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

Putey, A., Popowycz, F., Do, Q.T., Bernard, P., Talapatra, S.K., Kozielski, F., Galmarini, C.M. and Joseph, B. (2009) Indolobenzazepin-7-ones and 6-, 8-, and 9-Membered Ring Derivatives as Tubulin Polymerization Inhibitors: Synthesis and Structure−Activity Relationship Studies. Journal of Medicinal Chemistry, 52(19), pp. 5916-5925. (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-g-one (1m) was found to be the most potent derivative inhibiting the cell growth of several cancer cell lines in the lower nanomolar range.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kozielski, Professor Frank and Talapatra, Mr Sandeep
• Authors: Putey, A., Popowycz, F., Do, Q.T., Bernard, P., Talapatra, S.K., Kozielski, F., Galmarini, C.M., and Joseph, B.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Journal of Medicinal Chemistry
• ISSN: 0022-2623