Synthesis of Glitazone Analogues as Anti-Diabetic Drugs

Abstract

In this study, three series of novel glitazones (acetates, glycinates and alaninates) were designed and prepared by using appropriate synthetic methods to incorporate aromatic ring, alicyclic amines and alanine moiety instead of glycine moiety as a linker via two carbons. This was done over five reaction steps. Compounds were synthesized using conventional methods from step one with nucleophilic substitution to Knoevenagel condensation reaction as the final step and were characterized by using a combination of 1H NMR, 13C NMR, IR spectroscopies as well as HRMS analysis. Fourteen final compounds were successfully obtained in good to excellent yields. Furthermore, the same compounds were subjected to in vitro screening for their inhibitory activities against α-glucosidase and α-amylase. Among all the synthesized compounds, 36f exhibited excellent antidiabetic activities against α-glucosidase. Compounds 36a, 36b, 36i and 36j also displayed good activities and have potential to be further investigated whereas compounds 36c, 36e, 36g and 36h exhibited moderated activities against α-glucosidase. Only compounds 36a, 36b, 36f, 36i and 36j displayed weak activities against α-amylase and the rest of the compounds were not active at all against α-amylase.