Design and biological activity of (S)-4-(5-([1-(3-chlorobenzyl)-2-oxopyrrolidin-3-ylamino]methyl)imidazol-1-ylmethyl)benzonitrile, a 3-aminopyrrolidinone farnesyltransferase inhibitor with excellent cell potency.
J Med Chem
; 44(18): 2933-49, 2001 Aug 30.
Article
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| MEDLINE
| ID: mdl-11520202
ABSTRACT
The synthesis, structure-activity relationships, and biological properties of a novel series of imidazole-containing inhibitors of farnesyltransferase are described. Starting from a 3-aminopyrrolidinone core, a systematic series of modifications provided 5h, a non-thiol, non-peptide farnesyltransferase inhibitor with excellent bioavailability in dogs. Compound 5h was found to have an unusually favorable ratio of cell potency to intrinsic potency, compared with other known FTIs. It exhibited excellent potency against a range of tumor cell lines in vitro and showed full efficacy in the K-rasB transgenic mouse model.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirrolidinonas
/
Transferasas Alquil y Aril
/
Inhibidores Enzimáticos
/
Imidazoles
/
Lactamas
/
Antineoplásicos
/
Nitrilos
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos