Abstract: 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.

Abstract: There are provided methods of making an N-demethylated derivative of morphine namely, normorphine. The normorphine can be substituted at the N—H position with various ligands that may result in new useful morphine derivatives. These derivatives may have increased analgesic efficacy, have less addictive properties, and/or have effective anti-opiate properties capable of rescuing overdosed persons or lead to recovery from conditions caused by opiate drug abuse.

Abstract: Methods for removing residual solvent from Nalmefene Hydrochloride (HCl) and producing crystalline Nalmefene HCl monohydrate, monosolvate or crystalline Nalmefene HCl dihydrate are described. In embodiments, the methods include recrystallizing Nalmefene HCl from a solvate that includes Nalmefene HCl, water, and a first solvent, wherein the first solvent has a molar volume of at least 98 cm3. Crystalline Nalmefene HCl with a desirably low amount of residual solvent is also described.

Abstract: The present invention provides compounds useful for the treatment of opioid dependence, alcohol dependence, alcohol use disorder, or the prevention of relapse to opioid dependence in a subject in need thereof. Related pharmaceutical compositions and methods are also provided herein.

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 presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydromorphone (4,5-?-epoxy-3-hydroxy-17-methyl morphinan-6-one) to form novel prodrugs/compositions of hydromorphone. The hydromorphone prodrugs of the present technology have decreased side effects and decreased potential for abuse compared to unconjugated hydromorphone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.

Abstract: 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.

Abstract: The invention relates to an improved method of preparing buprenorphine, a salt thereof, analogs of buprenorphine and their salts. In particular, the invention relates to a method of preparing buprenorphine and related products and salts in economic and ecologic ways having increased yields.

Abstract: The present invention provides (+)-morphinans comprising Toll-like receptor 9 (TLR9) antagonist activity, as well as methods for using the (+)-morphinans to treat a variety of disorders.

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: An invention includes a process for the preparation of (S)-2((4R,4aS,6R,7R,7aR,12bS)-7,9-dimethoxy-1,2,3,4,5,6,7,7a-octahydro-4a,7-ethano-4,12-methanobenzofuro[3,2-e]isoquinolin-6-yl)-3,3-dimethylbutan-2-ol.

Abstract: The presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydromorphone (4,5-?-epoxy-3-hydroxy-17-methyl morphinan-6-one) to form novel prodrugs/compositions of hydromorphone. The hydromorphone prodrugs of the present technology have decreased side effects and decreased potential for abuse compared to unconjugated hydromorphone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.

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 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: 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 present invention relates to new nalmefene salts which salts fall within at least one of the two following categories: non-hydrate forming salts and non-solvate forming salts. In particular, the invention relates to the hydrogen adipate salt, the hydrogen malonate salt, the lactate salt, the hydrogen fumarate salt, the hydrogen succinate salt, the benzene sulfonate salt, the hydrogen maleate salt and the salicylate salt of nalmefene. The present invention also relates to such salts for use in therapy.

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 present invention relates to new nalmefene salts which salts fall within at least one of the two following categories: non-hydrate forming salts and non-solvate forming salts. In particular, the invention relates to the hydrogen adipate salt, the hydrogen malonate salt, the lactate salt, the hydrogen fumarate salt, the hydrogen succinate salt, the benzene sulfonate salt, the hydrogen maleate salt and the salicylate salt of nalmefene. The present invention also relates to such salts for use in therapy.

Abstract: The presently described technology provides compositions comprising aryl carboxylic acids and, for example NSAIDs, chemically conjugated to oxymorphone (4,5-?-epoxy-3,14-dihydroxy-17-methylmorphinan-6-one) to form novel prodrugs/compositions of oxymorphone, including benzoates, salicylates, propionates, fenamates, and acetates, which have a decreased potential for abuse of oxymorphone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.

Abstract: The invention relates to an improved method of preparing oxymorphone or a salt thereof from oripavine. In particular, the invention relates to a method of preparing oxymorphone with a content of alpha-beta-unsaturated ketones (ABUK)<10 ppm, wherein the content of 8,14-dihydroxydihydromorphinone in the prepared oxymorphone is >10 ppm.

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 present invention is directed to an improved process to convert morphine into noroxymorphone having economic and ecological advantages.

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 present disclosure is directed to crystalline forms of morphine sulfate and pharmaceutical compositions comprising any of the crystalline forms of morphine sulfate. Also provided are processes for the preparation of crystalline forms of morphine sulfate.

Abstract: An improved process for the N-alkylation of tertiary morphinan alkaloid bases to form the corresponding quaternary morphinan alkaloid derivatives.

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 application is directed to compounds of Formula I and pharmaceutically acceptable salts, prodrugs, and solvates thereof, wherein G, R2-R5, and are defined as set forth in the specification. The invention is also directed to use of compounds of Formula I as synthetic intermediates or to treat disorders responsive to the modulation of one or more opiopid receptors. Certain compounds of the present invention are especially useful for treating pain.

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: Naloxol-polyethylene glycol conjugates of the formula: are provided in oxalate or phosphate salt forms including crystalline forms. Methods of preparing the salt forms and pharmaceutical compositions comprising the salt forms are also provided.

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 compounds of Formula I or II, or pharmaceutically acceptable salts, esters, or prodrugs thereof: which relates to mophinan compounds useful as ?, ? and/or ? receptor opioid compounds and pharmaceuticals containing same that may be useful for mediating analgesia, combating drug addiction, alcohol addiction, drug overdose, mental illness, bladder dysfunctions, neurogenic bladder, interstitial cystitis, urinary incontinence, premature ejaculation, inflammatory pain, peripherally mediated and neuropathic pain, cough, lung edema, diarrhea, cardiac disorders, cardioprotection, depression, and cognitive, respiratory, diarrhea, irritable bowel syndrome and gastro-intestinal disorders, immunomodulation, and anti-tumor agents.

Abstract: The present invention provides processes for preparing normorphinans from N-substituted morphinans. In particular, the invention provides methods for removing the N-substituent from the N-substituted morphinan to from a normorphinan carbamate, and then removing the carbamate functionality from the normorphinan carbamate to form the normorphinan.

Abstract: The present invention relates to methods for the synthesis of morphine, codeine, intermediates, salts and derivatives thereof. In preferred embodiments, the invention relates to methods for improving the efficiency, steroselectivity, and overall yield of said codeine and morphine related derivatives and intermediates thereof. The present invention relates to new codeine and morphine related derivative compositions.

Abstract: The present invention provides a process for the preparation of a compound of formula (VI), or a salt or derivative thereof, wherein R1 and R2 are independently C1-8 alkyl and * represents a stereocentre.

Abstract: Described herein are methods of preparing 6-hydroxy N-alkyl morphinan-6-ols from morphinan-6-ones, as illustrated below: wherein the variables R1, R2, R3, R10, R11, R14, and are as defined herein and wherein the reactions occur in a one-pot procedure using a boron based reducing agent.

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 present invention provides processes for preparing nal-opiates without the isolation of intermediates. In general, the process provides for alkylation and reduction in the same pot to give the nal-opiate.

Abstract: Naloxol-polyethlyene glycol conjugates of the formula: are provided in oxalate or phosphate salt forms including crystalline forms. Methods of preparing the salt forms and pharmaceutical compositions comprising the salt forms are also provided.

Abstract: The present application is directed to an efficient conversion of C-14 hydroxylated morphine alkaloids to various morphine analogs, such as naltrexone, naloxone and nalbuphone. One feature of this process is an intramolecular functional group transfer from the C-14 hydroxyl to the N-17 nitrogen atom following a palladium-catalyzed N-demethylation.

