title: Adamantyl analogues of paracetamol as potent analgesic drugs via inhibition of TRPA1.
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.
authors.affiliation: Instituto de Química Médica, IQM-CSIC, Madrid, Spain.
authors.forename: Nieves
authors.initials: N
authors.lastname: Fresno
authors.affiliation: Instituto de Química Médica, IQM-CSIC, Madrid, Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: Pérez-Fernández
authors.affiliation: Departamento de Farmacología y Nutrición, Unidad Asociada de I+D+i al CSIC, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Goicoechea
authors.affiliation: Instituto de Química Médica, IQM-CSIC, Madrid, Spain.
authors.forename: Ibon
authors.initials: I
authors.lastname: Alkorta
authors.affiliation: Institute of Molecular and Cellular Biology, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Asia
authors.initials: A
authors.lastname: Fernández-Carvajal
authors.affiliation: Institute of Molecular and Cellular Biology, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: de la Torre-Martínez
authors.affiliation: Institute of Molecular and Cellular Biology, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Quirce
authors.affiliation: Institute of Molecular and Cellular Biology, Universidad Miguel Hernández, Alicante, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferrer-Montiel
authors.affiliation: Departamento de Farmacología y Nutrición, Unidad Asociada de I+D+i al CSIC, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Martín
authors.affiliation: Instituto de Química Médica, IQM-CSIC, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Goya
authors.affiliation: Instituto de Química Médica, IQM-CSIC, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Elguero
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D008297:Male; D051379:Mice; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D059265:Visceral Pain / Q000188:drug therapy*
chemical_list: D000700:Analgesics; D050051:Transient Receptor Potential Channels; D000082:Acetaminophen