76-42-6

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• Synthesis of (-)-Oxycodone
• Our novel synthetic route to (-)-oxycodone, a semisynthetic opioid analgesic, features a palladium-catalyzed direct intramolecular arylation of an aryl bromide, oxidative dearomatization of a dihydrophenanthrenol, formation of a benzylic quaternary carbon by an intramolecular Michael addition of a malonate moiety, and construction of the morphinan skeleton via a Hofmann rearrangement/lactamization cascade.
• Kimishima, Atsushi,Umihara, Hirotatsu,Mizoguchi, Akihiro,Yokoshima, Satoshi,Fukuyama, Tohru

• p. 6244 - 6247

  (2014)
• Read Online

• Synthesis and opiate receptor binding properties of 17-methyl-6,7- dehydro-3,14-dihydroxy-4,5α-epoxy-6,7:4',5'-pyrimidinomorphinans
• A class of opioid receptor active derivatives of oxymorphone has been synthesized using a common enaminone intermediate. The derivatives have heterocyclic groups fused to the 6,7-positions of the morphinan system and all were synthesized in high yield. A pyrazolo derivative is an agonist for the μ and δ receptors and an antagonist for the κ receptor.
• Xu, Wei,Huang, Liang-Fu,Bauer, Ludwig,Bhargava, Hemendra N.,Dunn III, William J.

• p. 3375 - 3380

  (1999)
• Read Online

• PROCESSES FOR PREPARING NOR-OPIOID COMPOUNDS AND OPIOID ANTAGONISTS BY ELECTROCHEMICAL N-DEMETHYLATION
• The present invention relates to a process for preparing a nor-opioid compound wherein an opioid precursor compound is electrochemically N-demethylated. The present invention further relates to a process for preparing an opioid antagonist compound, wherein an opioid precursor compound is electrochemically N-demethylated and the thus obtained nor-opioid compound is alkylated again at its secondary amine functional group.
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• Page/Page column 26-27

  (2021/12/31)
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• Structural elucidation and synthesis of a dimeric degradation impurity during long-term stability studies of oxycodone hydrochloride injection
• Oxycodone is one of the most prescribed narcotic medications for the treatment of moderate to severe pain in clinical practice. During long-term stability studies of oxycodone hydrochloride for injection performed as per ICH Q1A (R2) guidelines, an unknown degradation product, impurity-I, increased over time and reached a level of 0.21% after 24 months, based on the results of HPLC analysis. The observed impurity was preliminarily characterized as an oxycodone aldol dimer by using two-dimensional (2D) liquid chromatography (LC) coupled with quadrupole time-of-flight mass spectrometry (QTOF MS/MS) analysis. Impurity-I was synthesized and its molecular structure confirmed based on detailed analysis of 1D-NMR (1H, 13C, and DEPT) and 2D-NMR (1H-1H COSY, HSQC, and HMBC) spectroscopy data. The plausible mechanism for the formation of impurity-I was an aldol condensation reaction under weakly acidic conditions. In addition, the potential toxicity of impurity-I was assessed by in silico toxicity predictions using the TOPKAT software.
• Du, Wei,Jin, Jian,Liang, Lingzhi,Liu, Bifeng,Liu, Xin,Ma, Yurong,Ren, Xia,Zhang, Guisen,Zhuang, Tao

• p. 18651 - 18658

  (2021/10/25)
• 

• Electrochemical N-Demethylation of 14-Hydroxy Morphinans: Sustainable Access to Opioid Antagonists
• The most challenging step in the preparation of many opioid antagonists is the selective N-demethylation of a 14-hydroxymorphinan precursor. This process is carried out on a large scale using stoichiometric amounts of hazardous chemicals like cyanogen bromide or chloroformates. We have developed a mild reagent- and catalyst-free procedure for the N-demethylation step based on the anodic oxidation of the tertiary amine. The ensuing intermediates can be readily hydrolyzed to the target nor-opioids in very good yields.
• Cantillo, David,Glotz, Gabriel,Kappe, C. Oliver
• supporting information

