Abstract
Paracetamol also known as acetaminophen, is a widely used analgesic and antipyretic agent. We report the synthesis and biological evaluation of adamantyl analogues of paracetamol with important analgesic properties. The mechanism of nociception of compound 6a/b, an analog of paracetamol, is not exerted through direct interaction with cannabinoid receptors, nor by inhibiting COX. It behaves as an interesting selective TRPA1 channel antagonist, which may be responsible for its analgesic properties, whereas it has no effect on the TRPM8 nor TRPV1 channels. The possibility of replacing a phenyl ring by an adamantyl ring opens new avenues in other fields of medicinal chemistry.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetaminophen / administration & dosage
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Acetaminophen / analogs & derivatives*
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Analgesics / administration & dosage
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Analgesics / chemical synthesis*
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Analgesics / chemistry
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Analgesics / pharmacology*
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Animals
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Cell Line
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Disease Models, Animal
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Drug Design
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Humans
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Male
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Mice
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Transient Receptor Potential Channels / metabolism*
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Visceral Pain / drug therapy*
Substances
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Analgesics
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Transient Receptor Potential Channels
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Acetaminophen
Grants and funding
The present work has been supported by grants RTA (RED Trastornos Adictivos RD06/001/0014), SAF2012-40075-C02, BFU2009-08346, and BFU2012-39092-C02-01, CONSOLIDER INGENIO2010 Program (CSD2008-00005), and PROMETEO/2010/046. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.