Abstract: A therapeutic and/or prophylactic agent for constipation induced by a compound having an opioid ? receptor agonist activity, which agent comprises as an effective ingredient a compound having an opioid ? receptor antagonist activity, e.g., a compound of Formula (I): (wherein R1 represents hydrogen, lower alkyl, cycloalkyl lower alkyl or the like; R2 and R3 independently represent hydrogen, hydroxy or the like; R4 is hydrogen, hydroxy or the like; R5 is hydrogen; R4 and R5 may optionally form —O— or the like; R6 represents hydrogen, lower alkyl or the like (wherein X represents —O— or —N(R10)— or the like; R7, R8, R9a and R9b independently represent hydrogen, lower alkyl, lower alkoxycarbonyl or the like; r represents an integer of 0 to 5; Y represents —CH— or the like; Z represents a crosslinkage composed of 2 to 5 atoms) or a pharmaceutically acceptable salt thereof or a solvate of either.

Abstract: The present invention relates to compounds of formula I, synthesis thereof, and methods of using the same.

Abstract: A method for extracting at least one alkaloid from opium that includes dissolving opium in a solvent, heating the dissolved opium solution, cooling the dissolved opium solution, adjusting the pH of the dissolved opium solution with at least one first weak acid, filtering the dissolved opium solution to recover a filtrate; and then separating and purifying at least one alkaloid in the filtrate. Preferably, this includes an additional step of chilling the opium solution after adjusting the pH of the dissolved opium solution with at least one first acid. The preferred method for separating and purifying at least one alkaloid in the filtrate includes utilizing preparative liquid chromatography, however, solvent extraction and filtration can also be utilized.

Abstract: The present invention is directed to novel codrugs comprising bupropion or hydroxybupropion and an opioid antagonist or an opioid agonist joined together by chemical bonding. The codrugs provide a significant increase in the transdermal flux across human skin, as compared to the basic opioid antagonist or opioid agonist.

Abstract: The invention relates to new morphine compounds of the formula: where R1 represents a C1-6 alkyl radical and the radicals R2 and R3 are independently selected from the group consisting of hydrogen atoms, methyl groups and acetyl groups.

Abstract: The present invention provides methods for the conversion of thebaine to a morphine derivative, such as hydrocodone. Novel ketal intermediates of the conversion are provided. A one-pot procedure for the conversion comprises treating thebaine with an acid in the presence of a metal catalyst.

Abstract: The present invention provides a method for the N-demethylation of an N-methylated heterocycle, particularly a morphine or tropane alkaloid or derivative thereof. The method comprises reacting the heterocycle with a metal catalyst and a solvent in the presence of an oxidizing agent.

Abstract: Analogs of 6-monoacetyl morphine (6-MAM) are described. These include analogs derivatized at either the C-3 position, the C-6 position, or the nor position of the molecule. These analogs allow for elaboration with linkers terminated by a functional group such as an activated ester, the functional groups being useful for attaching the molecule to other entities such as proteins, polysaccharides, and reporter groups.

Abstract: The present invention relates to process for the preparation of a 14-hydroxynormorphinone derivative of formula IV comprising reacting the compound of formula III, with a cobalt (II) oxidant in the presence of a mild base and air or oxygen as the cooxidant; wherein R1 is (1C-7C)alkyl optionally substituted with one or more chlorines, butenyl, vinyl, benzyl, phenyl or naphthyl; and R2 is benzyl or benzyl substituted with one or more (1C-6C)alkoxy group or benzyl substituted with one or more halogen. The process is very suitable in the production of noroxymorphone.

Abstract: Novel N-oxides of 4,5-epoxy-morphinanium analogs are disclosed. Pharmaceutical compositions containing the N-oxides of 4,5-epoxy-morphinanium analogs and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as modulators of opioid receptors.

Abstract: Novel methods of synthesis of known and novel 14-hydroxyl opiates through 1-halothebaine and derivatives are described.

