Synthesis and evaluation of tacrine-E2020 hybrids as acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.
Tacrine-E2020 hybrids and some related compounds were prepared and their bioactivities on the Alzheimer's disease were assayed. The optimum hybrid inhibitor 3 is 37-fold more potent and 31-fold more selective than tacrine in vitro.
Shanghai Institute of Materia Medica, Shanghai Institute for Biological Sciences, Graduate School of the Chinese Academy of Sciences, 555 Zhu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.
Dong
D
Shao
Chunyan
C
Zou
Cheng
C
Luo
Xican
X
Tang
Yuanchao
Y
Li
D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000077265:Donepezil; D066298:In Vitro Techniques; D007189:Indans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D008958:Models, Molecular; D018697:Nootropic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D007189:Indans; D008024:Ligands; D018697:Nootropic Agents; D010880:Piperidines; D013619:Tacrine; D000077265:Donepezil; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase