Abstract: An improved method for the preparation of oxymorphone from oripavine is provided. Oripavine is oxidized to form 14-hydroxymorphinone after which the oxidation reaction is quenched to prevent the formation of 1-1?-dimer side products. The 14-hydroxymorphinone is then reduced, typically by catalytic hydrogenation to form oxymorphone. The inventive method disclosed is further applicable to the production of morphinan derivatives.

Abstract: The present invention relates to an opioid controlled release oral dosage form comprising at least one opioid for the manufacture of a medicament to treat patients with restless leg syndrome (RLS).

Abstract: A drug substance with a pharmaceutically acceptable organic acid addition salt of an opioid wherein said organic acid is selected from Structure A: wherein R1-R4 are independently selected from H, alkyl or substituted alkyl of 1-6 carbons, adjacent groups may be taken together to form a cyclic alkyl, cyclic alkyl-aryl, or cyclic aryl moiety; R5 is selected from H, or an alkali earth cation; R6 and R7 are independently selected from H, alkyl of 1-6 carbons, an alkali earth cation, and aryl of 6 to 12 carbons, in a number sufficient to complete the valence bonding of X, and wherein X is selected from nitrogen, oxygen or sulfur; and wherein the drug substance has a morphology selected from amorphous and crystalline.

Abstract: Disclosed are methods for making aldehydes and ketones comprising allowing the corresponding primary or secondary alcohol to react in the presence of trichoroisocyanuric acid, a compound of formula R1SR2 and a base. In one embodiment, the alcohol is a compound of formula (I): wherein R3 is a protecting group. Also disclosed are methods for making 3-O-protected morphine dienol carboxylates comprising allowing a compound of formula (I) to oxidize in the presence of a chlorine-containing compound and a compound of formula R1SR2; and allowing the product of the oxidation step to react with an acylating agent.

Abstract: Crystalline particles of N-(17-cyclopropylmethyl-4,5?-epoxy-3,14-dihydroxy-morphinan-6?-yl)-phthalimide or a pharmaceutically acceptable salt thereof are disclosed. The crystalline particles have a particle diameter distribution in which a particle diameter (D50) at the point where cumulative frequency of volume distribution cumulatively calculated from particles having a smaller diameter reaches 50% is within a range of 1 to 30 ?m, and a particle diameter (D90) at the point where cumulative frequency of volume distribution cumulatively calculated from particles having a smaller diameter reaches 90% is not more than 90 ?m, which crystalline particles have a degree of crystallinity of not less than 80%. By the crystalline particles, bioavailability of the active substance may be increased while ensuring storage stability of the compound.

Abstract: A novel compound which is useful as an agent for treating and/or preventing emesis, vomiting and/or constipation. A compound represented by the formula (I): wherein R1 and R2 are each independently hydrogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted cycloalkyl, optionally substituted aryl etc., R3 is hydrogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted lower alkoxy etc., R4 is hydrogen or lower alkyl, R5 is hydrogen, lower alkyl, cycloalkyl lower alkyl or lower alkenyl, or a pharmaceutically acceptably salt, or a solvate thereof is provided.

Abstract: The invention relates generally to anti-angiogenesis agents and related methods of using to anti-angiogenesis agents for biomedical applications including direct monotherapy and combination therapy for treatment of an angiogenesis related condition. In an embodiment, the invention provides a class of opioid compounds and structurally related opioid derivatives exhibiting anti-VEGF activity for use in therapeutic procedures, including phototherapy. Opioid compounds and structurally related opioid derivatives of the invention may be administered alone or in combination with administration of a phototherapy agent and/or other therapeutic agent.

Abstract: A method of treating schizophrenia, which method can treat especially positive symptoms of schizophrenia and does not cause impaired information processing related to cognitive deficiencies or the like which is a symptom of schizophrenia. The method of treating schizophrenia includes as an effective ingredient a compound having a specific morphinan skeleton or a pharmaceutically acceptable acid addition salt thereof.

Abstract: A novel (+)-3-hydroxymorphinan derivatives and a pharmaceutical composition comprising the same as an active ingredient, which are useful for preventing or treating a neurodegenerative disease, are provided.

