Abstract: The present invention provides processes for the preparation of saturated ketone morphinan compounds from a morphinan comprising an allyl alcohol ring moiety, wherein the final product has a low metal content. In particular, the invention provides processes that utilize isomerization reactions catalyzed by transition metal catalysts and the subsequent removal of the transition metal using metal scavengers.

Abstract: A synthetic method is provided, wherein the method comprises stereoselectively reducing a ketone of a morphinone to form a reduced morphinone and optionally covalently attaching a water soluble polymer to the reduced morphinone.

Abstract: The present invention relates to an improved process for preparing morphinane analogues of formula (1) wherein the substituents R1, R2, R3, R4, R5 and Y have the same meanings as defined in the specification.

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: Stable crystalline forms of a compound represented by the formula (IA): an acid addition salt, and/or a solvate thereof are provided by the present invention. Said crystalline forms are extremely useful as materials for preparing medicines. Novel processes for preparing 6,7-unsaturated-7-carbamoyl morphinan derivatives are also provided by the present invention.

Abstract: Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise a phenol-modified opioid prodrug that provides enzymatically-controlled release of a phenolic opioid, and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the phenolic opioid from the phenol-modified opioid prodrug so as to modify enzymatic cleavage of the phenol-modified opioid prodrug.

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: A therapeutic or prophylactic agent for biliary tract diseases includes as an effective component a specific compound having a morphinan skeleton represented by Compound 1, or a pharmaceutically acceptable acid addition salt thereof:

Abstract: This invention relates to the synthesis of (R),(R)-2,2?-bis-MNTX, as shown in Formula (I), and related methods and products.

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: The present invention relates to a method for the preparation of morphine compounds comprising a low content of ?,?-unsaturated compounds, which comprises the steps of: (i) bringing the crude morphine compound into contact with a base, at a pH of greater than 13, under conditions which make possible the Michael addition reaction on the ?,?-unsaturated compound(s) present; (ii) separating the morphine compound from the reaction mixture; and (iii) if appropriate, separating the addition product formed from the morphine compound. It also relates to a composition comprising at least 99% by dry weight of morphine compound or of a pharmaceutically acceptable salt thereof, and an ?,?-unsaturated compound in a content of less than 100 ppm.

Abstract: The present invention provides a compound of formula I: wherein X?, R1, and R2 are as defined herein, and compositions thereof.

Abstract: The present invention relates to novel therapeutic and diagnostic dendrimers. In particular, the present invention is directed to dendrimer-linker conjugates, methods of synthesizing the same, compositions comprising the conjugates, as well as systems and methods utilizing the conjugates (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer) diagnosis and/or therapy, pain therapy, etc.)). Accordingly, dendrimer-linker conjugates of the present invention may further comprise one or more components for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and/or monitoring response to therapy.

Abstract: A compound of formula I is disclosed. Compounds of formula I are useful as analgesics, anti-inflammatory agents, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.

Abstract: The present invention provides (+)-morphinanium quaternary salts. The invention also provides processes for producing (+)-morphinanium quaternary salts from tertiary N-substituted (+)-morphinan compounds.

Abstract: The present disclosure provides improved methods for N-dealkylation of tertiary amines, including methods for N-demethylation of alkaloids and opioids, in which the dealkylation reaction is carried out in a solvent comprising a tertiary alcohol. The present disclosure also provides improved processes for preparing semi-synthetic opioids that incorporate the disclosed methods for N-dealkylation of tertiary amines.

Abstract: The present disclosure provides processes for the N-dealkylation of tertiary amines and the use of transition metal catalysts to prepare tertiary N-allyl amine derivatives and secondary amine derivatives thereof. The tertiary amines can be alkaloids and, more particularly, the tertiary amines can be opioids. In specific embodiments, the present disclosure provides methods for use in processes for the synthesis of naloxone and naltrexone from oripavine.

Abstract: The embodiments provide Compound PC-5, [2-((S)-2-malonylamino-6-amino-hexanoyl amino)-ethyl]-ethyl-carbamic acid hydromorphone ester, or acceptable salts, solvates, and hydrates thereof. The present disclosure also provides pharmaceutical compositions, and their methods of use, where the pharmaceutical compositions comprise a prodrug, Compound PC-5, that provides enzymatically-controlled release of hydromorphone, and, optionally, a trypsin inhibitor that interacts with the enzyme that mediates the enzymatically-controlled release of hydromorphone from the prodrug so as to attenuate enzymatic cleavage of the prodrug.

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 novel crystalline forms of naltrexone hydrochloride including hydrated and solvated forms and a novel amorphous form. The invention also describes methods of preparing the various crystalline forms. The present invention also relates to pharmaceutical compositions containing crystalline and amorphous forms of naltrexone hydrochloride, as well as methods of treating addictive behavior by administering the pharmaceutical compositions.

Abstract: The invention relates to processes for the production of alkaloids without the isolation of intermediates.

Abstract: The present invention relates to active agent delivery systems and more specifically to compositions that comprise amino acids, as single amino acids or peptides, covalently attached to active agents and methods for administering conjugated active agent compositions.

