title: Novel 3',6'-anhydro and N12,N13-bridged glycosylated fluoroindolo[2,3-a]carbazoles as topoisomerase I inhibitors. Fluorine as a leaving group from sp3 carbon.
abstract: [reaction: see text] Both 6'- and 4'-fluoro-glycosylated indolo[2,3-a]carbazoles are substrates for base-induced loss of fluorine as a leaving group from sp3 carbon. In the case of alpha-N-glycosylated substrate 3, loss of fluorine from the 6'-position leads to 3,6-anhydroglucose analogue 1. A novel N12,N13-bridged sugar analogue 2 results from loss of 4'-fluorine from beta-N-glycosylated analogue 4. Both analogues 1 and 2 display topo I inhibitory potencies similar to camptothecin.
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, Connecticut 06492, USA. mark.saulnier@bms.com
authors.forename: Mark G
authors.initials: MG
authors.lastname: Saulnier
authors.forename: David R
authors.initials: DR
authors.lastname: Langley
authors.forename: David B
authors.initials: DB
authors.lastname: Frennesson
authors.forename: Byron H
authors.initials: BH
authors.lastname: Long
authors.forename: Stella
authors.initials: S
authors.lastname: Huang
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.forename: Dedong
authors.initials: D
authors.lastname: Wu
authors.forename: Craig R
authors.initials: CR
authors.lastname: Fairchild
authors.forename: Edward
authors.initials: E
authors.lastname: Ruediger
authors.forename: Kurt
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Denis R
authors.initials: DR
authors.lastname: St Laurent
authors.forename: Balu N
authors.initials: BN
authors.lastname: Balasubramanian
authors.forename: Dolatrai M
authors.initials: DM
authors.lastname: Vyas
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005461:Fluorine / Q000737:chemistry*; D006027:Glycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006572:Heterocyclic Compounds, Bridged-Ring / Q000138:chemical synthesis* / Q000494:pharmacology; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D007941:Leukemia P388; D008968:Molecular Conformation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
chemical_list: D002227:Carbazoles; D004791:Enzyme Inhibitors; D006027:Glycosides; D006572:Heterocyclic Compounds, Bridged-Ring; D006845:Hydrocarbons, Fluorinated; D007211:Indoles; D059004:Topoisomerase I Inhibitors; D005461:Fluorine; D002244:Carbon