1.
J Med Chem
; 48(7): 2258-61, 2005 Apr 07.
Artículo
en Inglés
| MEDLINE
| ID: mdl-15801816
RESUMEN
A series of fluoroglycosylated fluoroindolocarbazoles was examined with respect to their topoisomerase I activity, cytotoxicity, and selectivity. The lead clinical candidate from this series, BMS-250749, displays broad spectrum antitumor activity superior to CPT-11 against some preclinical xenograft models, including curative antitumor activity against Lewis lung carcinoma.
Asunto(s)
Antineoplásicos/síntesis química , Camptotecina/análogos & derivados , Camptotecina/farmacología , Carbazoles/síntesis química , Glucósidos/síntesis química , Indoles/síntesis química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Carbazoles/química , Carbazoles/farmacología , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Glucósidos/química , Glucósidos/farmacología , Humanos , Técnicas In Vitro , Indoles/química , Indoles/farmacología , Irinotecán , Ratones , Microsomas Hepáticos/metabolismo , Inhibidores de Topoisomerasa I , Trasplante Heterólogo
2.
J Med Chem
; 47(7): 1609-12, 2004 Mar 25.
Artículo
en Inglés
| MEDLINE
| ID: mdl-15027851
RESUMEN
A series of fluoroindolocarbazoles were studied with respect to their topoisomerase I activity, cytotoxicity, selectivity, and in vivo antitumor activity. Emerging from this series was BMS-251873, a potential clinical candidate possessing a robust pharmacological profile including curative antitumor activity against prostate carcinoma.