Synthesis and Antidiabetic Screening of Chalcone-Based N-Acetyl Pyrazoles

Objective: To synthesize chalcone-based N-acetyl pyrazoles and evaluate their antidiabetic activity. Methods: A total of 19 pyrazole analogues based on the chalcone scaffold were synthesized via reflux and screened for α-glucosidase inhibitory activity using acarbose as a positive control (IC50 = 12.50 ± 0.20 μM). Results and Discussion: The compounds generally exhibited excellent inhibitory activity, with some exceptions. Compounds (10), (13), (14), (17), and (18) were the most potent compared to standard acarbose. The inhibitory potentials of selected analogues were as follows: (2j) 10.66 ± 0.88 μM; (2m) 9.81 ± 0.66 μM; (2n) 4.12 ± 0.12 μM; (2q) 6.22 ± 0.90 μM; (2r) 3.60 ± 0.98 μM. The remaining 14 analogues showed moderate to satisfactory activity. Conclusions: Structure–activity relationship (SAR) analysis indicated that the presence of electron-donating and electron-withdrawing groups, particularly at the ortho and para positions of the phenyl ring, enhanced inhibitory activity. Structural confirmation was carried out using various spectroscopic techniques, including 1H, 13C NMR, and HR-EI-MS.