Synthesis, cholinesterase inhibitory activity, and in silico studies of novel pyrazolopyrazine derivatives as selective acetylcholinesterase inhibitors

In this study, a series of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives (8a-i) were synthesized. The moleculer structures of the synthesized compounds were determined by 1H NMR, 13C NMR, and LC-MS/MS analyses. The inhibitory activities of the compounds against AChE and BuChE were evaluated. Compound 8e exhibited the highest inhibitory activity against AChE, with an IC50 value of 3.795 ± 0.057 µM, whereas compound 8h showed the highest inhibitory activity against BuChE, with an IC50 value of 15.484 ± 0.188 µM. The docking scores for compound 8e and donepezil were -8.39 and -11.06 kcal/mol, respectively. The selective acetylcholinesterase inhibitor 8e exhibited interaction patterns comparable to those of donepezil within the active site of AChE.