  p. 6891 - 6896

  (2020/09/15)
• 

• Total Synthesis of (-)-Oxycodone via Anodic Aryl-Aryl Coupling
• A fully regio- and diastereoselective electrochemical 4a-2′-coupling of a 3′,4′,5′-trioxygenated laudanosine derivative enables the synthesis of the corresponding morphinandienone. This key intermediate is further transformed into (-)-oxycodone through conjugate nucleophilic substitution for E-ring closure and [4 + 2] cycloaddition with photogenerated singlet oxygen to accomplish diastereoselective hydroxylation at C-14. The anodic transformation provides high yields and can be performed under constant current conditions both in a simple undivided cell or in continuous flow.
• Lipp, Alexander,Selt, Maximilian,Ferenc, Dorota,Schollmeyer, Dieter,Waldvogel, Siegfried R.,Opatz, Till

• p. 1828 - 1831

  (2019/03/07)
• 

• NOVEL OPIOID COMPOUNDS AND USES THEREOF
• This invention relates to novel opioid derivatives of Formula I: or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R3, R4 and Z are as defined herein in the disclosure. The invention also relates to the use of such compounds for the treatment or prevention of, for example, pain.
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• Paragraph 0519-0523

  (2019/09/12)
• 

• HYDROGENATION PROCESS FOR PREPARING OXYCODONE HYDROCHLORIDE FROM 14-HYDROXYCODEINONE
• A process for preparing oxycodone hydrochloride, said process comprising hydrogenating 14- hydroxycodeinone in an alcoholic solvent and hydrochloric acid to form oxycodone hydrochloride, wherein (a) the hydrogenation is carried out in the presence of a heterogeneous platinum group metal (PGM) catalyst and hydrogen gas, (b) the hydrogenation is carried out at one or more temperatures greater than ambient temperature in the presence of a hydrogenation catalyst and hydrogen gas, wherein the solution of 14- hydroxycodeinone and hydrochloric acid is heated to temperature before it is exposed to the hydrogen gas, (c) the oxycodone hydrochloride comprises 6a-oxycodol in an amount about 0.300 area % as determined by HPLC, characterized in that (d) the pH of the solution of 14-hydroxycodeinone and hydrochloric acid is in the range of about ≥ 2.5 to about ≤ 4.5; (e) the process is carried out in one pot, and (f) the oxycodone hydrochloride precipitates out of the solution.
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• Page/Page column 10

  (2019/01/10)
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• PROCESS FOR IMPROVED OXYCODONE SYNTHESIS
• Processes for preparing oxycodone are provided. Said processes encompass a step which is a hydrogenation of an 14-hydroxycodeinone salt in the presence of trifluoroacetic acid and/or a glycol.
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• Paragraph 0585-0599

  (2017/02/24)
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• An Integrated Continuous-Flow Synthesis of a Key Oxazolidine Intermediate to Noroxymorphone from Naturally Occurring Opioids
• A telescoped procedure for the direct preparation of an advanced intermediate towards noroxymorphone from the naturally occurring alkaloids oripavine and thebaine is presented. The reaction procedure involves an intensified continuous-flow hydroxylation, followed by a continuous solvent switch and hydrogenation in a packed-bed hydrogenator (H-Cube). The obtained reaction mixture, containing oxymorphone as intermediate in excellent yield and purity, can be then directly converted into the desired noroxymorphone oxazolidine intermediate through palladium catalyzed N-methyl oxidation.
• Mata, Alejandro,Cantillo, David,Kappe, C. Oliver

• p. 6505 - 6510

  (2017/12/02)
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• Processes for Making Opioids Including 14-Hydroxycodeinone and 14-hydroxymorphinone
• Improved processes for making opioid products having low impurity levels including making 14-hydroxycodeinone and 14-hydroxymorphinone from thebaine and oripavine, respectively.
• -
• Paragraph 0122; 0123; 0124

