Structure-activity studies of a novel series of 5,6-fused heteroaromatic ureas as TRPV1 antagonists.
Bioorg Med Chem
; 14(14): 4740-9, 2006 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-16621571
ABSTRACT
Novel 5,6-fused heteroaromatic ureas were synthesized and evaluated for their activity as TRPV1 antagonists. It was found that 4-aminoindoles and indazoles are the preferential cores for the attachment of ureas. Bulky electron-withdrawing groups in the para-position of the aromatic ring of the urea substituents imparted the best in vitro potency at TRPV1. The most potent derivatives were assessed in in vivo inflammatory and neuropathic pain models. Compound 46, containing the indazole core and a 3,4-dichlorophenyl group appended to it via a urea linker, demonstrated in vivo analgesic activity upon oral administration. This derivative also showed selectivity versus other receptors in the CEREP screen and exhibited acceptable cardiovascular safety at levels exceeding the therapeutic dose.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ureia
/
Canais de Cátion TRPV
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos