Design, synthesis and in vitro testing of 7-methoxytacrine-amantadine analogues: a novel cholinesterase inhibitors for the treatment of Alzheimer’s disease

A series of cholinesterase inhibitors acting as dual binding site heterodimers for the management of Alzheimer’s disease were developed. The series of 7-methoxytacrine (7-MEOTA)-amantadine ureas (11–17) was designed, prepared evaluated in vitro towards human acetyl/butyryl cholinesterase (hAChE, hBChE) and compared with the series of 7-MEOTA-amantadine thioureas (4–10). The heterodimers have different length of linkers combining 7-MEOTA and amantadine moieties. In comparison with 7-MEOTA, the newly synthesized compounds were better inhibitors of both cholinesterases. The urea analogues did not have the anticipated benefit of increased inhibitory activity and have comparable IC50 values with thiourea derivatives.