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.
Shao
Dong
D
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.
Zou
Chunyan
C
Luo
Cheng
C
Tang
Xican
X
Li
Yuanchao
Y
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