Design, synthesis, and evaluation of indanone derivatives as acetylcholinesterase inhibitors and metal-chelating agents

• Published in: Bioorganic & medicinal chemistry letters 2012-07, Vol.22 (13), p.4462-4466
• Main Authors: Meng, Fan-Chao, Mao, Fei, Shan, Wen-Jun, Qin, Fangfei, Huang, Ling, Li, Xing-Shu
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Acetylcholinesterase - chemistry; Acetylcholinesterase - metabolism; Acetylcholinesterase inhibitors; Alzheimer disease; Alzheimer Disease - drug therapy; Alzheimer’s disease; Biological and medical sciences; Chelating Agents - chemical synthesis; Chelating Agents - chemistry; Chelating Agents - therapeutic use; chemistry; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - therapeutic use; donepezil; Drug Design; Humans; Indanone derivatives; Indans - chemical synthesis; Indans - chemistry; Indans - therapeutic use; inhibitory concentration 50; Kinetics; Medical sciences; Metal-chelating agents; Metals - chemistry; Pharmacology. Drug treatments; Piperidine; piperidines; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - therapeutic use; Spacer; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.04.029

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 IC50 of 0.0018μM 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. 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 IC50 of 0.0018μM 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.