title: Long-acting fentanyl analogues: synthesis and pharmacology of N-(1-phenylpyrazolyl)-N-(1-phenylalkyl-4-piperidyl)propanamides.
abstract: The synthesis of new fentanyl analogues in which the benzene ring of the propioanilido group has been replaced by phenylpyrazole is described. Antinociceptive activity was evaluated using the writhing and hot plate tests in mice. Two compounds, and, showed interesting analgesic properties, being more potent than morphine and less than fentanyl but with longer duration of action. These compounds inhibited the electrically evoked muscle contraction of guinea pig ileum and mouse vas deferens but not that of rabbit vas deferens and the effects could be reversed by antagonists (naloxone and/or CTOP), thus indicating that the compounds acted as mu agonists. Finally, the binding data confirmed that the compounds had high affinity and selectivity for the mu receptor.
authors.affiliation: Instituto de Química Médica, CSIC, Juan de la Cierva, 3, E-28006 Madrid, Spain.
authors.forename: Nadine
authors.initials: N
authors.lastname: Jagerovic
authors.forename: Carolina
authors.initials: C
authors.lastname: Cano
authors.forename: José
authors.initials: J
authors.lastname: Elguero
authors.forename: Pilar
authors.initials: P
authors.lastname: Goya
authors.forename: Luis F
authors.initials: LF
authors.lastname: Callado
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Meana
authors.forename: Rocío
authors.initials: R
authors.lastname: Girón
authors.forename: Raquel
authors.initials: R
authors.lastname: Abalo
authors.forename: David
authors.initials: D
authors.lastname: Ruiz
authors.forename: Carlos
authors.initials: C
authors.lastname: Goicoechea
authors.forename: M A Isabel
authors.initials: MA
authors.lastname: Martín
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001921:Brain; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D010146:Pain / Q000188:drug therapy / Q000517:prevention & control; D011720:Pyrazoles / Q000737:chemistry; D011817:Rabbits; D017450:Receptors, Opioid, mu / Q000819:agonists; D013329:Structure-Activity Relationship; D013997:Time Factors; D014649:Vas Deferens
chemical_list: D000577:Amides; D000701:Analgesics, Opioid; D011720:Pyrazoles; D017450:Receptors, Opioid, mu; D005283:Fentanyl