Synthesis and biological evaluation of (4H-1,2,4-triazol-4-yl)isoquinoline derivatives as selective glycine transporter 1 inhibitors

A series of 4H-1,2,4-triazole derivatives with heteroaromatic rings at the 4-position were synthesized as selective GlyT1 inhibitors. The modification of 5 led to identification of 15 with improved selectivity, solubility, and in vivo activity.