  (2016/03/14)
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• A method for synthesizing hydrochloric acid hydroxy morphinones
• The invention discloses a synthesis method of oxymorphone hydrochloride. The synthesis method mainly comprises the following steps of: 1) alkalifying to obtain free alkali by taking oxycodone hydrochloride as an initial a raw material; 2) carrying out a demethylation reaction to obtain oxymorphone; 3) carrying out a hydrogenation reaction on the oxymorphone under acidic condition; and 4) salifying the hydrogenated product with hydrochloric acid to obtain the target product oxymorphone hydrochloride. The synthesis method disclosed by the invention has the advantages of available raw materials, high product purity and is easy to operate and is applicable to industrial production.
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• Paragraph 0048-0050

  (2017/02/17)
• 

• An enzyme and its optional [...] modified ketone and inhibitor composition comprising (by machine translation)
• PROBLEM TO BE SOLVED: ketone-containing acrylic misuse, abuse or overload is prevented for a new takable amt. provitamin drag pain. SOLUTION: a compound represented by the following formula is represented, in which the drag oxystyrene provitamin hydrocodone ketone-containing acrylic. Pre-selected drug profile is modified and the ketone and schisandrin [...] holding hung contg. compsn. method for administration to a patient. Selected drawing: no (by machine translation)
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• Paragraph 0364; 0371

  (2017/01/23)
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• Method for synthesis of naloxone hydrochloride
• The invention belongs to the technical field of medicament synthesis, and relates to a synthetic method of naloxone hydrochloride. The method comprises the following steps: by adopting thebaine as a starting material, oxidizing and then reducing thebaine to obtain a compound 2, reacting the compound 2 with acetic anhydride to obtain an ester compound 3, then removing methyl and performing hydrolysis to obtain a compound 4, reacting the compound 4 with an alkylating reagent (such as the reagent selected from chloropropene, bromopropene, iodopropylene or the combination thereof), performing allylation on the Nth bit of a mother nucleus structure to obtain a compound 5, then removing methyl to obtain naloxone free alkali, then forming acid addition salts with hydrochloric acid, and then refining to obtain naloxone hydrochloride which can be used as a medicinal raw material medicament. By adopting the method disclosed by the invention, a high-quality medicinal raw material medicament can be prepared.
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• Paragraph 0103-0110

  (2017/03/22)
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• Active agent prodrugs with heterocyclic linkers
• The embodiments provide prodrug compounds of Formulae I-XVII. The present disclosure also provides compositions, and their methods of use, where the compositions comprise a prodrug compound of Formulae I-XVII that provides controlled release of an active agent. Such compositions can optionally provide a trypsin inhibitor that interacts with the enzyme that mediates the controlled release of an active agent from the prodrug so as to attenuate enzymatic cleavage of the prodrug.
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• Page/Page column 136

  (2015/10/28)
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• CONVERSION OF OXYCODONE BASE TO OXYCODONE HYDROCHLORIDE
• Synthetic methods are provided for preparation of oxycodone and salts thereof with an improved impurity profile. Thebaine is converted to 14-hydroxycodeinone sulfate intermediate to minimize a 7,8-dihydro-8,14-dihydroxycodeinone impurity. Efficient methods for conversion of oxycodone base to oxycodone hydrochloride are provided to minimize 14-hydroxycodeinone impurity in the final product.
• -

• (2015/06/24)
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• SYNTHESIS OF OXYCODONE HYDROCHLORIDE
• Synthetic methods are provided for preparation of oxycodone and salts thereof with an improved impurity profile. Thebaine is converted to 14-hydroxycodeinone sulfate intermediate to minimize a 7,8-dihydro-8,14-dihydroxycodeinone impurity. Efficient methods for conversion of oxycodone base to oxycodone hydrochloride are provided to minimize 14-hydroxycodeinone impurity in the final product.
• -

• (2015/06/24)
• 

• PROCESS FOR IMPROVED OXYCODONE SYNTHESIS
• Processes for preparing oxycodone are provided. Said processes encompass a step which is a hydrogenation of an 14-hydroxycodeinone salt in the presence of trifluoroacetic acid and/or a glycol.
• -
• Paragraph 00487-00500

  (2015/08/03)
• 

• On the selection of an opioid for local skin analgesia: Structure-skin permeability relationships
• Recent studies demonstrated that post-herpetical and inflammatory pain can be locally managed by morphine gels, empirically chosen. Aiming to rationalize the selection of the most suitable opioid for the cutaneous delivery, we studied the in vitro penetration through human epidermis of eight opioids, evidencing the critical modifications of the morphinan core. Log P, log D, solid-state features and solubility were determined. Docking simulations were performed using supramolecular assembly made of ceramide VI. The modifications on position 3 of the morphinan core resulted the most relevant in determining both physicochemical characteristics and diffusion pattern. The 3-methoxy group weakened the cohesiveness of the crystal lattice structure and increased the permeation flux (J). Computational studies emphasized that, while permeation is essentially controlled by molecule apolarity, skin retention depends on a fine balance of polar and apolar molecular features. Moreover, ChemPLP scoring the interactions between the opioids and ceramide, correlated with both the amount retained into the epidermis (Qret) and J. The balance of the skin penetration properties and the affinity potency for μ-receptors evidenced hydromorphone as the most suitable compound for the induction of local analgesia.
• Musazzi, Umberto M.,Matera, Carlo,Dallanoce, Clelia,Vacondio, Federica,De Amici, Marco,Vistoli, Giulio,Cilurzo, Francesco,Minghetti, Paola

• p. 177 - 185

  (2015/05/20)
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• A METHOD FOR PREPARING OXYCODONE
• The present invention provides a process for preparing an oxycodone acid adduct, said process comprising hydrogenating an aqueous solution of 14-hydroxycodeinone and an acid to form a solution of the oxycodone acid adduct, wherein the hydrogenation is carried out at one or more temperatures greater than ambient temperature in the presence of a hydrogenation catalyst and hydrogen gas, wherein the solution of oxycodone acid adduct comprises 6α-oxycodol in an amount ≤ about 0.800 area % as determined by HPLC.
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• Page/Page column 20; 21; 22; 23

  (2014/02/16)
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• PROCESS
• The present invention provides a process for preparing an oxycodone acid adduct, said process comprising hydrogenating an aqueous solution of 14-hydroxycodeinone and an acid to form a solution of the oxycodone acid adduct, wherein the hydrogenation is carried out at one or more temperatures greater than ambient temperature in the presence of a hydrogenation catalyst and hydrogen gas, wherein the solution of oxycodone acid adduct comprises 6α-oxycodol in an amount ≦about 0.800 area % as determined by HPLC.
• -
• Paragraph 0131; 0132; 0133; 0134; 0135

  (2014/03/21)
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• Preparation of 14-hydroxycodeinone sulfate
• Synthetic methods are provided for preparation of oxycodone and salts thereof with an improved impurity profile. Thebaine is converted to 14-hydroxycodeinone sulfate intermediate to minimize a 7,8-dihydro-8,14-dihydroxycodeinone impurity. Efficient methods for conversion of oxycodone base to oxycodone hydrochloride are provided to minimize 14-hydroxycodeinone impurity in the final product.
• -

• (2014/10/15)
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• Opioid prodrugs with heterocyclic linkers
• The embodiments provide prodrug compounds of Formulae I-XV. The present disclosure also provides compositions, and their methods of use, where the compositions comprise a prodrug compound of Formulae I-XV that provides controlled release of an opioid. Such compositions can optionally provide a trypsin inhibitor that interacts with the enzyme that mediates the controlled release of an opioid from the prodrug so as to attenuate enzymatic cleavage of the prodrug.
• -
• Page/Page column

