3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu5: Identification of easily prepared tool compounds with CNS exposure in rats

Development of SAR in a 3-cyano-5-fluoro-N-arylbenzamide series of non-competitive antagonists of mGlu5 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.