Abstract: Novel opiate intermediate compositions and methods of synthesis that include changing the substitution pattern on the aromatic ring of the pre-Grewe intermediate are provided. The intermediates are morphinane derivatives of formula (10), wherein X is a F or Cl and R is selected from the group consisting of an H, alkyl, aryl, acyl, formyl, COR?, CONHR?, COOR, Bn(benzyl), alkyl(methyl), and sulfonamide SO2CH2COPh.

Abstract: The invention provides a process for the N-alkylation of normorphinan compounds to produce N-alkylated morphinan compounds. In particular, the process relates to the alkylation of a normorphinan compound by a carboxaldehyde in the presence of a reducing agent to form an N-alkylated morphinan.

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: A computer readable medium holding data of a molecular model of a ligand-gated ion channel receptor and/or a computer system for modeling said receptor are provided by the instant invention. The molecular model can be used to design novel compounds having activity as non-competitive inhibitors of the ion channel. A preferred embodiment of the invention relates to nicotinic acetylcholine receptors. Compounds having activity as non-competitive inhibitors of ligand-gated ion channel receptors and methods for inhibiting the receptor and treating diseases or disorders mediated by function of the receptor are also disclosed.

Abstract: Compounds of the formula wherein R1, R2, R3, R4, R5, R6, R66, m, n, p, and G are as defined herein.

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 is directed to a novel prodrug of (+)-3-hydroxymorphinan compound of formula (I) or a pharmaceutically acceptable salt thereof, a method for preparing the same, and its use for preventing or treating Parkinson's disease.

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

Abstract: The invention provides processes for the preparation of morphinans having a tertiary amine. In particular, the present invention provides processes for the formation of tertiary amine alkaloids by direct N-alkylation of secondary amine alkaloids, the processes co-mediated by an alkylating agent and a protic solvent or a mixture of a protic solvent and an aprotic solvent.

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: A method for inhibiting therapeutic drug resistance within a cell over-expressing a membrane protein is provided. The method comprises synthesizing a dimeric prodrug inhibitor of a monomeric therapeutic agent; administering the dimeric prodrug inhibitor to the membrane protein together with the monomeric therapeutic agent; and occupying at least one substrate binding site of the membrane protein with the synthesized dimeric prodrug to allow the monomeric therapeutic agent to accumulate within the cell. The dimeric prodrug inhibitor contains a crosslinking agent that is adapted to breakdown under reducing conditions within the cytosol of the cell to cause the dimeric prodrug to revert back to a form equivalent to the monomeric therapeutic agent.

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 is directed to processes for the synthesis of morphinan-6-ones and salts, intermediates, and analogs thereof.

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 present invention relates in part to nettle extracts that are useful for treating or preventing seasonal allergies, allergic rhinitis, and other inflammatory conditions.

Abstract: A class of novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-?B activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I) its stereoisomers thereof, or a solvate thereof, or a prodrug thereof, or a pharmaceutically acceptable salt thereof, where Z is CONR1R2 or CH2NR1R2 and where at least one of X1-X8 is N, and R, Ra, Rb, Rc and Rd are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.

Abstract: A process for purifying plant extracts which consist essentially of noroxymorphone compounds and which comprise, as impurities, ?,?-unsaturated noroxymorphone compounds, by (a) converting the plant extract or the product of a subsequent stage in the synthesis of a selected noroxymorphone compound in a reaction which converts the hydroxyl groups present in the mixture to leaving groups of the formula —OR2 in which R2 is the introduced radical of the leaving group, (b) these leaving groups are optionally detached again, then (c) the resulting mixture is subjected to a selective hydrogenation, so that a saturated bond is formed in the ?,?-position of the unsaturated noroxymorphone compounds and any remaining leaving groups are each converted to a hydroxyl group and then optionally (d) the pure noroxymorphone compound is isolated; processing of the noroxymorphone purified in this way to naltrexone or naloxone or a salt of these compounds or a quaternary derivative of these compounds; pharmaceutical formulations c

Abstract: Compounds of formulas: are disclosed. The compounds are useful for ameliorating the side effects of therapeutic opiates.

Abstract: An antitussive, which can be used for therapy or prophylaxis of coughing, is disclosed. The antitussive comprises as an effective ingredient a morphinan derivative having a nitrogen-containing cyclic substituent or a pharmaceutically acceptable acid addition salt thereof, having a specific structure, such as the compound below [N-(17-cyclopeopylmethyl-4,5?-epoxy-3,14-dihydroxy-morphinan-6?-yl)-3,4,5,6-tetrahydrophthalimide]. The antitussive has an excellent therapeutic or prophylactic effect against coughing and the side effects thereof are small.

