Design and synthesis of substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides as positive allosteric modulators of the metabotropic glutamate receptor subtype 5

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Zou, Mu-Fa¹  Cao, Jianjing¹  Rodriguez, Alice L.²  Conn, P. Jeffrey²  Newman, Amy Hauck¹ 

[1] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA

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

关键词: mGluR5;    MPEP;    CDPPB;    Allosteric modulators;   

DOI  :  10.1016/j.bmcl.2010.12.110

来源: Elsevier

【 摘 要 】

Based on SAR in the alkyne class of mGlu5 receptor negative allosteric modulators and a set of amide-based positive allosteric modulators, optimized substitution of the aryl 'b' ring was used to create substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides. Results from an mGlu5 receptor functional assay, using calcium fluorescence, revealed varying efficacies and potencies that provide evidence that subtle changes in compounds within a close structural class can have marked effects on functional activity including switches in modes of efficacy (i.e., negative to positive allosteric modulation). Published by Elsevier Ltd.

【 授权许可】

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