title: Synthesis of 4-[(diethylamino)methyl]-phenol derivatives as novel cholinesterase inhibitors with selectivity towards butyrylcholinesterase.
abstract: A series of novel cholinesterase inhibitors, being composed of 4-[(diethylamino)methyl]-phenoxy and secondary amine which were linked with a different length alkyl chain, were designed and synthesized from the starting material p-hydroxybenzaldehyde. These compounds were evaluated as acetylcholinesterase and butyrylcholinesterase (AChE/BChE) inhibitors. Compounds 25-31 having a secondary amine moiety connected to the phenyl ring via eight CH(2) units spacer were found to be the most potent inhibitors with IC(50) value lower than 220nM and 48nM against AChE and BChE, respectively. Interestingly, these inhibitors showed a surprising selectively toward BChE, and compounds 26, 27, and 30 displayed 12.5, 18.6, and 18.8-fold higher affinity to BChE. The inhibition kinetics analyzed by Linewear-Burk plots revealed that such compounds were mix-type inhibitors.
authors.affiliation: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.forename: Rihui
authors.initials: R
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.forename: Qin
authors.initials: Q
authors.lastname: Yan
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.forename: Wenlie
authors.initials: W
authors.lastname: Peng
authors.forename: Huacan
authors.initials: H
authors.lastname: Song
mesh_terms: D002091:Butyrylcholinesterase / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D010636:Phenols / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D010636:Phenols; D002091:Butyrylcholinesterase