Structure-activity relationship refinement and further assessment of indole-3-glyoxylamides as a lead series against prion disease.
ChemMedChem
; 6(1): 115-30, 2011 Jan 03.
Article
en En
| MEDLINE
| ID: mdl-21154498
ABSTRACT
Structure-activity relationships within the indole-3-glyoxylamide series of antiprion agents have been explored further, resulting in discovery of several new compounds demonstrating excellent activity in a cell line model of prion disease (EC50 <10â
nM). After examining a range of substituents at the para-position of the N-phenylglyoxylamide moiety, five-membered heterocycles containing at least two heteroatoms were found to be optimal for the antiprion effect. A number of modifications were made to probe the importance of the glyoxylamide substructure, although none were well tolerated. The most potent compounds did, however, prove largely stable towards microsomal metabolism, and the most active library member cured scrapie-infected cells indefinitely on administration of a single treatment. The present results thereby confirm the indole-3-glyoxylamides as a promising lead series for continuing in vitro and in vivo evaluation against prion disease.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Compuestos de Sulfonilurea
/
Priones
/
Enfermedades por Prión
/
Bibliotecas de Moléculas Pequeñas
/
Indoles
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2011
Tipo del documento:
Article