  (2014/04/17)
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• PROCESS FOR IMPROVED OPIOID SYNTHESIS
• Compounds and compositions for use as starting materials or intermediate materials in the preparation of opioids including, e.g., oxycodone base and/or an oxycodone salt; processes for preparing these compounds and compositions; uses of these compounds and compositions in the preparation of APIs and pharmaceutical dosage forms; and uses of said APIs and pharmaceutical dosage forms in the treatment of medical conditions.
• -
• Paragraph 00536-00549

  (2014/02/15)
• 

• PROCESS FOR THE SYNTHESIS AND PURIFICATION OF OXYCODONE
• A method of preparing oxycodone includes forming 14-hydroxycodeine by reduction of 14-hydroxycodeinone and rearrangement of the 14-hydroxycodeine to form the oxycodone. During the reduction step, the ketone group of an undesirable contaminant precursor, 8, 14-dihydroxy-7,8-dihydrocodeinone, is reduced to a hydroxyl group thus forming a triol. This triol is substantially inert with respect to reforming 14- hydroxycodeinone and can be readily separated from oxycodone.
• -

• (2012/01/15)
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• Compositions Comprising Enzyme-Cleavable Oxycodone Prodrug
• The embodiments provide Compound KC-7, N-1-[(S)-2-(oxycodone-6-enol-carbonyl-methyl-amino)-2-carbonyl-sarcosine-ethyl amine]-arginine-glycine-acetate, or acceptable salts, solvates, and hydrates thereof. The present disclosure also provides compositions, and their methods of use, where the compositions comprise a prodrug, Compound KC-7, that provides controlled release of oxycodone. Such compositions can optionally provide a trypsin inhibitor that interacts with the enzyme that mediates the controlled release of oxycodone from the prodrug so as to attenuate enzymatic cleavage of the prodrug.
• -
• Page/Page column 25

  (2012/07/27)
• 

• Compositions Comprising Enzyme-Cleavable Oxycodone Prodrug
• The embodiments provide Compound KC-8, N-1-[3-(oxycodone-6-enol-carbonyl-methyl-amino)-2,2-dimethyl-propylamine]-arginine-glycine-malonic acid, or acceptable salts, solvates, and hydrates thereof. The present disclosure also provides compositions, and their methods of use, where the compositions comprise a prodrug, Compound KC-8, that provides controlled release of oxycodone. Such compositions can optionally provide a trypsin inhibitor that interacts with the enzyme that mediates the controlled release of oxycodone from the prodrug so as to attenuate enzymatic cleavage of the prodrug.
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• Page/Page column 26

  (2012/07/27)
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• COMPOSITIONS FOR REDUCING RISK OF ADVERSE EVENTS CAUSED BY DRUG-DRUG INTERACTIONS
• The present disclosure provides a composition comprising a GABAA agonist and a GI enzyme inhibitor. The present disclosure also provides a composition comprising (a) a GI enzyme inhibitor and (b) a first drug that interacts with a second drug to produce an adverse effect when the second drug is co-ingested as a GI enzyme-cleavable prodrug with the first drug. Such an interaction can be additive or synergistic.
• -

• (2012/09/22)
• 

• Opioid Prodrugs with Heterocyclic Linkers
• The embodiments provide prodrug compounds of Formulae I-XV. The present disclosure also provides compositions, and their methods of use, where the compositions comprise a prodrug compound of Formulae I-XV that provides controlled release of an opioid. Such compositions can optionally provide a trypsin inhibitor that interacts with the enzyme that mediates the controlled release of an opioid from the prodrug so as to attenuate enzymatic cleavage of the prodrug.
• -

