Design, synthesis, and evaluation of benzophenone derivatives as novel acetylcholinesterase inhibitors.
Starting from a structure-based drug design, new acetylcholinesterase inhibitors were designed and synthesized as analogues of donepezil. The compounds were composed by an aromatic function and a tertiary amino moiety connected by a suitable spacer. In particular, the benzophenone nucleus and the N,N-benzylmethylamine function were selected. The easily accessible three-step synthesis of these compounds resulted to be significantly less difficult and expensive than that of donepezil. Several compounds possess anti-cholinesterase activity in the order of micro and sub-micromolar. Particularly, compounds 1 and 10 were the most potent inhibitors of the series.
Belluti
Federica
F
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. federica.belluti@unibo.it
Piazzi
Lorna
L
Bisi
Alessandra
A
Gobbi
Silvia
S
Bartolini
Manuela
M
Cavalli
Andrea
A
Valenti
Piero
P
Rampa
Angela
A
D000110:Acetylcholinesterase / Q000187:drug effects*; D001577:Benzophenones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization
D001577:Benzophenones; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase