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: The present invention relates to monoclonal antibodies that specifically bind buprenorphine and/or at least one metabolic product thereof. The present invention further relates to buprenorphine metabolite conjugates for the production of monoclonal antibodies that specifically bind buprenorphine and/or at least one metabolic product thereof and hybridoma cells that produce the monoclonal antibodies. The invention also relates to immunoassay methods for determining buprenorphine and/or one or more buprenorphine metabolites in a sample using the novel antibodies and conjugates of the present invention.

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: N-substituted 3-hydroxy-4-pyridinones and metal chelates, methods of preparing N-substituted 3-hydroxy-4-pyridinones and metal chelates, and pharmaceutical compositions containing new N-substituted 3-hydroxy-4-pyridinones and/or their metal chelates. Use of N-substituted 3-hydroxy-4-pyridinones and their metal chelates as pharmaceutical agents for the treatment of diseases, such as parasitic and viral infections, conditions associated with inflammation and infection, and conditions mediated by cell-proliferation or collagen formation.

Abstract: Benzimidazo[4,5-f]isoquinolinone derivatives are inhibitors of Janus protein tyrosine kinases (Jak), and as such are useful as immunosuppressants, and in the treatment of diseases including asthma, allergies, autoimmune diseases.

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: 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: Heterocycle condensed morphinoid derivatives of formula (I) have therapeutic utility as analgesics, in collagen disease, as anti-allergic and anti-inflammatory agents, brain cell protectants, in gastritis, diarrhoea, cardiovascular and respiratory diseases, cough, mental illness, epilepsy, for the preservation of organs during transplant operations, and for the treatment of those pathological conditions which customarily can be treated with agonists of the delta opioid receptor.

Abstract: Structurally novel kappa opioid receptor antagonists are provided 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: Disclosed are a process for the preparation of a compound represented by the formula (1), which comprises treating a compound represented by the formula (2) with methanesulfonic acid and then subjecting the thus-treated compound to recrystallization; and Compound (1) so obtained. This Compound (1) is free of hygroscopicity, excellent in filterability and solubility and easy in handling. Furthermore, according to the preparation process of the present invention, an unnecessary isomer can be converted into the target one and separation of the target isomer can be conducted easily.

Abstract: A method for the preparation of a ketone from a narcotic alkaloid having an allyl alcohol moiety is disclosed. The method includes mixing the narcotic alkaloid with an acid in the presence of a catalyst wherein the method is carried out in the substantial absence of hydrogen gas. The method is useful for preparing hydromorphone and hydrocodone compositions having novel impurity profiles. Compositions comprising hydromorphone and hydrocodone are also disclosed.

Abstract: This invention provides an antipuritic comprising an opiate &kgr; receptor agonist as an effective component, a new morphian quaternary ammonium salt derivative and a new morphian-N-oxide derivative which are useful in treating puritus complicated with some diseases.

Abstract: Heterocycle-condensed morphinoid derivatives of formula (I), or solvates or salts thereof, are potent and selective delta opioid agonists and antagonists and are useful as i.a. analgesics. Pharmaceutical compositions containing such compounds, the use of such compounds as therapeutic agents, a method of treatment comprising the administration of such compounds, and a process for the preparation of such compounds are also described.

Abstract: A compound comprising a ligand portion which has binding affinity for an opioid receptor, and a therapeutically or diagnostically effective group selected from radionuclide chelating agents, fluorochromes, toxins, drugs, polyboron moieties, proteins, biological response modifiers, chemical moieties capable of binding to other molecules of interest, and radioisotopes selected from therapeutically effective alpha and beta emitters, and diagnostically effective gamma emitters. The compound may be used in a method of treating cancer, and in a method of imaging opioid receptors either inside or outside of the central nervous system.

Abstract: A morphinan derivative or its pharmacologically allowed acid addition salt represented with compound I, an analgesic and diuretic having its derivative or its salt as the active ingredient, and its production process are described. The compound of the present invention possesses strong analgesic activity and diuretic action as a highly selective &kgr;-opioid agonist, allowing it to be used as a useful analgesic and diuretic.

Abstract: This invention provides an antipruritc comprising an opiate &kgr; receptor agonist as an effective component, a new morphinan quaternary ammonium salt derivative and a new morphinan-N-oxide derivative which are useful in treating pruritus complicated with some diseases.

