Indolobenzazepin-7-ones and 6-, 8-, and 9-membered ring derivatives as tubulin polymerization inhibitors: synthesis and structure--activity relationship studies.
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.
Putey
Aurélien
A
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.
Popowycz
Florence
F
Do
Quoc-Tuan
QT
Bernard
Philippe
P
Talapatra
Sandeep K
SK
Kozielski
Frank
F
Galmarini
Carlos M
CM
Joseph
Benoît
B
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*
D000970:Antineoplastic Agents; D001552:Benzazepines; D007211:Indoles; D050257:Tubulin Modulators