title: Indolobenzazepin-7-ones and 6-, 8-, and 9-membered ring derivatives as tubulin polymerization inhibitors: synthesis and structure--activity relationship studies.
abstract: Several small weight indole derivatives (D-64131, D-24851, BPR0L075, BLF 61-3, and ATI derivatives) are potent tubulin polymerization inhibitors and show nanomolar antiproliferative activity. Among them, indolobenzazepin-7-ones were recently disclosed as potent antimitotic agents. In an effort to improve this structure, we prepared new derivatives in order to evaluate their antiproliferative activity. 5,6,7,9-Tetrahydro-8H-indolo[2,3-e][3]benzazocin-8-one (1m) was found to be the most potent derivative inhibiting the cell growth of several cancer cell lines in the lower nanomolar range.
authors.affiliation: Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, UMR-CNRS 5246, Laboratoire de Chimie Organique 1, Université de Lyon, Université Claude Bernard-Lyon 1, Villeurbanne, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Putey
authors.forename: Florence
authors.initials: F
authors.lastname: Popowycz
authors.forename: Quoc-Tuan
authors.initials: QT
authors.lastname: Do
authors.forename: Philippe
authors.initials: P
authors.lastname: Bernard
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Talapatra
authors.forename: Frank
authors.initials: F
authors.lastname: Kozielski
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Galmarini
authors.forename: Benoît
authors.initials: B
authors.lastname: Joseph
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis; D001552:Benzazepines / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis*
chemical_list: D000970:Antineoplastic Agents; D001552:Benzazepines; D007211:Indoles; D050257:Tubulin Modulators