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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 13405. Отображено 100.
26-01-2012 дата публикации

Methods for making 3-o-protected morphinones and 3-o-protected morphinone dienol carboxylates

Номер: US20120022259A1
Автор: Andreas Stumpf
Принадлежит: Purdue Pharma LP

Disclosed are methods for making aldehydes and ketones comprising allowing the corresponding primary or secondary alcohol to react in the presence of trichoroisocyanuric acid, a compound of formula R 1 SR 2 and a base. In one embodiment, the alcohol is a compound of formula (I): wherein R 3 is a protecting group. Also disclosed are methods for making 3-O-protected morphine dienol carboxylates comprising allowing a compound of formula (I) to oxidize in the presence of a chlorine-containing compound and a compound of formula R 1 SR 2 ; and allowing the product of the oxidation step to react with an acylating agent.

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09-02-2012 дата публикации

N-Demethylation of 6-Keto Morphinans

Номер: US20120035366A1
Принадлежит: Mallinckrodt LLC

The present invention provides processes for the demethylation of an N-methyl morphinan comprising a ketone functional group. In particular, the invention provides methods for the protection of the ketone functional group such that impurities are not generated during the demethylation of the N-methyl morphinan.

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29-03-2012 дата публикации

Light-driven rotary molecular motors

Номер: US20120074336A1
Принадлежит: Nevada System of Higher Education NSHE

Compounds of Formula ( 1 ) are disclosed: C b is a carbocyclic or heterocyclic group having an atom within the cyclic structure selected from C, N, Si, and C r and singly bound to A. A is CR, COR, CSR, CNR 2 , CCN, CCONR 2 , CNO 2 , CNNAr, CX′, or N. C r is a chromophore having a substantially planar cyclic structure. The compounds function as nanometer-scale rotary molecular motors powered and controlled by light energy. The design of the molecular motor devices is flexible so that the rotary direction, drive light wavelength, and other physical characteristics can be varied. The compounds can be chemically functionalized to allow it to be integrated into or attached to a variety of structures. The device can be used in applications where mechanical power, positional control, and information encoding are to be generated at the size scale of individual molecules.

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10-05-2012 дата публикации

Porphyrin compounds comprising one or more pyridone moieties

Номер: US20120115901A1
Принадлежит: VENTANA RESEARCH Corp

Various porphyrin compounds comprising one or more pyridone moieties, intermediates thereof, compositions thereof, and, methods of making and using thereof.

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10-05-2012 дата публикации

Method for the manufacturing of naltrexone

Номер: US20120116085A1
Принадлежит: H Lundbeck AS

The present invention relates to an improved process for producing naltrexone[17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxy-morphinan-6-one] from noroxymorphone[4,5-α-epoxy-3,14-dihydroxy-morphinan-6-one] by alkylation with a cyclopropylmethyl halide.

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10-05-2012 дата публикации

Sinomenine Derivatives and Processes for their Synthesis

Номер: US20120116086A1
Принадлежит: Mallinckrodt LLC

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.

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14-06-2012 дата публикации

Heterocyclic Radical or Diradical, The Dimers, Oligomers, Polymers, Dispiro Compounds and Polycycles Thereof, the Use Thereof, Organic Semiconductive Material and Electronic or Optoelectronic Component

Номер: US20120146012A1
Принадлежит: NOVALED GMBH

The present invention relates to heterocyclic radicals or diradicals, the dimers, oligomers, polymers, dispiro compounds and polycycles thereof, to the use thereof, to organic semiconductive materials and to electronic and optoelectronic components.

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26-07-2012 дата публикации

Compositions and methods for dna sequencing

Номер: US20120190012A1
Принадлежит: Lumiphore Inc

The invention provides compositions and methods useful in DNA sequencing. In exemplary embodiments, a detectable label such as a luminescent macrocycle is used.

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15-11-2012 дата публикации

Modified colored pigments

Номер: US20120285347A1
Принадлежит: Cabot Corp

The present invention relates to a modified colored pigment comprising a colored pigment having an attached organic group. The organic group is attached to the colored pigment via at least one carbon atom of a C—C single bond or double bond, wherein the C—C single bond or double bond is not a component of an aromatic system. The organic group further comprises at least one activating group on at least one carbon atom of the C—C single bond or double bond. A method of preparing a modified colored pigment is also disclosed, as are aqueous and non-aqueous dispersions, e.g., including ink jet inks, comprising the modified colored pigments.

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22-11-2012 дата публикации

Opioid Prodrugs with Heterocyclic Linkers

Номер: US20120295834A1
Принадлежит: Individual

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.

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22-11-2012 дата публикации

Gabaergic receptor subtype selective ligands and their uses

Номер: US20120295892A1
Принадлежит: UWM Research Foundation Inc

Described herein are α3 or α2 or α2/α3 GABAergic receptor subtype selective ligands, pharmaceutical compositions, and methods of use of such ligands and compositions in treatment of anxiety disorders, epilepsy and schizophrenia with reduced sedative and ataxic side effects. In embodiments, such as α3 or α2 or α2/α3 GABAergic receptor subtype selective ligands lack ester linkages and may be thus relatively insensitive to hydrolysis by esterases.

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29-11-2012 дата публикации

Copolymer containing fluorenylporphyrin-anthracene, preparation method and application thereof

Номер: US20120302717A1

A copolymer containing fluorenylporphyrin-anthracene is disclosed, which comprises a polymer represented by formula (1), in which R 1 , R 2 , R 3 and R 4 , which may be identical or different, are C 1 -C 16 alkyl, and n is an integer of 1 to 100. A preparation method of the copolymer containing fluorenylporphyrin-anthracene and the application thereof in manufacture of solar cell devices, organic field-effect transistors, organic electroluminescent devices, organic optical storage device, organic nonlinear materials or organic laser devices are also disclosed.

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29-11-2012 дата публикации

Long Wavelength Absorbing Porphyrin Photosensitizers for Dye-Sensitized Solar Cells

Номер: US20120302743A1
Принадлежит: Individual

A long wavelength absorbing porphyrin/metalloporphyrin molecule is provided, made up of a porphyrin macrocycle and an anchor group for attachment to a substrate. A molecular linking element is interposed between the porphyrin macrocycle and the anchor group. The porphyrin/metalloporphyrin molecule also includes an (aminophenyl)amine group, either N,N-(4-aminophenyl)amine or N-phenyl-N-(4-aminophenyl)amine, where an amino moiety of the 4-aminophenyl group is derivatized by an element such as hydrogen, haloalkanes, aromatic hydrocarbons, halogenated aromatic hydrocarbons, heteroarenes, halogenated heteroarenes, or combinations of the above-mentioned elements.

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06-12-2012 дата публикации

HIV Integrase Inhibitors

Номер: US20120309698A1
Принадлежит: Bristol Myers Squibb Co

The disclosure generally relates to the novel compounds of formula I, including their salts, which inhibit HIV integrase and prevent viral integration into human DNA. This action makes the compounds useful for treating HIV infection and AIDS. The invention also encompasses pharmaceutical compositions and methods for treating those infected with HIV.

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20-12-2012 дата публикации

Ionic liquid containing sulfonate ions

Номер: US20120321967A1
Принадлежит: FLUIDIC Inc

Embodiments are related to ionic liquids and more specifically to ionic liquids used in electrochemical metal-air cells in which the ionic liquid includes sulfonate ions as the anion.

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27-12-2012 дата публикации

Novel Tricyclic Compounds

Номер: US20120330012A1
Принадлежит: ABBOTT LABORATORIES

The invention provides compounds of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

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24-01-2013 дата публикации

Controlled Release Formulations of Opioids

Номер: US20130022646A1
Принадлежит: Individual

Pharmaceutical formulations containing opioid components that each has a release profile. The components may provide immediate or controlled release of the opioid. The invention is also directed to methods of controlling release of one or more opioid compounds and methods of treating pain.

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21-02-2013 дата публикации

4-fluoro-4-arylpiperdin-1-yl derivatives as mu opioid function moderators

Номер: US20130045165A1
Автор: David J. Fairfax
Принадлежит: KINENTIA BIOSCIENCES LLC

4-Fluoro-4-phenylpiperidin- 1 -yl μ antagonists of general structure as well as pharmaceutical compositions comprising compounds of formula I, are disclosed. These compounds and compositions are useful as treatments of conditions or diseases associated with binding opioid receptors including pain, obesity, hyperalgesia, inflammation, osteoarthritis, drug addiction, and cancer. These compounds and compositions are also useful as treatments for tardive dyskinesia.

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21-03-2013 дата публикации

MODULAR SUPRAMOLECULAR APPROACH FOR CO-CRYSTALLIZATION OF DONORS AND ACCEPTORS INTO ORDERED NETWORKS

Номер: US20130069010A1
Принадлежит: Northwestern University

Organic charge-transfer (CT) co-crystals in a mixed stack system are disclosed, wherein a donor molecule (D) and an acceptor molecule (A) occupy alternating positions (DADADA) along the CT axis. A platform is provided which amplifies the molecular recognition of donors and acceptors and produces co-crystals at ambient conditions, wherein the platform comprises (i) a molecular design of the first constituent (α-complement), (ii) a molecular design of the second compound (β-complement), and (iii) a solvent system that promotes co-crystallization. 1. An organic charge-transfer (CT) co-crystal consisting essentially of an electron acceptor molecule (A) and an electron donor molecule (D) , wherein one of A and D is an α-complement and the other one of A and D is a β-complement , such that the β-complement is incorporated into the α-complement through molecular linkages in a solvent system to form a co-crystalline supramolecular network , wherein one or more of the molecular linkages between the α-complement and the β-complement use adaptive intermolecular recognition to form the one or more molecular linkages , the co-crystal characterized by having a crystal superstructure comprising a mixed stack lattice (DADADA) and a topological hydrogen-bonded network.2. An organic CT co-crystal according to claim 1 , wherein A is a diimide.3. An organic CT co-crystal according to claim 2 , wherein A is selected from the group consisting of 1α claim 2 , 2α claim 2 , 3β and 4β; and D is selected from the group consisting of 5α claim 2 , 6α; 7β claim 2 , 8β claim 2 , 9β claim 2 , 10β claim 2 , 11β and 12β.4. An organic CT co-crystal according to claim 1 , wherein the solvent system is one or more organic solvents.5. An organic CT co-crystal according to claim 4 , wherein the solvent system is selected from the group consisting of dichloroethane/diethyl ether and N-methylpyrrolidone.6. An organic CT co-crystal according to claim 1 , wherein the α-complement has an α′-arm that is a ...

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21-03-2013 дата публикации

Rapid Melt Controlled Release Taste-Masked Compositions

Номер: US20130071476A1
Принадлежит:

Rapid melt tablets that dissolve and release an active component in the oral cavity are comprised of a pharmaceutical active ingredient such as dextromethorphan complexed with a resin that is effective in taste-masking the otherwise bitter taste of the active making it convenient for oral administration. The drug/resin-complexed particles can be coated with water swellable or water insoluble polymers to impart controlled release properties to the active ingredient. A rapid melt tablet also comprises diluents, sweeteners, flavors, disintegrants and other excipients to form granules that can be compressed into tablets at low pressure without the need for a binding agent. 1. A rapid melt composition for the relief of coughs and chest congestion comprising one or more bitter-tasting actives that is incorporated within a drug-resin ion-exchange complex micro-encapsulated within a carrier composition selected from the group consisting of polymers , biopolymers , fats , waxes , gums and mixtures thereof which is further incorporated within a fast dissolving polymer matrix selected from the group consisting of cellulose and cellulose derivatives , thermoplastic polymers , hydrogels , gums and mixtures thereof.2. The rapid melt composition of wherein said active is selected from the group consisting of antitussives claim 1 , expectorants claim 1 , antihistamines claim 1 , decongestants and mixtures thereof.3. The rapid melt composition of wherein said active is selected from the group consisting of dextromethorphan claim 2 , diclofenac claim 2 , ibuprofen claim 2 , phenylephrine claim 2 , doxylamine claim 2 , pseudoephedrine claim 2 , imenhydrinate claim 2 , brompheniramine claim 2 , chlorpheniramine claim 2 , brompheniramine maleate claim 2 , chlorpheniramine maleate claim 2 , phenylepherine hydrochloride claim 2 , pseudoephedrine claim 2 , their salts and mixtures thereof.4. The rapid melt composition of said active is encapsulated within a drug-resin complex wherein the ...

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21-03-2013 дата публикации

NEW ABUSE-RESISTANT PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF OPIOID DEPENDENCE

Номер: US20130071477A1
Автор: Fischer Andreas
Принадлежит: OREXO AB

There is provided pharmaceutical compositions for the treatment of e.g. opioid dependency comprising microparticles of a pharmacologically-effective amount of buprenorphine, or a pharmaceutically-acceptable salt thereof, in associative admixture with particles comprising a weak acid, or particles comprising weakly-acidic buffer forming materials. The composition may further comprise a disintegrant and/or particles of a pharmacologically-effective amount of naloxone, or a pharmaceutically-acceptable salt thereof. The compositions are useful in the treatment of opioid dependency/addiction and/or pain. 1. A pharmaceutical composition comprising microparticles of a pharmacologically-effective amount of buprenorphine , or a pharmaceutically-acceptable salt thereof , in associative admixture with particles comprising a weak acid , or particles comprising weakly-acidic buffer forming materials.2. A composition as claimed in claim 1 , wherein the microparticles of buprenorphine have a weight based mean diameter of less than about 15 μm.3. A composition as claimed in or claim 1 , wherein the weakly acidic material comprises citric acid claim 1 , tartaric acid claim 1 , malic acid claim 1 , fumaric acid claim 1 , adipic acid claim 1 , succinic acid claim 1 , lactic acid claim 1 , acetic acid claim 1 , oxalic acid claim 1 , maleic acid claim 1 , ammonium chloride or a combination thereof.4. A composition as claimed in or claim 1 , wherein the buffer forming materials comprise a combination of a weakly acidic material and a salt of a weakly acidic material.5. A composition as claimed in claim 1 , wherein the weakly acidic material is as defined in .6. A composition as claimed in or claim 1 , wherein the salt is sodium citrate claim 1 , potassium citrate claim 1 , sodium tartrate or potassium tartrate.7. A composition as claimed in any one of the preceding claims wherein the buffer system is citric acid/sodium citrate.8. A composition as claimed in any one of the preceding ...

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21-03-2013 дата публикации

PYRIMIDYL CYCLOPENTANES AS AKT PROTEIN KINASE INHIBITORS

Номер: US20130072500A1
Принадлежит: ARRAY BIOPHARMA INC.

The present invention provides compounds of Formula I including tautomers, resolved enantiomers, resolved diastereomers, solvates, metabolites, salts and pharmaceutically acceptable prodrugs thereof. 2. The method of claim 1 , wherein Ris H claim 1 , CH claim 1 , CHCH claim 1 , CH═CH claim 1 , CHOH claim 1 , CF claim 1 , CHFor CHF.3. The method of claim 1 , wherein m is 2 and n is 1.4. The method of claim 1 , wherein m is 2 and n is 2.5. The method of claim 1 , wherein m is 3 and n is 1.6. The method of claim 1 , wherein m is 3 and n is 2.7. The method of claim 1 , wherein m is 4 and n is 1.8. The method of claim 1 , wherein m and n are independently 1 or 2 claim 1 , provided that m and n taken together are 3.9. The method of claim 1 , wherein m and n are independently 1 claim 1 , 2 or 3 claim 1 , provided that m and n taken together are 4.10. The method of claim 1 , wherein p is 1 or 2 and Ris F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , CN claim 1 , (CH)NRRor (CH)OR.15. The method of claim 1 , wherein Ris (CRR)C-Caryl claim 1 , wherein said aryl is optionally substituted by F claim 1 , Cl claim 1 , Br or I.18. The method of claim 1 , wherein Ris O(CRR)C-Caryl claim 1 , wherein said aryl is optionally substituted by F claim 1 , Cl claim 1 , Br or I.19. The method of claim 18 , wherein t is 0 claim 18 , 1 claim 18 , 2 or 3; Ris independently selected from H claim 18 , OH claim 18 , O(C-Calkyl) or (CH)NRR claim 18 , or two Rare taken together to form oxo;{'sup': 11', '11, 'sub': 1', '3', '3', '6, 'and Ris independently selected from H or C-Calkyl, or two Rare taken together to form a C-Cheterocyclyl, optionally substituted by methyl or ethyl.'}21. The method of claim 1 , wherein Ris C-Calkyl or (CRR)C-Ccycloalkyl claim 1 , wherein said alkyl and cycloalkyl are optionally substituted by F.22. The method of claim 21 , wherein Ris methyl claim 21 , ethyl claim 21 , n-propyl claim 21 , iso-propyl claim 21 , cyclopropyl claim 21 , cyclobutyl claim 21 , cyclopentyl ...

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21-03-2013 дата публикации

METHOD OF ALCOHOL CESSATION AND TREATMENT

Номер: US20130072516A1
Принадлежит: EAGLE ADVANCEMENT INSTITUTE LLC

A method of alcohol cessation and treatment for a patient generally comprises the steps of administering a multi-vitamin to the patient, administering a medication group to the patient, and monitoring the patient. In various embodiments, the medication group may be administered to the patient via a first and second injection solution. The first injection solution generally comprises a therapeutically effective amount of an anti-addictive agent, such as naltrexone palmitate. The second injection solution generally comprises a therapeutically effective amount of an inhibitor of alcohol dehydrogenase, such as disulfiram. The method, which may also be referred to as procedure, may include various pre- and/or post-procedural steps as described herein. 1. A method of alcohol cessation and treatment for a patient , said method comprising the steps of:administering a multi-vitamin to the patient;administering a medication group to the patient; andmonitoring the patient.2. The method as set forth in wherein the step of administering the medication group is further defined as injecting the medication group into at least one muscle of the patient.3. The method as set forth in wherein the medication group comprises a therapeutically effective amount of an anti-addictive agent.4. The method as set forth in wherein the anti-addictive agent is naltrexone palmitate.5. The method as set forth in wherein the therapeutically effective amount of is about 500 milligrams (mg).6. The method as set forth in wherein the medication group further comprises a therapeutically effective amount of an inhibitor of alcohol dehydrogenase.7. The method as set forth in wherein the inhibitor is disulfiram.8. The method as set forth in wherein the therapeutically effective amount is from about 1 to about 2 grams (g).9. The method as set forth in wherein the multi-vitamin is administered to the patient intravenously.10. The method as set forth in wherein the step of monitoring the patient is further ...

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21-03-2013 дата публикации

PHARMACEUTICAL COMPOSITIONS COMPRISING DEXTROMETHORPHAN AND QUINIDINE FOR THE TREATMENT OF NEUROLOGICAL DISORDERS

Номер: US20130072517A1
Принадлежит: Avanir Pharmaceuticals, Inc.

Pharmaceutical compositions and methods for treating neurological disorders by administering same are provided. The compositions comprise dextromethorphan in combination with quinidine. 1. A method for treating traumatic brain injury , the method comprising administering to a patient in need thereof dextromethorphan in combination with quinidine , wherein the amount of dextromethorphan administered comprises from about 20 mg/day to about 60 mg/day and wherein the amount of quinidine administered comprises from about 10 mg/day to about 30 mg/day with the proviso that the weight-to-weight ratio of dextromethorphan to quinidine is 1:0.75 or less of quinidine.2. The method of claim 1 , wherein the dextromethorphan and the quinidine are administered as one combined dose per day.3. The method of claim 1 , wherein the dextromethorphan and the quinidine are administered as at least two combined doses per day.4. The method of claim 1 , wherein the amount of quinidine administered comprises from about 20 mg/day to 30 mg/day.5. The method of claim 1 , wherein the amount of dextromethorphan administered comprises from about 40 mg/day to 60 mg/day.6. The method of claim 1 , wherein at least one of the quinidine and the dextromethorphan is in a form of a pharmaceutically acceptable salt.7. The method of claim 1 , wherein at least one of the quinidine and the dextromethorphan is in a form of a pharmaceutically acceptable salt selected from the group consisting of salts of free acids claim 1 , inorganic salts claim 1 , salts of sulfate claim 1 , salts of hydrochloride claim 1 , and salts of hydrobromide.8. The method of claim 1 , wherein about 20 mg quinidine sulfate is administered per day.9. The method of claim 1 , wherein about 60 mg dextromethorphan hydrobromide is administered per day.10. The method of wherein the dextromethorphan and quinidine are administered in separate doses.11. The method of wherein the weight-to-weight ratio of dextromethorphan to quinidine is 1:0.65 or ...

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21-03-2013 дата публикации

Process for Preparing Modulators of Cystic Fibrosis Transmembrane Conductance Regulator

Номер: US20130072687A1
Принадлежит: VERTEX PHARMACEUTICALS INCORPORATED

The present invention relates to processes for preparing solid state forms of N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide, including Compound 1 Form A, Compound 1 Form A-HCl, Compound 1 Form B, and Compound 1 Form B-HCl, any combination of these forms, pharmaceutical compositions thereof, and methods of treatment therewith. 143-. (canceled)45. The process of claim 44 , wherein step (a) is performed in the presence of a base such as KCO claim 44 , EtN claim 44 ,N-methylmorpholine (NMM) claim 44 , pyridine or diisopropylethyl aniline (DIEA).46. The process of or claim 44 , wherein step (a) is performed in the presence of pyridine or DIEA.4746. The process of any of - claims 44 , wherein step (a) is performed in the presence of pyridine.4847. The process of any of - claims 44 , wherein step (a) is performed in the presence of a polar aprotic solvent.4948. The process of any of - claims 44 , wherein the polar aprotic solvent is selected from the group consisting of ethyl acetate claims 44 , isopropyl acetate claims 44 , tetrahydrofuran claims 44 , methylethyl ketone claims 44 , N-Methyl-2-pyrrolidone claims 44 , acetonitrile claims 44 , N claims 44 ,N-dimethyl formamide claims 44 , or 2-methyltetrahydrofuran.5049. The process of any of - claims 44 , wherein the coupling of Compound 2 and 3-HCl is performed in the presence of a 2-methyltetrahydrofuran.5150. The process of any of - claims 44 , wherein step (a) is performed at a reaction temperature that is maintained between 10° C. and 80° C.5251. The process of any of - claims 44 , wherein step (a) is performed at a reaction temperature that is maintained between 15° C. and 70° C.5352. The process of any of - claims 44 , wherein the time of step (a) is from about 1.5 hours to about 72 hours.5453. The process of any of - claims 44 , wherein HCl gas is used in step (b).5554. The process of any of - claims 44 , wherein HCl gas is bubbled into ...

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28-03-2013 дата публикации

Peripheral Opioid Agonists and Peripheral Opioid Antagonists

Номер: US20130079364A1
Принадлежит: SIGNATURE THERAPEUTICS, INC.

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. 9. (canceled)10. A method of treating or preventing pain in a patient claim 1 , which comprises administering an effective amount of a composition comprising the compound of .1113-. (canceled)14. A method of treating or preventing an unwanted side effect associated with use of an opioid agonist in a patient claim 1 , which comprises administering an effective amount of a composition comprising the compound of .15. (canceled)1723-. (canceled)25. A composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of .26. A composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of .27. A method of treating or preventing pain in a patient claim 5 , which comprises administering an effective amount of a composition comprising the compound of .28. A method of treating or preventing an unwanted side effect associated with use of an opioid agonist in a patient claim 5 , which comprises administering an effective amount of a composition comprising the compound of .29. A method of claim 28 , wherein the unwanted side effect is selected from constipation claim 28 , cough suppression claim 28 , dry mouth claim 28 , heartburn claim 28 , myocardial depression claim 28 , nausea claim 28 , pruritus claim 28 , urinary retention claim 28 , vomiting claim 28 , bloating claim 28 , dry-mouth or heartburn.30. A method of claim 14 , wherein the unwanted side effect is selected from constipation claim 14 , cough suppression claim 14 , dry mouth claim 14 , heartburn claim 14 , myocardial depression claim 14 , nausea claim 14 ...

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28-03-2013 дата публикации

NORBORNANE-2-SPIRO-alpha-CYCLOALKANONE-alpha'-SPIRO-2''-NORBORNANE-5,5'',6,6''-TETRACARBOXYLIC DIANHYDRIDE, NORBORNANE-2-SPIRO-alpha-CYCLOALKANONE-alpha'-SPIRO-2''-NORBORNANE-5,5'',6,6''-TETRACARBOXYLIC ACID AND ESTER THEREOF, METHOD FOR PRODUCING NORBORNANE-2-SPIRO-alpha-CYCLOALKANONE-alpha'-SPIRO-2''-NORBORNANE-5,5'',6,6''-TETRACARBOXYLIC DIANHYDRIDE, POLYIMIDE OBTAINED BY USING THE SAME, AND METHOD FOR PRODUCING POLYIMIDE

Номер: US20130079490A1
Принадлежит: JX Nippon Oil and Energy Corp

A norbornane-2-spiro-α-cycloalkanone-α′-spiro-2″-norbornane-5,5″,6,6″-tetracarboxylic dianhydride represented by the following general formula (1): [in the formula (1), n represents an integer of 0 to 12, and R 1 s, R 2 , R 3 each independently represents a hydrogen atom or the like].

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11-04-2013 дата публикации

Compositions Comprising Enzyme-Cleavable Hydromorphone Prodrug

Номер: US20130089504A1
Принадлежит: SIGNATURE THERAPEUTICS, INC.

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. 3. (canceled)4. A method of treating or preventing pain in a patient in need thereof claim 2 , which comprises administering an effective amount of a composition of to the patient.5. (canceled)7. The composition of claim 6 , wherein the trypsin inhibitor is an arginine mimic or a lysine mimic.8. The composition of claim 7 , wherein the arginine mimic or lysine mimic is a synthetic compound.15. The composition of claim 6 , wherein the trypsin inhibitor is selected from(S)-ethyl 4-(5-guanidino-2-(naphthalene-2-sulfonamido)pentanoyl)piperazine-1-carboxylate;(S)-ethyl 4-(5-guanidino-2-(2,4,6-triisopropylphenylsulfonamido)pentanoyl)piperazine-1-carboxylate;(S)-ethyl 1-(5-guanidino-2-(naphthalene-2-sulfonamido)pentanoyl)piperidine-4-carboxylate;(S)-ethyl 1-(5-guanidino-2-(2,4,6-triisopropylphenylsulfonamido)pentanoyl)piperidine-4-carboxylate;(S)-6-(4-(5-guanidino-2-(naphthalene-2-sulfonamido)pentanoyl)piperazin-1-yl)-6-oxohexanoic acid;4-aminobenzimidamide;3-(4-carbamimidoylphenyl)-2-oxopropanoic acid;(S)-5-(4-carbamimidoylbenzylamino)-5-oxo-4-((R)-4-phenyl-2-(phenylmethylsulfonamido)butanamido)pentanoic acid;6-carbamimidoylnaphthalen-2-yl-4-(diaminomethyleneamino)benzoate; and4,4′-(pentane-1,5-diylbis(oxy))dibenzimidamide.16. (canceled)17. A method of treating or preventing pain in a patient in need thereof claim 6 , which comprises administering an effective ...

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18-04-2013 дата публикации

Compounds for the Treatment of Hepatitis C

Номер: US20130095066A1
Принадлежит:

The disclosure provides compounds of formula I, including pharmaceutically acceptable salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV. 2. A compound of where Ris haloalkyl; Ris hydrogen; Ris hydrogen; Ris hydrogen; Aris pyridindiyl claim 1 , pyrimidindiyl claim 1 , or pyrazoldiyl; X is O or NR; Y is an alkylene or alkenylene chain containing 0-6 groups selected from the group consisting of O claim 1 , NR claim 1 , C(O) claim 1 , C(O)O claim 1 , C(O)NR claim 1 , OC(O)NR claim 1 , NRC(O)NR claim 1 , NRC(NR)NR claim 1 , and Z claim 1 , provided that O claim 1 , NR claim 1 , C(O) claim 1 , C(O)O claim 1 , C(O)NR claim 1 , OC(O)NR claim 1 , NRC(O)NR claim 1 , and NRC(NR)NRdo not directly bond to each other claim 1 , such that ring A is 14-36 membered; and where the alkylene or alkenylene chain is substituted with 0-6 alkyl substituents; and Z is phenylene; or a pharmaceutically acceptable salt thereof.3. A compound of where Ris trifluoroethyl or a pharmaceutically acceptable salt thereof.4. A compound of where Aris pyridindiyl or a pharmaceutically acceptable salt thereof.5. A compound of where Aris pyrimidindiyl or a pharmaceutically acceptable salt thereof.6. A compound of where Aris pyrazoldiyl or a pharmaceutically acceptable salt thereof.7. A compound of where X is O or a pharmaceutically acceptable salt thereof.8. A compound of where X is NRor a pharmaceutically acceptable salt thereof.9. A composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.10. The composition of further comprising at least one additional compound having therapeutic benefits for HCV wherein the compound is selected from the group consisting of interferons claim 9 , cyclosporins claim 9 , interleukins claim 9 , HCV metalloprotease inhibitors claim 9 , HCV serine protease ...

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25-04-2013 дата публикации

TRANSDERMAL DELIVERY PATCH

Номер: US20130101660A1
Принадлежит: PHOSPHAGENICS LIMITED

A composition suitable for use in a transdermal delivery patch for administration of an opioid, the composition comprising a phosphate compound of tocopherol and a polymer carrier. 1. A transdermal delivery patch comprising:(i) a backing layer, and a) a composition comprising a mixture of a mono-tocopheryl phosphate compound and a di-tocopheryl phosphate compound, and a polymer carrier, wherein the polymer carrier is present in an amount of about 20% w/w to about 90% w/w of the total weight of the composition, and', 'b) an opioid., '(ii) a matrix layer comprising2. The transdermal delivery patch of claim 1 , wherein mono-tocopheryl phosphate compound is selected from the group consisting of mono-(tocopheryl) phosphate claim 1 , mono-(tocopheryl) phosphate monosodium salt claim 1 , mono-(tocopheryl) phosphate disodium salt claim 1 , mono-(tocopheryl) phosphate monopotassium salt and mono-(tocopheryl) phosphate dipotassium salt claim 1 , and the di-tocopheryl phosphate compound is selected from the group consisting of di-(tocopheryl) phosphate claim 1 , di-(tocopheryl) phosphate monosodium salt and di-(tocopheryl) phosphate monopotassium salt.3. The transdermal delivery patch of claim 1 , wherein the mixture of the mono-tocopheryl phosphate compound and the di-tocopheryl phosphate compound is present in an amount within the range of about 0.01% w/w to about 10% w/w of the total concentration of the composition.4. The transdermal delivery patch of claim 1 , wherein the mixture of the mono-tocopheryl phosphate compound and the di-tocopheryl phosphate compound is present in an amount within the range of about 0.1% w/w to about 5% w/w of the total concentration of the composition.5. The transdermal delivery patch of claim 1 , wherein the mixture of the mono-tocopheryl phosphate compound and the di-tocopheryl phosphate compound is present in an amount within the range of about 0.05% w/w to about 3% w/w of the total concentration of the composition.6. The transdermal ...

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25-04-2013 дата публикации

PYRAZOLOPYRIMIDINE DERIVATIVE

Номер: US20130102620A1
Принадлежит: KYOWA HAKKO KIRIN CO., LTD.

