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.
AstraZeneca, R&D Mölndal, Pepparedsleden 1, S-431 83 Mölndal, Sweden. udo.bauer@astrazeneca.com
Udo
U
Bauer
Fabrizio
F
Giordanetto
Martin
M
Bauer
Gavin
G
O'Mahony
Kjell E
KE
Johansson
Wolfgang
W
Knecht
Judith
J
Hartleib-Geschwindner
Eva Töppner
ET
Carlsson
Cristofer
C
Enroth
D014150:Antipsychotic Agents / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D009287:Naphthyridines / Q000737:chemistry* / Q000494:pharmacology*; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D009287:Naphthyridines; D009570:Nitriles; D010726:Phosphodiesterase Inhibitors; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases