Synthesis of tacrine-lophine hybrids via one-pot four component reaction and biological evaluation as acetyl- and butyrylcholinesterase inhibitors

被引：50

作者：

da Costa, Jesse Sobieski ^{[1
]}

Bizarro Lopes, Joao Paulo ^{[1
]}

Russowsky, Dennis ^{[1
]}

Petzhold, Cesar Liberato ^{[1
]}

de Amorim Borges, Antonio Cesar ^{[1
]}

Ceschi, Marco Antonio ^{[1
]}

Konrath, Eduardo ^{[2
]}

Batassini, Cristiane ^{[2
]}

Lunardi, Paula Santana ^{[2
]}

Saraiva Goncalves, Carlos Alberto ^{[2
]}

机构：

[1] Univ Fed Rio Grande do Sul, Inst Quim, BR-91501970 Porto Alegre, RS, Brazil

[2] Univ Fed Rio Grande do Sul, Dept Bioquim, BR-90035003 Predio Anexo, Brazil

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 62卷

关键词：

Tacrine; Lophine; Four component reaction; Indium trichloride; AChE inhibitory activity; SITE ACETYLCHOLINESTERASE INHIBITORS; LEWIS-ACID CATALYSTS; ALZHEIMERS-DISEASE; CHOLINERGIC HYPOTHESIS; AGENTS; ANALOGS; PROTEIN; DESIGN; ACHE;

D O I：

10.1016/j.ejmech.2013.01.029

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of tacrine-lophine hybrids was synthesized and tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC50 in the nanomolar concentration scale. The key step is the one-pot four component condensation reaction of 9-aminoalkylamino-1,2,3,4-tetrahydroacridines, benzil, different substituted aromatic aldehydes and NH4OAc, using InCl3 as the best catalyst. Tacrine-lophine hybrids were found to be potent and selective inhibitors of cholinesterases. As an extension of the four component approach to tetrasubstituted imidazoles, a new series of bis-(2,4,5-triphenyl-1H-imidazoles) or bis(n)-lophines was tested against AChE and BuChE. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：556 / 563

页数：8

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