Synthesis and Biological Evaluation of 3-Biphenyl-4-yl-4-phenyl-4<i>H</i>-1,2,4-triazoles as Novel Glycine Transporter 1 Inhibitors

Abstract

We describe the preparation and evaluation of a novel series of glycine transporter 1 (GlyT1) inhibitors derived from a high-throughput screening hit. The SAR studies resulted in the discovery of 3-biphenyl-4-yl-4-(2-fluorophenyl)-5-isopropyl-4H-1,2,4-triazole (6p). A pharmacokinetic study was also conducted and revealed that 6p had excellent oral bioavailability and ameliorated learning impairment in passive avoidance tasks in mice.