3-[(2-Methyl-1, 3-thiazol-4-yl) ethynyl]-pyridine: a potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity

…, L Bristow, J Brodkin, X Jiang, I McDonald…

文献索引：Cosford, Nicholas D. P.; Tehrani, Lida; Roppe, Jeffrey; Schweiger, Edwin; Smith, Nicholas D.; Anderson, Jeffrey; Bristow, Linda; Brodkin, Jesse; Jiang, Xiaohui; McDonald, Ian; Rao, Sara; Washburn, Mark; Varney, Mark A. Journal of Medicinal Chemistry, 2003 , vol. 46, # 2 p. 204 - 206

全文：HTML全文

被引用次数: 347

摘要

2-Methyl-6-(phenylethynyl) pyridine (3), a potent noncompetitive mGlu5 receptor antagonist widely used to characterize the pharmacology of mGlu5 receptors, suffers from a number of shortcomings as a therapeutic agent, including off-target activity and poor aqueous solubility. Seeking to improve the properties of 3 led to the synthesis of compound 9, a highly selective mGlu5 receptor antagonist that is 5-fold more potent than 3 in the rat fear- ...