title: 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-beta-D-glucopyranosyl]-5H,13H-benzo[b]- thienyl[2,3-a]pyrrolo[3,4-c]carbazole- 5,7(6H)-dione (BMS-251873) with curative antitumor activity against prostate carcinoma xenograft tumor model.
abstract: 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.
authors.affiliation: The Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford Connecticut 06492, USA. balu@bms.com
authors.forename: Balu N
authors.initials: BN
authors.lastname: Balasubramanian
authors.forename: Denis R
authors.initials: DR
authors.lastname: St  Laurent
authors.forename: Mark G
authors.initials: MG
authors.lastname: Saulnier
authors.forename: Byron H
authors.initials: BH
authors.lastname: Long
authors.forename: Carol
authors.initials: C
authors.lastname: Bachand
authors.forename: Francis
authors.initials: F
authors.lastname: Beaulieu
authors.forename: Wendy
authors.initials: W
authors.lastname: Clarke
authors.forename: Milind
authors.initials: M
authors.lastname: Deshpande
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Eummer
authors.forename: Craig R
authors.initials: CR
authors.lastname: Fairchild
authors.forename: David B
authors.initials: DB
authors.lastname: Frennesson
authors.forename: Robert
authors.initials: R
authors.lastname: Kramer
authors.forename: Frank Y
authors.initials: FY
authors.lastname: Lee
authors.forename: Mikael
authors.initials: M
authors.lastname: Mahler
authors.forename: Alain
authors.initials: A
authors.lastname: Martel
authors.forename: B Narasimhulu
authors.initials: BN
authors.lastname: Naidu
authors.forename: William C
authors.initials: WC
authors.lastname: Rose
authors.forename: John
authors.initials: J
authors.lastname: Russell
authors.forename: Edward
authors.initials: E
authors.lastname: Ruediger
authors.forename: Carola
authors.initials: C
authors.lastname: Solomon
authors.forename: Karen M
authors.initials: KM
authors.lastname: Stoffan
authors.forename: Henry
authors.initials: H
authors.lastname: Wong
authors.forename: John J
authors.initials: JJ
authors.lastname: Wright
authors.forename: Kurt
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Dolatrai M
authors.initials: DM
authors.lastname: Vyas
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012995:Solubility; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D014867:Water; D023041:Xenograft Model Antitumor Assays
chemical_list: C484861:3,9-difluoro-12,13-dihydro-13-(6-aminoglucopyranosyl)-5H,13H-benzo(b)thienyl(2,3-a)pyrrolo(3,4-c)carbazole-5,7(6H)-dione; D000970:Antineoplastic Agents; D002227:Carbazoles; D005960:Glucosides; D059004:Topoisomerase I Inhibitors; D014867:Water