1.
J Med Chem
; 48(7): 2258-61, 2005 Apr 07.
Article
de Anglais
| MEDLINE
| ID: mdl-15801816
RÉSUMÉ
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.
Sujet(s)
Antinéoplasiques/synthèse chimique , Camptothécine/analogues et dérivés , Camptothécine/pharmacologie , Carbazoles/synthèse chimique , Glucosides/synthèse chimique , Indoles/synthèse chimique , Animaux , Antinéoplasiques/composition chimique , Antinéoplasiques/pharmacologie , Carbazoles/composition chimique , Carbazoles/pharmacologie , Lignée cellulaire tumorale , Évaluation préclinique de médicament , Résistance aux médicaments antinéoplasiques , Tests de criblage d'agents antitumoraux , Glucosides/composition chimique , Glucosides/pharmacologie , Humains , Techniques in vitro , Indoles/composition chimique , Indoles/pharmacologie , Irinotécan , Souris , Microsomes du foie/métabolisme , Inhibiteurs de la topoisomérase-I , Transplantation hétérologue
2.
J Med Chem
; 47(7): 1609-12, 2004 Mar 25.
Article
de Anglais
| MEDLINE
| ID: mdl-15027851
RÉSUMÉ
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.