Synthesis of potential new pyrazole ring-containing bicyclic molecules in the treatment of hyperglycemia

Numerous drugs have been developed for the treatment of diabetes. Pyrazole derivatives have been reported in the literature as potent antidiabetic agents. In particular, heterocyclic systems fused with pyrimidine have mostly been shown to be effective enzyme inhibitors related to diabetes, especially α-glucosidase and/or α-amylase. Enzymes such as α-amylase and α-glucosidase, which break down starch into glucose, are of vital importance for the regulation of blood glucose levels. Inhibitors of α-amylase and α-glucosidase delay this process, thereby reducing the amount of glucose absorbed. However, some of the drugs currently used in treatment have been reported to cause side effects such as hypoglycemia, weight gain, gastrointestinal distress, and even increased cancer risk. Therefore, the design of new therapeutic agents has gained importance. Although there are studies in the literature that highlight the biological potential of the pyrazole ring and the antihyperglycemic properties of bicyclic structures containing pyrazole, no research has been found specifically on molecules containing a pyrazolopyrazinone structure. It is anticipated that the molecules to be synthesized and their related activity studies within the scope of this project will contribute to the literature. In this thesis study, the design of a novel bicyclic pyrazolopyrazinone ring system containing a pyrazole moiety was initially carried out. New derivatives were synthesized, purified, and characterized using a method different from those reported in the literature. To investigate their potential for treating hyperglycemia, the inhibition of the alpha-amylase enzyme by the synthesized compounds was measured. When compared with the standard inhibitor Acarbose, the nine newly synthesized compounds did not significantly reduce α-amylase activity at concentrations of 5, 10, 20, and 40 μM, indicating no statistically significant inhibition.