The invention provides a pyrazolopyrimidine derivative of formula (I), wherein, for example, Rrepresents —NRR(wherein Rand Rare the same or different and each is a hydrogen atom or aralkyl), Rrepresents formula (Ya) [wherein k and m each represents an integer of 0-2, n represents an integer of 0-4, L represents a single bond, Rrepresents halogen, Rrepresents aryl, X represents —CR(wherein Rrepresents a hydrogen atom), and Rrepresents a hydrogen], Rrepresents —SOR[wherein Rrepresents lower alkoxy, —NRC(═O)R(wherein Rrepresents a hydrogen atom, and Rrepresents lower alkyl)], and Rrepresents a hydrogen atom, or a pharmaceutically acceptable salt thereof. The invention also provides a medicament containing the pyrazolopyrimidine derivative, as well as a method of using the pyrazolopyrimidine derivative to prevent and/or treat skin diseases. 3. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Lis a single bond.4. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris aryl optionally having substituent(s).5. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris phenyl optionally having substituent(s).6. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris an aromatic heterocyclic group optionally having substituent(s).7. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris a hydrogen atom.8. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris a hydrogen atom claim 2 , and Ris lower alkyl optionally having substituent(s).9. The pyrazolopyrimidine derivative or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris a hydrogen atom claim 2 , and Ris COR(wherein Ris as defined ...

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25-04-2013 дата публикации

PHOTOCHROMIC MATERIAL

Номер: US20130102775A1
Принадлежит: MITSUBISHI GAS CHEMICAL COMPANY, INC.

The present invention is a photochromic material formed of a biimidazole compound represented by general formula (1-1): The present invention relates to a photochromic material, and more particularly, to a photochromic material formed of a novel biimidazole compound.Photochromic materials are typically materials that have a function (light modulation function) that enables them to reversibly change color (visible light transmittance) as a result of undergoing an isomerization reaction when irradiated with light, and not only materials prior to being irradiated with light, but also materials formed after being irradiated with light, are referred to as photochromic materials. Consequently, photochromic materials are used as eyeglasses for preventing glare, optical switches as well as display materials such as ink having the ability to switch between display and non-display status. In addition, research is also proceeding on their application to optical discs and other recording materials as well as holograms.Changes in color demonstrated by photochromic materials are typically expressed as a reversible chemical reaction of a material that is induced when the material is irradiated with light. Typical known examples of photochromic materials include spiropyran-based compounds, spirooxadine-based compounds, naphthopyran-based compounds, fulgide-based compounds, and diarylethene-based compounds (see, for example, Non-Patent Document 1). In addition, compounds having a novel structure that demonstrate rapid photoreactivity have also been recently reported (see, for example, Non-Patent Document 2).Photochromic materials are broadly divided into those that exhibit a phenomenon referred to as positive photochromism, which causes these materials to change from an uncolored form to a colored form (colored state) accompanying a structural change when irradiated with light, and those that exhibit a phenomenon referred to as negative photochromism (reverse photochromic materials ...

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25-04-2013 дата публикации

TRANSITION METAL-CATALYZED PROCESSES FOR THE PREPARATION OF N-ALLYL COMPOUNDS AND USE THEREOF

Номер: US20130102780A1
Принадлежит: Rhodes Technologies

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. 3. The method of claim 1 , wherein the transition metal catalyst comprises a transition metal selected from the group consisting of Pd[0] claim 1 , Pd[II] claim 1 , Ni[0] claim 1 , Ni[II] claim 1 , Mo[0] claim 1 , Ru[II] claim 1 , Rh[I] claim 1 , and combinations of two or more thereof.4. The method of claim 3 , wherein the transition metal catalyst is selected from the group consisting of Pd(PPh) claim 3 , Pd(PhP(CH)PPh) claim 3 , Ni(PPh) claim 3 , Ni(PhP(CH)PPh) claim 3 , ((pentamethylcyclopentadienyl)RuCl) claim 3 , [Pd(DBA)]/PPh claim 3 , [Pd(OAc)]/PPh claim 3 , [Ni(COD)]/PPh claim 3 , NiCl/PPh claim 3 , Ni[P(OEt)] claim 3 , [Mo(CO)-DPPE] claim 3 , RhH(PPh)-P(n-Bu) claim 3 , and combinations of two or more thereof.6. The method of claim 5 , wherein the solvent is selected from the group consisting of ether solvents claim 5 , acetonitrile claim 5 , benzene claim 5 , N claim 5 ,N-dimethylformamide claim 5 , dimethyl sulfoxide claim 5 , N claim 5 ,N-dimethylpropionamide claim 5 , 1 claim 5 ,3-dimethyl-3 claim 5 ,4 claim 5 ,5 claim 5 ,6-tetrahydro-2(1H)-pyrimidinone claim 5 , 1 claim 5 ,3-dimethyl-2-imidazolidinone claim 5 , 1 claim 5 ,2-dimethoxyethane claim 5 , N claim 5 ,N-dimethylacetamide claim 5 , N-methylpyrrolidinone claim 5 , ethyl acetate claim 5 , ethyl formate claim 5 , ethyl-methyl ketone claim 5 , iso-butylmethylketone claim 5 , formamide claim 5 , hexamethylphosphoramide claim 5 , methyl acetate claim 5 , N-methylacetamide claim 5 , N-methylformamide claim 5 , nitrobenzene claim 5 , nitromethane claim 5 ...

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25-04-2013 дата публикации

PROCESS FOR N-DEALKYLATION OF TERTIARY AMINES

Номер: US20130102784A1
Принадлежит: Rhodes Technologies

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. 2. The method of claim 1 , wherein the solvent consists essentially of a tertiary alcohol.3. The method of claim 1 , wherein the tertiary alcohol is tert-amyl alcohol.4. The method of claim 1 , wherein said contacting is carried out in the presence of NaI.5. The method of claim 1 , wherein Ris —CH.7. The method of claim 6 , wherein the solvent consists essentially of a tertiary alcohol.9. The method of claim 8 , wherein the tertiary alcohol is selected from the group consisting of tert-amyl alcohol claim 8 , tert-butyl alcohol claim 8 , 3-methyl-3-pentanol claim 8 , 2 claim 8 ,3-dimethyl-3-pentanol claim 8 , 3-ethyl-3-pentanol claim 8 , 2-methyl-2-hexanol claim 8 , and mixtures of two or more thereof.10. The method of claim 9 , wherein the tertiary alcohol is tert-amyl alcohol.11. The method of claim 6 , wherein the 7 claim 6 ,8-bond is a single bond.12. The method of claim 6 , wherein Rand Rare each —OH and Ris ═O.13. The method of claim 6 , wherein Ris —OCH claim 6 , Ris —OH claim 6 , and Ris ═O.14. The method of claim 6 , wherein said contacting is carried out in the presence of an iodide salt.15. The method of claim 14 , wherein the iodide salt is NaI.20. The method of claim 19 , wherein the solvent consists essentially of a tertiary alcohol.21. The method of claim 19 , wherein the tertiary alcohol is tert-amyl alcohol.22. The method of claim 19 , wherein the 7 claim 19 ,8-bond is a single bond.23. The method of claim 19 , wherein Rand Rare —OH and Ris ═O.24. The method of claim 19 , wherein Ris —OCH claim 19 , Ris —OH claim 19 , and Ris ═O.25. The ...

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02-05-2013 дата публикации

PROCESSES FOR MAKING ZILPATEROL AND SALTS THEREOF

Номер: US20130109673A1
Принадлежит:

This invention generally relates to processes for making zilpaterol and salts thereof, as well as processes for making intermediates that, inter alia, may be used to make zilpaterol and salts thereof. This invention also relates to methods of treatment using zilpaterol and salts prepared in accordance with this invention to increase the rate of weight gain, improve feed efficiency, and/or increase carcass leanness in livestock, poultry, and fish. 115-. (canceled)16. A method of increasing the rate of weight gain in a bovine animal comprising administering a single oral daily dose of zilpaterol or a salt thereof in the bovine animal's feed wherein the concentration of the zilpaterol or salt thereof in the feed is between 0.01 ppm and 75 ppm.17. The method of claim 16 , wherein the zilpaterol salt is zilpaterol hydrochloride.18. The method of claim 16 , wherein the concentration of the zilpaterol or salt thereof in the feed is between 0.01 ppm and 38 ppm.19. The method of claim 16 , wherein the concentration of the zilpaterol or salt thereof in the feed is between 0.5 ppm and 20 ppm.20. The method of claim 16 , wherein the concentration of the zilpaterol or salt thereof in the feed is between 3 ppm and 8 ppm.21. The method of claim 16 , wherein the concentration of the zilpaterol or salt thereof in the feed is between 3.7 ppm and 7.5 ppm.22. The method of claim 16 , wherein the zilpaterol or salt thereof is administered in a daily dose of 0.01 mg/kg body weight to 50 mg/kg body weight.23. The method of claim 16 , wherein the zilpaterol or salt thereof is administered in a daily dose of 0.01 mg/kg body weight to 10 mg/kg body weight.24. The method of claim 16 , wherein the zilpaterol or salt thereof is administered in a daily dose of 0.05 mg/kg body weight to 2 mg/kg body weight.25. The method of claim 16 , wherein the zilpaterol or salt thereof is administered in a daily dose of 0.1 mg/kg body weight to 1 mg/kg body weight.26. The method of claim 16 , wherein the ...

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02-05-2013 дата публикации

HETEROCYCLIC COMPOUNDS CONTAINING AN INDOLE CORE

Номер: US20130109679A1
Принадлежит:

Disclosed are novel compounds which inhibit RSK, methods of making such compounds and pharmaceutical compositions comprising such compounds. Also disclosed are methods of treating RSK2 regulated disorders using compounds of the invention. 1. A compound selected from the group consisting of:N-(2-methoxypyridin-4-yl)-1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide;N-(1-ethyl-1H-benzimidazol-2-yl)-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-(1-ethyl-1H-benzimidazol-2-yl)-cis-3,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;4R)—N-{1-[3-(dimethylamino)propyl]-1H-benzimidazol-2-yl}-4-methyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-(1-ethyl-1H-benzimidazol-2-yl)-5-methyl-1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide;5-methyl-1-oxo-N-[1-(propan-2-yl)-1H-benzimidazol-2-yl]-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide;(4R)—N-(1-benzyl-1H-pyrazol-4-yl)-4-methyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-(1H-benzimidazol-2-yl)-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;(3S,4R)—N-(1-benzyl-1H-pyrazol-4-yl)-3,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-(1H-benzimidazol-2-yl)-4-methyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;4,4-dimethyl-N-(1-methyl-1H-benzimidazol-2-yl)-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-{1-[3-(dimethylamino)propyl]-1H-benzimidazol-2-yl}-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;4-methyl-N-(1-methyl-1H-benzimidazol-2-yl)-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;(5R)-5-methyl-1-oxo-N-[1-(propan-2-yl)-1H-benzimidazol-2-yl]-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide;N-(1-ethyl-1H-benzimidazol-2-yl)-4-methyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxamide;N-(1H-benzimidazol-2-yl)-5-methyl-1-oxo-2,3,4,5-tetrahydro-1H-[1,4] ...

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09-05-2013 дата публикации

ESTROGEN RECEPTOR MODULATORS AND USES THEREOF

Номер: US20130116232A1
Принадлежит: ARAGON PHARMACEUTICALS, INC.

Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '1', 'sub': 1', '4, 'Ris C-Calkyl;'}{'sup': 2a', '2b, 'Rand Rare taken together with the N atom to which they are attached to form a substituted or unsubstituted monocyclic heterocycloalkyl, a substituted or unsubstituted bicyclic heterocycloalkyl, a substituted or unsubstituted monocyclic heteroaryl, or a substituted or unsubstituted bicyclic heteroaryl;'}{'sup': '3', 'sub': 1', '4', '1', '4, 'Ris C-Calkyl or C-Cfluoroalkyl;'}{'sup': 4', '9', '9', '10', '10, 'sub': 2', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'each Ris independently selected from H, halogen, —CN, —OH, —OR, —SR, —S(═O)R, —S(═O)R, C-Calkyl, C-Cfluoroalkyl, C-Cfluoroalkoxy, C-Calkoxy, and C-Cheteroalkyl;'}{'sup': 5', '9, 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'each Ris independently selected from H, halogen, —CN, —OH, —OR, C-Calkyl, C-Cfluoroalkyl, C-Cfluoroalkoxy, C-Calkoxy, and C-Cheteroalkyl;'}{'sup': '6', 'sub': 1', '6', '1', '6', 'r', '6', '1', '6, 'each Ris independently selected from H, halogen, —CN, —OH, C-Calkyl, C-Cfluoroalkyl, CCfluoroalkoxy, and C-Calkoxy;'}{'sup': '7', 'sub': '3', 'Ris H or —CH;'}Y is —O— or —S—.46-. (canceled)7. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein:{'sup': '1', 'sub': '3', 'Ris —CH;'}{'sup': '3', 'sub': 3', '3, 'Ris —CHor —CF;'}{'sup': 2a', '2b, 'Rand Rare taken together with the N atom to which they are attached to form a substituted or unsubstituted pyrrolidinyl;'}X is —O—;Y is —O—.8. (canceled)11. (canceled)13. The compound ...

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16-05-2013 дата публикации

SUBSTITUTED BENZYLSPIROINDOLIN-2-ONE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M1

Номер: US20130123236A1
Принадлежит: VANDERBILT UNIVERSITY

In one aspect, the invention relates to substituted benzylspiroindolin-2-one analogs compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M(mAChR M); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 2. The compound of claim 1 , wherein Qis CR; wherein Qis CR; wherein Qis CR; and wherein Qis CR.3. The compound of claim 1 , wherein Qis CR; wherein Qis CR; wherein Qis CR; and wherein Qis CR.4. The compound of claim 1 , wherein Qis NR.5. The compound of claim 4 , wherein Qis NR claim 4 , and wherein Ris selected from cyclopentyl and cyclohexyl.6. The compound of claim 1 , wherein Ris 1H-pyrazol-4-yl; and wherein Ris monosubstituted with methyl.7. The compound of claim 1 , wherein m is 0 claim 1 , n is 2 claim 1 , and q is 2.8. The compound of claim 1 , wherein m is 0 claim 1 , n is 2 claim 1 , and q is 1.14. The method of claim 13 , wherein the mammal has been diagnosed with a need for treatment of the disorder prior to the administering step.15. The method of claim 13 , further comprising the step of identifying a mammal in need of treatment of the disorder.16. The method of claim 15 , wherein the disorder is associated with a mAChR Mdysfunction.17. The method of claim 13 , wherein the disorder is a neurological and/or psychiatric disorder associated with mAChR Mdysfunction.18. The method of claim 13 , wherein the disorder is selected from Alzheimer's disease claim 13 , schizophrenia claim 13 , a sleep disorder claim 13 , a pain disorder and a cognitive disorder.19. The method of claim 18 , wherein the disorder is ...

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16-05-2013 дата публикации

Method for Purifying a Fused Pyrrolocarbazole Derivative

Номер: US20130123499A1
Принадлежит:

The present invention relates a method for purifying a fused pyrrolocarbazole compound known as 11-isobutyl-2-methyl-8-(2-pyrimidinylamino)-2,5,6,11,12,13-hexahydro-4Hindazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one using an acid complex thereof. The present invention also relates to a crystalline form of the acid complex. 2. The acid complex according to claim 1 , wherein R is methyl.4. The method according to claim 3 , wherein the solvent is an alcohol having a boiling point above 100° C.5. The method according to claim 4 , wherein the solvent is n-butanol.6. The method according to claim 3 , wherein the base is a tertiary amine.7. The method according to claim 6 , wherein the base is a trialkylamine.8. The method according to claim 7 , wherein the base is triethylamine.9. The method according to claim 3 , wherein the optional step of recovering the resulting acid complex of formula (Ia) comprises:a) crystallizing the complex of formula (Ia); andb) recovering the crystallized complex of formula (Ia).10. An acid complex of formula (Ia) obtainable according to the method according to .12. The method according to claim 11 , wherein the purified compound of formula (I) has a purity of more than 98%.13. The method according to claim 11 , wherein the compound of formula (I) has a purity of more than 99%.14. The method of further comprising the step of:i) contacting the acid complex of formula (Ia) with a decolorizing agent.15. The method according to claim 11 , wherein the step of converting the acid complex of formula (Ia) into the compound of formula (I) is carried out by drying the complex at a temperature comprised in the range of 70° C. to 90° C.16. The method according to claim 11 , wherein the step of converting the acid complex of formula (Ia) into the compound of formula (I) is carried out by dissolving the complex of formula (Ia) in a solvent selected in the list consisting of 1-butanol; 1-pentanol; 1-propanol; 2-butanol; 2-butanone; 2-pentanone; 3-pentanone; ...

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23-05-2013 дата публикации

SPIROCYCLIC COMPOUNDS

Номер: US20130131041A1
Принадлежит: Merck Sharp & Dohme Corp.

The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo. 6. A pharmaceutical composition comprising a pharmaceutically effective amount of the compound according to any one of to , and a pharmaceutically acceptable carrier.7. The use of the compound according to any one of to for the preparation of a medicament useful in the treatment or prevention of cancer in a mammal. This application is a divisional application of U.S. application Ser. No. 12/085,396, which is a §371 application of PCT/US06/044754 that was filed on Nov. 17, 2006, which claims priority from the U.S. Provisional Application No. 60/739,324, filed on Nov. 23, 2005, now expired.The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present ...

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13-06-2013 дата публикации

Compositions and Methods for Treatment of Cancer

Номер: US20130150310A1
Принадлежит: ArQule, Inc.

The present invention relates to pyrroloquinolinyl-pyrrolidine-2,5-dione compounds in combination with chemotherapeutic agents. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a pyrroloquinolinyl-pyrrole-2,5-dione compound or pyrroloquinolinyl-pyrrolidine-2,5-dione compound of the present invention and also administering a effective amount of a chemotherapeutic agent. 115-. (canceled)1716. The pharmaceutical composition of , wherein said second chemotherapeutic agent is selected from the group consisting of tamoxifen , raloxifene , anastrozole , exemestane , letrozole , trastuzumab , imatinib , paclitaxel , cyclophosphamide , lovastatin , mimosine , gemcitabine , araC , 5-fluorouracil , methotrexate , docetaxel , goserelin , vinctristine , vinblastine , nocodazole , teniposide , etoposide , gemcitabine , epothilone , navelbine , camptothecin , daunorubicin , dactinomycin , mitoxantrone , amsacrine , doxorubicin , epirubicin or idarubicin.1826-. (canceled)28. The method of claim 27 , wherein said second chemotherapeutic agent is selected from the group consisting of tamoxifen claim 27 , raloxifene claim 27 , anastrozole claim 27 , exemestane claim 27 , letrozole claim 27 , trastuzumab claim 27 , imatinib claim 27 , paclitaxel claim 27 , cyclophosphamide claim 27 , lovastatin claim 27 , mimosine claim 27 , gemcitabine claim 27 , araC claim 27 , 5-fluorouracil claim 27 , methotrexate claim 27 , docetaxel claim 27 , goserelin claim 27 , vinctristine claim 27 , vinblastine claim 27 , nocodazole claim 27 , teniposide claim 27 , etoposide claim 27 , gemcitabine claim 27 , epothilone claim 27 , navelbine claim 27 , camptothecin claim 27 , daunorubicin claim 27 , dactinomycin claim 27 , mitoxantrone claim 27 , amsacrine claim 27 , doxorubicin claim 27 , epirubicin or idarubicin.29. The method of wherein said treating said cell proliferative ...

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13-06-2013 дата публикации

PYRROLOPYRIMIDINE COMPOUNDS AS INHIBITORS OF CDK4/6

Номер: US20130150342A1
Принадлежит: NOVARTIS AG

The invention is directed to novel pyrrolopyrimidine compounds of formula (I) wherein R, R, R, R-R, A and L are defined herein and to salts, including pharmaceutically acceptable salts thereof. The compounds of the present invention are CDK4/6 inhibitors and could be useful in the treatment of diseases and disorders mediated by CDK4/6, such as cancer, including mantle cell lymphoma, liposarcoma, non small cell lung cancer, melanoma, squamous cell esophageal cancer and breast cancer. The invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting CDK4/6 activity and to the treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention. 3. The compound according to wherein L is C(O) claim 1 , or a pharmaceutically acceptable salt thereof.4. The compound according to wherein L is a bond claim 1 , or a pharmaceutically acceptable salt thereof.5. The compound according to wherein A is CH and Ris hydrogen; or a pharmaceutically acceptable salt thereof.6. The compound according to wherein Ris C(R)(R)(R) and R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare hydrogen claim 1 , or a pharmaceutically acceptable salt thereof.7. The compound according to wherein Ris Ccycloalkyl optionally substituted with one Calkyl claim 1 , or a pharmaceutically acceptable salt thereof.8. The compound according to wherein Ris cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , or cycloheptyl claim 1 , or a pharmaceutically acceptable salt thereof.9. The compound according to wherein Ris unsubstituted cyclopentyl claim 1 , or a pharmaceutically acceptable salt thereof.10. The compound according to wherein Ris unsubstituted claim 1 , or a pharmaceutically acceptable salt thereof.14. The compound according to wherein A is CH; or a pharmaceutically acceptable salt thereof.15. The compound ...

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13-06-2013 дата публикации

BENZOIC ACID, BENZOIC ACID DERIVATIVES AND HETEROARYL CARBOXYLIC ACID CONJUGATES OF HYDROMORPHONE, PRODRUGS, METHODS OF MAKING AND USE THEREOF

Номер: US20130150395A1
Принадлежит: KemPharm, Inc.

The presently described technology provides compositions comprising aryl carboxylic acids chemically conjugated to hydromorphone (4,5-α-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. 1. A prodrug composition comprising at least one conjugate , the conjugate comprising at least one hydromorphone , and at least one aryl carboxylic acid.2. The prodrug composition of claim 1 , wherein the at least one aryl carboxylic acid is selected from the group consisting of benzoates and heteroaryl carboxylic acids.3. The prodrug composition of claim 2 , wherein the heteroaryl carboxylic acid is selected from the group consisting of pyridine claim 2 , diazine and triazine.5. The prodrug composition of claim 2 , wherein the benzoate is selected from the group consisting of aminobenzoates claim 2 , hydroxybenzoates and aminohydroxybenzoates claim 2 , mixtures thereof and derivatives thereof.6. The prodrug composition of claim 5 , wherein the aminobenzoate is selected from the group consisting of anthranilic acid claim 5 , 3-aminobenzoic acid claim 5 , 4 claim 5 ,5-dimethylanthranilic acid claim 5 , N-methylanthranilic acid claim 5 , N-acetylanthranilic acid claim 5 , fenamic acids claim 5 , 2 claim 5 ,4-diaminobenzoic acid (2 claim 5 ,4-DABA) claim 5 , 2-acetylamino-4-aminobenzoic acid claim 5 , 4-acetylamino-2-aminobenzoic acid and 2 claim 5 ,4-diacetylaminobenzoic acid claim 5 , mixtures thereof and derivatives thereof.7. The prodrug composition of claim 5 , wherein the hydroxybenzoate is selected from the group consisting of benzoic acid claim 5 , salicylic acid claim 5 , acetylsalicylic acid (aspirin) claim 5 , 3-hydroxybenzoic ...

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20-06-2013 дата публикации

7-AZONIABICYCLO[2.2.1]HEPTANE DERIVATIVES, METHODS OF PRODUCTION, AND PHARMACEUTICAL USES THEREOF

Номер: US20130157989A1
Принадлежит: Theron Pharmaceuticals, Inc.

Muscarinic acetylcholine receptor antagonists and methods of using them for the treatment of muscarinic acetylcholine receptor-mediated diseases, such as pulmonary diseases, are provided. 127.-. (canceled)29. The compound of claim 28 , wherein the compound is compound (2).30. The compound of claim 28 , wherein the compound is compound (3).31. The compound of claim 28 , wherein the compound is (2) or (3) and has a duration of bronchoprotection effect of at least 24 h in guinea pig as defined by the following protocol:(i) the compound and control (water) are administered to male Dunkin Hartley guinea pigs (250-350 g) via inhalation, by placing the guinea pigs in a dosing chamber and exposing them for 25 min to nebulized drug solution or control using a Pari nebulizer, then returning the animals to their cages;(ii) twenty-four hours after dosing and thirty minutes prior to the start of pulmonary evaluation, the animals are anesthetized with intramuscular ketamine (55.8 mg/kg), xylazine (3.9 mg/kg) and acepromazine (1 mg/kg), and after anesthesia, the trachea is dissected free and cannulated with a 14G steel tube connected to a pressure transducer (for the measurement of pulmonary inflation pressure) and to a constant volume rodent respirator set to deliver an appropriate tidal volume (2.5 ml) at a rate determined by the animal's weight (100 breath/min), the carotid artery is cannulated with a 5 U/ml heparin/saline-filled PE-50 cannula and connected to a pressure transducer for the measurement of blood pressure and heart rate, and the jugular vein is catheterized with a saline filled polyethylene catheter (PE-10) to be used deliver bolus challenges of the bronchoconstrictor methacholine (MCh);(iii) intravenous ascending doses of MCh (1 to 300 μg/kg) are administered, after the response to the previous dose returns to baseline; and(iv) pulmonary inflation pressure and blood pressure are recorded using an appropriate system and/or software.33. The pharmaceutical ...

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20-06-2013 дата публикации

SUBSTITUTED 3-PHENYL-1,2,4-OXADIAZOLE COMPOUNDS

Номер: US20130158001A1
Принадлежит:

Disclosed are compounds of Formula (I): (I) or stereoisomers, salts, or prodrugs thereof, wherein: (i) R1 and R2 are independently C-Calkyl, or (ii) Rand Rtogether with the carbon atom to which they are attached, form a cyclic group; and Q is H, Calkyl, phenyl or 5- to 6-membered heteroaryl substituted with zero to 3 substituents, and G is defined herein. Also disclosed are method of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. There compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and chronic inflammatory disease. 4. The compound according to or a stereoisomer or a salt thereof claim 3 , wherein Ris —CHand Ris C-Calkyl.5. The compound according to or a stereoisomer or a salt thereof claim 3 , wherein Rand Rtogether with the carbon atom to which they are attached claim 3 , form a cyclic group selected from adamantanyl claim 3 , Ccycloalkyl claim 3 , and a 5- to 6-membered heterocycloalkyl claim 3 , wherein each of said cycloalkyl and heterocycloalkyl rings is substituted with zero to 4 R.6. The compound according to or a salt thereof claim 1 , wherein said compound is selected from 1-(4-(5-(2-(1-phenylcyclohexyl)ethyl)-1 claim 1 ,2 claim 1 ,4-oxadiazol-3-yl)benzyl) azetidine-3-carboxylic acid (1); 1-(4-(5-(2-(2-oxo-1-phenylcyclohexyl)ethyl)-1 claim 1 ,2 claim 1 ,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid (2); 2-(2-(3-(4-((S)-2 claim 1 ,3-dihydroxypropoxy)-3 claim 1 ,5-dimethylphenyl)-1 claim 1 ,2 claim 1 ,4-oxadiazol-5-yl)ethyl)-2-(4-fluorophenyl)cyclohexanone (3); 2-(2-(3-(4-((S)-2 claim 1 ,3-dihydroxypropoxy)-3 claim 1 ,5-dimethylphenyl)-1 claim 1 ,2 claim 1 ,4-oxadiazol-5-yl)ethyl)-2-(4-fluorophenyl)cyclohexanone (4); 1-(4-(5-(2-(1-(3 claim 1 ,4-difluorophenyl)cyclohexyl)ethyl)-1 claim 1 ,2 claim 1 ,4-oxadiazol-3-yl)benzyl) azetidine-3-carboxylic acid ...

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20-06-2013 дата публикации

2-AMINOPYRIMIDINE MODULATORS OF THE HISTAMINE H4 RECEPTOR

Номер: US20130158258A1
Принадлежит: Janssen Pharmaceutica NV

2-Aminopyrimidine compounds are described, which are useful as Hreceptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by Hreceptor activity, such as allergy, asthma, autoimmune diseases, and pruritis. 2. A chemical entity as in claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , tert-butyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , benzyl claim 1 , tetrahydrofuran-3-yl claim 1 , or tetrahydropyran-4-yl.3. A chemical entity as in claim 1 , wherein Ris cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , or cyclohexyl.4. A chemical entity as in claim 1 , wherein Ris H.11. A chemical entity as in claim 1 , wherein Ris H.12. A chemical entity as in claim 1 , wherein Rand Rare each independently H or methyl.13. An chemical entity selected from:4-Cyclopentyl-6-piperazin-1-yl-pyrimidin-2-ylamine;4-Cyclopentyl-6-(4-methyl-piperazin-1-yl)-pyrimidin-2-ylamine;(R)-4-(3-Amino-piperidin-1-yl)-6-cyclopentyl-pyrimidin-2-ylamine;(R)-4-Cyclopentyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;trans-1-(2-Amino-6-cyclopentyl-pyrimidin-4-yl)-4-methylamino-pyrrolidin-3-ol;4-Cyclopentyl-6-(cis-hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-pyrimidin-2-ylamine;4-Cyclopentyl-6-(cis-octahydro-pyrrolo[3,4-b]pyridin-6-yl)-pyrimidin-2-ylamine;4-Isopropyl-6-piperazin-1-yl-pyrimidin-2-ylamine;(R)-4-(3-Amino-piperidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;(S)-4-(3-Amino-piperidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;(R)-4-Isopropyl-6-(3-methylamino-pyrrolidin-1-yl)-pyrimidin-2-ylamine;(R)-4-(3-Amino-pyrrolidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine;trans-1-(2-Amino-6-isopropyl-pyrimidin-4-yl)-4-methylamino-pyrrolidin-3-ol;(S,S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-6-isopropyl-pyrimidin-2-ylamine;(R,R)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-6-isopropyl-pyrimidin-2-ylamine;4-(cis-Hexahydro-pyrrolo[3,4-b] ...

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27-06-2013 дата публикации

PHOSPHATE ESTERS OF NORIBOGAINE

Номер: US20130165414A1
Принадлежит: DEMERX, INC.

Disclosed herein are phosphate esters of noribogaine and dihydronoribogaine, and esters and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising such compounds, and the methods of their use, including in the treatment of addiction and/or pain. 2. The compound of claim 1 , wherein R is a monophosphate.3. The compound of claim 1 , wherein Ris hydrogen.4. The compound of claim 1 , wherein R is a monophosphate and Ris hydrogen.5. A pharmaceutical composition comprising a therapeutically effective amount of the compound of and at least a pharmaceutically acceptable excipient.7. A method for treating pain in a patient which method comprises administering to said patient a therapeutically effective amount of the compound of .8. A method for treating addiction in a patient which method comprises administering to said patient a therapeutically effective amount of the compound of . This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 61/569,150, filed Dec. 9, 2011, which is incorporated herein by reference in its entirety.This invention is directed to phosphate esters of noribogaine.Noribogaine is a metabolite of ibogaine and is sometimes referred to as 12-hydroxyibogaine. U.S. Pat. No. 2,813,873 claims noribogaine albeit as “12-O-demethylibogaine” while providing an incorrect structural formula for ibogaine. Noribogaine can be depicted by the following formula:Noribogaine and its pharmaceutically acceptable salts have recently received significant attention as a non-addictive alkaloid useful in treating drug dependency (U.S. Pat. No. 6,348,456) and as a potent analgesic (U.S. Pat. No. 7,220,737).Noribogaine is typically administered orally or intravenously and becomes systemically available to the treated patient.This invention is directed in part to phosphate esters of noribogaine and a vicinal dihydro derivative of noribogaine and compositions thereof. The phosphate esters of this invention can be a ...

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27-06-2013 дата публикации

SULFATE ESTERS OF NORIBOGAINE

Номер: US20130165425A1
Принадлежит: DEMERX, INC.