Abstract: The invention relates to a method for altering alkaloid biosynthesis in a plant, comprising: i) introducing into cells of a plant, an expressible exogenous nucleic acid comprising or consisting of an (S)-N-methylcoclaurine 3?-hydroxylase gene (cyp80b) or a derivative thereof, and ii) optionally propagating the plant, wherein expression of the exogenous nucleic acid in the plant or in its progeny results in altered levels of alkaloid biosynthesis.

Abstract: The present invention generally relates to catalysts of formula (III) [M(P(Ra)(Rb)N(Rc)(Rd))2Xn]mYp that selectively convert morphine/codeine to hydromorphone/hydrocodone, and methods of use thereof.

Abstract: This invention relates to a method for N-demethylating an N-methyl morphinane comprising the steps of: (i) treating said N-methyl morphinane with an oxidizing agent to form the N-oxide morphinane; and (ii) treating said N-oxide morphinane with a reducing agent. This invention also relates to a method for oxidizing a ?7-morphinane compound to a ?6, ?8-morphinane compound, comprising the steps of treating said ?7-morphinane with ?-MnO2 for a time and under conditions sufficient to oxidize said ?7-morphinane, and treating the ?-MnO2 with glycol or a derivative thereof, and/or an inorganic salt.

Abstract: Compounds including an opioid, and a cannabinoid covalently bound by a linker; pharmaceutical formulations including codrugs; methods of manufacture as well as methods of treatment are disclosed.

Abstract: The present invention generally relates to catalysts of formula (III) [M(P(Ra)(Rb)N(Rc)(Rd))2Xn]mYp that selectively convert morphine/codeine to hydromorphone/hydrocodone, and methods of use thereof.

Abstract: A method for the catalytic production of hydrocodone derivatives and hydromorphone derivatives, respectively, utilizing a transition metal catalyst of the formula [M(PR4R5R6)nXm]p; wherein M is a Group VIII transition metal; R4, R5 and R6 are selected from the group consisting of alkyl, aryl, alkoxyl, phenoxy and combinations thereof; X is a halide or an anion; n is 1, 2, 3 or 4; m is 1 or 2; and p is at least 1.

Abstract: The present invention provides compositions and methods for treating pain by the administration of analgesics. The analgesics are encapsulated in diacylglycerol-polyethyleneglycol (DAG-PEG) liposomes and delivered sublingually as aerosols.

Abstract: The present invention is directed to a process for reducing the level of ?, ?-unsaturated ketone in an opioid analgesic composition by hydrogenation with diimide or a diimide progenitor.

Abstract: The present invention includes a process for the manufacture of dihydrothebaine, dihydrocodeinone enol acetate, hydrocodone, and analogs thereof by reacting dihydrocodeine or analogs thereof with benzophenone in the presence of potassium tert-alkylate in a hydrocarbon solvent to generate a reaction mixture containing an enolate of the corresponding ketone, followed by addition of the reaction mixture to the electrophilic agent and isolation of the product.

Abstract: The present disclosure is directed to modulators of opiate- and/or NMDA receptors and pharmaceutically acceptable salts and prodrugs thereof, the chemical synthesis thereof, and the use of such compounds for the treatment and/or management of pain, anxiety, neurodegeneration, drug dependence, coughing, muscular tension, and/or glaucoma and any other condition in which it is beneficial to modulate an opiate- and/or NMDA receptor.

Abstract: A method for the catalytic conversion of codeine, morphine or analogs thereof into hydrocodone, hydromorphone or analogs thereof utilizing a transition metal complex of a tertiary phosphine halide as catalyst.

Abstract: The invention provides a morphinan derivative of the Formula (I): wherein R1 is methyl, cyclopropylmethyl or the like; R2 and R3 are hydroxy, methoxy, acetoxy or the like; both Y and Z are valence bonds, —C(?O)— or the like; X is C2-C5 carbon chain (one of the carbon atoms may be substituted by oxygen, sulfur or nitrogen) constituting a part of the ring structure, or the like; (R4)k is substituted or non-substituted benzene fused ring, carbonyl group or the like; R9 is hydrogen or the like; R10 and R11 are bound to represent —O—, or the like, and R6 is hydrogen or the like or a pharmaceutically acceptable acid addition salt thereof. The invention also provides a therapeutic or prophylactic agent for urinary frequency or urinary incontinence, comprising as an effective ingredient the morphinan derivative or the pharmaceutically acceptable acid addition salt thereof; a method for therapy or prophylaxis of the diseases.

Abstract: A method for the catalytic conversion of codeine, morphine or analogs thereof into hydrocodone, hydromorphone or analogs thereof utilizing a transition metal catalyst of the formula [M(PR3R4R5)nXm]p; wherein R1 is H, alkyl, aryl or acyl; M is a Group VIII transition metal; R3, R4 and R5 are selected from the group consisting of alkyl, aryl, alkoxyl, phenoxyl and combinations thereof; X is a halide or an anion; n is 1, 2, 3 or 4; m is 1 or 2; and p is at least 1.

Abstract: The invention provides compounds of the invention pharmaceutical compositions comprising a compound of the invention, processes for preparing compounds of the invention, intermediates useful for preparing compounds of the invention, and therapeutic methods for treating cancer and other topoisomerase mediated conditions.

Abstract: The present invention relates to novel crystalline polymorphic forms of levorphanol including hydrated, solvated, and non-hydrated (non-solvated) forms. The invention also describes methods of preparing the various polymorphic forms. The present invention also relates to pharmaceutical compositions containing crystalline polymorphs of levorphanol, as well as methods of relieving pain by administering the pharmaceutical compositions.

Abstract: A process for the preparation of a quaternary derivative of the morphinan alkaloid, the process comprising contacting a tertiary N-substituted morphinan alkaloid with an alkyl halide in an anhydrous solvent system, wherein the solvent system comprises an aprotic dipolar solvent with the aprotic dipolar solvent constituting at least 25 wt. % of the solvent system.

Abstract: This invention relates to the discovery of novel polymorphic forms of naltrexone, including solvates, hydrates, anhydrous and other crystalline forms and combinations thereof. These novel forms of naltrexone impart advantages in pharmaceutical formulations incorporating them, including sustained release, or long acting, formulations.

Abstract: The abuse potential of a bioavailable drug such as an opiate analgesic agent is reduced and its duration of action is extended by converting it to a poorly absorbed ester prodrug or other prodrug derivative prior to formulation. Unlike many existing sustained release formulations of active pharmaceutical agents wherein an active pharmaceutical agent can be released by chewing, crushing, or otherwise breaking tablets or capsule beads containing the active pharmaceutical agent, such mechanical processing of tablets or capsule beads containing a prodrug of this invention neither releases the active drug nor compromises the controlled conversion of prodrug to drug. Moreover, tablets and capsule beads containing prodrugs of this invention or other drugs can be formulated with a sufficient amount of a thickening agent such as hydroxypropylmethylcellulose or carboxymethylcellulose to impede inappropriate intravenous and nasal administration of formulations that are not indicated for these modes of administration.

Abstract: The present disclosure concerns compounds of formula (I) and pharmaceutically acceptable salts, hydrates, solvates, pharmaceutically acceptable derivatives, pro-drugs, tautomers and/or isomers thereof.

Abstract: Novel compounds which selectively bind to the ?-opioid receptor have been designed. These compounds have greater selectivity, improved water (blood) solubility, and enhanced therapeutic value as analgesics. Because agonists with selectivity for the ?-opioid receptor have shown promise in providing enhanced analgesis without the addictive properties, the compounds of the present invention are better than morphine, naltrindole (NTI), spiroindanyloxymorphone (SIOM), and other known ?-opioid receptor selectors as analgesics.

Abstract: 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.

Abstract: In certain embodiments the invention is directed to a process for preparing an oxycodone hydrochloride composition having less than 25 ppm of 14-hydroxycodeinone.

Abstract: A morphine component, e.g., a concentrate of poppy straw, is converted into codeine in high yield and high purity and in a highly controlled manner. The conversion process involves the following steps: (a) providing a solution or suspension of a morphine component in an inert solvent or a mixture of solvents; (b) methylating the resultant solution or suspension with a methylating agent in the presence of an alkaline ingredient; and (c) recovering the resultant codeine as the free base or as a salt.

Abstract: Methods for making thebaine and an acid salt of thebaine are disclosed herein. In one embodiment, an acid salt of thebaine is made from codeinone or an acid salt of one or more of the following: 8-methoxy-?6-dihydrothebaine, codeinone dimethyl ketal, and neopinone dimethyl ketal.

Abstract: A morphine component, e.g., a concentrate of poppy straw, is converted into codeine in high yield and high purity and in a highly controlled manner. The conversion process involves the following steps: (a) providing a solution or suspension of a morphine component in an inert solvent or a mixture of solvents; (b) methylating the resultant solution or suspension with a methylating agent in the presence of an alkaline ingredient; and (c) recovering the resultant codeine as the free base or as a salt.

Abstract: A protected 2?-deoxycytidine is purified by precipitating the protected 2?-deoxycytidine represented by general formula (3) in the form of a hydrated crystal from a solution containing the protected 2?-deoxycytidine and water, and by recovering the protected 2?-deoxycytidine: wherein R1 represents a 4-methoxytrityl, 4, 4?-dimethoxytrityl, or triphenylmethyl group; and B1 represents a cytosine group having a protected amino group. The compound represented by general formula (3) is, in particular, a protected 2?-deoxycytidine represented by formula (4): The 2?-deoxycytidine is used as a raw material for antisense DNA.

Abstract: 8-Substituted-2,6-methano-3-benzazocines of general structure I in which A is —CH2—OH, —CH2NH2, —NHSO2CH3, and Y is O, S or NOH are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications. 8-Carboxamides, thiocarboxamides, hydroxyamidines and formamides are preferred.

Abstract: A process for the preparation of dihydrocodeine by hydrogenating codeine or a salt thereof in aqueous solution in the presence of a catalytic metal and deactivating agent that decreases impurities formation.

Abstract: Oxycodone is manufactured in high yields and with a high purity using codeine or a salt of codeine as the starting material. The manufacturing process involves the following steps: (a) codeine or a codeine salt (e.g.

Abstract: This invention relates to N-substituted hydromorphones of Formula I: or a pharmaceutically acceptable salt thereof, wherein R is C1-6 alkyl. These compounds act as &mgr; opioid receptor agonists. The invention is also directed to the use of compounds of Formula I for the treatment, prevention or amelioration of both acute and chronic pain.

Abstract: The abuse potential of a bioavailable drug such as an opiate analgesic agent is reduced and its duration of action is extended by converting it to a poorly absorbed ester prodrug or other prodrug derivative prior to formulation. Unlike many existing sustained release formulations of active pharmaceutical agents wherein an active pharmaceutical agent can be released by chewing, crushing, or otherwise breaking tablets or capsule beads containing the active pharmaceutical agent, such mechanical processing of tablets or capsule beads containing a prodrug of this invention neither releases the active drug nor compromises the controlled conversion of prodrug to drug. Moreover, tablets and capsule beads containing prodrugs of this invention or other drugs can be formulated with a sufficient amount of a thickening agent such as hydroxypropylmethylcellulose or carboxymethylcellulose to impede inappropriate intravenous and nasal administration of formulations that are not indicated for these modes of administration.

Abstract: A salt of a codrug of at least two drug compounds covalently linked to one another via a labile bond to form a single codrug, and methods of use of the codrug salt for the treatment of various medical conditions. The codrug salt may be administered by itself or in the form of a bioerodible or nonbioerodible substance.

