Z. Naturforsch. 2012,
67b, 1297 – 1304
doi:10.5560/ZNB.2012-0258
Isolation, Structure, Synthesis and Cytotoxicity of an Unprecedented Flupirtine Dimer
René
Csuk1,
Sven
Sommerwerk1,
Jana
Wiese1,
Christoph
Wagner2,
Bianka
Siewert1,
Ralph
Kluge1, and
Dieter
Ströhl1
1 Martin-Luther-Universität Halle-Wittenberg, Bereich Organische Chemie, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany
2 Martin-Luther-Universität Halle-Wittenberg, Bereich Anorganische Chemie, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany
Received October 2, 2012 / published online November 30, 2012
A previously unknown dimer of the well-established analgesic flupirtine has been found, and its structure was revealed by ESI-MS, NMR spectroscopy and an independent synthesis. Thus, starting from 2-amino-6-chloro-3-nitro-pyridine the target compound was obtained in a four-step synthesis. Key-step of this synthesis is a nickel-mediated aryl-aryl coupling. The dimer 4 did not show any cytotoxicity, and its IC50 values were >30 μm for all six human cancer cell lines and mouse fibroblasts used in this study.
Key words: Flupirtine, Dimerization, Aryl-Aryl Coupling