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 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.
Gelmi
Maria Luisa
ML
Istituto di Chimica Organica A. Marchesini, Facoltà di Farmacia, Università di Milano, Via Venezian 21, I-20133 Milano, Italy.
Pocar
Donato
D
Pontremoli
Guido
G
Pellegrino
Sara
S
Bombardelli
Ezio
E
Fontana
Gabriele
G
Riva
Antonella
A
Balduini
Walter
W
Carloni
Silvia
S
Cimino
Mauro
M
Johnson
Francis
F
D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006027:Glycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D009118:Muscimol / Q000378:metabolism; D009465:Neuromuscular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism; D018009:Receptors, Glycine / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D013331:Strychnine / Q000378:metabolism
D006027:Glycosides; D009465:Neuromuscular Agents; D018079:Receptors, GABA; D018009:Receptors, Glycine; D009118:Muscimol; D013331:Strychnine; D003078:Colchicine