Synthesis of 1-azolylcytizines

Chemistry of 1,2,3-triazoles

“…A series of 5-amino-2-aryl-2H-1,2,3-triazoles were successfully prepared by oxidation of arylhydrazonoacetamidines with copper(II) salt in pyridine [269][270][271][272][273][274]. The oxidative cyclization of 2-arylhydrazonoacetamidines 214 was carried out with copper(II) acetate or sulfate in pyridine at 60 C under vigorous stirring and afforded aminotriazoles 216 in good yield (Scheme 75) [270][271][272]274].…”

“…The oxidative cyclization of 2-arylhydrazonoacetamidines 214 was carried out with copper(II) acetate or sulfate in pyridine at 60 C under vigorous stirring and afforded aminotriazoles 216 in good yield (Scheme 75) [270][271][272]274]. This synthetic approach allows to introduce amino, amide, and cyano groups in 1,2,3-triazoles, as well as various pharmacophores and fragments of natural products (e.g., tryptamine) and alkaloids (cytosine, piperazine) (Scheme 75).…”

“…Currently, the following three drugs are used therapeutically in the treatment of non-insulin-dependent diabetes as antiglucosidases: 1-(2-hydroxyethyl)-2-(hydroxymethyl)-1-deoxynojirimycin (156, Miglitol or Glyset) [266], N-butyl-1-deoxynojirimycin (157, Zavesca) and voglibose (158, Vogli, Basen, or Prandial) (Scheme 21). New compounds with inhibitory activity on glycosidases led to the discovery that five-membered azaheterocycles mimic the sugar moieties; thus, various compounds containing the pyrrole, imidazole [267,268], tetrazolo-glyco-derivatives, and [1,2,3]-1Htriazole [269][270][271][272][273][274][275] groups were prepared and evaluated. Because the alkyl chain linker of N-butyl-1-deoxynojirimycin (157) does not have a deleterious effect on the inhibition of α-glucosidases on glycosidase activity, Zhou and coworkers [276] designed and synthesized a series of triazoles linked to nojirimycin (154) and evaluated their ability to inhibit α-glucosidase from Bacillus stearothermophilus.…”

“…Because of the reduction of blood glucose levels, there is a decrease in the glycosylated hemoglobin in patients with diabetes mellitus type II (non-insulin dependent). Following the previous pattern of introducing the triazoles ring into the structure's natural product, several compounds were synthesized and tested as glycosidase inhibitors [271]. Surprisingly, the mimetic triazole (168) did not improve the inhibitory activity.…”