Abstract: The present disclosure generally relates to catalytic methods for producing opioid derivatives. More particularly, the present disclosure relates to the preparation of hydrocodone, hydromorphone, or a derivative thereof, by means of a conversion or an isomerization of codeine, morphine, or a derivative thereof, respectively, using a heterogeneous ruthenium metal catalyst.

Abstract: An abuse-deterrent pharmaceutical composition has been developed to reduce the likelihood of improper administration of drugs, especially drugs such as opiods. In the preferred embodiment, a drug is modified to increase its lipophilicity. In preferred embodiments the modified drug is homogeneously dispersed within microparticles composed of a material that is either slowly soluble or not soluble in water. The abuse-deterrent composition retards the release of drug, even if the physical integrity of the formulation is compromised (for example, by chopping with a blade or crushing) and the resulting material is placed in water, snorted, or swallowed. However, when administered as directed, the drug is slowly released from the composition as the composition is broken down or dissolved gradually within the GI tract by a combination of enzymatic degradation, surfactant action of bile acids, and mechanical erosion.

Abstract: The present invention provides to an improved process for preparing alkaloid salts. In particular, the process comprises a stepwise addition of an acid to an alkaloid chosen from hydrocodone, codeine, and dihydrocodeine to form a flowable mixture of the alkaloid salt.

Abstract: 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.

Abstract: The present disclosure generally relates to a process for converting a fused, tricyclic compound to a fused, tetracyclic compound that includes a furan ring therein. More particularly, the present disclosure related to a process for preparing a hydrocodone compound, or a compound structurally related thereto, and in particular (+)-hydrocodone, by subjecting a structurally corresponding sinomenine starting compound to a super acid-assisted furan ring closure reaction.

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: Pharmaceutical compositions and dosage forms comprising an adsorbent, and an adverse agent, such as an opioid antagonist. In one embodiment, at least a portion of the adverse agent is on the surface or within the micropore structure of an adsorbent material. The pharmaceutical compositions and dosage forms comprising the adsorbent and the adverse agent are useful for preventing or discouraging tampering, abuse, misuse or diversion of a dosage form containing an active pharmaceutical agent, such as an opioid. The present invention also relates to methods for treating a patient with such a dosage form, as well as kits containing such a dosage form with instructions for using the dosage form to treat a patient. The present invention further relates to process for preparing such pharmaceutical compositions and dosage forms.

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: This invention relates to stereoselective synthesis of R-MNTX and intermediates thereof, pharmaceutical preparations comprising R-MNTX or intermediates thereof and methods for their use.

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, C(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 is a reductive alkylation in the presence of hydrogen and a reductive alkylation catalyst.

Abstract: Process for the preparation of N-methylnaltrexone bromide, wherein a compound of the general formula (I): wherein X? represents an anion other than the bromide anion, and R represents hydrogen or a leaving group, is dissolved or dispersed in a suitable polar solvent, the solution or dispersion is mixed with a compound containing bromide anions, and the resulting reaction mixture is stirred until N-methylnaltrexone bromide has formed and crystallized, wherein, in the case where R represents a leaving group, that group is removed during or after the reaction.

Abstract: The present invention provides processes for the preparation of 10-keto and/or 10-hydroxy morphinans. In particular, the invention provides to processes for preparing a 10-keto morphinan by chromium-catalyzed benzylic oxidation of a morphinan with a periodic acid.

Abstract: 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.

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: A method of providing a patient with controlled release of a phenolic opioid using a prodrug capable, upon enzymatic activation, of releasing the phenolic opioid through intra-molecular cyclization leading to formation of a cyclic urea, carbamate or thiocarbamate.

Abstract: The invention discloses and claims N-Methylnaltrexone zwitterion, of formula (I), substantially in the anhydrous form or a hydrate thereof:

Abstract: 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.

Abstract: The invention relates to a process for the synthesis of quaternized compounds of formula:

Abstract: The present invention relates to a novel functional peripherally-acting ? opioid receptor antagonist of Formula I: The novel compounds of the present invention have reduced oral bioavailability without compromising opiate-induced analgesia in the CNS. The compounds of the present invention are further efficacious at low doses and are useful in treating gastrointestinal conditions associated with opioid analgesic therapy.

Abstract: The present invention is directed to the preparation of 6-keto morphinans.

Abstract: The present invention is generally directed to a process for the preparation of a ketomorphinan comprising maintaining a ketone group as unprotected and performing reductive amination using a hydrogen source and a catalyst.

Abstract: 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 Cr3+. N-demethylated heterocycles prepared by the methods of the present invention are also provided.

Abstract: The present invention relates to novel therapeutic and diagnostic dendrimers. In particular, the present invention is directed to dendrimer-linker conjugates, methods of synthesizing the same, compositions comprising the conjugates, as well as systems and methods utilizing the conjugates (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer) diagnosis and/or therapy, pain therapy, etc.)). Accordingly, dendrimer-linker conjugates of the present invention may further comprise one or more components for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and/or monitoring response to therapy.

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 present invention provides processes for the synthesis of five and six membered rings. In particular, the present invention provides processes for the synthesis of five and six membered rings in alkaloids.

Abstract: The present invention provides a process whereby morphinan-6-ones can be converted stereospecifically to the corresponding morphinan-6?-ols by catalytic hydrogenation under basic conditions.

Abstract: 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.

Abstract: 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.