Discovery of 8-azabicyclo[3.2.1]octan-3-yloxy-benzamides as selective antagonists of the kappa opioid receptor. Part 1.
Bioorg Med Chem Lett
; 20(19): 5847-52, 2010 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-20727752
ABSTRACT
Initial high throughput screening efforts identified highly potent and selective kappa opioid receptor antagonist 3 (κ IC(50)=77 nM; µκ and δκ IC(50) ratios>400) which lacked CNS exposure in vivo. Modification of this scaffold resulted in development of a series of 8-azabicyclo[3.2.1]octan-3-yloxy-benzamides showing potent and selectivity κ antagonism as well as good brain exposure. Analog 6c (κ IC(50)=20 nM; µκ=36, δκ=415) was also shown to reverse κ-agonist induced rat diuresis in vivo.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tropanos
/
Benzamidas
/
Receptores Opioides kappa
Idioma:
En
Revista:
Bioorg Med Chem Lett
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos