Diaryl urea analogues of SB-334867 as orexin-1 receptor antagonists.
Bioorg Med Chem Lett
; 21(10): 2980-5, 2011 May 15.
Article
em En
| MEDLINE
| ID: mdl-21478014
ABSTRACT
As a part of our program to develop OX1-CB1 bivalent ligands, we required a better understanding of the basic structure-activity relationships (SARs) of orexin antagonists. A series of SB-334867 analogues were synthesized and evaluated in calcium mobilization assays. SAR results suggest that the 2-methylbenzoxazole moiety may be replaced with a disubstituted 4-aminophenyl group without loss of activity and an electron-deficient system is generally preferred at the 1,5-naphthyridine moiety for OX1 antagonist activity. In particular, substitution of larger potential linkers such as n-hexyl provided compound 33 with equivalent activity at the OX1 receptor compared to the lead compound SB-334867. These compounds should be of value in the development of ligands targeting the orexin-1 receptor and its potential heterodimers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ureia
/
Benzoxazóis
/
Receptores de Neuropeptídeos
/
Receptores Acoplados a Proteínas G
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article