Discovery of 4-hydroxy-1,6-naphthyridine-3-carbonitrile derivatives as novel PDE10A inhibitors.

A series of 1,6-naphthyridine-based compounds was synthesized as potent phosphodiesterase 10A (PDE10A) inhibitors. Structure-based chemical modifications of the discovered chemotype served to further improve potency and selectivity over DHODH, laying the foundation for future optimization efforts.