Discovery and structure-activity relationships of pyrrolone antimalarials.
J Med Chem
; 56(7): 2975-90, 2013 Apr 11.
Article
en En
| MEDLINE
| ID: mdl-23517371
ABSTRACT
In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC(50) ~ 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirroles
/
Descubrimiento de Drogas
/
Antimaláricos
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido