Synthesis and Biological Evaluation of Novel Pyrazole-Barbiturate Hybrids as Alpha-Glucosidase Inhibitors

Objective: Type 2 diabetes is a global health problem marked by chronic hyperglycemia. α-Glucosidase inhibitors help regulate postprandial glucose levels, but current drugs have side effects and limited efficacy. This study aimed to develop novel pyrazole–barbiturate hybrids as more effective α-glucosidase inhibitors.Material and Method: Type 2 diabetes is a global health problem marked by chronic hyperglycemia. α-Glucosidase inhibitors help regulate postprandial glucose levels, but current drugs have side effects and limited efficacy. This study aimed to develop novel pyrazole–barbiturate hybrids as more effective α-glucosidase inhibitors.Result and Discussion: Only compound 17f, featuring a 4-biphenyl group, showed strong α-glucosidase inhibition (IC₅₀=35.28±1.14 µM), outperforming the reference drug acarbose. The other compounds were inactive (IC₅₀>200 µM). The findings highlight the importance of aromatic bulk and hydrophobicity in enzyme binding. Molecular docking supported the observed activity of 17f, indicating favorable π–π stacking and hydrophobic interactions. These results suggest 17f as a promising candidate for further development as an antidiabetic agent.