Abstract: A morphinan derivative or its pharmacologically allowed acid addition salt represented with compound I, an analgesic and diuretic having its derivative or its salt as the active ingredient, and its production process are described. The compound of the present invention possesses strong analgesic activity and diuretic action as a highly selective &kgr;-opioid agonist, allowing it to be used as a useful analgesic and diuretic.

Abstract: The nalbuphine polyester derivative is related to a novel long acting agent. The nalbuphine polyester derivative is R—[CO-NAL]n wherein n is an integer from 2-4 and, in which the R is selected from a saturated or nonsaturated, substituted or unsubstituted, aliphatic or aromatic group having 1 to 40 carbon atoms. The process for producing the derivative includes esterifying nalbuphine with a saturated or unsaturated fatty acid or a halogen compound of the fatty acid with an acid anhydride. A pharmaceutical composition contains the derivative and a pharmaceutically acceptable carrier, which can be administered to an animal or person for treating pain.

Abstract: Novel morphinan derivatives and pharmaceutically acceptable acid addition salts thereof as compounds having abilities to bind to opioid &egr;-receptor, which have agonist or antagonist activities, are disclosed. The morphinan derivatives according to the present invention are represented by the formula (I).

Abstract: A morphinan derivative or its pharmaceutically acceptable acid addition salt represented with, for example, and an analgesic, diuretic, antitussive and brain cell protector having its derivative or its salt as the active ingredient are described. The compound of the present invention possesses strong analgesic activity, diuretic action and antitussive action as a highly selective &kgr;-opioid agonist, allowing it to be used as a useful analgesic, diuretic and antitussive. On the other hand, the compound of the present invention also possesses remarkable cerebro-neuroprotective activity, thus allowing it be used as a useful cerebro-neuroprotective agents.

Abstract: The present invention pertains to a process for the preparation of the 10-keto analogs of morphinan compounds. In the case of compounds having a 3-hydroxyl group, the 3-methyl ether protected analog is synthesized by selective phenolic methylation in the presence of the basic amino group. When nalbuphine, morphine, or codeine is used as the starting material, the additional 6-hydroxyl group is protected using acetylation. The protected analog is selectively oxidized by treatment with cerium ammonium nitrate to provide the 10-(S)-hydroxy adduct. The 10-(S)-hydroxy adduct is further oxidized to the 10-keto analog. Any protecting groups that were added prior to oxidation are cleaved subsequent to oxidation to form the desired 10-ketomorphinan.

Abstract: The present invention relates to morphine and diamorphine salts of anionic non-narcotic analgesics belonging to the type of substituted carboxylic acids, preferably the morphine and diamorphine salts of diclofenac (Formula 1); to processes for their production, the use of these salts in the treatment of diseases, as well as to pharmaceutical preparations comprising these salts.

Abstract: Morphine derivatives of formula (I), process for perparing them and their use and use as analgesics.

Abstract: For the synthesis of 3-methylnaltrexone from codeine in this invention, codeine is converted to 6-acetylcodeine, which is N-demethylated to 6-acetylcodeine hydrochloride, followed by alkylating the nitrogen to form 17-cyclopropylmethylnorcodeine. The latter is oxidized to 17-cyclopropylmethylnorcodeinone. For the synthesis of naltrexone from morphine in this invention, morphine is converted to 3-benzylnormorphine as described above in the synthesis of noroxymorphone. 3-Benzylnormorphine is reacted with cyclopropylmethyl halide to produce 3-benzyl-17cyclopropylmethylnormorphine, a novel compound, which is oxidized to 3-benzyl-17-cyclopropylmethyl-normorphinone, a novel compound, by Swern oxidation.

Abstract: A process is provided for preparing oxycodone from codeine comprising either:(A) the steps of(1) oxidizing codeine so as to form codeinone;(2) converting codeinone to oxycodone in a two-step-one-pot reaction: first reacting codeinone with hydrogen peroxide in water in the presence of an acid at from about 15.degree. to about 70.degree. C. to form 14-hydroxycodeinone and then catalytically hydrogenating 14-hydroxycodeinone in its original reaction mixture to form oxycodone; or(B) the steps of(1) oxydizing codeine so as to form codeinone;(2) reacting codeinone with an acylating agent so as to form codeinone dienol acylate;(3) oxidizing codeinone dienol acylate with an oxidation agent in water or a solubilizing solvent mixture in the presence of an acid at from about 15.degree. to about 70.degree. C. to form 14-hydroxycodeinone;(4) hydrogenating 14-hydroxycodeinone in its original reaction mixture to form oxycodone.

