Design, synthesis, and evaluation of indanone derivatives as acetylcholinesterase inhibitors and metal-chelating agents.
A series of novel indanone derivatives was designed, synthesised and evaluated as potential agents for Alzheimer's disease. Among them, compound 6a, with a piperidine group linked to indone by a two-carbon spacer, exhibited the most potent inhibitor activity, with an IC(50) of 0.0018 μM for AChE; the inhibitory activity of this compound was 14-fold more potent than that of donepezil. Furthermore, these compounds also exhibited good metal-chelating ability.
Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Fan-Chao
FC
Meng
Fei
F
Mao
Wen-Jun
WJ
Shan
Fangfei
F
Qin
Ling
L
Huang
Xing-Shu
XS
Li
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D007700:Kinetics; D008670:Metals / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D002614:Chelating Agents; D002800:Cholinesterase Inhibitors; D007189:Indans; D008670:Metals; D011725:Pyridines; C013352:indacrinone; D000110:Acetylcholinesterase