3-Demethoxy-3-glycosylaminothiocolchicines:  Synthesis of a New Class of Putative Muscle Relaxant Compounds

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 reacti...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2006-09, Vol.49 (18), p.5571-5577
Main Authors: Gelmi, Maria Luisa, Pocar, Donato, Pontremoli, Guido, Pellegrino, Sara, Bombardelli, Ezio, Fontana, Gabriele, Riva, Antonella, Balduini, Walter, Carloni, Silvia, Cimino, Mauro, Johnson, Francis
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Biological and medical sciences
Cerebral Cortex - metabolism
Colchicine - analogs & derivatives
Colchicine - chemical synthesis
Colchicine - pharmacology
Glutamatergic system (aspartate and other excitatory aminoacids)
Glycosides - chemical synthesis
Glycosides - pharmacology
In Vitro Techniques
Medical sciences
Muscimol - metabolism
Neuromuscular Agents - chemical synthesis
Neuromuscular Agents - pharmacology
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Radioligand Assay
Rats
Receptors, GABA - metabolism
Receptors, Glycine - metabolism
Spinal Cord - metabolism
Strychnine - metabolism
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm060585t