Potential nonequilibrium analgetic receptor inactivators. Synthesis and biological activities of N-acylanileridines

Portoghese, Philip S.; Telang, V. G.; Takemori, A. E.; Hayashi, Gosuke

doi:10.1021/jm00284a015

Cited by 17 publications

(4 citation statements)

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“…An early effort to design affinity labels with the anileridine pharmacophore afforded equivocal results (53). Derivatives containing electrophilic moieties attached to the anilino nitrogen ( Figure 6) all possessed analgesic activity in mice, but only the fumaramido ethyl ester (2) appeared to cause fairly long lasting (> 6 hours) blockade of morphine analgesia.…”

Section: Agonistsmentioning

confidence: 99%

Affinity Labels for Opioid Receptors

Takemori

Portoghese

1985

Annu. Rev. Pharmacol. Toxicol.

103

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Section: Agonistsmentioning

confidence: 99%

Affinity Labels for Opioid Receptors

Takemori

Portoghese

1985

Annu. Rev. Pharmacol. Toxicol.

103

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“…Brain homogenates were prepared and receptor binding was performed with [3H] naltrexone or 3H-labeled [d-Ala2,Met5] enkephalinamide as previously described.22 In brief, brains were homogenized in 50 mM Tris buffer (pH 7.7 at 25 °C) and extensively washed to remove any endogenous or exogenous opioids. The standard wash procedure included: (1) centrifugation, 40000g X 15 min; (2) resuspension, 50 vol (w/v); (3) incubation at 37 °C for 30 min; (4) centrifugation as before; (5) resuspension and assay. Assays were performed in triplicate on 2-mL aliquots in the presence and absence of levallorphan (1 µ ) at 25 °C for 30 min.…”

Section: Ms (Chemical Ionization) Intensementioning

confidence: 99%

Long-acting opiate agonists and antagonists: 14-hydroxydihydromorphinone hydrazones

Pasternak¹,

Hahn²

1980

J. Med. Chem.

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Two new long-acting hydrazone derivatives of 14-hydroxydihydromorphinones have been synthesized, oxymorphazone and naltrexazone. Both derivatives show high affinity for opiate binding sites in vitro, similar to naloxazone, the hydrazone analogue of naloxone. Sodium and manganese shifts imply that naltrexazone, like naloxazone, is a pure antagonist. By contrast, oxymorphazone inhibition of receptor binding is dramatically reduced by sodium and potentiated by manganese, suggesting it is an agonist. When given in vivo, all agents produce a significant inhibition of receptor binding for over 24 h despite extensive washing of the brain homogenates. Oxymorphone, naltrexone, and naloxone are without effect. Twenty-four hours after in vivo administration of oxymorphazone, 82% of mice are still analgetic compared to only 17% of oxymorphone-treated mice (p less than 0.005). Twenty-four hours after naltexazone or naloxazone treatment all mice were protected from morphine analgesia (12 mg/kg; p less than 0.005), while naltrexone- and naloxone-treated animals did not differ significantly from saline-treated controls.

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“…Anal, (for ortho, meta, and para isomers) (C9H10BrNO2) C, , N. Method A. 3-Hydroxy-17-nitrophenalkylmorphinan (1)(2)(3)(4)(5)(6). A mixture of 1.0 mmol of 3-hydroxymorphinan6 prepared from levorphanol according to the procedure of Abdel-Monem and Portoghese,161.5 mmol of nitrophenalkyl bromide, and anhydrous K2C03 (3 mmol) was heated in freshly distilled DMF (2 mL) under N2 at 105 °C for 24 h. The reaction mixture was cooled and filtered, and the solvent was removed from the filtrate in vacuo.…”

Section: Methodsmentioning

confidence: 99%

3-Hydroxy-17-aralkylmorphinans as potential opiate receptor-site-directed alkylating agents

et al. 1977

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In an effort to develop opiate receptor-site-directed alkylating agents, a series of 3-hydroxy-17-aralkylmorphinans containing reactive groups was synthesized and tested for analgesic and opiate antagonist activity. Many of the target compounds exhibited the characteristics of agonists and, among this group, some were found to be active blockers of morphine analgesia. One of the more potent antagonists (41) was investigated further and it was found that while its action is specifically associated with opiate receptors, 41 could not be classified either as a competitive or noncompetitive antagonist in the classical sense. The duration of antagonist action in vivo of 41 and its in vitro receptor binding characteristics suggest that covalent association with opiate receptors is not not an important factor.

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Potential nonequilibrium analgetic receptor inactivators. Synthesis and biological activities of N-acylanileridines

Cited by 17 publications

References 0 publications

Affinity Labels for Opioid Receptors

Affinity Labels for Opioid Receptors

Long-acting opiate agonists and antagonists: 14-hydroxydihydromorphinone hydrazones

3-Hydroxy-17-aralkylmorphinans as potential opiate receptor-site-directed alkylating agents

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