Abstract: Method for producing nalmefene hydrochloride from naltrexone, which method is particular well adapted for large-scale industrial application, and has been found to be efficient, to give a high yield and to afford highly pure nalmefene hydrochloride salt.

Abstract: The present invention relates to an improved process for producing naltrexone[17-(cyclopropylmethyl)-4,5?-epoxy-3,14-dihydroxy-morphinan-6-one] from noroxymorphone[4,5-?-epoxy-3,14-dihydroxy-morphinan-6-one] by alkylation with a cyclopropylmethyl halide.

Abstract: The invention generally provides processes and intermediate compounds useful for the production of sinomenine derivatives. In particular, the process may encompass synthetic routes for the production of (+)-sinomenine derivatives and their intermediates.

Abstract: The invention provides compounds that are chemically modified by covalent attachment of a water-soluble oligomer. A compound of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from those of the compound not attached to the water-soluble oligomer.

Abstract: The invention provides processes for the conversion of a 6-keto morphinan to a 6-hydroxy morphinan. In particular, the invention provides a stereoselective process for the conversion of a 6-keto morphinan to a 6-beta-hydroxy morphinan.

Abstract: Methods of modifying the rate of systemic absorption of a drug administered to a subject by a pulmonary route, the method comprising covalently conjugating a hydrophilic polymer to a drug, wherein the drug has a half-life of elimination from the lung of less than about 180 minutes, to form a drug-polymer conjugate, wherein the drug-polymer conjugate has a net hydrophilic character and a weight average molecular weight of from about 50 to about 20,000 Daltons, and wherein the half-life of elimination from the lung of the drug-polymer conjugate is at least about 1.5-fold greater than the half-life of elimination from the lung of the drug, wherein the half-life of elimination from the lung is measured by bronchoalveolar lavage followed by assaying residual lung material.

Abstract: Methods are provided which include converting oripavine to other opiates, including converting oripavine to 14-hydroxymorphinone and/or converting 14-hydroxymorphinone to oxymorphone. Purification and salt formation are optionally included.

Abstract: The present application describes processes for the synthesis of morphinane and morphinone compounds, useful as pharmaceutical agents. Also included are novel intermediates useful in the preparation of these compounds. The process comprises quaternization of oripavine to provide a mixture of the R- and S-isomeric (at the nitrogen) quaternary salts. The R-isomer is readily isolated and converted to various N-(R)-morphinane and N-(S)-morphinone compounds. The R-isomer, S-isomer or a mixture of R- and S-isomers may be demethylated and converted to various morphinane and morphinone compounds.

Abstract: The present invention describes a series of therapeutically active compounds of formula I, X—Y—Z??(I) that are useful for treating a disorder in a mammal. In the formula I, X and Z, which may be same or different, are independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclic group or substituted or unsubstituted heterocyclylalkyl; and Y is a linker selected from —O—, —S—, —NH—, —(CH2)n—, —CO—, —CONRa—, —NRaCO—, —NRaCOO—, —COO—, —CONRaCO—, —CONRaCOO— and —COOCOO—.

Abstract: A process for preparing a compound of formula (A), (B) or (C): wherein P is H, CH3 or a hydroxyl protecting group; X is O, a protected ketone, OH, a protected hydroxyl group or H; Y is OH, a protected hydroxyl group or H; W is C(CH3)2OH, (CH3)(C(CH3)3)OH or COCH3; Z is C2-C10 alkyl or C2-C10 arylalkyl; and is a single bond or a double bond, is disclosed. The process includes reductive alkylation in the presence of hydrogen and a reductive alkylation catalyst.

Abstract: The present invention provides processes for the preparation of N-alkyl morphinans without the isolation of nor-morphinan intermediates. In particular, the invention provides tandem hydrolysis/alkylation reactions for the synthesis of N-alkyl morphinans.

Abstract: The present invention is directed to novel crystalline and amorphous forms of nalbuphine hydrochloride.

Abstract: This invention relates to intermediates useful in the preparation of opiate alkaloids, particularly morphinane compounds. The invention also relates to processes for preparing such intermediates and to processes which utilise such intermediates in the synthesis of morphinane compounds.

