Quinolone–benzylpiperidine derivatives as novel acetylcholinesterase inhibitor and antioxidant hybrids for Alzheimer Disease

Design, synthesis and evaluation of new acetylcholinesterase inhibitors by combining quinolinecarboxamide to a benzylpiperidine moiety are described. Then, a series of hybrids have been developed by introducing radical scavengers. Molecular modeling was performed and structure activity relationships...

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Veröffentlicht in:Bioorganic & medicinal chemistry 2014-04, Vol.22 (8), p.2496-2507
Hauptverfasser: Pudlo, Marc, Luzet, Vincent, Ismaïli, Lhassane, Tomassoli, Isabelle, Iutzeler, Anne, Refouvelet, Bernard
Format: Artikel
Sprache:eng
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Zusammenfassung:Design, synthesis and evaluation of new acetylcholinesterase inhibitors by combining quinolinecarboxamide to a benzylpiperidine moiety are described. Then, a series of hybrids have been developed by introducing radical scavengers. Molecular modeling was performed and structure activity relationships are discussed. Among the series, most potent compounds show effective AchE inhibitions, high selectivities over butyrylcholinesterase and high radical scavenging activities. On the basis of this work, the ability of quinolone derivatives to serve in the design of N-benzylpiperidine linked multipotent molecules for the treatment of Alzheimer Disease has been established.
ISSN:0968-0896
0960-894X
1464-3391
DOI:10.1016/j.bmc.2014.02.046