Disclosed herein are sulfate esters of noribogaine or 9,17 dihydronoribogaine, and pharmaceutically acceptable salts of each thereof, pharmaceutical compositions comprising such compounds, and methods of their use, including in treating addiction and/or pain. 2. The compound of claim 1 , wherein Ris hydrogen.3. The compound of claim 1 , wherein Ris SOOR.4. The compound of claim 1 , wherein R is hydrogen.5. The compound of claim 1 , wherein R is SOOR.6. A pharmaceutical composition comprising a compound of and at least one pharmaceutically acceptable excipient.7. A method for treating pain in a patient which method comprises administering to said patient a therapeutically effective amount of the compound of .8. A method for treating addiction in a patient which method comprises administering to said patient a therapeutically effective amount of the compound of . This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application Nos. 61/569,144, filed Dec. 9, 2011, which is incorporated herein by reference in its entirety.This invention is directed to sulfate esters of noribogaine.Noribogaine is a metabolite of ibogaine and is sometimes referred to as 12-hydroxyibogaine. U.S. Pat. No. 2,813,873 claims noribogaine albeit as “12-O-demethylibogaine” while providing an incorrect structural formula for ibogaine. Noribogaine can be depicted by the following formula:Noribogaine and its pharmaceutically acceptable salts have recently received significant attention as a non-addictive alkaloid useful in treating drug dependency (U.S. Pat. No. 6,348,456) and as a potent analgesic (U.S. Pat. No. 7,220,737).Noribogaine is typically administered orally or intravenously and becomes systemically available to the treated patient.This invention is directed to sulfate esters of noribogaine and a vicinal dihydro derivative of noribogaine, and compositions comprising each of them. As used herein, the sulfate esters include pharmaceutically acceptable salts and ...

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27-06-2013 дата публикации

STEREOSELECTIVE TOTAL SYNTHESIS OF NORIBOGAINE

Номер: US20130165647A1
Принадлежит: DEMERX, INC.

This invention relates generally to methods for synthesizing the non-addictive alkaloid noribogaine. 5. The method of claim 1 , wherein greater than 90% of the noribogaine 1 is of the 2R claim 1 , 4S claim 1 , 5S claim 1 , 18R stereochemical configuration.6. The method of claim 1 , wherein greater than 95% of the noribogaine 1 is of the 2R claim 1 , 4S claim 1 , 5S claim 1 , 18R stereochemical configuration.7. The method of claim 1 , wherein greater than 99% of the noribogaine 1 is of the 2R claim 1 , 4S claim 1 , 5S claim 1 , 18R stereochemical configuration.8. The method of claim 1 , wherein the method further comprises the step of separating two or more stereoisomers. This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application Nos. 61/568,568, filed Dec. 8, 2011, which is incorporated herein by reference in its entirety.This invention relates generally to methods for synthesizing the non-addictive alkaloid noribogaine. This invention is further directed to intermediates used in the chiral directed synthesis of noribogaine.Noribogaine is a well known member of the ibogaine family of alkaloids and is sometimes referred to as 12-hydroxyibogaine. U.S. Pat. No. 2,813,873 claims noribogaine albeit as “12-O-demethylibogaine” while providing an incorrect structural formula for ibogaine. The structure of noribogaine has now been determined and found to combine the features of tyrptamine, tetrahydrohavaine and indolazepines. Noribogaine can be depicted by the following formula:where the configuration at the 2, 4, 5, 6 and 18 atoms are 2(R), 4(S), 5(S), 6(S) and 18(R).Noribogaine and its pharmaceutically acceptable salts have recently received significant attention as a non-addictive alkaloid useful in treating drug dependency (U.S. Pat. No. 6,348,456) and as a potent analgesic (U.S. Pat. No. 7,220,737).Conventionally, noribogaine is prepared by the O-demethylation of naturally occurring ibogaine:which is isolated from a shrub of West Africa. ...

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04-07-2013 дата публикации

METHOD OF RESTORING THE INCRETIN EFFECT

Номер: US20130172380A1
Автор: Clemens Anton H.
Принадлежит: NEURENDO PHARMA, LLC

The present invention relates to methods of treating metabolic syndrome, Type 2 diabetes mellitus, atherogenic dyslipidemia and/or obesity. The present invention also relates to methods of restoring the incretin effect, to restoring physiologic control of glucagon levels, to restoring first-phase insulin secretion, and to restoring the physiologic glucose-dependent insulin secretion. The methods of the present invention comprise administration of a selective κ-receptor antagonist, such as guanidinylated naltrindole (GNTI), or pharmaceutically acceptable derivatives thereof to a subject in need thereof. 155-. (canceled)56. A method of treating atherogenic dyslipidemia , comprising administering to a subject a therapeutically effective amount of a selective kappa-receptor antagonist , or a pharmaceutically acceptable derivative thereof.57. The method of claim 56 , wherein the selective kappa-receptor antagonist is GNTI.58. The method of claim 56 , wherein the selective kappa-receptor antagonist is administered weekly or daily.59. The method of claim 58 , wherein the selective kappa-receptor antagonist is administered weekly in an amount from about 30 ng to about 300 ng per kg of body weight weekly.60. The method of claim 58 , wherein the selective kappa-receptor antagonist is administered daily in an amount from about 8 ng to about 80 ng per kg of body weight daily.61. The method of claim 56 , wherein the selective kappa-receptor antagonist is administered sublingually claim 56 , orally claim 56 , enterally claim 56 , parenterally claim 56 , topically claim 56 , systemically or injected intravascularly claim 56 , subcutaneously claim 56 , peritoneally.62. The method of claim 56 , further comprising co-administration of an effective amount of an insulinogenic agent.63. The method of claim 62 , wherein the insulinogenic agent is an extended release composition.64. The method of claim 56 , wherein a μ-agonist is not co-administered.6577-. (canceled) This application ...

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04-07-2013 дата публикации

USE OF DERIVATIVES OF PENTAPHYRINE AS ANTIMICROBIAL AND DISINFECTANT AGENTS

Номер: US20130172396A1
Принадлежит: UNIVERSITA' DEGLI STUDI DI UDINE

The invention relates to the use of 20-(4-carboxyphenyl)-2,13-dimethyl-3,12-diethyl-[22] pentaphyrine as antibacterial agent in photodynamic treatment. This expanded porphyrin derivatized in position 4 with a carboxyphenyl group proved very active after photo-oxidation both against and . Its high antibacterial activity and its low toxicity make this pentaphyrine particularly useful as antimicrobial agent both for photodynamic therapy against bacterial infections and in the disinfection of microbiologically contaminated liquids. 1. A derivative of pentaphyrine consisting of 20-(4-carboxyphenyl)-2 ,13-dimethyl-3 ,12-diethyl-[22] pentaphyrine , its metallated derivatives and salts thereof having an antimicrobial activity by photodynamic activation.2. The derivative of pentaphyrine according to claim 1 , wherein the metals of the metallated derivatives are selected from Si claim 1 , Ge claim 1 , Lu claim 1 , Yb claim 1 , Ln claim 1 , Al claim 1 , Mn claim 1 , Fe claim 1 , Ru claim 1 , Hg claim 1 , Zn claim 1 , Cu claim 1 , Mg claim 1 , Ni claim 1 , Pd claim 1 , Pt claim 1 , Ag and Au.3. A derivative of pentaphyrine selected from the group consisting of 20-(4-carboxyphenyl)-2 claim 1 ,13-dimethyl-3 claim 1 ,12-diethyl-[22] pentaphyrine claim 1 , its metallated derivatives and salts thereof for use as photodynamically-activated antimicrobial agent In photodynamic treatment.4. A method of treatment of microbial infections by photodynamic therapy comprising the administration in a subject in a need thereof of an effective amount of at least one derivative of pentaphyrine selected from the group consisting of 20-(4-carboxyphenyl)-2 claim 1 ,13-dimethyl-3 claim 1 ,12-diethyl-[22] pentaphyrine claim 1 , its metallated derivatives and salts thereof.5. The method of treatment according to claim 4 , wherein the microbial infections are bacterial infections.6. A method of disinfection comprising the treatment with an effective amount of at least one derivative of pentaphyrine ...

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11-07-2013 дата публикации

Novel pharmaceutical intermediates and methods for preparing the same

Номер: US20130178618A1
Принадлежит: William Allen Boulanger

A pharmaceutical intermediate including a first indole moiety which is associated with an optionally carboxylated hexahydroazepino moiety, an optionally carboxylated azonane moiety, or a second, optionally carboxylated indole moiety, having an alkyl, allyl, phenylallyl, cinnamyl, alkenyl, and/or alkyl-alkenyl substituent pendant from a nitrogen atom of the same.

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18-07-2013 дата публикации

Compositions And Methods For Treating Neoplasia, Inflammatory Disease And Other Disorders

Номер: US20130184264A1
Принадлежит: Dana Farber Cancer Institute Inc

The invention features compositions and methods for treating or preventing a neoplasia. More specifically, the invention provides compositions and methods for disrupting the interaction of a BET family polypeptide comprising a bromodomain with chromatin (e.g., disrupting a bromodomain interaction with an acetyl-lysine modification present on a histone N-terminal tail).

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25-07-2013 дата публикации

PYRIDO [4,3-B] INDOLE AND PYRIDO [3,4-B] INDOLE DERIVATIVES AND METHODS OF USE

Номер: US20130190293A1
Принадлежит:

This disclosure is directed to tetracyclic pyrido[4,3-b]indole and pyrido[3,4-b]indoles. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. 9. The compound of claim 8 , wherein one or more of X claim 8 , X claim 8 , Xand Xis N.10. The compound of claim 8 , wherein Xand Xare CH and Xis CR.13. The compound of claim 12 , wherein one or more of X claim 12 , X claim 12 , Xand Xis N.14. The compound of claim 12 , wherein Xand Xare CH and Xis CR.17. The compound of claim 1 , wherein Xis N.18. The compound of claim 1 , wherein Xis CH or CR.22. A compound selected from the group consisting of compounds 2-231 claim 1 , or a pharmaceutically acceptable salt thereof.23. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.24. A method of treating a cognitive disorder claim 1 , psychotic disorder claim 1 , neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of a compound of or a salt or solvate thereof.25. A method of treating a cognitive disorder claim 1 , psychotic disorder claim 1 , neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of a compound or a salt or solvate thereof claim 1 , wherein the compound is selected from the group consisting of compounds 1-231.26. (canceled)27. A kit comprising a compound according to or a pharmaceutically acceptable salt thereof and instructions for use in the treatment of a cognitive disorder claim 1 , psychotic disorder claim 1 , neurotransmitter-mediated disorder or a neuronal disorder. This application claims ...

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25-07-2013 дата публикации

DIHYDROPYRIDOPHTHALAZINONE INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (PARP)

Номер: US20130190306A1
Автор: Chu Daniel, WANG Bing
Принадлежит: Biomarin Pharmaceutical Inc.

A compound having the structure set forth in Formula (I) and Formula (II): 3. The compound of wherein Y is an aryl group which is optionally substituted with 1 claim 1 , 2 claim 1 , or 3 R; or a single isomer claim 1 , stereoisomer claim 1 , or enantiomer claim 1 , or mixture thereof claim 1 , optionally as a salt thereof.4. The compound of wherein the aryl group is a phenyl group which is optionally substituted with 1 claim 3 , 2 claim 3 , or 3 R; or a single isomer claim 3 , stereoisomer claim 3 , or enantiomer claim 3 , or mixture thereof claim 3 , optionally as a salt thereof.5. The compound of wherein the phenyl group is substituted with 1 claim 4 , 2 claim 4 , or 3 Rselected from the group consisting of Br claim 4 , Cl claim 4 , F claim 4 , and I; or a single isomer claim 4 , stereoisomer claim 4 , or enantiomer claim 4 , or mixture thereof claim 4 , optionally as a salt thereof.6. The compound of wherein the phenyl group is substituted with 1 claim 4 , 2 claim 4 , or 3 Rselected from the group consisting of (NRR)C-Calkylene claim 4 , (NRR)carbonyl claim 4 , (NRR)carbonylalkylene claim 4 , (NRR)sulfonyl claim 4 , and (NRR)sulfonylalkylene; or a single isomer claim 4 , stereoisomer claim 4 , or enantiomer claim 4 , or mixture thereof claim 4 , optionally as a salt thereof.7. The compound of wherein Ris (NRR)C-Calkylene; or a single isomer claim 6 , stereoisomer claim 6 , or enantiomer claim 6 , or mixture thereof claim 6 , optionally as a salt thereof.8. The compound of wherein Rand Rare each independently hydrogen claim 7 , C-Calkyl claim 7 , or C-Ccycloalkyl; or a single isomer claim 7 , stereoisomer claim 7 , or enantiomer claim 7 , or mixture thereof claim 7 , optionally as a salt thereof.9. The compound of wherein (NRR) is azetidine claim 7 , pyrrolidine claim 7 , piperidine or morpholine; or a single isomer claim 7 , stereoisomer claim 7 , or enantiomer claim 7 , or mixture thereof claim 7 , optionally as a salt thereof.10. The compound of wherein Ris ...

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25-07-2013 дата публикации

FUSED HETEROARYLS AND THEIR USES

Номер: US20130190307A1
Принадлежит:

Provided are certain fused heteroaryls, compositions thereof and methods of use therefor. 3. The compound according to claim 2 , wherein said Ris chosen from H claim 2 , OH claim 2 , CN claim 2 , NO claim 2 , halo claim 2 , C-Calkyl claim 2 , C-Calkenyl claim 2 , C-Calkynyl claim 2 , aryl claim 2 , C-Ccycloalkyl claim 2 , heteroaryl claim 2 , and heterocycle claim 2 , wherein each of the alkyl claim 2 , alkenyl claim 2 , alkynyl claim 2 , aryl claim 2 , cycloalkyl claim 2 , heteroaryl claim 2 , and heterocycle is optionally substituted by one or more groups independently chosen from optionally substituted alkyl claim 2 , optionally substituted alkenyl claim 2 , optionally substituted alkynyl claim 2 , optionally substituted aryl claim 2 , optionally substituted cycloalkyl claim 2 , —OH claim 2 , oxo claim 2 , —C(O)R claim 2 , —C(O)OR claim 2 , —CN claim 2 , —C(O)NRR claim 2 , —NRR claim 2 , —NRC(O)R claim 2 , —NRS(O)R claim 2 , —NRS(O)NRR claim 2 , —NRC(O)OR claim 2 , —NRC(O)NRR claim 2 , —NO claim 2 , OR claim 2 , —S(O)R claim 2 , —S(O)NRR claim 2 , halo claim 2 , optionally substituted haloalkyl claim 2 , optionally substituted heteroaryl claim 2 , and optionally substituted heterocycle.6. The compound according to claim 1 , wherein Ais N or CH.7. The compound according to claim 1 , wherein Ais N or CH.8. The compound according to claim 1 , wherein A claim 1 , A claim 1 , and Aare CH.9. The compound according to claim 1 , wherein Aand Aare CH claim 1 , and Ais N.13. A compound selected from compounds 1 to 184 and/or at least one pharmaceutically acceptable salt.14. A pharmaceutical composition comprising at least one compound and/or at least one pharmaceutically acceptable salt thereof according to and at least one pharmaceutically acceptable carrier.15. A method of inhibiting the activity of PI3K and/or mTOR comprising contacting the enzyme with an effective amount of at least one compound and/or at least one pharmaceutically acceptable salt thereof according to ...

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25-07-2013 дата публикации

N1-PYRAZOLOSPIROKETONE ACETYL-CoA CARBOXYLASE INHIBITORS

Номер: US20130190334A1
Принадлежит: PFIZER INC.