Abstract: Disclosed are methods for making aldehydes and ketones comprising allowing the corresponding primary or secondary alcohol to react in the presence of trichoroisocyanuric acid, a compound of formula R1SR2 and a base. In one embodiment, the alcohol is a compound of formula (I): wherein R3 is a protecting group. Also disclosed are methods for making 3-O-protected morphine dienol carboxylates comprising allowing a compound of formula (I) to oxidize in the presence of a chlorine-containing compound and a compound of formula R1SR2; and allowing the product of the oxidation step to react with an acylating agent.

Abstract: The invention provides a process for the conversion of opioid derivatives into normorphinan compounds useful for making “nal” compound analgesics and antagonists. In particular, the process may be used for the production of pure normorphinan salts from crude opioid substrates.

Abstract: The present invention relates to a process for the preparation of quaternary N-alkyl morphin or morphinan alkaloid derivatives. This is achieved by using a nucleophilic nitrogen, phosphor or sulfur containing base in the reaction mixture.

Abstract: substances and the nasal administration thereof, in particular as one of a liquid, as a suspension or solution, or a powder, to the nasal airway of a subject, in particular the posterior region of the nasal airway, and in particular the upper posterior region of the nasal airway, which includes the olfactory bulb, in particular in the treatment of neurological conditions and disorders.

Abstract: Methods of modifying the rate of systemic absorption of a drug administered to a subject by a pulmonary route, the method comprising covalently conjugating a hydrophilic polymer to a drug, wherein the drug has a half-life of elimination from the lung of less than about 180 minutes, to form a drug-polymer conjugate, wherein the drug-polymer conjugate has a net hydrophilic character and a weight average molecular weight of from about 50 to about 20,000 Daltons, and wherein the half-life of elimination from the lung of the drug-polymer conjugate is at least about 1.5-fold greater than the half-life of elimination from the lung of the drug, wherein the half-life of elimination from the lung is measured by bronchoalveolar lavage followed by assaying residual lung material.

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

Abstract: The use of opioids or opioid mimetics is suggested for the manufacture of a medicament for the treatment of resistant cancer patients.

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates to the Nalmefene hydrochloride dihydrate, methods of manufacturing Nalmefene hydrochloride dihydrate, a pharmaceutical composition comprising Nalmefene hydrochloride dihydrate and a method of treatment comprising administering Nalmefene hydrochloride dehydrate.

Abstract: The invention provides small molecule drugs that are chemically modified by covalent attachment of a water-soluble oligomer obtained from a monodisperse or bimodal water-soluble oligomer composition. A conjugate of the invention, when administered by any of a number of administration routes, exhibits a reduced biological membrane crossing rate as compared to the biological membrane crossing rate of the small molecule drug not attached to the water-soluble oligomer.

Abstract: The invention provides opioid agonists covalently bound to a water-soluble oligomer having reduced potential for substance abuse and uses thereof. The compounds of the invention possess altered pharmacokinetic profiles relative to the opioid agonists alone, but are not subject to the risk of physical tampering that allows for the recovery and abuse of the opioid agonist associated with certain alternative delivery formulations.

Abstract: A method of converting a treatment for pain comprising intravenous administration of opioids, to a treatment for pain comprising oral administration of a first dose of an immediate release morphine-oxycodone combination in patients in need of analgesia. The method may comprise (1) determining a four-hour average oral morphine equivalents or determining a net average hourly intravenous dose, and (2) orally administering to the patient a first dose of a morphine-oxycodone combination in a 3:2 ratio by weight every four to six hours. Also, a method of treating pain in patients who had been administered opioids intravenously, comprising using a dosing algorithm to determine the first dose of the immediate release morphine-oxycodone combination.

Abstract: Disclosed are methods for making aldehydes and ketones comprising allowing the corresponding primary or secondary alcohol to react in the presence of trichoroisocyanuric acid, a compound of formula R1SR2 and a base. In one embodiment, the alcohol is a compound of formula (I): wherein R3 is a protecting group. Also disclosed are methods for making 3-O-protected morphine dienol carboxylates comprising allowing a compound of formula (I) to oxidize in the presence of a chlorine-containing compound and a compound of formula R1SR2; and allowing the product of the oxidation step to react with an acylating agent.

