Sodium-glucose cotransporter 2 (SGLT2) inhibitors belong to a novel class of oral anti-hyperglycemic agents that reduce plasma glucose concentrations by the inhibition of glucose reabsorption in the kidney thereby inducing glucosuria.[1,2]
Marketed SGLT2 inhibitors [1] also called gliflozins are C-glycosyl derivatives having diaryl methane type aglycone (1), in which the second aryl moiety can be a heteroaromatic ring (thiophene or benzothiophene), as well. Several promising inhibitors were found among glucose derivatives wherein the first aryl unit was replaced by a hetrarene ring such as thiophene, pyrrole, thiazole, pyridine, pyrazine and pyridazine.[2] In connection with this, synthesis of similar arylmethyl substituted C-β-D-glucopyranosyl heterocycles (i.e. pyrimidines (2a) and oxadiazoles (2b,c)) was envisaged in order to broaden the structure-activity relationship studies of such type of SGLT2 inhibitors.
In the presentation the syntheses of 2a-c and preliminary results of SGLT2 inhibition will be reported.
- Aguillón, A. R.; Mascarello, A.; Segretti, N. D.; de Azevedo, H. F. Z. C.; Guimaraes, R. W.; Miranda, L. S. M.; de Souza. R. O. M. A. Synthetic strategies toward SGLT2 inhibitors. Org. Process Res. Dev. 2018, 22, 467-488.
- Bokor, É.; Kun, S.; Goyard, D.; Tóth, M.; Praly, J.-P.; Vidal, S.; Somsák, L. C-Glycopyranosyl arenes and hetarenes: synthetic methods and bioactivity focused on antidiabetic potential. Chem. Rev. 2017, 117, 1687-1764.
