Isoquinoline derivatives as potent CRTH2 receptor antagonists: synthesis and SAR.
Bioorg Med Chem Lett
; 22(9): 3305-10, 2012 May 01.
Article
en En
| MEDLINE
| ID: mdl-22469703
Synthesis and structure-activity relationship of a novel series of isoquinoline CRTH2 receptor antagonists are described. One of the most potent compounds, TASP0376377 (6m), showed not only potent binding affinity (IC(50)=19 nM) but also excellent functional antagonist activity (IC(50)=13 nM). TASP0376377 was tested for its ability of a chemotaxis assay to show the effectiveness (IC(50)=23 nM), which was in good agreement with the CRTH2 antagonist potency. Furthermore, TASP0376377 showed sufficient selectivity for binding to CRTH2 over the DP1 prostanoid receptor (IC(50)>1 µM) and COX-1 and COX-2 enzymes (IC(50)>10 µM).
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de Prostaglandina
/
Receptores Inmunológicos
/
Isoquinolinas
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido