Abstract: A probe for imaging EGFR expressing cells includes an EGFR targeting moiety, a reporter moiety, and a hydrophilic linker that links the EGFR targeting moiety to the reporter moiety. The hydrophilic linker enhances solubility of the probe in an aqueous media as well as binding affinity of the probe to EGFR expressing cells.

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

Abstract: The present invention provides a method for the N-demethylation and N-functionalization of an N-methylated heterocycle such as a morphine alkaloid or tropane alkaloid. The method comprises reacting the heterocycle with an functionalization agent in the presence of a transition metal catalyst in air or in the presence of an oxidant.

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 presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydrocodone (morphinan-6-one, 4,5-alpha-epoxy-3-methoxy-17-methyl) to form novel prodrugs/compositions of hydrocodone, including benzoates and heteroaryl carboxylic acids, 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: 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 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: 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: Processes for reducing the amount of impurities, especially ?,?-unsaturated ketones (ABUK), in materials containing morphine. Novel compounds, namely low ABUK morphine sulfate methanolic solvate, and a novel crystal form are also described. The method for making morphine sulfate methanolic solvate comprises mixing a morphine free base composition with methanol to form a solution and adding a liquid comprising sulfuric acid to the solution to form a morphine sulfate methanolic solvate precipitate. A method of making a morphine sulfate compound comprises drying the morphine sulfate methanolic solvate in the presence of water vapor, such that methanol molecules are removed and replaced with water vapor molecules. A composition for treating pain comprises the morphine sulfate compound and at least one pharmaceutically acceptable excipient.

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 relates to a X-form crystal of 17-cyclopropylmethyl-3,14?-dihydroxy-4,5?-epoxy-6?-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan hydrochloride and the manufacturing method thereof, wherein the X-form crystal of the compound has characteristic diffraction peaks at positions of 2? of 13.6°(±0.2°), 17.2°(±0.2°), 19.1°(±0.2°), 23.2°(±0.2°), and 23.8°(±0.2°) in a powder X-ray diffraction pattern thereof. The present invention also relates to a pharmaceutical composition comprising the above-mentioned X-form crystal of morphinan derivative hydrochloride.

Abstract: An improved process for preparing buprenorphine and a method for increasing the yield of buprenorphine or a derivative thereof.

Abstract: The disclosed opioid-related compounds and pharmaceutical compositions thereof, are useful in a variety of applications relating to the modulation of receptors and receptor signaling within and outside the nervous system. For example, the compounds and compositions are useful in methods for the treatment of addictions and other CNS-related disorders. The disclosed compounds can be delivered or administered to a mammal including humans, alone in the form of a pharmaceutically acceptable salt or hydrolysable precursor thereof, or in the form of a pharmaceutical composition, wherein a therapeutically effective amount of a compound is mixed with suitable carriers or excipients.

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: Embodiments of the present disclosure provide for BHQ-conjugates and protected BHQ-conjugate precursor compounds, methods of making BHQ-conjugates and protected BHQ-conjugate precursor compounds, methods of using BHQ-conjugates and protected BHQ-conjugate precursor compounds, and the like.

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 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 disclosure describes morphinan compounds and methods for their synthesis. Preferred methods according to the disclosure allow for large-scale preparation of diastereomerically enriched morphinans. Preferred methods according to the disclosure may also allow for the preparation of diastereomerically enriched morphinans using less time, and/or using fewer reaction steps, and/or providing better yield than previously used methods for preparing morphinans. The methods disclosed herein find utility in synthetic organic chemistry as well as medicinal chemistry.

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 presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydrocodone (morphinan-6-one, 4,5-alpha-epoxy-3-methoxy-17-methyl) to form novel prodrugs/compositions of hydrocodone, including benzoates and heteroaryl carboxylic acids, 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: The presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydrocodone (morphinan-6-one, 4,5-alpha-epoxy-3-methoxy-17-methyl) to form novel prodrugs/compositions of hydrocodone, including benzoates and heteroaryl carboxylic acids, 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: 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 present invention is directed to the preparation of 6-hydroxy morphinans having formula (II) or N-alkylated 6-hydroxy morphinans having formula (III).

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: The present invention provides processes for the enrichment of buprenorphine in a product. In particular, the present invention provides processes for the enrichment of buprenorphine in a product using chromatographic techniques.

Abstract: An analgesic which may be applied to wide variety of pain from various causes is disclosed.

Abstract: 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.

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

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 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.

Abstract: A high-yielding method for the N-demethylation of oxycodone- and oxymorphone-N-oxides by the reaction of these compounds with cyclodehydration reagents has been performed. This method has been utilized to improve the synthesis of various morphine analogs, such as naltrexone, nalbuphone and naloxone.

Abstract: Indole alkaloid derivatives having an opioid receptor agonistic effect, their synthesis, and therapeutic compositions containing these derivatives, and methods of treating conditions with these compounds and therapeutic compositions, are provided.

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: Fluorinated compounds and methods of making fluorinated compounds are described herein.

Abstract: The presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydrocodone (morphinan-6-one, 4,5-alpha-epoxy-3-methoxy-17-methyl) to form novel prodrugs/compositions of hydrocodone, including benzoates and heteroaryl carboxylic acids, 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: A process is provided for the N-demethylation of certain morphinans by reaction with ?-chloroethyl chloroformate followed by hydrolysis of the resulting intermediate.

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: Kappa opioid receptor antagonists are provided that yield significant improvements in functional binding assays to kappa opioid receptors, and the use of these antagonists in treatment of disease states that are ameliorated by binding of the kappa opioid receptor such as heroin or cocaine addictions.

Abstract: The invention generally provides processes and intermediate compounds useful for the production of normorphinans and derivatives of normorphinans.

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: The present invention relates to a process for the synthesis of a compound of formula I:

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: 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.

Abstract: 8-Substituted-2,6-methano-3-benzazocines of general structure are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.

Abstract: 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.

Abstract: The disclosure relates to a method for preparing morphine-6-glucuronide or one of the deritives thereof comprising reacting a compound of formula (I): wherein R1 is as defined in the disclosure, with a glucuronic acid derivative of formula (II): wherein PG, X, and R4 are as defined in the disclosure, in the presence of an aromatic solvent and trimethylsilyl trifluoromethanesulfonate; (ii) reacting the product obtained in step (i) with a strong basic agent; and then (iii) recovering the product obtained in step (ii).