• (2012/12/13)
• 

• Investigation of structure, vibrational and NMR spectra of oxycodone and naltrexone: A combined experimental and theoretical study
• In this work, two important opioid antagonists, naltrexone and oxycodone, were prepared from thebaine and were characterized by IR, 1H NMR and 13C NMR spectroscopy. Moreover, computational NMR and IR parameters were obtained using density functional theory (DFT) at B3LYP/6-311++G* * level of theory. Complete NMR and vibrational assignment were carried out using the observed and calculated spectra. The IR frequencies and NMR chemical shifts, determined experimentally, were compared with those obtained theoretically from DFT calculations, showed good agreements. The RMS errors observed between experimental and calculated data for the IR absorptions are 85 and 105 cm-1, for the 1H NMR peaks are 0.87 and 0.17 ppm and for those of 13C NMR are 5.6 and 5.3 ppm, respectively for naltrexone and oxycodone.
• Tavakol, Hossein,Esfandyari, Maryam,Taheri, Salman,Heydari, Akbar
• scheme or table

  p. 574 - 582

  (2011/07/31)
• 

• A METHOD FOR THE N-DEMETHYLATION OF N-METHYL HETEROCYCLES
• The present invention provides methods of N-demethylating, N-methylated heterocycles and N-methyl, N-oxide heterocycles using a transition metal with an oxidation state of zero, ferrocene or substituted derivatives thereof, or Cr 3+ .N-demethylated heterocycles prepared by the methods of the present invention are also provided.
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• Page/Page column 15-16

  (2011/04/19)
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• COMPOSITIONS COMPRISING ENZYME-CLEAVABLE PRODRUGS OF ACTIVE AGENTS AND INHIBITORS THEREOF
• The present disclosure provides pharmaceutical compositions, and their methods of use, where the pharmaceutical compositions comprise a prodrug that provides enzymatically-controlled release of a drug and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the drug from the prodrug so as to attenuate enzymatic cleavage of the prodrug. The disclosure provides pharmaceutical compositions which comprise an enzyme inhibitor and a prodrug that contains an enzyme-cleavable moiety that, when cleaved, facilitates release of the drug.
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• Page/Page column 297

  (2011/11/06)
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• COMPOSITIONS COMPRISING ENZYME-CLEAVABLE OPIOID PRODRUGS AND INHIBITORS THEREOF
• Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise an opioid prodrug that provides enzymatically-controlled release of an opioid, and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the opioid from the opioid prodrug so as to attenuate enzymatic cleavage of the opioid prodrug.
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• Page/Page column 149-150

  (2011/11/06)
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• PREPARATION OF LOW IMPURITY OPIATES IN A CONTINUOUS FLOW REACTOR
• The present invention relates to a novel process for preparing opiates or salts thereof. More particularly, the present invention relates to oxidizing the starting material in a continuous flow reactor, followed by either an isolation of the intermediate, or a direct reduction reaction.
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• Page/Page column 11

  (2011/10/13)
• 

• Preparation of low impurity opiates in a continuous flow reactor
• The present invention relates to a novel process for preparing opiates or salts thereof. More particularly, the present invention relates to oxidizing the starting material in a continuous flow reactor, followed by either an isolation of the intermediate, or a direct reduction reaction.
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• Page/Page column 6

  (2011/11/01)
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• PERIPHERAL OPIOID AGONISTS AND PERIPHERAL OPIOID ANTAGONISTS
• The present disclosure provides compositions, and their methods of use, where the compositions comprise a ketone-modified opioid drug, wherein the drug comprises a ketone-modified opioid and a substituent on the opioid that mediates retention of the drug in the peripheral nervous system as opposed to the central nervous system following ingestion by a subject.
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• Page/Page column 73

  (2011/11/06)
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• COMPOSITIONS COMPRISING ENZYME-CLEAVABLE PRODRUGS OF ACTIVE AGENTS AND INHIBITORS THEREOF
• The present disclosure provides pharmaceutical compositions, and their methods of use, where the pharmaceutical compositions comprise a prodrug that provides enzymatically-controlled release of a drug and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the drug from the prodrug so as to attenuate enzymatic cleavage of the prodrug. The disclosure provides pharmaceutical compositions which comprise an enzyme inhibitor and a prodrug that contains an enzyme-cleavable moiety that, when cleaved, facilitates release of the drug.
• -