Abstract: Thebaine is manufactured in high yields and with a high purity using codeine or a salt of codeine as the starting material. The manufacturing process involves the following steps: (a) codeine or a codeine salt (e.g., codeine phosphate) is converted into the intermediate N-carboalkoxy- or N-carboaryloxynorcodeine; (b) the intermediate N-carboalkoxy- or N-carboaryloxynorcodeine resulting from step (a) is oxidized to yield the intermediate N-carboalkoxy- or N-carboaryloxynorcodeine; (c) the intermediate N-carboalkoxy- or N-carboaryloxynorcodeinone resulting from step (b) is enolized with a base and the resultant enolate is thereafter methylated to yield the intermediate N-carboalkoxy- or N-carboaryloxynorthebaine; and (d) the intermediate N-carboalkoxy- or N-carboaryloxynorthebaine resulting from step (c) is reduced to yield thebaine.

Abstract: This invention relates to novel structural analogues and derivatives of compounds with general analgesic or related pharmacological activity. In particular the invention relates to derivatives of opioid compounds, particularly morphine and related compounds, in which an opioid compound is linked via the nitrogen at position 17 to a spacer group, which in turn is linked to a charged group, or a pharmaceutically acceptable salt thereof. In particularly preferred embodiments the opioid compound is morphine, codeine, or buprenorphine.

Abstract: 8-Substituted-2,6-methano-3-benzazocines of general structure I in which A is —CH2—OH, —CH2NH2, —NHSO2CH3, and Y is O, S or NOH are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications. 8-Carboxamides, thiocarboxamides, hydroxyamidines and formamides are preferred.

Abstract: The subject invention concerns novel analogs of fentanyl opioids. The subject invention also concerns methods for synthesizing the compounds of the invention. The invention also concerns methods for treating pain in a patient by administering a compound of the invention to a person in need of such treatment.

Abstract: Glucoside and glucuronide derivatives of hydromorphone, dihydromorphine, and dihydroisomorphine and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising a glucoside or glucuronide derivative of hydromorphone, dihydromorphine, or dihydroisomorphine or a pharmaceutically acceptable salt thereof; and methods for treating or preventing pain in a patient comprising administering to a patient in need thereof a glucoside or glucuronide derivative of hydromorphone, dihydromorphine, or dihydroisomorphine or a pharmaceutically acceptable salt thereof are disclosed.

Abstract: This invention relates to a method for N-demethylating an N-methyl morphinane comprising the steps of: (i) treating said N-methyl morphinane with an oxidizing agent to form the N-oxide morphinane; and (ii) treating said N-oxide morphinane with a reducing agent. This invention also relates to a method for oxidizing a &Dgr;7-morphinane compound to a &Dgr;6, &Dgr;8-morphinane compound, comprising the steps of treating said &Dgr;7-morphinane with &ggr;-MnO2 for a time and under conditions sufficient to oxidize said &Dgr;7morphinane, and treating the &ggr;-MnO2 with glycol or a derivative thereof, and/or an inorganic salt.

Abstract: The invention relates to pharmaceutically active substances from the group comprising midazolam and compounds with a methyl-substituted nitrogen atom that is the ring atom of a nitrogenous heterocycle. These substances are used to reduce the oxygen consumption during a physical activity. They can be administered together with an effective amount of D-glucose, D-maltose, ethanol, a glucogenic amine, a glucogenic amino acid or an amino acid metabolizable via glyoxylate or a dipeptide or a pharmaceutically acceptable salt of such an amino acid and an effective amount of thiamine, of a pharmaceutically acceptable thiamine salt or of a combination of folic acid and cyanocobalamine, with the proviso that the third component is thiamine or a pharmaceutically acceptable thiamine salt if the second component is D-glucose, D-maltose, a glucogenic amine, a glucogenic amino acid non-metabolizable via glyoxylate, or a dipeptide or a pharmaceutically acceptable salt of such an amino acid.