Abstract: The invention provides processes for the conversion of normorphinone and its derivatives, which can be synthesized from morphine, to the corresponding 14-hydroxynormorphinone and its derivatives including oxycodone, oxymorphone, noroxymorphone and naltrexone. Noroxymorphone is a key intermediate for the production of important narcotic analgesics and antagonists. The invention also provides certain novel intermediates.

Abstract: A method for removing residual organic solvents from a bulk substance, for example from a pharmaceutical drug substance, comprises drying the bulk substance in the presence of water vapor, such that the residual organic solvent molecules are displaced with water vapor molecules.

Abstract: A process is provided for preparing 14-hydroxynormorphinones having the formula: ##STR1## which comprises reacting normorphinones having the formula: ##STR2## wherein R is selected from the group consisting of lower alkyl of 1 to 7 carbon atoms, cycloalkyl-lower alkyl with 3-6 ring carbon atoms, benzyl and a substituted-benzyl having the formula: ##STR3## wherein Q and Q.sup.1 are individually selected from the group consisting of hydrogen, lower alkyl, trifluoromethyl, nitro, dialkylamino and cyano;R' is selected from the group consisting of R, 2-(4-morpholinyl)ethyl, benzyloxy carbonyl and R"C(O)-- wherein R" is lower alkyl of 1-4 carbon atoms;with hydrogen peroxide at a temperature of from about 15.degree. C. to about 70.degree. C. in the presence of an acid and an aqueous solvent system to solubilize the reactant for a period of time so as to form the 14-hydroxynormorphinones.

Abstract: Normorphine and normorphinone derivatives are provided as compositions of matter.

Abstract: This invention provides a compound of the following formula: ##STR1## and the pharmaceutically acceptable salts thereof, wherein R is hydrogen, C.sub.1 -C.sub.5 alkyl or an O-protecting group; B is a dircet bond, C.sub.1 -C.sub.5 alkylene or C.sub.2 -C.sub.5 alkenylene; R.sup.1 is C.sub.1 -C.sub.5 alkyl, C.sub.2 -C.sub.5 alkenyl or C.sub.3 -C.sub.7 cycloalkyl-C.sub.1 -C.sub.3 alkyl; R.sup.2 is hydroxy or C.sub.1 -C.sub.5 alkoxy; R.sup.3 is hydrogen, hydroxy or C.sub.1 -C.sub.5 alkoxy; and R.sup.4 is hydrogen, phenyl or heteroaryl selected from furyl, thienyl and pyrrolyl, the phenyl and heteroaryl being optionally substituted by one to five substitutents selected from halo, hydroxy, C.sub.1 -C.sub.3 allyl, C.sub.1 -C.sub.3 alkoxy and C.sub.2 -C.sub.5 alkenyl.

Abstract: Substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts, pharmaceutical compositions containing them, and methods for the treatment or prevention of neurodegenerative disorders or neurotoxic injuries utilizing them.

Abstract: Substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts, pharmaceutical compositions containing them, and methods for the treatment of neurodegenerative disorders or neurotoxic injuries utilizing them, wherein the substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts have the formula: ##STR1## wherein: R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, X and p are as defined in the specification.

Abstract: The subject compounds, which are adapted for the site-specific/sustained delivery of centrally acting drug species to the brain, are:(a) compounds of the formula[D-DHC] (I)wherein [D] is a centrally acting drug species, and [DHC] is the reduced, biooxidizable, blood-brain barrier penetrating lipoidal form of a dihydropyridine .revreaction. pyridinium salt redox carrier, with the proviso that when [DHC] is ##STR1## wherein R is lower alkyl or benzyl and [D] is a drug species containing a single NH.sub.2 or OH functional group, the single OH group when present being a primary or secondary OH group, said drug species being linked directly through said NH.sub.2 or OH functional group to the carbonyl function of [DHC], then [D] must be other than a sympathetic-stimulant, steroid sex hormone or long chain alkanol; and(b) non-toxic pharmaceutically acceptable salts of compounds of formula (I). The corresponding ionic pyridinium salt type drug/carrier entities [D-QC].sup.+ X.sup.- are also disclosed.

Abstract: The present invention is directed to a fluorescence polarization assay for opiate alkaloids and their metabolites, to the various components needed for preparing and carrying out such an assay and to methods of making these components. Specifically, tracers, immunogens and antibodies are disclosed, as well as methods for making them. The tracers and the immunogens are made from substituted opiate alkaloids. A fluorescein moiety is included in the tracers, while a poly(amino acid) forms a part of the immunogens. The assay is conducted by measuring the degree of polarization retention of the fluorescence resulting when a sample mixed with antiserum and tracer is irradiated with plane-polarized light.

Abstract: The present invention is directed to a fluorescence polarization assay for opiate alkaloids and their metabolites, to the various components needed for preparing and carrying out such an assay and to methods of making these components. Specifically, tracers, immunogens and antibodies are disclosed, as well as methods for making them. The tracers and the immunogens are made from substituted opiate alkaloids. A fluorescein moiety is included in the tracers, while a poly(amino acid) forms a part of the immunogens. The assay is conducted by measuring the degree of polarization retention of the fluorescence resulting when a sample mixed with antiserum and tracer is irradiated with plane-polarized light.

Abstract: The present invention relates to novel morphinane-skeletoned compounds of the formula (I) ##STR1## wherein Y in-NH phenyl or --NH dintro phenyl, Z is --CH.sub.2 -- CH.sub.2, R.sub.2 is hydroxyl and R.sub.3 is H or methyl, the steric isomers and the pharmaceutically acceptable salts thereof, a novel process for producing the same and pharmaceutical compositions comprising the same as active ingredients.The novel compounds can be used in the therapy as analgetic or morphine-antagonistic agents.

Abstract: N-oxide prodrug derivatives of 3-hydroxy morphinan and partial morphinan analgesics, agonist-antogonists, and narcotic antagonists are useful therapeutic entities which provide enhanced bioavailability of 3-hydroxy morphinans and partial morphinans from orally administered dosage forms.

Abstract: The present invention is directed to a fluorescence polarization assay for opiate alkaloids and their metabolites, to the various components needed for preparing and carrying out such an assay and to methods of making these components. Specifically, tracers, immunogens and antibodies are disclosed, as well as methods for making them. The tracers and the immunogens are made from substituted opiate alkaloids. A fluorescein moiety is included in the tracers, while a poly(amino acid) forms a part of the immunogens. The assay is conducted by measuring the degree of polarization retention of the fluorescence resulting when a sample mixed with antiserum and tracer is irradiated with plane-polarized light.

Abstract: Compounds of formula I ##STR1## wherein X and Y each denotes hydrogen or together denote -0-,R.sub.1 denotes allyl optionally substituted by 1 to 3 alkyl groups, the substituent or substituents having in total a maximum of 3 carbon atoms, cyclopropyl-methyl or 3-furylmethyl,R.sub.2 denotes hydrogen, alkyl with 1 to 10 C-atoms, cycloalkyl with 5 or 6 carbon atoms, optionally substituted phenyl or optionally substituted phenyl-alkyl with 7 to 12 C-atoms,R.sub.3 denotes hydrogen, alkyl with 1 to 10 C-atoms or phenyl,R.sub.4 denotes hydrogen, OH, NR.sub.6 R.sub.7, NHCOR, NHSO.sub.2 R' or NHCOOR",R.sub.6 and R.sub.7, independently of one another, denote hydrogen or alkyl with 1 to 3 C-atoms,R denotes alkyl with 1 to 6 C-atoms, phenyl or --A--COOR",A denotes alkylene or alkenylene each with 2 to 4 C-atoms,R' denotes alkyl with 1 to 6 C-atoms or phenyl,R" denotes methyl or ethyland wherein either R.sub.3 is in the .alpha.-positionand R.sub.4 is in the .beta.-position, or R.sub.3 is in the .beta.position and R.sub.

