Synthesis, AChE and BuChE Inhibitory Activity, and Computational Evaluation of Pyrazole‐Based Acrylonitrile Derivatives

Abstract 2,3‐disubstituted heteroaryl acrylonitrile derivatives ( 7a‐e ) were synthesized by Konevenagel reaction of pyrazole aldehyde ( 5 ) with substituted benzylacetonitrile compounds. The moleculer structures of the synthesized compounds were determined by IR, 1 H‐NMR, and 13 C‐NMR spectroscopic techniques. The inhibition properties of acrylonitrile derivatives against AChE and BuChE enzymes were investigated. The molecule ( 7e ) showed the best result for both enzymes in the inhibition tests using with tacrine as a reference. ( 7e ) molecule showed the best AChE inhibition (IC 50 : 1.195 µM) and BuChE inhibition (IC 50 : 5.172 µM). The binding affinity of compound ( 7e ) to proteins (4EY7 and 4BDS) was found to be highest for −7.806 at 4EY7 and −7.417 kcal/mol 4BDS, respectively.