Synthesis, antitubulin, and antiproliferative SAR of analogues of 2-Methoxyestradiol-3,17-O,O-bis-sulfamate

Fabrice Jourdan, Mathew P. Leese, Wolfgang Dohle, Ernest Hamel, Eric Ferrandis, Simon P. Newman, Atul Purohit, M. J. Reed, Barry V. L. Potter

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40 Citations (SciVal)


The synthesis and antiproliferative activity of analogues of estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) are discussed. Modifications of the C-17 substituent reveal that an H-bond acceptor is essential for high antiproliferative activity. The local environment in which this H-bond acceptor lies can be varied to an extent. The C-17-oxygen linker can be deleted or substituted with an electronically neutral methylene group, and replacement of the terminal NH2 with a methyl group is also acceptable. Mesylates 10 and 14 prove equipotent to the E2bisMATEs 2 and 3, while sulfones 20 and 35 display enhanced in vitro antiproliferative activity. In addition, the SAR of 2-substituted estradiol-3-O-sulfamate derivatives as inhibitors of tubulin polymerization has been established for the first time. These agents inhibit the binding of radiolabeled colchicine to tubulin.
Original languageEnglish
Pages (from-to)2942-2951
JournalJournal of Medicinal Chemistry
Issue number7
Publication statusPublished - 8 Apr 2010


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