Finally, docking and molecular dynamic studies are carried out to understand the effects of chemical modifications on affinity to the H3R. Considering the great need to find new therapeutic alternatives for the treatment of neurodegenerative diseases, this work contributes to medicinal chemistry through the discovery of easily accessible compounds with high affinity to the H3R, with low toxicity in the cell lines evaluated and with a promising ADME profile. This evidence concerns the gene HRH3 and neurodegenerative disease.