3-氰基-5-氟-N-芳基苯甲酰胺作为 mGlu(5)的负变构调节剂：在大鼠中具有 CNS 暴露的易于制备的工具化合物的鉴定。
3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu(5): Identification of easily prepared tool compounds with CNS exposure in rats.
机构信息
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
出版信息
Bioorg Med Chem Lett. 2010 Aug 1;20(15):4390-4. doi: 10.1016/j.bmcl.2010.06.064. Epub 2010 Jun 15.
Abstract
Development of SAR in a 3-cyano-5-fluoro-N-arylbenzamide series of non-competitive antagonists of mGlu(5) using a functional cell-based assay is described in this Letter. Further characterization of selected potent compounds in in vitro assays designed to measure their metabolic stability and protein binding is also presented. Subsequent evaluation of two new compounds in pharmacokinetic studies using intraperitoneal dosing in rats demonstrated good exposure in both plasma and brain samples.
摘要
本文介绍了使用基于功能细胞的测定法，对 3-氰基-5-氟-N-芳基苯甲酰胺系列非竞争 mGlu(5) 拮抗剂的 SAR 发展情况。本文还进一步介绍了在设计用于测量其代谢稳定性和蛋白结合的体外测定中对选定的有效化合物的进一步特征描述。随后，在使用腹腔内给药的大鼠进行的药代动力学研究中对两种新化合物进行了评估，结果表明在血浆和脑组织样本中均具有良好的暴露量。
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