Long-acting fentanyl analogues: synthesis and pharmacology of N-(1-phenylpyrazolyl)-N-(1-phenylalkyl-4-piperidyl)propanamides.
The synthesis of new fentanyl analogues in which the benzene ring of the propioanilido group has been replaced by phenylpyrazole is described.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.
Jagerovic
Nadine
N
Instituto de Química Médica, CSIC, Juan de la Cierva, 3, E-28006 Madrid, Spain.
Cano
Carolina
C
Elguero
José
J
Goya
Pilar
P
Callado
Luis F
LF
Meana
J Javier
JJ
Girón
Rocío
R
Abalo
Raquel
R
Ruiz
David
D
Goicoechea
Carlos
C
Martín
M A Isabel
MA
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
D000577:Amides; D000701:Analgesics, Opioid; D011720:Pyrazoles; D017450:Receptors, Opioid, mu; D005283:Fentanyl