Peripheral site acetylcholinesterase inhibitors targeting both inflammation and cholinergic dysfunction

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:20

Article

Young, Sherri¹  Fabio, Karine¹  Guillon, Christophe¹  Mohanta, Pramod¹  Halton, Timothy A.¹  Heck, Diane E.²  Flowers, Robert A., II¹  Laskin, Jeffrey D.³  Heindel, Ned D.¹ 

[1] Lehigh Univ, Dept Chem, Bethlehem, PA 18015 USA

[2] New York Med Coll, Sch Publ Hlth, Dept Environm Hlth Sci, Valhalla, NY 10595 USA

[3] UMDNJ, Rutgers State Univ, CounterACT Ctr Excellence, Piscataway, NJ 08854 USA

关键词: NSAIDs;    Acetylcholinesterase inhibitors;    Prodrugs;    Noncompetitive inhibitor;   

DOI  :  10.1016/j.bmcl.2010.02.102

来源: Elsevier

【 摘 要 】

The design and study of two classes of noncompetitive acetylcholinesterase inhibitors (AChEIs) which also function as NSAID prodrugs are reported. The most potent AChEIs disclosed contain an aromatic alkyl-aryl linker between an NSAID and a lipophilic choline mimic and they inhibit acetylcholinesterase (AChE) in the submicromolar range. These agents have the therapeutic potential to dually target inflammation by releasing an NSAID in vivo and activating the cholinergic anti-inflammatory pathway via cholinergic up-regulation. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

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