The invention provides a compound of Formula (I) Z N N O N O A1R2 R1 R3R 3 L A2 (I) or a pharmaceutically acceptable salt of the compound, wherein R1, R2, R3,Z, A1, L and A 5 2 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal. 2. The compound of wherein Ris (C-C)alkyl claim 1 , (C-C)cycloalkyl claim 1 , or tetrahydrofuranyl; Ris hydrogen or methyl; each Ris hydrogen; and L is a direct bond or O; or a pharmaceutically acceptable salt thereof.3. The compound of wherein Ris (C-C)alkyl; Aand Aare each independently phenyl claim 2 , pyrazolyl claim 2 , imidazolyl claim 2 , triazolyl claim 2 , pyridinyl claim 2 , pyrimidinyl claim 2 , indolyl claim 2 , benzopyrazinyl claim 2 , benzoimidazolyl claim 2 , benzoimidazolonyl claim 2 , pyrrolopyridinyl claim 2 , pyrrolopyrimidinyl claim 2 , pyrazolopyridinyl claim 2 , pyrazolopyrimidinyl claim 2 , indazolyl claim 2 , indolinonyl claim 2 , naphthyridinyl claim 2 , quinolinyl claim 2 , quinolinonyl claim 2 , dihydroquinolinonyl claim 2 , oxo-dihydroquinolinonyl claim 2 , isoquinolinyl claim 2 , isoquinolinonyl claim 2 , dihydroisoquinonyl or oxo-dihydroisoquinonyl claim 2 , wherein each Aand Aare optionally substituted with one to three substituents independently selected from fluoro claim 2 , chloro claim 2 , methyl claim 2 , methoxy claim 2 , amino claim 2 , methylamino claim 2 , dimethylamino claim 2 , amido or cyano; or a pharmaceutically acceptable salt thereof.4. The compound of wherein Ris isopropyl or t-butyl; and Ris hydrogen; or a pharmaceutically acceptable salt thereof.5. The compound of wherein Ais phenyl claim 4 , pyridinyl claim 4 , indazolyl claim 4 , indolyl claim 4 , benzoimidazolyl claim 4 , pyrrolopyridinyl or pyrrolopyrimidinyl; each optionally substituted with one methyl claim 4 , methoxy claim 4 , methylamino or dimethylamino; or a pharmaceutically ...

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25-07-2013 дата публикации

FLUORESCENT ANTAGONISTS OF THE A3 ADENOSINE RECEPTOR

Номер: US20130190335A1
Принадлежит:

Disclosed are compounds of the formula (I) which are fluorescently labeled antagonists of the Aadenosine receptor: 4. The compound or salt of claim 3 , wherein p is 2 claim 3 , 3 claim 3 , 4 claim 3 , or 5.6. The compound or salt of claim 1 , wherein Ris C-Calkyl.7. The compound or salt of claim 1 , wherein R is halo claim 1 , C-Calkyl claim 1 , halo C-Calkyl claim 1 , cyano C-Calkyl claim 1 , nitro C-Calkyl claim 1 , or aryl C-Calkyl.8. The compound or salt of claim 1 , wherein the fluorophore moiety is a moiety of an Alexa Fluor dye claim 1 , a fluorescein dye claim 1 , or a cyanine dye.9. The compound or salt of claim 1 , wherein the fluorophore is moiety is a moiety of FITC claim 1 , NBD claim 1 , Dansyl claim 1 , Squaraine Rotaxane claim 1 , Bodipy FL claim 1 , Bodipy TR claim 1 , Bodipy-630/650 claim 1 , Texas Red claim 1 , Cy5 claim 1 , 1-pyrene claim 1 , EVOBlue 30 claim 1 , Alexa Fluor 532 claim 1 , Alexa Fluor 488-5 claim 1 , 6 claim 1 , or mixture thereof claim 1 , Tamra claim 1 , Tamra 5/6-X-SE claim 1 , Alexa Fluor 488 azide 5 isomer claim 1 , NIR dye 700 claim 1 , or NIR dye 800.10. The compound or salt of claim 1 , wherein m is 4-6.11. The compound or salt of claim 10 , wherein m is 6.12. The compound or salt of claim 1 , wherein n is 1-3.13. The compound or salt of claim 12 , wherein n is 3.16. A diagnostic composition comprising a compound or salt of and a pharmaceutically acceptable carrier.17. A diagnostic method for determining a treatment of a patient for a possible antagonist of the Aadenosine receptor claim 1 , the treatment comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) administering a compound or salt of ;'}(b) obtaining a biological sample from the patient;{'sub': '3', '(c) determining the level of expression of Aadenosine receptor in the biological sample;'}{'sub': '3', '(d) comparing the level of expression of the Aadenosine receptor to that of a normal population; and'}{'sub': '3', "(e) if the patient's level of ...

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25-07-2013 дата публикации

HIGH BIOAVAILABILITY OPIOID FORMULATIONS

Номер: US20130190341A1
Принадлежит: CAMURUS AB

A high bioavailability opioid depot precursor formulation comprising: 1. A high bioavailability opioid depot precursor formulation comprising:a) a controlled-release matrix;b) at least oxygen containing organic solvent;c) at least one active agent selected from buprenorphine and salts thereof.2. The high bioavailability opioid depot precursor formulation of which forms a depot composition upon administration to the body of a subject.3. The high bioavailability opioid depot precursor formulation of having a bioavailability claim 1 , measured as the area under a curve of plasma concentration against time in a human subject claim 1 , of no less than 7 hours*ng/ml per mg of administered buprenorphine.4. The high bioavailability opioid depot precursor formulation of wherein the controlled release matrix component a) comprises a lipid controlled release formulation.5. The high bioavailability opioid depot precursor formulation of wherein the lipid controlled release formulation comprises:i) least one neutral diacyl lipid and/or a tocopherol; andii) at least one phospholipid;6. The high bioavailability opioid depot precursor formulation of wherein component i) comprises at least 50% of components C16 to C18 acyl groups and having zero claim 5 , one or two unsaturations.7. The high bioavailability opioid depot precursor formulation of wherein component ii) comprises at least 50% of components C16 to C18 acyl groups and having zero claim 5 , one or two unsaturations.8. The high bioavailability opioid depot precursor formulation of wherein component b) comprises NMP.9. The high bioavailability opioid depot precursor formulation of for a once-weekly administration having a dose in the range 3 to 40 mg buprenorphine (calculated as buprenorphine free base).10. The high bioavailability opioid depot precursor formulation of for a once-fortnightly administration having a dose in the range 6 to 60 mg buprenorphine.11. The high bioavailability opioid depot precursor formulation of ...

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25-07-2013 дата публикации

COMPOSITIONS OF BUPRENORPHINE AND µ ANTAGONISTS

Номер: US20130190342A1
Принадлежит: ALKERMES PHARMA IRELAND LIMITED

The invention relates to a composition comprising buprenorphine and a μ opioid receptor antagonist, wherein the composition is characterized by an Agonist Antagonist Activity Index (AAnAI) of between about 0.7 and about 2.2; wherein; 2. The composition according to claim 1 , wherein said AAnAI is between about 0.8 and about 2.1 claim 1 , or between about 0.9 and about 2.0 claim 1 , or between about 1.0 and about 1.8 claim 1 , or between about 1.1 and about 1.6 claim 1 , or between about 1.2 and about 1.4.10. A method of treating a depressive disorder comprising administering a composition according to to a subject in need thereof.11. The method according to claim 10 , wherein said depressive disorder is selected from major depressive disorder claim 10 , chronic depression claim 10 , severe unipolar recurrent major depressive episodes claim 10 , dysthymic disorder claim 10 , depressive neurosis and neurotic depression claim 10 , melancholic depression claim 10 , atypical depression claim 10 , reactive depression claim 10 , treatment resistant depression claim 10 , seasonal affective disorder and pediatric depression; premenstrual syndrome claim 10 , premenstrual dysphoric disorder claim 10 , hot flashes claim 10 , bipolar disorders or manic depression claim 10 , bipolar I disorder claim 10 , bipolar II disorder and cyclothymic disorder.12. The method according to claim 10 , wherein said depressive disorder is major depressive disorder.13. The method according to claim 11 , wherein said major depressive disorder is resistant to two or more antidepressants.14. The method according to claim 12 , wherein the antidepressants are selected from the group comprising selective serotonin reuptake inhibitors (SSRIs) claim 12 , Serotonin-norepinephrine reuptake inhibitors (SNRIs) claim 12 , Monoamine oxidase inhibitors (MAOIs) and Tricyclic antidepressants.15. The method according to claim 10 , wherein said depressive disorder is treatment resistant depression.16. The method ...

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25-07-2013 дата публикации

NEW 2,3,4,5-TETRAHYDRO-1H-PYRIDO [4,3-B] INDOLE COMPOUNDS AND METHODS OF USE THEREOF

Номер: US20130190348A1
Принадлежит: MEDIVATION TECHNOLOGIES, INC.

This disclosure relates to new tricyclic compounds that may be used to modulate a histamine receptor in an individual. Compounds are described, including new 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole compounds. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. 136-. (canceled)38. The compound of claim 37 , or a salt thereof claim 37 , wherein if each m and q is 0 claim 37 , Rand Rare H claim 37 , and each R claim 37 , R claim 37 , R claim 37 , R claim 37 , Rand Ris H claim 37 , then Ris other than isopropyl.39. The compound of claim 37 , or a salt thereof claim 37 , wherein Ris other than isopropyl.40. The compound of claim 37 , or a salt thereof claim 37 , wherein one of X claim 37 , X claim 37 , Xand Xis N and three of X claim 37 , X claim 37 , Xand Xare CR.41. The compound of claim 37 , or a salt thereof claim 37 , wherein two of X claim 37 , X claim 37 , Xand Xis N and two of X claim 37 , X claim 37 , Xand Xare CR.42. The compound of claim 37 , or a salt thereof claim 37 , wherein Xis N.43. The compound of claim 42 , or a salt thereof claim 42 , wherein Ris substituted C-Calkyl claim 42 , or unsubstituted C-Calkyl other than isopropyl.44. The compound of claim 43 , or a salt thereof claim 43 , wherein Ris methyl.45. The compound of claim 42 , or a salt thereof claim 42 , wherein each X claim 42 , Xand Xis CH.46. The compound of claim 42 , or a salt thereof claim 42 , wherein each R claim 42 , R claim 42 , R claim 42 , R claim 42 , Rand Ris H.47. The compound of claim 42 , or a salt thereof claim 42 , wherein q is 0 and m is 1.48. The compound of claim 42 , or a salt thereof claim 42 , wherein Q is acyclic acylamino claim 42 , aminoacyl or carbonylalkoxy.49. The compound of claim 37 , or a salt thereof claim 37 , wherein Q is acyclic ...

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25-07-2013 дата публикации

BRIDGED HETEROCYCLIC COMPOUNDS AND METHODS OF USE

Номер: US20130190359A1
Принадлежит: MEDIVATION TECHNOLOGIES, INC.

This disclosure relates to new compounds that may be used to modulate a histamine receptor in an individual. Novel compounds are described, including new bridged heterocyclic [4,3-b]indole compounds. Pharmaceutical compositions are also provided. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. 4. A compound selected from the group consisting of compounds 1 to 7 , J-1 to J-30 , K-1 to K-60 and L-1 to L-61 , or a pharmaceutically acceptable salt thereof.5. A compound according to any formulae detailed herein.6. The compound of any of to wherein the compound modulates at least one of the following receptors: adrenergic receptor (e.g. , a , a , a , a , aand/or a) , serotonin receptor (e.g. , 5-HT , 5-HT , 5-HT , 5-HT , 5-HTand/or 5-HT) , dopamine receptor (e.g. , D) and histamine receptor (e.g. , H , Hand/or H).7. A method of treating a cognitive disorder , psychotic disorder , neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of compound of any of to .8. A pharmaceutical composition comprising a compound according to any of to and a pharmaceutically acceptable carrier.9. A kit comprising a compound according to any of to and instructions for use in the treatment of a cognitive disorder , psychotic disorder , neurotransmitter-mediated disorder or a neuronal disorder. This application claims priority to U.S. Provisional Patent Application No. 61/245,151, filed Sep. 23, 2009, the disclosure of which is hereby incorporated herein by reference in its entirety.Not applicable.Neurotransmitters such as histamine, serotonin, dopamine and norepinephrine mediate a large number of processes in the central nervous system (CNS) as well as outside the ...

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25-07-2013 дата публикации

Flindersia Alkaloids, Derivatives and Analogs: Compositions and Methods for Producing the Same

Номер: US20130190511A1
Принадлежит:

The present invention provides methods for chemically synthesizing naturally-occurring alkaloids, for example, alkaloids, and their analogs and derivatives. Generally, the precursor borrerine is synthesized from tryptamine in the presence of an alkylating agent, an acylating agent and a reducing agent and dimerized in the presence of an acid, for example, tetrafluoroacetic acid, hydrochloric acid or acetic acid to yield the products. Analog and derivative compounds are produced by derivatizing one or more of the tryptamine, alkylating agent or acylating agent. Also provided are the synthetic alkaloids and derivatives and analogs thereof produced by the synthetic methods. 1. A method for chemically synthesizing a naturally occurring alkaloid compound , comprising the steps of:synthesizing a precursor of the alkaloid compound; anddimerizing the synthesized precursor in the presence of an acid to yield the synthetic alkaloid compound.2. The method of claim 1 , wherein the precursor is borrerine claim 1 , said synthesizing step comprising:adding an alkylating agent to tryptamine or to a derivative thereof;adding an acylating agent in the presence of a base to form a substituted piperidinyl-N-carbamate intermediate; andadding a strong reducing agent to the intermediate to produce borrerine.3. The method of claim 2 , wherein the tryptamine is derivatized independently at one or more of C4 claim 2 , C5 claim 2 , C6 claim 2 , and C7 with hydroxy claim 2 , methoxy claim 2 , acetoxy claim 2 , benzyloxy claim 2 , sulfomethyl claim 2 , amino claim 2 , acetate claim 2 , methyl claim 2 , ethyl claim 2 , iso-propyl claim 2 , t-butyl claim 2 , trifluoromethyl claim 2 , cyano claim 2 , methylformate claim 2 , nitrate claim 2 , or halide.4. The method of claim 2 , wherein the alkylating agent is 3-methyl 2-butenal claim 2 , the acylating agent is methyl chloroformate and the strong reducing agent is lithium aluminum hydride.5. The method of claim 2 , wherein the alkylating agent is ...

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25-07-2013 дата публикации

METHODS OF TREATING PAIN AND MORPHINE TOLERANCE VIA MODULATION OF HEDGEHOG SIGNALLING PATHWAY

Номер: US20130191933A1

Described herein are methods of treating nociception by administering to a subject in need thereof a therapeutic amount of one or more compounds which modulate the Hedgehog signaling pathway. 1. A method of treating nociception comprising the step of administering to a subject in need thereof a therapeutic amount of a compound that modulates the Hedgehog signaling pathway.2. The method of claim 1 , wherein morphine is administered to the subject in combination with the compound that modulates the Hedgehog signaling pathway.3. A method of treating allodynia comprising the step of administering to a subject in need thereof a therapeutic amount of a compound that modulates the Hedgehog signaling pathway.4. The method of claim 1 , wherein morphine is administered to the subject in combination with the compound that modulates the Hedgehog signaling pathway.5. A method of treating hyperalgesia comprising the step of administering to a subject in need thereof a therapeutic amount of a compound that modulates the Hedgehog signaling pathway.6. The method of claim 1 , wherein morphine is administered to the subject in combination with the compound that modulates the Hedgehog signaling pathway.7. A method of reducing tolerance to opioid analgesics comprising the step of administering a therapeutic amount of cyclopamine to a subject in need thereof in combination with a therapeutic amount of opioid analgesic.8Drosphilia. A transgenic fly comprising either dominant-negative Patched transgene claim 1 , or constitutively active Smoothened transgene in larval nociceptive sensory neurons. This patent application claims priority to U.S. Patent Application Ser. No. 61/353,716 filed Jun. 11, 2010 which is incorporated by reference herein in its entiretyThe present invention is directed to novel methods of treating nociception, allodynia and hyperalgesia by using compounds which modulate the Hedgehog Signaling Pathway.None.None.This disclosure includes a sequence listing submitted as a ...

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01-08-2013 дата публикации

HETEROGENEOUS IMPLANTABLE DEVICES FOR DRUG DELIVERY

Номер: US20130195951A1
Принадлежит: Titan Pharmaceuticals, Inc.

