2. Academic Validation
  3. Indolobenzazepin-7-ones and 6-, 8-, and 9-membered ring derivatives as tubulin polymerization inhibitors: synthesis and structure--activity relationship studies

Indolobenzazepin-7-ones and 6-, 8-, and 9-membered ring derivatives as tubulin polymerization inhibitors: synthesis and structure--activity relationship studies

  • J Med Chem. 2009 Oct 8;52(19):5916-25. doi: 10.1021/jm900476c.
Aurélien Putey 1,  Florence Popowycz,  Quoc-Tuan Do,  Philippe Bernard,  Sandeep K Talapatra,  Frank Kozielski,  Carlos M Galmarini,  Benoît Joseph
Affiliations

Affiliation

  • 1 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.
PMID: 19743863 DOI: 10.1021/jm900476c
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.

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