5140-28-3Relevant academic research and scientific papers
Synthesis of 7β-hydroxy-8-ketone opioid derivatives with antagonist activity at mu- and delta-opioid receptors
Ahonen, Tiina J.,Rinne, Maiju,Grutschreiber, Peter,M?tlik, Kert,Airavaara, Mikko,Schaarschmidt, Dieter,Lang, Heinrich,Reiss, David,Xhaard, Henri,Gaveriaux-Ruff, Claire,Yli-Kauhaluoma, Jari,Moreira, Vania M.
, p. 495 - 507 (2018/04/14)
Despite extensive years of research, the direct oxidation of the 7,8-double bond of opioids has so far received little attention and knowledge about the effects of this modification on activity at the different opioid receptors is scarce. We herein report
Synthesis and pharmacological evaluation of novel selective MOR agonist 6β-pyridinyl amidomorphines exhibiting long-lasting antinociception
Urai, ákos,Váradi, András,Sz?cs, Levente,Komjáti, Balázs,Le Rouzic, Valerie,Hunkele, Amanda,Pasternak, Gavril W.,Majumdar, Susruta,Hosztafi, Sándor
, p. 152 - 157 (2017/02/05)
It was previously reported that 6β-aminomorphinan derivatives show high affinity for opiate receptors. Novel 6β-heteroarylamidomorphinanes were designed based on the MOR selective antagonist NAP. The 6β-aminomorphinanes were prepared by stereoselective Mitsunobu reaction and subsequently acylated with nicotinic acid and isonicotinic acid chloride hydrochlorides. The receptor binding and efficacy were determined in vitro and the analgesic activity was studied in vivo. The in vitro studies revealed moderate selectivity for the MOR. At least two compounds in this series exhibited a long-lasting analgesic response when administered subcutaneously and intracerebroventricularly. When the substances were given intracerebroventricularly to mice, they showed analgesic potency comparable to morphine.
POLYPEPTIDE-OPIOID CONJUGATES AND USES THEREOF
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Page/Page column 39, (2013/04/25)
The invention features polypeptide-opioid conjugates capable of crossing the blood-brain barrier. The polypeptide-opioid conjugates can be used to treat a condition that is modulated by opioid receptors such as pain (e.g., postoperative pain, cancer pain, acute pain, and chronic pain).
Novel 6β-acylaminomorphinans with analgesic activity
Váradi, András,Hosztafi, Sándor,Le Rouzic, Valerie,Tóth, Gergo,Urai, ákos,Noszál, Béla,Pasternak, Gavril W.,Grinnell, Steven G.,Majumdar, Susruta
supporting information, p. 786 - 789 (2013/10/22)
Aminomorphinans are a relatively young class of opioid drugs among which substances of high in vitro efficacy and favorable in vivo action are found. We report the synthesis and pharmacological evaluation of novel 6β-acylaminomorphinans. 6β-Morphinamine a
Sulfate esters of morphine derivatives: Synthesis and characterization
Váradi, András,Gergely, András,Béni, Szabolcs,Jankovics, Péter,Noszál, Béla,Hosztafi, Sándor
experimental part, p. 65 - 72 (2012/03/09)
Sixteen 3-O- and 6-O-sulfate esters of morphine, codeine and some of their N-methyl quaternary derivatives were synthesized by means of sulfation with pyridine-SO3 complex and sulfuric acid/N,N′- dicyclohexylcarbodiimide. Complete 1H- and 13C-NMR assignments are given for each of the synthesized compounds based on one- and two-dimensional homo- and heteronuclear measurements. Comparative analysis of chiral properties by circular dichroism and optical rotatory dispersion revealed characteristic differences in the spectra due to changes in charge, polarity and intramolecular association by strong hydrogen bonds in aqueous solution. The synthesized sulfate esters are prospective peripheral analgesics lacking central side effects and are also useful as reference substances for various analytical studies involving sulfate ester metabolites.
