Discovery of molecular switches within the ADX-47273 mGlu 5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu 5 NAMs, PAMs and partial …

…, CM Niswender, AL Rodriguez, DF Venable…

文献索引：Lamb, Jeffrey P.; Engers, Darren W.; Niswender, Colleen M.; Rodriguez, Alice L.; Venable, Daryl F.; Conn, Jeffrey P.; Lindsley, Craig W. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 9 p. 2711 - 2714

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被引用次数: 45

摘要

This Letter describes a chemical lead optimization campaign directed at a weak mGlu5 NAM discovered while developing SAR for the mGlu5 PAM, ADX-47273. An iterative parallel synthesis effort discovered multiple, subtle molecular switches that afford potent mGlu5 NAMs, mGlu5 PAMs as well as mGlu5 partial antagonists.