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 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 present invention is directed to methods and compositions for inducing, promoting or otherwise facilitating pain relief. More particularly the present invention discloses the combination of a nitric oxide donor and an opioid analgesic in the therapeutic management of vertebrate animals including humans, for the prevention or alleviation of pain, particularly moderate to severe pain. In particular, the nitric oxide donor is a slow-release nitric oxide donor or is formulated to provide a sustained release of a low dose of nitric oxide.

Abstract: 8-Substituted-2,6-methano-3-benzazocines of general structure I in which A is —CH2OH, —CH2NH2, —NHSO2CH3, Q is O or S and Y is O, S or NOH are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.

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: The present invention relates to the preparation and pharmacological use of sinomenine derivatives of formula I. The approach disclosed herein is the modification of D ring by-substituting for R. Additional substitutions in the other rings are also provided herein. Several of the sinomenine derivatives have significantly greater anti-inflammation activity when compared with the parent compound.

Abstract: Azonafide derivatives are obtained by reacting azonafide with aldehydes, acyl halides, thioacyl halides, monoisocyanates, isothiocyanates, sulfonyl halides, monohalogenoalkanes, monohalogenoalkenes or monohalogenoalkynes, and are useful as active ingredients of pharmaceutical compositions for the prevention and treatment of cell proliferative disorders, in particular several forms of Cancer.

Abstract: This disclosure relates to novel morphinan compounds and their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This disclosure also provides compositions comprising a compound of this disclosure and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a ?1 receptor agonist that also has NMDA antagonist activity.

Abstract: The present invention is directed to processes for the synthesis of morphinans. In particular, a process for cyclizing a ?,?-bicyclic ketone compound to form a nordihydrothebainone product using the Grewe cyclization reaction is improved by forming a reaction mixture comprising a ?,?-bicyclic ketone compound, a cyclizing acid and a water scavenging cyclization additive. In one embodiment, the Grewe transformation occurs in the presence of an acid anhydride as the cyclization additive. Further, the present invention is directed to processes for converting ?,?-bicyclic ketone compounds (e.g., by-products of the Grewe cyclization reaction) to ?,?-bicyclic ketone compounds, wherein the ?,?-bicyclic ketone compounds may be recovered to further undergo Grewe cyclization and form the nordihydrothebainone product.

Abstract: Provided herein are assays for detecting enzyme activity using Raman Spectroscopy.

Abstract: Bridged phenanthridine compounds having the structure of formula I or of formula II are provided: These compounds are useful as cannabinoid receptor ligands and can be prepared as pharmaceutical compositions for the prophylaxis or treatment of a variety of diseases, disorders and conditions including inflammatory pain, visceral pain, postoperative pain, cancer pain, neuropathic pain, musculoskeletal pain, dysmenorrhea, menstrual pain, migraine, headache as well as inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, psoriasis, eczema, multiple sclerosis, diabetes and thyroiditis. The compounds can also be used in the treatment of skin disorders, lung disorders, ophthalmic disorders, gastrointestinal disorders, cardiovascular disorders, as well as neurodegenerative, neuroinflammatory and certain psychiatric disorders.

Abstract: A process for the production of morphinans with higher purity and yield, when compared to the conventional process, is described. Specifically, the process may be used to prepare levorphanol, levorphanol tartrate, and levorphanol tartrate dihydrate in high yields and substantially free from several process impurities.

Abstract: The present invention provides compositions and methods for treating pain by the administration of analgesics. The analgesics are encapsulated in diacylglycerol-polyethyleneglycol (DAG-PEG) liposomes and delivered sublingually as aerosols.

Abstract: A mixture of isolated or synthetic affinity molecules in a liquid carrier is disclosed. The mixture comprises at least two different affinity molecules, each with affinity for a predetermined analyte, for use in a single or multi flow cell piezoelectric crystal micro balance apparatus. Each isolated or synthetic affinity molecule forms together with the predetermined analyte an interaction pair selected from the group consisting of anion-cation, antibody-antigen, receptor-ligand, enzyme-substrate, oligonucleotide-oligonucleotide with complementary sequence, oligonucleotide-protein, oligonucleotide-cell, and peptide nucleic acid (PNA) oligomer-polynucleotide, wherein the polynucleotide may be selected from the group consisting of RNA, DNA and PNA polymers complementary to PNA oligomer. Use of the mixture for introduction into the liquid flow of a single or multi flow cell piezoelectric crystal micro balance apparatus is also described, as well as a kit containing the mixture.

Abstract: The invention provides a morphinan derivative of the Formula (I): wherein R1 is methyl, cyclopropylmethyl or the like; R2 and R3 are hydroxy, methoxy, acetoxy or the like; both Y and Z are valence bonds, —C(?O)— or the like; X is C2-C5 carbon chain (one of the carbon atoms may be substituted by oxygen, sulfur or nitrogen) constituting a part of the ring structure, or the like; (R4)k is substituted or non-substituted benzene fused ring, carbonyl group or the like; R9 is hydrogen or the like; R10 and R11 are bound to represent —O—, or the like, and R6 is hydrogen or the like or a pharmaceutically acceptable acid addition salt thereof. The invention also provides a therapeutic or prophylactic agent for urinary frequency or urinary incontinence, comprising as an effective ingredient the morphinan derivative or the pharmaceutically acceptable acid addition salt thereof; a method for therapy or prophylaxis of the diseases.

