Novel, potent, selective, and brain penetrant phosphodiesterase 10A inhibitors.
Bioorg Med Chem Lett
; 29(3): 406-412, 2019 02 01.
Article
in En
| MEDLINE
| ID: mdl-30587449
ABSTRACT
Herein we report the discovery of a novel series of phosphodiesterase 10A inhibitors. Optimization of a HTS hit (17) resulted in potent, selective, and brain penetrant 23 and 26; both exhibited much lower clearance in vivo and decreased volume of distribution (rat PK) and have thus the potential to inhibit the PDE10A target in vivo at a lower efficacious dose than the reference compound WEB-3.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Phosphodiesterase Inhibitors
/
Pyrazines
/
Thiazoles
/
Phosphoric Diester Hydrolases
/
Heterocyclic Compounds, 2-Ring
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2019
Type:
Article