Design and synthesis of a fluoroindolocarbazole series as selective topoisomerase I active agents.: Discovery of water-soluble 3,9-difluoro-12,13-dihydro-13-[6-amino-β-D-glucopyranosyl]-5H,13H-benzo[b]-thienyl[2,3-α]pyrrolo[3,4-c]carbazole-5,7(6H)-dione (BMS-251873) with curative antitumor activity against prostate carcinoma xenograft tumor model

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.