The present invention comprises compositions, methods and kits for delivering drugs. The invention provides an implantable device for delivery of a pharmaceutical substance to a patient, comprising a core comprising a core polymeric material optionally containing a core pharmaceutical substance, surrounded by a first layer comprising a first-layer pharmaceutical substance and a first-layer polymeric material, optionally surrounded by one or more additional layers comprising an additional pharmaceutical substance and an additional polymeric material, where the core, first, and optional additional polymeric materials may be the same or different, and where the optional core pharmaceutical substance, first-layer pharmaceutical substance, and optional additional pharmaceutical substances are the same or different. Implantation of the device allows a controlled release of drug for an extended period of time. The device may be implanted subcutaneously in an individual in need of continuous treatment with a drug. 130-. (canceled)31. An implantable device for delivery of a pharmaceutical substance to a patient , comprising:a core comprising a core polymeric material and optionally comprising a core pharmaceutical substance; anda first layer comprising a first-layer pharmaceutical substance and a first-layer polymeric material surrounding the core; andoptionally comprising one or more additional layers comprising an additional pharmaceutical substance and an additional polymeric material, where the core polymeric material, first-layer polymeric material, and additional polymeric materials are the same or different, and where the core pharmaceutical substance (if present), first-layer pharmaceutical substance, and additional pharmaceutical substances are the same or different;wherein at least one of the core pharmaceutical substance (if present), first-layer pharmaceutical substance, and additional pharmaceutical substances is buprenorphine.32. The device of claim 31 , ...

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01-08-2013 дата публикации

PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF ACUTE DISORDERS

Номер: US20130195976A1
Принадлежит: OREXO AB

A pharmaceutical composition for the treatment of acute disorders is described. The composition comprises an essentially water-free, ordered mixture of at least one pharmaceutically active agent in the form of microparticles which are adhered to the surfaces of carrier particles which are substantially larger than the particles of the active agent or agents, and are essentially water-soluble, in combination with the bioadhesion and/or mucoadhesion promoting agent. The invention also relates to a method for preparing the composition and to the use of the composition for the treatment of acute disorders. 1(a) water-soluble carrier particles having exterior surfaces,(b) microparticles of buprenorphine or a pharmaceutically-acceptable salt thereof, wherein said microparticles are smaller than the carrier particles and are admixed with the carrier particles, and(c) particles of a bioadhesion and/or mucoadhesion promoting agent consisting essentially of a polymer that swells when brought into contact with saliva, admixed with the carrier particles,wherein the microparticles of buprenorphine or a pharmaceutically-acceptable salt thereof are presented at the exterior surfaces of the carrier particles.. A pharmaceutical composition in the form of a tablet sized for placement under a tongue, wherein the composition comprises This application is a continuation of U.S. patent application Ser. No. 13/302,694, filed on Nov. 22, 2011, which is a continuation-in-part ofco-pending U.S. patent application Ser. No. 10/851,215, filed on May 24, 2004, and entitled “Pharmaceutical Composition for the Treatment of Acute Disorders,” which is a continuation of U.S. patent application Ser. No. 09/787,888, filed on Jun. 8, 2001 (now U.S. Pat. No. 6,761,910), which is the national phase of PCT International Application No. PCT/SE99/01687, filed on Sep. 24, 1999 under 35 U.S.C. §371, which claims the priority benefit of Sweden Patent Application No. 9803240-2, filed on Sep. 24, 1998 under 35 U. ...

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01-08-2013 дата публикации

NON-ABUSABLE PHARMACEUTICAL COMPOSITION COMPRISING OPIOIDS

Номер: US20130195981A1
Автор: PETTERSSON ANDERS
Принадлежит: OREXO AB

There is provided pharmaceutical compositions for the treatment of pain comprising a pharmacologically-effective amount of an opioid analgesic, or a pharmaceutically-acceptable salt thereof, presented in particulate form upon the surfaces of carrier particles comprising a pharmacologically-effective amount of an opioid antagonist, or a pharmaceutically-acceptable salt thereof, which carrier particles are larger in size than the particles of the opioid analgesic. The compositions are also useful in prevention of opioid abuse by addicts. 1. A particulate transmucosal pharmaceutical composition comprising a pharmacologically-effective amount of an opioid analgesic, or a pharmaceutically-acceptable salt thereof, presented in particulate form upon the surfaces of carrier particles comprising a pharmacologically-effective amount of an opioid antagonist, or a pharmaceutically-acceptable salt thereof, which carrier particles are larger in size than the particles of the opioid analgesic, wherein both of said opioid analgesic and said opioid antagonist are delivered transmucosally, wherein the opioid analgesic is selected from fentanyl, alfentanil, sufentanil, remifentanil and buprenorphine, and the opioid antagonist is selected from nalmefene, methylnaltrexone, naltrexone and naloxone. This application is a continuation of U.S. application Ser. No. 12/312,995, filed Jan. 12, 2010, which is the national stage of PCT/GB2007/0004627, filed Dec. 3, 2007, which claims priority to U.S. Provisional Application Ser. No. 60/872,496, filed Dec. 4, 2006, the disclosures of which are each incorporated herein by reference in their entireties.This invention relates to new, fast acting, non-abusable pharmaceutical compositions that are useful in the treatment of pain, which compositions may be administered transmucosally and in particular sublingually.Opioids are widely used in medicine as analgesics. Indeed, it is presently accepted that, in the palliation of more severe pain, no more ...

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01-08-2013 дата публикации

NON-ABUSABLE PHARMACEUTICAL COMPOSITION COMPRISING OPIOIDS

Номер: US20130195982A1
Автор: PETTERSSON ANDERS
Принадлежит: OREXO AB

There is provided pharmaceutical compositions for the treatment of pain comprising a pharmacologically-effective amount of an opioid analgesic, or a pharmaceutically-acceptable salt thereof, presented in particulate form upon the surfaces of carrier particles comprising a pharmacologically-effective amount of an opioid antagonist, or a pharmaceutically-acceptable salt thereof, which carrier particles are larger in size than the particles of the opioid analgesic. The compositions are also useful in prevention of opioid abuse by addicts. 1. A method of treating a subject in need thereof comprising, administering a particulate transmucosal pharmaceutical composition comprising a pharmacologically-effective amount of an opioid analgesic, or a pharmaceutically-acceptable salt thereof, presented in particulate form upon the surfaces of carrier particles comprising a pharmacologically-effective amount of an opioid antagonist, or a pharmaceutically-acceptable salt thereof, which carrier particles are larger in size than the particles of the opioid analgesic, wherein both of said opioid analgesic and said opioid antagonist are delivered transmucosally, wherein the opioid analgesic is selected from fentanyl, alfentanil, sufentanil, remifentanil and buprenorphine, and the opioid antagonist is selected from nalmefene, methylnaltrexone, naltrexone and naloxone. This application is a continuation of U.S. application Ser. No. 12/312,995, filed Jan. 12, 2010, which is the national stage of PCT/GB2007/0004627, filed Dec. 3, 2007, which claims priority to U.S. Provisional Application Ser. No. 60/872,496, filed Dec. 4, 2006, the disclosures of which are each incorporated herein by reference in their entireties.This invention relates to new, fast acting, non-abusable pharmaceutical compositions that are useful in the treatment of pain, which compositions may be administered transmucosally and in particular sublingually.Opioids are widely used in medicine as analgesics. Indeed, it is ...

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01-08-2013 дата публикации

SUBSTITUTED INDOLES, ANTIVIRAL ACTIVE COMPONENT, METHOD FOR PREPARATION AND USE THEREOF

Номер: US20130196991A1
Принадлежит: ALLA CHEM, LLC

The invention relates to novel antiviral active components of the general formula 1, pharmaceutical composition, antiviral medicament, method for prophylaxis and treatment of viral diseases, particularly caused by hepatisis C viruses (HCV). In the general formula 1 58-. (canceled)9. A medicament in the form of a tablet claim 1 , a sheath or an injection placed in a pharmaceutically acceptable package for prophylaxis or treating a viral disease caused by hepatitis C virus (HCV) comprising a pharmaceutical composition of .10. (canceled)11. A method for treating a viral disease caused by hepatisis C viruses (HCV) claim 1 , comprising administering a pharmaceutical composition of in an effective amount to a subject in need thereof. The present invention relates to novel antiviral component, pharmaceutical composition, antiviral medicament, method for prophylaxis and treatment of viral diseases, particularly caused by hepatitis C virus (HCV).Virus infections may cause a great number of diseases that create a serious threat for health and existence of mankind For the last 20 years no less than 30 essentially new infectious agents have been discovered such as: HIV, viral hepatitises, acute and long-lasting diarrhea, hemorrhagic fever (Ebola, Venezuelan, Brazilian, Rift valleys) [a) Lednicky J. A., Rayner J. O. Uncommon respiratory pathogens. 2006, 12(3), 235-239. b) Hayden F. G. Respiratory viral threats. 2006, 19(2), 169-178]. In particular, special anxiety is caused by the risk of infection by so named avian influenza. [a) Liu J. P. Avian influenza—a pandemic waiting to happen? 2006, 39(1), 4-10. b) Henter J. I.; Chow C. B.; Leung C. W, Lau Y. L. Cytotoxic therapy for severe avian influenza A (H5N1) infection. 2006 367(9513), 870-873. Review]. According to statistical data 60-65% of epidemic infections have viral ethiology. Because of the complexity of interaction in triad “virus—host's organism—drug”, most of modern antiviral drugs display side effects in the course of ...

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01-08-2013 дата публикации

3-AMINOCYCLOPENTANECARBOXAMIDES AS CHEMOKINE RECEPTOR AGONISTS

Номер: US20130197008A1
Принадлежит: PFIZER INC.

There is provided a compound of Formula I(a) or I(b): 4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Ris methyl.9. A compound selected from the group consisting of:1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-ethyl-3-({(1S,4S)-5-[4-(trifluoromethyl)pyridin-2-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol;1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-ethyl-3-({(1S,4S)-5-[4-(trifluoromethyl)pyrimidin-2-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol;1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-ethyl-3-({(1S,4S)-5-[6-(trifluoromethyl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol;1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-ethyl-3-({(1S,4S)-5-[6-(trifluoromethyl)pyrazin-2-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol;1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-ethyl-3-({(1S,4S)-5-[2-(trifluoromethyl)pyrimidin-4-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol;1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-ethyl-3-({(1S,4S)-5-[6-(trifluoromethyl)pyridin-2-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol;1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-ethyl-3-({(1S,4S)-5-[2-trifluoromethyl)pyridin-4-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol;1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-ethyl-3-({(1S,4S)-5-[3-fluoro-4-trifluoromethyl)pyridin-2-yl]-2,5-diazabicylco[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol;1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-methyl-3-({(1S,4S)-5-[4-trifluoromethyl)pyridin-2-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)cyclopentyl]amino}-4-O-methyl-D-erythro-pentitol;1,5-anhydro-2,3-dideoxy-3-{[(1R,3S)-3-methyl-3-({(1S,4S)-5-[6-trifluoromethyl)pyrazin-2-yl]-2,5-diazabicyclo[2.2.1]hept-2-yl} ...

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01-08-2013 дата публикации

COMBINATION OF ACTIVE LOADED GRANULES WITH ADDITIONAL ACTIVES

Номер: US20130197021A1
Принадлежит: Euro-Celtique S.A.

The present invention relates to prolonged release pharmaceutical dosage forms, the manufacture thereof as well as their use for administration to human being 1. A method of manufacturing an oral prolonged release pharmaceutical composition comprising:a) producing granules comprising a prolonged release material and a first pharmaceutically active agent;b) optionally selecting granules of step a) of substantially uniform size;c) blending said granules of step a) or step b) with an additional pharmaceutically active agent;d) compressing said blended granules of step c) to obtain an oral prolonged release pharmaceutical composition in the form of a tablet.2. The method according to claim 1 , further comprising the step of:e) curing said tablet of step d).3. The method according to claim 1 , wherein the granules of step a) are milled prior to step b) or step c).4. The method according to claim 1 , wherein granules of a mean size in the range of about 100 μm to about 2.0 mm are selected in step b).5. The method according to claim 1 , wherein the additional active pharmaceutically active agent is substantially pure.6. The method according to claim 1 , wherein step d) takes place directly after step c) with no further intermediate steps.7. The method according to claim 2 , wherein curing takes place at a temperature in the range of about 40° C. to about 100° C. and for a time in the range of about 10 min to about 3 hours.8. The method according to claim 1 , wherein the prolonged release material is selected from the group consisting of hydrophobic or hydrophilic polymers claim 1 , protein-derived material claim 1 , gums claim 1 , waxes claim 1 , oils claim 1 , fatty acids claim 1 , fatty alcohols claim 1 , and any combination thereof.9. The method according to claim 8 , wherein the polymers are selected from the group consisting of cellulose ethers claim 8 , (meth)acrylic acid (co)polymers claim 8 , and any combination thereof.10. The method according to claim 1 , wherein ...

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08-08-2013 дата публикации

One Pot Process for Producing 6-Hydroxyl Nal-Opiate

Номер: US20130203999A1
Принадлежит: Mallinckrodt LLC

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. 1. A one pot process for preparing a 6-hydroxyl nal-opiate from a 6-keto nor-opiate , the process comprising:(a) contacting the 6-keto nor-opiate with an alkylating reagent to form a 6-keto nal-opiate, wherein the 6-keto nal-opiate is not isolated; and(b) contacting the 6-keto nal-opiate with a reducing agent and a proton acceptor to form the 6-hydroxyl nal-opiate.2. The process of claim 1 , wherein the alkylating reagent comprises an alkyl halide and the reducing agent is chosen from a hydrosulphite claim 1 , a sulfinic acid reducing agent claim 1 , a borohydride reagent claim 1 , and a catalytic hydrogen transfer reduction regent.3. The process of claim 1 , wherein a 6-β-epimer of 6-hydroxyl nal-opiate is produced in a ratio of greater than 75:25 to a 6-α-epimer.4. The process of claim 1 , wherein a 6-α-epimer of 6-hydroxyl nal-opiate is produced in a ratio of greater than 75:25 to a 6-β-epimer.6. The process of claim 5 , wherein the alkylating reagent comprises Rand a leaving group.7. The process of claim 5 , wherein the alkylating reagent comprises allyl bromide.8. The process of claim 5 , wherein Ris chosen from methyl claim 5 , allyl claim 5 , methanecyclopropyl claim 5 , and methanecyclobutyl.9. The process of claim 5 , wherein R claim 5 , R claim 5 , R claim 5 , R claim 5 , R claim 5 , R claim 5 , R claim 5 , R claim 5 , R claim 5 , R claim 5 , R claim 5 , R claim 5 , R claim 5 , and Rare hydrogen.10. The process of claim 5 , wherein Rand Rare chosen from hydrogen claim 5 , hydroxyl and OR.11. The process of claim 5 , wherein the reducing agent is chosen from a hydrosulphite claim 5 , a sulfinic acid reducing agent claim 5 , a borohydride reagent claim 5 , and a catalytic hydrogen transfer reduction regent.12. The process of claim 11 , wherein the ...

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15-08-2013 дата публикации

ABUSE-RESISTANT FORMULATIONS

Номер: US20130209560A1
Автор: HAMED Ehab, Kraling Carrie
Принадлежит: CIMA LABS INC.

This disclosure relates to a sustained-release oral dosage form suitable for twice-a-day administration comprising a matrix containing a viscosity modifier and coated granules containing hydrocodone. The dosage form can have a release profile such that 6 hours following administration, less than about 80 percent of the hydrocodone is released. In addition, the dosage form may have alcohol and/or crush resistance. 1. A sustained-release oral dosage form comprising:a matrix, wherein the matrix comprises a viscosity modifier in an amount from about 1 to about 10 percent by weight of the dosage form; andcoated granules comprising hydrocodone or a salt form thereof, wherein the core of the coated granules contains less than 5% fat/wax; a) the release of hydrocodone from the dosage form 30 minutes after simulated oral tampering is less than about 50 percent; or', 'b) the percent of hydrocodone released after 2 hours in a solution of 0.1N hydrochloric acid and 40% alcohol is no more than 10 percentage points greater than the percent of hydrocodone released in a solution of 0.1N hydrochloric acid in the absence of alcohol; or', 'c) the release of hydrocodone from the dosage form 6 hours after testing is less than about 80 percent when tested in 500 ml of 0.1N hydrochloric acid solution using USP dissolution apparatus., 'wherein2. (canceled)3. (canceled)4. The dosage form of claim 1 , wherein the hydrocodone is hydrocodone bitartrate.5. The dosage form of claim 1 , wherein the viscosity modifier is selected from the group consisting of: sodium alginate claim 1 , hydroxypropyl-methylcellulose claim 1 , hydroxyethylcellulose claim 1 , hydroxypropylcellulose claim 1 , methylcellulose claim 1 , carboxymethylcellulose claim 1 , sodium carboxymethylcellulose claim 1 , polyvinylpyrrolidone claim 1 , crosslinked polyacrylic acid claim 1 , gelatin claim 1 , pectins claim 1 , gums claim 1 , polyethylene oxides claim 1 , Konjac flour claim 1 , carrageenan claim 1 , xanthan gum claim 1 ...

