Indolobenzazepin-7-ones and 6-, 8-, and 9-Membered Ring Derivatives as Tubulin Polymerization Inhibitors: Synthesis and Structure−Activity Relationship Studies

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• 作者：Aurlien Putey ; Florence Popowycz ; Quoc-Tuan Do ; Philippe Bernard ; Sandeep K. Talapatra ; Frank Kozielski ; Carlos M. Galmarini ; Benot Joseph
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：October 8, 2009
• 年：2009
• 卷：52
• 期：19
• 页码：5916-5925
• 全文大小：963K
• 年卷期：v.52,no.19(October 8, 2009)
• ISSN：1520-4804

文摘

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.