3-[Substituted]-5-(5-pyridin-2-yl-2H-tetrazol-2-yl) benzonitriles: Identification of highly potent and selective metabotropic glutamate subtype 5 receptor antagonists

…, TJ Seiders, DF Chapman, J Chung, M Cramer…

文献索引：Tehrani, Lida R.; Smith, Nicholas D.; Huang, Dehua; Poon, Steve F.; Roppe, Jeffrey R.; Seiders, Thomas Jon; Chapman, Deborah F.; Chung, Janice; Cramer, Merryl; Cosford, Nicholas D.P. Bioorganic and Medicinal Chemistry Letters, 2005 , vol. 15, # 22 p. 5061 - 5064

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被引用次数: 15

摘要

Structure–activity relationship studies on the phenyl ring of 3-(5-pyridin-2-yl-2H-tetrazol-2-yl) benzonitrile 2 led to the discovery that small, non-hydrogen bond donor substituents at the 3- position led to a substantial increase in in vitro potency. In particular, 3-fluoro-5-(5-pyridin-2- yl-2H-tetrazol-2-yl) benzonitrile (7) is a highly potent and selective mGlu5 receptor antagonist with good rat pharmacokinetics, brain penetration, and in vivo receptor ...