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

Bioorg Med Chem Lett. 2012 Mar 1;22(5):1944-8. doi: 10.1016/j.bmcl.2012.01.046. Epub 2012 Jan 26.

Abstract

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.

MeSH terms

  • Antipsychotic Agents / chemistry*
  • Antipsychotic Agents / pharmacology*
  • Humans
  • Models, Molecular
  • Naphthyridines / chemistry*
  • Naphthyridines / pharmacology*
  • Nitriles / chemistry
  • Nitriles / pharmacology
  • Phosphodiesterase Inhibitors / chemistry*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphoric Diester Hydrolases / chemistry
  • Phosphoric Diester Hydrolases / metabolism*
  • Structure-Activity Relationship

Substances

  • Antipsychotic Agents
  • Naphthyridines
  • Nitriles
  • Phosphodiesterase Inhibitors
  • PDE10A protein, human
  • Phosphoric Diester Hydrolases