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

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• 作者：Jessé ; Sobieski da Costa^a ; Joã ; o Paulo Bizarro Lopes^a ; Dennis Russowsky^a ; Cesar Liberato Petzhold^a ; Antonio Cé ; sar de Amorim Borges^a ; Marco Antonio Ceschi^a ; ^{mceschi@iq.ufrgs.br} ; Eduardo Konrath^b ; Cristiane Batassini^b ; Paula Santana Lunardi^b ; Carlos Alberto Saraiva Gonç ; alves^b
• 关键词：Tacrine ; Lophine ; Four component reaction ; Indium trichloride ; AChE inhibitory activity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：62
• 期：Complete
• 页码：556-563
• 全文大小：351 K

文摘

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.