Abstract
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.
2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Acetylcholinesterase / chemistry*
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Acetylcholinesterase / metabolism
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
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Anti-Inflammatory Agents, Non-Steroidal / chemistry*
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Cholinergic Agents / chemical synthesis
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Cholinergic Agents / chemistry*
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Cholinergic Agents / pharmacology
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Cholinesterase Inhibitors / chemical synthesis
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Cholinesterase Inhibitors / chemistry*
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Cholinesterase Inhibitors / pharmacology
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Drug Design
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Humans
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Prodrugs / chemical synthesis
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Prodrugs / chemistry
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Prodrugs / pharmacology
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cholinergic Agents
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Cholinesterase Inhibitors
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Prodrugs
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Acetylcholinesterase