Synthesis and SAR of centrally active mGlu5 positive allosteric modulators based on an aryl acetylenic bicyclic lactam scaffold

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Williams, Richard^1,3  Manka, Jason T.^1,3  Rodriguez, Alice L.^1,3  Vinson, Paige N.^1,3  Niswender, Colleen M.^1,3  Weaver, C. David^1,3  Jones, Carrie K.^1,3  Conn, P. Jeffrey^1,3  Lindsley, Craig W.^1,2,3  Stauffer, Shaun R.^1,2,3 

[1] Vanderbilt Univ Sch Med, Dept Pharmacol, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA

[3] Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA

关键词: mGluR;    Potentiator;    Positive allosteric modulator;    Schizophrenia;    Hyperlocomotion;   

DOI  :  10.1016/j.bmcl.2011.01.044

来源: Elsevier

【 摘 要 】

This Letter describes the hit-to-lead progression and SAR of a series of biphenyl acetylene compounds derived from an HTS screening campaign targeting the mGlu(5) receptor. 'Molecular switches' were identified that modulated modes of pharmacology, and several compounds within this series were shown to be efficacious in reversal of amphetamine induced hyperlocomotion in rats after ip dosing, a preclinical model that shows similar positive effects with known antipsychotic agents. Published by Elsevier Ltd.

【 授权许可】

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