Among the 11 synthetized compounds, we identified 6-amino-5-(4-methoxyphenyl)-2-phenyl-[1,2,4]triazolo[1′,5′:1,6]pyrido[2,3-d]pyrimi-dine-4-carbonitrile (3c) as the most balanced triazolopyridopyrimidine, exhibiting micromolar inhibition of AChE with IC50 equal to 1.32 μM and strong antioxidant activity, representing, thus, a new and very promising hit-triazolopyridopyrimidine for AD therapy. The gene discussed is ACHE; the disease is Alzheimer disease.