• (2011/11/06)
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• N-Demethylation of N-methyl alkaloids with ferrocene
• Under Polonovski-type conditions, ferrocene has been found to be a convenient and efficient catalyst for the N-demethylation of a number of N-methyl alkaloids such as opiates and tropanes. By judicious choice of solvent, good yields have been obtained for dextromethorphan, codeine methyl ether, and thebaine. The current methodology is also successful for the N-demethylation of morphine, oripavine, and tropane alkaloids, producing the corresponding N-nor compounds in reasonable yields. Key pharmaceutical intermediates such oxycodone and oxymorphone are also readily N-demethylated using this approach.
• Kok, Gaik B.,Scammells, Peter J.
• supporting information; experimental part

  p. 4499 - 4502

  (2010/09/15)
• 

• Two-step iron(0)-mediated N-demethylation of N -methyl alkaloids
• (Figure Presented) A mild and simple two-step Fe(0)-mediated N-demethylation of a number of tertiary N-methyl alkaloids is described. The tertiary N-methylamine is first oxidized to the corresponding N-oxide, which is isolated as the hydrochloride salt. Subsequent treatment of the N-oxide hydrochloride with iron powder readily provides the N-demethylated amine. Representative substrates include a number of opiate and tropane alkaloids. Key intermediates in the synthesis of semisynthetic 14-hydroxy pharmaceutical opiates such as oxycodone and oxymorphone are also readily N-demethylated using this method.
• Kok, Gaik B.,Pye, Cory C.,Singer, Robert D.,Scammells, Peter J.
• experimental part

  p. 4806 - 4811

  (2010/10/19)
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• PROCESS FOR THE SYNTHESIS OF N-DEMETHYLATED MORPHINANE COMPOUNDS
• The present invention relates to a process for the preparation of an N-demethyl morphinane or a protected form thereof. In one form the preparation of the N-demethyl morphinane or a protected form thereof involves the N-demethylation of an N-methyl morphinane or protected form thereof. In particular the present process is useful in the preparation N-demethyl morphinane or a protected form thereof by N-demethylation of N-methyl morphinanes or protected forms thereof extracted from plants of the genus Papaver of the family Papaveraceae. An example of a suitable N-methyl morphinane that may be usefully subjected to the process of the present invention is thebaine.
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• Page/Page column 18

  (2010/01/12)
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• Synthesis and opioid receptor activity of indolopropellanes
• A series of skeletal rearranged indolomorphinans 7a-d were obtained by N-demethylation of 3-methoxy-N-methyl-14-hydroxymorphinan-6-one 12 followed by N-realkylation, reduction and Fischer indole cyclization. The structure of the novel skeleton was confirmed by X-ray analysis. These new indoles displayed moderate binding affinity and selectivity at the μ receptor, with compound 7b showing the highest affinity at this receptor with a Ki value of 40 nM, and 6- and 25-fold selectivity against δ and κ receptors, respectively. Function assays showed that indolopropellanes 7b and 7c possessed full agonistic activity at all the opioid receptors indicating a different interaction model existed.
• Li, Fuying,Gaob, Linghuan,Yin, Chenlei,Chen, Jie,Liu, Jinggen,Xie, Xin,Zhang, Ao
• scheme or table

  p. 4603 - 4606

  (2010/04/29)
• 

• AN IMPROVED PROCESS FOR THE PREPARATION OF MORPHINANE ANALOGUES
• The present invention relates to an improved process for preparing morphinane analogues of formula (1) wherein the substituents R1, R2, R2a, R3, R4, R5 and Y have the meanings as defined in the specifications.
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• Page/Page column 31

  (2009/10/30)
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• Process for Reducing Impurities in Oxycodone Base
• The present invention is directed to a process for using n-butanol to prepare an oxycodone base compositions having reduced levels of impurities such as 14-hydroxycodeinone and DHDHC.
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• Page/Page column 6

  (2008/12/05)
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• Process For Preparing Oxycodone Having Reduced Levels Of 14-Hydroxycodeinone
• The present invention is directed to processes for preparing oxycodone base and oxycodone hydrochloride compositions having less than 10 ppm of 14-hydroxycodeinone.
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• Page/Page column 5

