Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia.
J Med Chem
; 62(8): 4218-4224, 2019 04 25.
Article
in En
| MEDLINE
| ID: mdl-30916555
ABSTRACT
To identify phosphodiesterase-9 (PDE9) as a novel target for the treatment of vascular dementia (VaD), a series of pyrazolopyrimidinone analogues were discovered based on a hit 1. Hit-to-lead optimization resulted in a potent inhibitor 2 with excellent selectivity and physicochemical properties to enable in vivo studies. Oral administration of 2 (5.0 mg/kg) caused notable therapeutic effects in the VaD mouse model, providing a promising lead or chemical probe for investigating the biological functions of PDE9 inhibition.
Full text:
1
Database:
MEDLINE
Main subject:
Phosphodiesterase Inhibitors
/
Drug Design
/
3',5'-Cyclic-AMP Phosphodiesterases
Language:
En
Journal:
J Med Chem
Year:
2019
Type:
Article