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

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.

Cytotoxic Colchicine Alkaloids: From Plants to Drugs

“…N-deacetyl-10-methylthiocolchicine 36 was converted into compounds: 37 [44], 38 and 39 [44]. 10-Methylthiocolchine was modified at C-3 position to compound 3-demethoxy-3-amino-10-methylthiocolchicine 40 and then to 3-demethoxy-3-glycosylaminothiocolchicines 41-47 ( Figure 5) [48]. From derivatives 48-52 Cytotoxic Colchicine Alkaloids: From Plants to Drugs http://dx.doi.org/10.5772/intechopen.72622 [51].…”

“…This compound is registered in different countries under the trade names of Colcamyl, Coltramyl, Coltrax, Miorel, and Musco-Ril. Muscle spasm is one of the main factors responsible for chronic pain, and because this particular drug reduces muscle tone, it is used in therapy for the treatment of contractures and inflammatory conditions that affect the muscular system [48].…”

Introduction of polar groups on the naphthalene scaffold of molecular tongs inhibiting wild-type and mutated HIV-1 protease dimerization

“…This reagent is commercially available and allows an easy deprotection of the amino function under mild conditions. 40 A Buchwald-Hartwig reaction was performed on compounds 18 and 19, using benzophenone imine to afford intermediates that were not isolated but immediately hydrolysed, using methanol in the presence of sodium acetate and hydroxylamine hydrochloride, to afford amines 22 (62% over two steps) and 23 (51% over two steps) in satisfactory yields (Scheme 3).…”

A Journey into Recent Microwave‐Assisted Carbohydrate Chemistry

“…Gelmi et al [65] prepared and tested for their muscle relaxant activity a novel class of thiocolchicines (91) by condensation of 89 with a series of pentose and hexose sugars (90). The new starting 89 was prepared in good yield from 3-O-demethylthiocolchicine using the Buchwald-Hartwig reaction and replacing CH with MWI, which represents the key improvement of the process (scheme 21.28).…”