  (2008/12/06)
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• NOVEL OPIATE REDUCTION UTILIZING CATALYTIC HYDROGEN TRANSFER REACTION
• An improved opiate synthesis scheme is provided. An improvement to the oxidation of oripavine and oripavine derivatives comprises the in-situ formation of the peroxacids required to oxidize the oripavine and oripavine derivatives to form an intermediate. An improvement to the reduction of the intermediate to form oxycodone and oxycodone derivatives comprises reduction utilizing a hydrogen transfer reagent. These improvements allow the production of oxycodone and oxycodone derivatives without isolation of the intermediate, providing a one-pot synthesis method.
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• Page/Page column 8-9

  (2008/12/08)
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• PRODRUGS AND METHODS OF MAKING AND USING THE SAME
• Prodrugs of parent drugs and methods of making and using the same are described. The prodrugs comprise an amine-containing parent drug moiety and a prodrug moiety, such as methoxyphosphonic acid or ethoxyphosphonic acid. The prodrugs may be employed in therapy for the treatment of various indications, such as pain, and in methods of decreasing the abuse potential of abuse-prone drugs and/or delaying the onset of parent drug activity and/or prolonging parent drug activity as compared to administration of a parent drug.
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• Page/Page column 75

  (2008/12/06)
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• PROCESSES FOR PREPARING MORPHINAN-6-ONE PRODUCTS WITH LOW LEVELS OF ALPHA, BETA-UNSATURATED KETONE COMPOUNDS
• The present invention generally relates to processes for preparing highly pure morphinan-6-one products. The processes involve reducing the concentration of alpha, beta unsaturated ketone compounds present as impurities in morphinan 6 one products or reaction mixtures including morphinan 6 one compounds by treatment with a sulfur-containing compound.
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• Page/Page column 33

  (2008/06/13)
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• A METHOD OF PREPARATION OF OXYCODONE
• A method of preparation of Oxycodone of formula (I) by reacting thebaine of formula (II), or its analogue of formula (III), wherein R represents a C2 to C5 alkyl, an alkylaryl, preferably benzyl, methoxybenzyl, or alkyl, with hydrogen peroxide or peroxoacids in the presence of oxalic acid in admixture with acetic or formic acid. From the resulting crystalline precipitate of 14-hydroxycodeinone oxalate, by addition of a base, 14-hydroxycodeinone of formula (IV) is released, which is hydrogenated with hydrogen in the presence of a catalyst to yield Oxycodone (I): Oxycodone is transformed to hydrochloride, which is used as the active ingredient in analgesic formulations.
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• Page/Page column 7

  (2008/06/13)
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• Preparation of oxycodone
• A process for preparing oxycodone or an oxycodone salt, wherein the oxycodone or oxycodone salt has low levels of impurities (especially 14-hydroxycodeinone) is disclosed. The process comprises the steps of: a) preparing a mixture comprising oxycodone and a solvent and adjusting the pH of the mixture to less than 6; and subsequently b) exposing the mixture to hydrogenation reagents for a period of at least 1 hour.
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• Page/Page column 2

  (2008/06/13)
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• METHODS OF TREATING PAIN
• The present invention is directed to methods and compositions for inducing, promoting or otherwise facilitating pain relief. More particularly the present invention discloses the combination of a nitric oxide donor and an opioid analgesic in the therapeutic management of vertebrate animals including humans, for the prevention or alleviation of pain, particularly moderate to severe pain. In particular, the nitric oxide donor is a slow-release nitric oxide donor or is formulated to provide a sustained release of a low dose of nitric oxide.
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  (2008/06/13)
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• Process for manufacturing opioid analgesics
• Oxycodone is manufactured in high yields and with a high purity using a composition including a thebaine component into 14-hydroxycodeinone and then reduction of 14-hydroxycodeinone to oxycodone.
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• (2008/06/13)
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