Structure-activity relationships of 1,5-biaryl pyrroles as EP1 receptor antagonists.
Bioorg Med Chem Lett
; 16(14): 3657-62, 2006 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-16697196
ABSTRACT
The preliminary SAR of a series of novel 1,5-biaryl pyrrole EP1 receptor antagonists derived from compound 1 is described. Replacement of the benzyl group of 1 with isosteric groups was investigated. The most effective replacement was found to be the isobutyl group. The cyclopentylmethyl and cyclohexylmethyl groups were also effective benzyl replacements. The cyclohexylmethyl derivative 19 demonstrated the lowest metabolic clearance within this series. In addition, several high affinity substituted benzyl analogues were also identified. Compound 39 was found to have good bioavailability in rats and demonstrated efficacy in the established FCA preclinical model of inflammatory pain with a calculated ED50 of 9.2mg/kg.
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Bases de datos:
MEDLINE
Asunto principal:
Pirroles
/
Benzoatos
/
Receptores de Prostaglandina E
/
Analgésicos
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Reino Unido