Journal of Medicinal Chemistry 2006-09-07

3-demethoxy-3-glycosylaminothiocolchicines: Synthesis of a new class of putative muscle relaxant compounds.

Maria Luisa Gelmi, Donato Pocar, Guido Pontremoli, Sara Pellegrino, Ezio Bombardelli, Gabriele Fontana, Antonella Riva, Walter Balduini, Silvia Carloni, Mauro Cimino, Francis Johnson

Index: J. Med. Chem. 49 , 5571, (2006)

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Abstract

A novel class of 3-demethoxy-3-glycosylaminothiocolchicines (7) was prepared and tested for muscle relaxant activity. The syntheses were performed starting from the new 3-amino-3-demethoxythiocolchicine (5) prepared in good yield from 3-O-demethylthiocolchicine (1c) using the Buchwald-Hartwig reaction. The condensation of 5 with a series of pentose and hexose sugars (6) gave a series of 3-demethoxy-3-glycosylaminothiocolchicines (7). Their preparation was accomplished by adapting and improving a previous procedure for the preparation of N-arylglycosylamines. In particular, replacing traditional heating with microwave irradiation represents the key improvement of the process. The biological activity of the 3-demethoxy-3-glycosylaminothiocolchicines (7) was evaluated on GABA and strychnine-sensitive glycine receptors present in rat brain and spinal cord.