Abstract: 4-Hydroxybenzomorphans containing carboxamide or thiocarboxamide at the 3-position are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.

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: A process for converting an aryl triflate, heteroaryl triflate, aryl halide or heteroaryl halide to an N-hydroxysuccinimido ester is disclosed. The process involves reacting the triflate or halide with carbon monoxide and N-hydroxysuccinimide in a solvent in the presence of a palladium catalyst and a base.

Abstract: Compounds of formula 1, in which Het is an unsubstituted or R6- and/or R7-substituted pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrimidinyl, pyrazinyl or pyradazinyl radical, or an unsubstituted or R6- and/or R7-substituted fused bi- or tricyclic ring system comprising at least one aromatic ring and up to 4 heteroatoms-selected from the group consisting of O (oxygen), S (sulfur), N (nitrogen)- which is bonded to the phenanthridinyl radical via one of the rings comprising one or more heteroatoms, are active PDE4 inhibitors.

Abstract: Magenta ink exhibiting excellent coloration on various recording materials is provided according to the present invention. The magenta ink can realize high image densities and can produce images having superior light resistance.

Abstract: The invention is based in part on the discovery that nonselective ? agonists that possess ? receptor-mediated effects in addition to their ? agonist effects can decrease cocaine self-administration more effectively and with fewer undesirable side effects than can highly selective ? agonists. The invention includes a number of new compounds having both nonselective ? opioid receptor agonist activity and additional activity at ? opioid receptors. These compounds are useful for the treatment of cocaine abuse, and can also be radiolabeled for use as imaging agents, e.g., the N-fluoroalkyl and iodoalkyl derivatives can be used, respectively, for positron emission tomography (PET) and single photon computed tomography (SPECT) brain imaging.

Abstract: This invention features opioid compounds having activity at kappa and mu receptors, methods for preparing the mu/kappa opioids, and methods for the treatment of pain or a dopamine dysregulation disease, such as schizophrenia, attention deficit hyperactivity disorder (ADHD), attention deficit hyperactivity disorder (ADD), Parkinson's disease, hyperprolactinemia, depression, and addiction.

Abstract: Novel non-steroidal compounds are provided which are glucocorticoid receptor modulators which are useful in treating diseases requiring glucocorticoid receptor agonist or antagonist therapy such as obesity, diabetes, inflammatory and immune disorders, and have the structure 1

Abstract: The invention pertains to a composition comprising dextromethorphan tannate and to a method for preparing dextromethorphan tannate by reacting dextromethorphan at a temperature of about 80 to about 180° C. with tannic acid either neat or as an aqueous slurry containing about 5 to about 30 wt. % water. The dextromethorphan tannate has extended release properties and is useful in pharmaceutical compositions as an antitussive for human beings.

Abstract: Compounds of the formula and their pharmaceutically acceptable salts, wherein R1, R2, and R3 are as defined herein; intermediates for the synthesis of such compounds, pharmaceutical compositions containing such compounds; and methods of using such compounds in the treatment of neurological and psychological disorders.

Abstract: The invention relates to compounds of formula (I), to a method for producing them and to their use in medicaments as NOS inhibitors.

Abstract: The invention is based in part on the discovery that nonselective &kgr; agonists that possess &mgr; receptor-mediated effects in addition to their &kgr; agonist effects can decrease cocaine self-administration more effectively and with fewer undesirable side effects than can highly selective &kgr; agonists. The invention includes a number of new compounds having both nonselective &kgr; opioid receptor agonist activity and additional activity at &mgr; opioid receptors. These compounds are useful for the treatment of cocaine abuse, and can also be radiolabeled for use as imaging agents, e.g., the N-fluoroalkyl and iodoalkyl derivatives can be used, respectively, for positron emission tomography (PET) and single photon computed tomography (SPECT) brain imaging.

Abstract: The N-oxides of the compounds of formula (I), in which R1, R2, R3, R31, R4, R5, R51 and R6 have the meanings indicated in the description, arm novel active bronchial therapeutics.

Abstract: The N-oxides of the compounds of formula (I), in which R1, R2, R3, R31, R4, R5, R51 and R6 have the meanings indicated in the description, are novel active bronchial therapeutics.

Abstract: Compounds of formula (I), in which R1, R2, R3, R31, R4, R5, R51 and R6 have the meanings indicated in the description, are novel active bronchial therapeutics.

Abstract: The present invention relates to compounds of formula (I) 1