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

Fan-Chao Meng; Fei Mao; Wen-Jun Shan; Fangfei Qin; Ling Huang; Xing-Shu Li

doi:10.1016/j.bmcl.2012.04.029

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

Bioorg Med Chem Lett. 2012 Jul 1;22(13):4462-6. doi: 10.1016/j.bmcl.2012.04.029. Epub 2012 Apr 13.

Authors

Fan-Chao Meng¹, Fei Mao, Wen-Jun Shan, Fangfei Qin, Ling Huang, Xing-Shu Li

Affiliation

¹ Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

PMID: 22633691
DOI: 10.1016/j.bmcl.2012.04.029

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / chemistry*
Acetylcholinesterase / metabolism
Alzheimer Disease / drug therapy
Chelating Agents / chemical synthesis*
Chelating Agents / chemistry
Chelating Agents / therapeutic use
Cholinesterase Inhibitors / chemical synthesis*
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / therapeutic use
Drug Design*
Humans
Indans / chemical synthesis*
Indans / chemistry
Indans / therapeutic use
Kinetics
Metals / chemistry*
Pyridines / chemical synthesis*
Pyridines / chemistry
Pyridines / therapeutic use
Structure-Activity Relationship

Substances

Chelating Agents
Cholinesterase Inhibitors
Indans
Metals
Pyridines
indacrinone
Acetylcholinesterase