6703-27-1Relevant articles and documents
Pivaloylcodeine, a new codeine derivative, for the inhibition of morphine glucuronidation. An in vitro study in the rat
Antonilli, Letizia,Togna, Anna Rita,Sabatini, Giovanna,Venditti, Alessandro,Guarcini, Laura,Togna, Giuseppina I.,Nicoletti, Rosario,Sanasi, Filomena,Bianco, Armandodoriano,Nencini, Paolo
, p. 7955 - 7963 (2013)
We have previously found that phenanthrenic opioids, including codeine, modulate morphine glucuronidation in the rat. Here codeine and five of its derivatives were compared in their effects on the synthesis of morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) from morphine by rat liver microsomal preparations, and by primary cultures of rat hepatocytes previously incubated for 72 h with either codeine or its derivatives. Acetylcodeine and pivaloylcodeine shared the capability of the parent compound of inhibiting the synthesis of M3G by liver microsomes through a noncompetitive mechanism of action. Their IC50 were 3.25, 2.27, and 4.32 μM, respectively. Dihydrocodeine, acetyldihydrocodeine, and lauroylcodeine were ineffective. In all the experimental circumstances M6G was undetectable in the incubation medium. In primary hepatocyte cultures codeine only inhibited M3G formation, but with a lower efficacy than that observed with microsomes (IC 50 20.91 vs 4.32 μM). Preliminary results show that at micromolar concentrations codeine derivatives exhibit a low rate of affinity for μ opiate receptors. In conclusion, acetyl and pivaloyl derivatives of codeine noncompetitively inhibit liver glucuronidation of morphine interacting with microsomes. This study further strengths the notion that phenanthrenic opioids can modulate morphine glucuronidation independently from their effects on μ opiate receptors.
A two-step one-pot radiosynthesis of the potent dopamine D 2/D3 agonist PET radioligand [11C]MNPA
Steiger,Finnema,Raus,Schou,Nakao,Suzuki,Pike,Wikstroem,Halldin
experimental part, p. 158 - 165 (2010/06/20)
(R)-(-)-2-[11C]Methoxy-N-n-propylnorapomorphine ([ 11C]MNPA ([11C]2)) is an agonist radioligand of interest for imaging D2/ D3 receptors in vivo. Here we sought to develop an improved radiosynthesis of this radioligand. Reference 2 was synthesized in nine steps with an overall yield of about 5%, starting from codeine. Trimethylsilyldiazomethane proved to be a practical improvement in comparison to diazomethane in the penultimate methylation step. A protected precursor for radiolabeling ((R)-(-)-2-hydroxy-10,11-acetonide-N-n- propylnoraporphine, 4) was prepared from (R)-(-)-2-hydroxy-N-n- propylnorapomorphine (1) in 30% yield. [11C]2 was prepared from 4 via a two-step one-pot radiosynthesis. The first step, methylation of 4 with [ 11C]methyl triflate, occurred in quantitative radiochemical yield. The second step, deprotection of the catechol moiety with HCl and heat, yielded 60-90% of [11C]2 giving an overall incorporation yield from [ 11C]methyl triflate of 60-90%. In a typical run more than 1 GBq of [11C]2, was produced from carbon-11 generated from a 10-min proton irradiation (16 MeV; 35 μA) of nitrogen-hydrogen target gas. The radiochemical purity of [11C]2 was > 99% and specific radioactivity at the time of injection was 901±342 GBq/μmol (n = 10). The total synthesis time was 35-38 min from the end of radionuclide production. The identity of [11C]2 was confirmed by comparing its LC-MS/MS spectrum with those of reference 2 and (R)-(-)-10-methoxy-2,11-dihydroxy-N-n- propylnoraporphine. Copyright
Preparation of 14-hydroxynormorphinones from normorphinone dienol acylates
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, (2008/06/13)
The invention provides processes for the conversion of normorphinone and its derivatives, which can be synthesized from morphine, to the corresponding 14-hydroxynormorphinone and its derivatives including oxycodone, oxymorphone, noroxymorphone and naltrexone. Noroxymorphone is a key intermediate for the production of important narcotic analgesics and antagonists. The invention also provides certain novel intermediates.