Abstract: There is provided a method for the synthesis of norbuprenorphine, and ultimately buprenorphine, utilizing oripavine as the starting material. Conventional methods of producing buprenorphine utilize thebaine as the starting material, requiring an O-demethylation step, typically a low to moderate yield transformation. The present use of oripavine as a starting material does not require an O-demethylation step, since the oripavine molecule lacks an O-3 methyl group.

Abstract: There is provided an efficient industrial process for the preparation of 21-cyclopropyl-7?-(2-hydroxy-3,3-dimethyl-2-butyl)-6,14-endo-ethano-6,7,8,14-tetrahydro-oripavine, i.e. buprenorphine of Formula-I in high yield and purity, with enhanced safety and eco-friendly norms. The invention further relates to an improved process for preparation of intermediates thereof in high yield and purity.

Abstract: Selective, non-peptide antagonists of the mu opioid receptor (MOR) and methods of their use are provided. The antagonists may be used, for example, to identify MOR agonists in competitive binding assays, and to treat conditions related to addiction in which MOR is involved, e.g. heroin, prescription drug and alcohol addiction, as well as in the treatment of opioid induced constipation (OIC).

Abstract: The oxazolidine derived from the reaction of oxymorphone with the Burgess reagent, temporarily protected at O-3 and C-6, reacts with Grignard or other suitable metallic or organometallic reagents to directly provide, for example, A/-allyl, A/-methylcyclopropyl and /V-methylcyclobutyl derivatives that are further converted into naltrexone, naloxone, nalbuphone and nalbuphine in excellent yields. These morphine analogs can be prepared from the oxazolidine in a one-pot synthesis.

Abstract: Provided are a PEG-naloxone conjugate of general formula (II) and a pharmaceutical composition comprising the conjugate. In the conjugate, n is an integer in the range of 1-20. Also provided is a three-branched or four-branched conjugate of PEG and naloxone. Structural modification of naloxone with a hydrophilic polymer improves the pharmacokinetic properties of the drug, increase the water solubility of naloxone, improve the in vivo distribution of the drug, reduce the side effects of naloxone on central nervous system, and relieve bowel dysfunction and constipation caused by chronic administration of opioids. Also provided are a pharmaceutical composition comprising the conjugate of the invention and use of the conjugate.

Abstract: The invention relates to a compound of Formula I, II, III, IV or a pharmaceutically acceptable ester or prodrug thereof:

Abstract: The presently described technology provides phenylethanoic acid, phenylpropanoic acid, phenylpropenoic acid, a salt thereof, a derivative thereof or a combination thereof chemically conjugated to hydrocodone (morphinan-6-one, 4,5-alpha-epoxy-3-methoxy-17-methyl) to form novel prodrugs or compositions of hydrocodone which have a decreased potential for abuse of hydrocodone. The present technology also provides methods of treating patients, pharmaceutical kits and methods of synthesizing conjugates of the present technology.

Abstract: Provided are a PEG-naloxone conjugate of general formula (II) and a pharmaceutical composition comprising the conjugate. In the conjugate, n is an integer in the range of 1-20. Also provided is a three-branched or four-branched conjugate of PEG and naloxone. Structural modification of naloxone with a hydrophilic polymer improves the pharmacokinetic properties of the drug, increase the water solubility of naloxone, improve the in vivo distribution of the drug, reduce the side effects of naloxone on central nervous system, and relieve bowel dysfunction and constipation caused by chronic administration of opioids. Also provided are a pharmaceutical composition comprising the conjugate of the invention and use of the conjugate.

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: Naloxol-polyethylene glycol conjugates of the formula: are provided in oxalate or phosphate salt forms including crystalline forms. Methods of preparing the salt forms and pharmaceutical compositions comprising the salt forms are also provided.

Abstract: The present invention provides (+)-morphinanium compounds comprising substituted 6-hydroxy or 6-amine groups. The invention also provides methods for inhibiting microglial activation by administering the compounds of the invention.