Potent acetylcholinesterase inhibitors: design, synthesis and structure–activity relationships of alkylene linked bis-galanthamine and galanthamine–galanthaminium salts

The syntheses, the anticholinesterase activities and structure–activity relationships of homodimeric (3a–c) and heterodimeric (6a–c) alkylene linked bis-galanthamine are reported. Compounds 6b–c were found to be more potent than galanthamine and tacrine in inhibiting AChE. Scheme 1. (a) Br(CH2)nBr, NEt3, CH3CN, 25 °C, 60 h. (b) NBS, CH3CN, 25 °C, 1 (70%). (c) Br(CH2)nBr, CH3CN, reflux, 20 h. (d) 2, Na2CO3, CH3CN, 25 °C, 7 d.