
• 期：2
• 页码：357-362
• 全文大小：304 K

文摘

Routine screening for human PPAR ligands yielded compounds 1 and 2, both of which were sub-micromolar hPPAR?? agonists. Synthetic modifications of these leads led to a series of potent substituted 3-benzyl-2-methyl indoles, a subset of which were noted to be selective PPAR?? modulators (SPPAR??Ms). SPPAR??M 24 displayed robust anti-diabetic activity with an improved therapeutic window in comparison to a PPAR?? full agonist in a rodent efficacy model.