Potent, easily synthesized huperzine A-tacrine hybrid acetylcholinesterase inhibitors.
Hybrid acetylcholinesterase inhibitors composed of a key fragment of huperzine A and an intact tacrine unit were prepared. The syntheses are quite direct, proceeding in a maximum of 4 linear steps from commercially available starting materials. The optimum hybrid inhibitor (+/-)-9g is 13-fold more potent than (-)-huperzine A, and 25-fold more potent than tacrine.
Carlier
P R
PR
Department of Chemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon. chpaul@ust.hk
Du
D M
DM
Han
Y
Y
Liu
J
J
Pang
Y P
YP
D000110:Acetylcholinesterase / Q000187:drug effects*; D000470:Alkaloids; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000737:chemistry*; D013619:Tacrine / Q000737:chemistry*
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D012717:Sesquiterpenes; C050426:huperzine A; D013619:Tacrine; D000110:Acetylcholinesterase