Potent mGluR5 antagonists: Pyridyl and thiazolyl-ethynyl-3,5-disubstituted-phenyl series

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Alagille, David¹  DaCosta, Herve¹  Chen, Yelin²  Hemstapat, Kamondanai²  Rodriguez, Alice²  Baldwin, Ronald M.³  Conn, Jeffrey P.²  Tamagnan, Gilles D.¹ 

[1] Inst Neurodegenerat Disorders, New Haven, CT 06510 USA

[2] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA

[3] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA

关键词: Glutamate;    mGluR5;    MPEP;    Antagonist;   

DOI  :  10.1016/j.bmcl.2011.04.047

来源: Elsevier

【 摘 要 】

We report the synthesis of four series of 3,5-disubstituted-phenyl ligands targeting the metabotropic glutamate receptor subtype 5: (2-methylthiazol-4-yl)ethynyl (1a-j,), (6-methylpyridin-2-yl)ethynyl (2a-j), (5-methylpyridin-2-yl)ethynyl (3a-j,), and (pyridin-2-yl)ethynyl (4a-j,). The compounds were evaluated for antagonism of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro assay. All compounds were found to be full antagonists and exhibited low nanomolar to subnanomolar activity. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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