3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: A potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity
3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: A potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity
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DOI：
10.1021/jm025570j
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发表时间：
2003-01-16
影响因子：
7.3
通讯作者：
Varney, MA
中科院分区：
文献类型：
--
作者：
Cosford, NDP;Tehrani, L;Varney, MA
2-甲基-6-（苯乙基）吡啶(3)是一种有效的非竞争性mGlu5受体拮抗剂，广泛用于表征mGlu5受体的药理学，但作为一种治疗剂存在许多缺点，包括脱靶活性和水溶性差。为了改善3的性质，合成了化合物9，这是一种高度选择性的mGlu5受体拮抗剂，在大鼠恐惧增强惊吓模型中的效力是3的5倍。
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-potentiated startle model of anxiety.