Opioids and efflux transporters. Part 2: P-glycoprotein substrate activity of 3- and 6-substituted morphine analogs
Cunningham, Christopher W.,Mercer, Susan L.,Hassan, Hazem E.,Traynor, John R.,Eddington, Natalie D.,Coop, Andrew
, p. 2316 - 2320 (2008/12/22)
Continuing our studies investigating opioids with reduced P-glycoprotein (P-gp) substrate activity, a series of known 3- and 6-hydroxy, -methoxy, and -desoxymorphine analogs was synthesized and analyzed for P-gp substrate activity and opioid binding affinity. 6-Desoxymorphine (7) showed high affinity for opioid receptors and did not induce P-gp-mediated ATP hydrolysis. Additionally, 7 demonstrated morphine-like antinociceptive potency in mice, indicating this compound as an ideal lead to further evaluate the role of P-gp in opioid analgesic tolerance development.
Non-CNS acting opiates bearing guanidino substituents
Subasinghe, Kamani R.,Jackson, W. Roy,Young, Jacqui F.,Papanastasiou, Maria,Jarrott, Bevyn
, p. 427 - 438 (2007/10/03)
A series of guanidino-substituted opiates based on morphine, diprenorphine, and buprenorphine have been synthesized. Guanidines with aryl and alkyl substituents as well as unsubstituted ones have been attached to the opiate nucleus with spacer units of varying length. The spacer groups have mainly been attached to the opiates via the opiate nitrogen atom. A few compounds involving attachment through opiate oxygen atoms have been prepared, but were found to be ineffective as analgesics. The activity of the compounds as analgesics has been evaluated using the phenylquinone (PQ) abdominal-constriction test and their ability to enter the CNS evaluated with the Straub tail response. The compounds most active in the PQ abdominal-constriction test and showing no Straub tail behaviour contained aryl-substituted guanidines.
Synthesis of [1-3H]morphine-6-β-D-glucuronide
Berrang, Bertold D.,Wyrick, Christopher D.,Carroll, F. Ivy,Seltzman, Herbert H.
, p. 851 - 857 (2007/10/03)
Tritiated morphine of high specific activity was protected at the 3-position by acetylation and subjected to glucuronidation by Koenigs-Knorr procedure with methyl 2,3,4-tri-O-acetyl-1-bromo-1-deoxy-D-glucopyranuronate and silver carbonate. Fully protected morphine-6-glucuronide was obtained in 42% yield and 95% radiochemical purity as determined by TLC-RAM. Alkali catalyzed solvolysis in two steps furnished [1-3H]morphine-6-β-D-glucuronide in 23% overall radiochemical yield and 99% radiochemical purity determined by HPLC-liquid scintillation counting and TLC-RAM.
Morphine 6-Glucuronide and Morphine 3-Glucuronide as Molecular Chameleons with Unexpected Lipophilicity
Carrupt, Pierre-Alain,Testa, Bernard,Bechalany, Antoine,Tayar, Nabil El,Descas, Patrick,Perrissoud, Daniel
, p. 1272 - 1275 (2007/10/02)
Morphine 6-glucuronide, but not morphine 3-glucuronide, is a highly potent opiate receptor agonist.In fact, there is converging evidence that much of the analgesic effect occurring after morphine treatment in humans is due to this metabolite rather than to the parent drug.Yet glucuronides as a rule are considered as highly polar metabolites unable to cross the blood-brain barrier and rapidly excreted by the urinary and/or biliary routes.Here, we report that morphine 6-glucuronide, and to a lesser extent morphine 3-glucuronide, are far more lipophilic than predicted, and in fact not much less lipophilic than morphine itself.Force-field and quantum mechanical calculations indicate that the two glucuronides can exist in conformational equilibrium between extendend and folded forms.The extended conformers, because they efficiently expose their polar groups, must be highly hydrophilic forms predominating in polar media such as water; in contrast, the folded conformers mask part of their polar groups, thus being more lipophilic and likely to predominate in media of low polarity such as biological membranes.
