设计并合成取代的 N-(1,3-二苯基-1H-吡唑-5-基)苯甲酰胺作为代谢型谷氨酸受体亚型 5 的正别构调节剂。
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.
机构信息
Medicinal Chemistry Section, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 333 Cassell Drive Baltimore, MD 21224, USA.
出版信息
Bioorg Med Chem Lett. 2011 May 1;21(9):2650-4. doi: 10.1016/j.bmcl.2010.12.110. Epub 2010 Dec 28.
Abstract
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).
摘要
基于 mGlu5 受体负变构调节剂的炔烃类中的 SAR 和一组酰胺基正变构调节剂，优化了芳基 'b' 环的取代基，以合成取代的 N-(1,3-二苯基-1H-吡唑-5-基)苯甲酰胺。使用钙荧光的 mGlu5 受体功能测定的结果表明，功效和效力存在差异，这表明在密切结构类别内的化合物的细微变化可能对功能活性产生显著影响，包括功效模式的转变（即，负变构调节到正变构调节）。
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