Abstract: Gut-selective agonist or antagonist opiates of the formula: ##STR1## wherein R is (C.sub.1 -C.sub.5) alkyl, C.sub.3 -C.sub.6 (cycloalkyl)alkyl, aryl, aralkyl or trans-(C.sub.2 -C.sub.5)alkenyl; Z is H or OH, R' is (C.dbd.O)-A(B)(C) wherein A is selected from the group consisting of (C.sub.1 -C.sub.5)alkyl, (C.sub.2 -C.sub.5)alkenyl and (C.sub.2 -C.sub.6)alkoxy (alkyl); B is selected from the group consisting of H, amino and a (C.sub.1 -C.sub.5)alkyl group optionally substituted with CO.sub.2 H, OH or phenyl and C is CO.sub.2 H, SO.sub.3 H, amino or guanidino; and R" is selected from the group consisting of NH-A(B) (C) or is guanidino; and the pharmaceutically-acceptable salts thereof.

Abstract: Fluorescent reagents useful as opioid receptor probes. Opioids labeled at the 3 position with fluorescers are useful in various in vivo and in vitro methods for the detection and quantification of receptor sites in tissue cells and subcellular particles.

Abstract: Disclosed are improved Wittig reaction processes wherein the Wittig reaction is conducted in an anisole containing solvent.

Abstract: Gut-selective agonist or antagonist opiates of the formula: ##STR1## wherein R is (C.sub.1 -C.sub.5)alkyl, C.sub.3 -C.sub.6 (cycloalkyl)alkyl, aryl, aralkyl or trans-(C.sub.2 -C.sub.5)alkenyl; Z is H or OH, R' is (C.dbd.O)-A(B)(C) wherein A is selected from the group consisting of (C.sub.1 -C.sub.5)alkyl, (C.sub.2 -C.sub.5)alkenyl and (C.sub.2 -C.sub.6)alkoxy (alkyl); B is selected from the group consisting of H, amino and a (C.sub.1 -C.sub.5)alkyl group optionally substituted with CO.sub.2 H, OH or phenyl and C is CO.sub.2 H, SO.sub.3 H, amino or guanidino; and R" is selected from the group consisting of NH-A(B)(C) or is guanidino; and the pharmaceutically-acceptable salts thereof.

Abstract: Substituted benzoate ester prodrug derivatives of 3-hydroxymorphinans are useful as analgesics or narcotic antagonists and provide enhanced bioavailability of 3-hydroxymorphinans from orally administered doses.

Abstract: An improved process for the dealkylation of alkyl aryl ethers to aryl phenols is provided. In this process, an alkyl aryl ether, such as a methyl ether of an opioid, is contacted with an aqueous acid selected from HBr, HCl, or HI which contains at least one equivalent weight, based on the ether, of boric acid or an inorganic salt of a metal selected from Li, Na, K, Al, Mg, Ca, Mn and Ni. MgBr.sub.2 in aqueous HBr is preferred in dealkylating an N-substituted 14-hydroxydihydronorcodeine.

Abstract: Curable epoxy resin compositions are provided resulting from the use of a silylnorbornane functional anhydride or imidoamine. The cured products show improved thermal and physical properties as compared to conventional curing agents.

Abstract: Novel bridged benzofuroisoquinoline compounds having analgesic, narcotic antagonist and anorexigenic properties.

Abstract: The invention provides a novel method of administering narcotic antagonists, narcotic analgesics and related compounds, and novel dosage forms containing those compounds which are adapted for nasal administration. The nasal dosage forms disclosed include solutions, suspensions, gels and ointments. Especially preferred compounds which can be advantageously administered in accordance with the invention include naloxone, naltrexone, nalbuphine, levorphanol, buprenorphine, butorphanol, .DELTA..sup.9 -tetrahydrocannabinol (THC), cannabidiol (CBD) and levonantradol.

Abstract: A selective opioid receptor, site-directed alkylating agent useful as a narcotic antagonist and non-addictive analgesic having the formula: ##STR1## wherein R is a Michael acceptor, a haloacetamide or isothiocyanate and R' is cyclopropylmethyl, allyl or substituted allyl. The Michael acceptors may be acrylamides or esters: ##STR2## wherein R.sup.2 is alkyl or aralkyl, and salts thereof. The preparation of the compounds is described, along with experiments involving the use of the compounds.