Long-Acting Fentanyl Analogues: Synthesis and Pharmacology of N-(1-Phenylpyrazolyl)-N-(1-phenylalkyl-4-piperidyl)propanamides

Jagerovic, Nadine; Cano, Carolina; Elguero, José; Goya, Pilar; Callado, Luís F.; Meana, J. Javier; Girón, Rocı́o; Abalo, Raquel; Ruiz, David A.; Goicoechea, Carlos; Martı́n, M.a Isabel

doi:10.1016/s0968-0896(01)00345-5

Cited by 34 publications

(21 citation statements)

References 34 publications

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“…Other fentanyl analogs in which the benzene ring of the propioanilido group was changed to a heterocyclic substituent, particularly for phenylpyrazole group also have been described [136–139]. Obtained compounds showed more potent analgesic properties than morphine, but less than fentanyl with longer duration of action.…”

Section: Insertion Of Substituents Other Than Methyl Into the Differementioning

confidence: 99%

Fentanyl-Related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications

2014

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Fentanyl and its analogs have been mainstays for the treatment of severe to moderate pain for many years. In this review, we outline the structural and corresponding synthetic strategies that have been used to understand the structure–biological activity relationship in fentanyl-related compounds and derivatives and their biological activity profiles. We discuss how changes in the scaffold structure can change biological and pharmacological activities. Finally, recent efforts to design and synthesize novel multivalent ligands that act as mu and delta opioid receptors and NK-1 receptors are discussed.

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Section: Insertion Of Substituents Other Than Methyl Into the Differementioning

confidence: 99%

Fentanyl-Related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications

2014

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“…The different receptor interactions of the N -propanamide substituents may explain the observed decrease in μ opioid agonist potency of 10 as compared to fentanyl (Table 1). 14,15…”

Section: Resultsmentioning

confidence: 99%

“Carba”-Analogues of Fentanyl are Opioid Receptor Agonists^‡‡ Dedicated to the memory of Ralph F. Hirschmann.

Weltrowska¹,

Chung²,

Lemieux³

et al. 2010

J. Med. Chem.

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There is evidence to indicate that the Asp residue in the third transmembrane helix (TMH) of opioid receptors forms a salt bridge with the positively charged nitrogen of endogenous and exogenous opioid ligands. To further examine the role of this electrostatic interaction in receptor binding and activation, we synthesized ‘carba’-analogues of a published fentanyl analogue containing a 3-(guanidinomethyl)-benzyl group in place of the phenyl moiety attached to the ethylamido group (C. Dardonville et al., Bioorg. Med. Chem. 2006, 14, 6570–6580 (1)), in which the piperidine ring nitrogen was replaced with a carbon. As expected, the resulting cis and trans isomers (8a and 8b) showed reduced μ and κ opioid receptor binding affinities as compared to 1, but surprisingly, retained opioid full agonist activity with about half the potency of leucine-enkephalin in the guinea pig ileum assay. In conjunction with performed receptor docking studies, these results indicate that the electrostatic interaction of the protonated nitrogen in the piperidine ring of fentanyl analogues with the Asp residue in the third TMH is not a conditio sine qua non for opioid receptor activation.

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“…It is one of the most frequent presenting symptoms of different pathologies and represents important medical and economic costs for the community (1). Current analgesic therapies, despite their proven efficacy in alleviating symptoms and providing pain relief, all have considerable side effects including gastrointestinal problems, renal damage, respiratory depression, emesis, and tolerance and/or addiction (2).…”

Section: Introductionmentioning

confidence: 99%

Antinociceptive Effect of Hydroalcoholic Extract of Iranian Green tea in the Formalin Test in Rats

Arzi

Ghorbanzadeh²,

Khorasgani³

2013

Jundishapur J Nat Pharm Prod

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Background: Tea (Camellia sinensis) has been utilised, since time immemorial, as a beverage possessing encouraging health benefits. Little scientific evidence exists in literature on the effect of this plant on pain. Objectives: To investigate the antinociceptive activity of Iranian green tea extract. Materials and Methods:The hydroalcoholic extract was administered to male Wistar rats. Formalin paw test was used to evaluate the antinociceptive activity. Plant extract (25, 50, 100 and 200 mg/kg, i.p.) (n = 6 for each group) or vehicle (n = 6) was administered 30 min before the subplantar formalin injection. Results: The extract caused a significant dose-related (50, 100, 200 mg /kg, i.p.) inhibition of the first phase and onset of chronic phase (200 mg /kg, i.p.) of formalin induced nociception. The results showed that the pre-treatment of rats with naloxone (1 mg/kg, i.p.) significantly (P < 0.001) reversed antinociception by Green tea extract (GTE) (200 mg/kg, i.p.) in the inflammatory phase and had no effect on phase 1. Conclusions: These results indicate that GTE produces dose-related antinociception in chemical pain model and one of its possible mechanisms involves opioid pathways.

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Long-Acting Fentanyl Analogues: Synthesis and Pharmacology of N-(1-Phenylpyrazolyl)-N-(1-phenylalkyl-4-piperidyl)propanamides

Cited by 34 publications

References 34 publications

Fentanyl-Related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications

Fentanyl-Related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications

“Carba”-Analogues of Fentanyl are Opioid Receptor Agonists^‡‡ Dedicated to the memory of Ralph F. Hirschmann.

Antinociceptive Effect of Hydroalcoholic Extract of Iranian Green tea in the Formalin Test in Rats

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Long-Acting Fentanyl Analogues: Synthesis and Pharmacology of N-(1-Phenylpyrazolyl)-N-(1-phenylalkyl-4-piperidyl)propanamides

Cited by 34 publications

References 34 publications

Fentanyl-Related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications

Fentanyl-Related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications

“Carba”-Analogues of Fentanyl are Opioid Receptor Agonists‡‡ Dedicated to the memory of Ralph F. Hirschmann.

Antinociceptive Effect of Hydroalcoholic Extract of Iranian Green tea in the Formalin Test in Rats

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“Carba”-Analogues of Fentanyl are Opioid Receptor Agonists^‡‡ Dedicated to the memory of Ralph F. Hirschmann.