Synthesis of novel C-glucopyranosyl heterocycles for the inhibition of sodium-dependent glucose cotransporter 2

PS1 Poster session 1 Odd numbers
Location (hall): 
Start/end time: 
Monday, July 1, 2019 - 15:45 to 17:15

Sándor Kun1, Eszter Szennyes1, Éva Bokor1, Nikolett Éva Hajnal1, Ádám Sipos2, Tibor Docsa2, László Somsák1

1Department Of Organic Chemistry, University Of Debrecen, Debrecen, Hungary, 2Department of Medical Chemistry, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary

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.

  1. 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.
  2. 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.