Abstract: This invention relates to S-MNTX, methods of producing S-MNTX, pharmaceutical preparations comprising S-MNTX and methods for their use.

Abstract: The present invention provides a method for the N-demethylation and/or N-acylation of an N-methylated heterocycle such as morphine alkaloids or tropane alkaloids. The method comprises reacting the heterocycle with an acylating agent in the presence of a metal catalyst.

Abstract: The present invention concerns prodrugs of opioid analgesics and pharmaceutical compositions containing such prodrugs. Methods for providing more consistent pain relief by increasing the bioavailability of the opioid analgesic with the aforementioned prodrugs are provided. The invention also provides for decreasing the adverse GI side effects of opioid analgesics.

Abstract: The present invention provides (+)-morphinans comprising Toll-like receptor 9 (TLR9) antagonist activity, as well as methods for using the (+)-morphinans to treat pain. Also provided are pharmaceutical combination compositions comprising a (+)-morphinan and an opioid agonist/monoamine reuptake inhibitor, as well as methods for using the combination compositions to treat pain.

Abstract: Methods are provided which include converting oripavine to other opiates, including converting oripavine to naltrexone, buprenorphine, 14-hydroxymorphinone and/or converting 14-hydroxymorphinone to oxymorphone. Purification and salt formation are optionally included.

Abstract: The present invention relates to the field of pain management, and more particularly to synergistic codrugs comprising an opioid and nornicotine which have been combined to form a single chemical codrug entity. When the codrug is administered it produces a synergistic analgesic response to pain.

Abstract: The present invention relates to the field of pain management, and more particularly to synergistic codrugs comprising an opioid and ketamine or norketamine which have been combined to form a single chemical codrug entity. When the codrug is administered it produces a synergistic analgesic response to pain.

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

Abstract: A process for the purification of an impure preparation containing naltrexone by means of a reverse phase preparative chromatography process is provided. In an illustrative embodiment a chromatographic column is loaded with a stationary phase, typically a silica particle having an organic ligand bound thereto. With a loading ratio of from about 10 to about 1000 the impure preparation is acidified and passed through the column. The column is eluted with typically an aqueous solution with acetonitrile and the purified naltrexone is obtained in a specified fraction.

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: A method of converting a treatment for pain comprising intravenous administration of opioids, to a treatment for pain comprising oral administration of a first dose of an immediate release morphine-oxycodone combination in patients in need of analgesia. The method may comprise (1) determining a four-hour average oral morphine equivalents or determining a net average hourly intravenous dose, and (2) orally administering to the patient a first dose of a morphine-oxycodone combination in a 3:2 ratio by weight every four to six hours. Also, a method of treating pain in patients who had been administered opioids intravenously, comprising using a dosing algorithm to determine the first dose of the immediate release morphine-oxycodone combination.

Abstract: The present disclosure generally relates to methods for producing opioid derivatives. More particularly, the present disclosure relates to the preparation of hydromorphone, hydrocodone, or a derivative thereof, by means of a non-catalytic hydrogenation reaction of thebaine, oripavine or a derivative thereof, respectively, using a hydrazide reagent, followed by hydrolysis of the hydrogenated intermediate at a low temperature and for a short period of time. Additionally, the present disclosure relates to a composition comprising the desired hydromorphone, hydrocodone, or a derivative thereof, in combination with a 6-beta compound that is structurally related thereto.

Abstract: The present invention relates to poppy cultivars and their use to produce thebaine. In specific forms, the present invention relates to cultivars of Papaver bracteatum that produce thebaine in the first growing season after germination.

Abstract: The invention relates to pharmaceutical compounds and compositions comprised of a chemical moiety attached to oxycodone in a manner that substantially decreases the potential for overdose. When delivered at the proper dosage the pharmaceutical composition provides therapeutic activity similar to that of oxycodone and may also provide sustained release characteristics and/or reduced side-effects. Further the compounds and compositions of the invention are useful in preventing addiction and susceptibility to addiction of oxycodone.