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15-08-2013 дата публикации

ABUSE-RESISTANT OPIOID DOSAGE FORM

Номер: US20130209561A1
Принадлежит: Endo Pharmaceuticals Inc.

We provide a pharmaceutical dosage form including an opioid antagonist surrounded by a controlled release matrix and an opioid agonist in a surrounding matrix. 1. A pharmaceutical dosage form comprising an opioid antagonist surrounded by a controlled release matrix and an opioid agonist in a surrounding matrix.2. pharmaceutical dosage form of claim 1 , Wherein the opioid antagonist is selected from the group consisting of naloxone claim 1 , naltrexone claim 1 , nalorphine claim 1 , diprenorphine claim 1 , levallorphan claim 1 , pentazocine claim 1 , metazocine claim 1 , cyclazocine claim 1 , etazocine claim 1 , N-cyclopropylmethyl -7 claim 1 ,8-dihydro-14-hydroxynormophinone claim 1 , 21-cyclopropyl-z claim 1 ,-(1-hydroxy-1-methylethyl)-6 claim 1 ,14-endo-ethano-tetrahydrooripavine claim 1 , 21-cyclopropyl-z claim 1 ,-(1-hydroxy-1-methylethyl)-6 claim 1 ,14-endo-ethano-tetrahydrodiphenorphine and pharmaceutically acceptable addition salts thereof;and the opioid agonist is selected from the group consisting of codeine, dihydrocodeine, hydrocodone, hydromorphone, levorphanol, meperidine, buprenorphine, fentanyl, fentanyl derivatives, dipipanone, heroin, tramadol, etorphine, dihydroetorphine, butorphanol, methadone, morphine, oxycodone, oxymorphone, propoxyphene and pharmaceutically acceptable salts thereof.3. The pharmaceutical dosage form of claim 2 , wherein the opioid antagonist surrounded by a controlled release matrix is in the form of a granule.4. The pharmaceutical dosage form of claim 3 , wherein the opioid antagonist surrounded by a controlled release matrix is located in the center of the pharmaceutical dosage form.5. The pharmaceutical dosage form of claim 4 , wherein the surrounding matrix releases the opioid agonist in a patient body and the dosage form is eliminated from the patient body prior to release of the opioid antagonist surrounded by a controlled release matrix when the pharmaceutical dosage form is administered intact to the patient body.6. The ...

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15-08-2013 дата публикации

THERMOSTABLE ENZYME TECHNOLOGY FOR ALGAL BIOCONVERSION

Номер: US20130210083A1
Принадлежит:

Thermostable enzyme technology for algal bioconversion The present invention relates to thermostable enzyme systems suitable for use in the production of biofuels and bio-products from algae, and to a method of producing energy feedstocks, stocks, specifically (i) fermentable sugars and (ii) lipid fractions from algae, for the production of biofuels such as bioethanol, biobutanol and bio-oils or biodiesel, as well as other value-added biomolecules (e.g. proteins, peptides, oils, pigments, nucleic acids). 1Talaromyces emersonii. A method of producing fermentable sugars from algal biomass comprising hydrolysing the dried biomass with an enzyme composition , the enzyme composition being derived from which has been grown in the presence of carob powder , or in the presence of a mixture of tea leaves and paper plates , or in the presence of algae and isolating the sugars from the resultant hydrolysate.2. A method as claimed in wherein the algal biomass is dried prior to hydrolysis.3. A method as claimed in wherein the algal biomass does not undergo chemical or extensive mechanical pretreatment prior to hydrolysis.4. A method as claimed in wherein the carob powder claim 1 , or the tea leaves and paper plates are present in the growth medium in an amount of about 2%(w/v).5. A method as claimed in wherein the algae are present in the growth medium in an amount of about 2%(w/v).6. A method as claimed in wherein cultures grown on algae are prepared from cells grown on carob powder or tea leaves and paper plates in the growth medium in an amount of about 2%(w/v).7. A method as claimed in wherein the hydrolysis is carried out for at least 18 hours.8. A method as claimed in wherein the hydrolysis is carried out for at least 6-24 hours.9. A method as claimed in wherein a ratio of enzyme to algal biomass of 0.5mL suitably diluted unconcentrated enzyme system (i.e. fermentation broth) to 50-500 mg algal biomass (dry weight) is used.10Laminaria saccharina, SargussumPalmaria ...

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15-08-2013 дата публикации

SMALL MOLECULE DYE CONJUGATES

Номер: US20130210113A1
Принадлежит: AnaSpec Incorporated

Chemically reactive carbocyanine dyes that are intramolecularly crosslinked between the 1-position and 3′-position, their bioconjugates and their uses are described. 1,3′-crosslinked carbocyanines are superior to those of conjugates of spectrally similar 1,1′-crosslinked or non-crosslinked dyes. The invention includes derivative compounds having one or more benzo nitrogens. 210-. (canceled)12. The conjugated substance according to claim 11 , wherein RGM is an activated ester of a carboxylic acid claim 11 , an imido ester claim 11 , or a maleimide.13. The conjugated substance according to claim 11 , wherein X is O.14. The conjugated substance according to claim 11 , wherein C is a non-conjugated chain of 10 to 50 linear atoms selected from a group consisting of carbon and nitrogen that are further substituted by substituents selected from a group consisting of hydrogen claim 11 , carbonyl claim 11 , and RGM. This application is a continuation application of U.S. patent application Ser. No. 12/925,505, filed Oct. 21, 2010, which is a continuation application of U.S. patent application Ser. No. 12/287,071, filed Oct. 6, 2008, issued as U.S. Pat. No. 7,820,783, which is a divisional application of U.S. patent application Ser. No. 11/256,581, filed Oct. 21, 2005, issued as U.S. Pat. No. 7,465,810 on Dec. 16, 2008, which claims priority to U.S. Provisional patent application Ser. No. 60/621,789, filed Oct. 25, 2004, the entire disclosures of which are incorporated by reference into this document.The invention relates to fluorescent chemicals, including reactive dyes and dye-conjugates; and to their uses.Luminescent probes are valuable reagents for the analysis and separation of molecules and cells and for the detection and quantification of other materials. A very small number of luminescent molecules can be detected under optimal circumstances. Barak and Webb visualized fewer than 50 fluorescent lipid analogs associated with the LDL reception of cells using a SIT camera, ...

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15-08-2013 дата публикации

Compositions Comprising Enzyme-Cleavable Phenol-Modified Opioid Prodrugs and Inhibitors Thereof

Номер: US20130210700A1
Принадлежит: SIGNATURE THERAPEUTICS, INC.

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. 1. A composition comprising:a phenol-modified opioid prodrug comprising a phenolic opioid covalently bound to a promoiety comprising a trypsin-cleavable moiety, wherein cleavage of the trypsin-cleavable moiety by trypsin mediates release of the phenolic opioid; anda trypsin inhibitor that interacts with the trypsin that mediates enzymatically-controlled release of the phenolic opioid from the phenol-modified opioid prodrug following ingestion of the composition.2. A dose unit comprising the composition of claim 1 , whereinthe phenol-modified opioid prodrug and trypsin inhibitor are present in the dose unit in an amount effective to provide for a pre-selected pharmacokinetic (PK) profile following ingestion.3. The dose unit of claim 2 , wherein the pre-selected PK profile comprises at least one PK parameter value that is less than the PK parameter value of phenolic opioid released following ingestion of an equivalent dosage of phenol-modified opioid prodrug in the absence of inhibitor.4. The dose unit of claim 3 , wherein the PK parameter value is selected from a phenolic opioid Cmax value claim 3 , a phenolic opioid exposure value claim 3 , and a (1/phenolic opioid Tmax) value.5. The dose unit of claim 2 , wherein the dose unit provides for a pre-selected PK profile following ingestion of at least two dose units.6. The dose unit of claim 5 , wherein the pre-selected PK profile is modified relative to the PK profile following ingestion of an equivalent dosage of phenol-modified opioid prodrug in the absence of ...

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15-08-2013 дата публикации

Compositions Comprising Enzyme-Cleavable Opioid Prodrugs and Inhibitors Thereof

Номер: US20130210701A1
Принадлежит: Signature Therapeutics Inc

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.

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15-08-2013 дата публикации

STRUCTURE, SYNTHESIS, AND APPLICATIONS FOR POLY (PHENYLENE) ETHYNYLENES (PPEs)

Номер: US20130210828A1
Принадлежит:

The present disclosure provides novel poly(phenylene ethynylene) (PPE) compounds, methods for synthesizing these compounds, and materials and substances incorporating these compounds. The various PPEs show antibacterial, antiviral and antifungal activity. 2. The poly-(phenylene ethynylene) of wherein A and B=CCH claim 1 , C is not present claim 1 , X claim 1 , Y claim 1 , and Z=H and Z=O(CH)(CHN)CH.3. The poly(phenylene ethynylene) of wherein A and B=CCH claim 1 , C is not present claim 1 , X claim 1 , Y claim 1 , and Z=H and Z=O(CH)SO.4. The poly(phenylene ethynylene) of wherein A and B=CCH claim 1 , C is not present claim 1 , X and Y=H claim 1 , Z=O(CH)N(CH) claim 1 , and Z=(OCHCH)OCH.5. The poly(phenylene ethynylene) of wherein k=6.6. The poly(phenylene ethynylene) of wherein A and B=CCH claim 1 , C is not present claim 1 , X and Y=H claim 1 , Z=O(CH)N(CH) and Z=(OCHCH)OCH.7. The poly(phenylene ethynylene) of wherein A=CCHS claim 1 , B=CCH claim 1 , C is not present claim 1 , X and Y=H claim 1 , Z=O(CH)N(CH) and Z=H.8. The poly(phenylene ethynylene) of wherein A and B=CCH claim 1 , C=CH claim 1 , X=[CCH]COOCHCH claim 1 , Y=COOCHCH claim 1 , Z=O(CH)N(CH) and Z=H.9. The poly(phenylene ethynylene) of wherein A and B=CCH claim 1 , C=CH claim 1 , X=[CCH]COOCHCH claim 1 , Y=COOCHCH claim 1 , Z=O(CH)(CHN)CH and Z=H.10. The poly(phenylene ethynylene) of wherein A=CCHS claim 1 , B=CCH claim 1 , C=CH claim 1 , X=[CCH]COOCHCH claim 1 , Y=COOCHCH claim 1 , Z=O(CH)N(CH) and Z=H.11. The poly(phenylene ethynylene) of wherein k=3.12. The poly(phenylene ethynylene) of wherein the poly(phenylene ethynylene) exhibits biocidal activity.13. The poly(phenylene ethynylene) of wherein the poly(phenylene ethynylene) exhibits antiviral activity.14. The poly(phenylene ethynylene) of wherein the poly(phenylene ethynylene) exhibits antifungal activity.15. The poly(phenylene ethynylene) of functionally attached to a material or substance so that the poly(phenylene ethynylene) can interfere ...

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15-08-2013 дата публикации

Compositions Comprising Enzyme-Cleavable Prodrugs of Active Agents and Inhibitors Thereof

Номер: US20130210854A1
Принадлежит: Signature Therapeutics Inc

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.

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22-08-2013 дата публикации

NOVEL TRICYCLIC COMPOUNDS

Номер: US20130216497A1
Принадлежит:

The invention provides compounds of Formula (I) and Formula (II) 3. The compound of wherein Ris -A-D-E-G and D is an optionally substituted (C-C)alkylene claim 1 , optionally substituted (C-C)cycloalkylene claim 1 , optionally substituted bridged (C-C)cycloalkenylene claim 1 , optionally substituted (C-C)bridged heterocyclylene or optionally substituted (C-C)heterocyclylene.4. The compound of wherein D is optionally substituted (C-C)alkylene claim 3 , optionally substituted (C-C)cycloalkylene claim 3 , optionally substituted bicyclo[2.2.2]octany-1-yl claim 3 , optionally substituted 2 claim 3 ,5-diazabicyclo[2.2.1]heptane claim 3 , optionally substituted 2 claim 3 ,6-diazabicyclo[3.2.1]octane claim 3 , optionally substituted octahydropyrrolo[3 claim 3 ,4-c]pyrrole claim 3 , optionally substituted octahydropyrrolo[3 claim 3 ,2-b]pyridine claim 3 , optionally substituted 1 claim 3 ,4-diazepane claim 3 , optionally substituted cubane claim 3 , optionally substituted 1 claim 3 ,4-dioxane-spiro[4.4]nonane claim 3 , optionally substituted 2 claim 3 ,5-diazaspiro[3.5]nonane claim 3 , optionally substituted piperidine claim 3 , optionally substituted piperazine claim 3 , optionally substituted pyrrolidine claim 3 , optionally substituted tetrahydrofuran or optionally substituted tetrahydropyran.6. The compound of wherein Ris -A-D-E-G and G is hydrogen claim 1 , deuterium claim 1 , —N(R)(R) claim 1 , halogen claim 1 , —OR claim 1 , —S(O)R claim 1 , —CN claim 1 , —C(O)N(R)(R) claim 1 , —N(R)C(O)R claim 1 , —CF claim 1 , —S(O)N(R)(R) claim 1 , an optionally substituted —(C-C)alkyl claim 1 , an optionally substituted —(C-C)cycloalkyl claim 1 , an optionally substituted —(C-C)heteroaryl claim 1 , an optionally substituted —(C-C) heterocyclyl claim 1 , or an optionally substituted —(C-C)aryl;{'sup': a', 'b', 'a', 'b', 'a', 'b, 'sub': 2', '10', '1', '10, 'wherein in a moiety containing —N(R)(R), the nitrogen, Rand Rmay form a ring such that —N(R)(R) represents an optionally ...

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29-08-2013 дата публикации

PORPHYRIN TREATMENT OF NEURODEGENERATIVE DISEASES

Номер: US20130225545A1
Принадлежит:

Compositions and methods of treating a neurodegenerative disorder are disclosed herein. 2. The compound of claim 1 , wherein the compound has the formula of Formula (II) and M is a metal ion.3. The compound of claim 1 , wherein the compound is the compound of formula II and wherein M is manganese.6. The compound of claim 1 , wherein X claim 1 , X claim 1 , Xand Xare fluorine.10. The compound of claim 9 , wherein R claim 9 , R claim 9 , R claim 9 , and Rare independently a substituted or unsubstituted C-Calkyl.11. The compound of claim 9 , wherein R claim 9 , R claim 9 , R claim 9 , and Rare independently unsubstituted methyl claim 9 , unsubstituted ethyl claim 9 , or unsubstituted propyl.13. The compound of claim 12 , wherein Rand Rare independently substituted or unsubstituted C-Calkyl.14. The compound of claim 12 , wherein Rand Rare independently hydrogen claim 12 , unsubstituted methyl claim 12 , unsubstituted ethyl claim 12 , or unsubstituted propyl.15. The compound of claim 12 , wherein Xand Xare fluorine.16. The compound of claim 1 , wherein Ris —C(X) claim 1 , Ris —C(X) claim 1 , Ris —C(X)and Ris —C(X).17. The compound of claim 16 , wherein X claim 16 , X claim 16 , Xand Xare fluorine.18. A method of treating a neurodegenerative disorder comprising administering to a patient in need thereof an effective amount of a compound of .19. The method of claim 18 , wherein said neurodegenerative disorder is Parkinson's disease claim 18 , Alzheimer's disease claim 18 , Pick's disease claim 18 , Huntington's disease claim 18 , amyotrophic lateral sclerosis claim 18 , prion diseases claim 18 , dystonia claim 18 , dementia with Lewy bodies claim 18 , multiple system atrophy claim 18 , progressive supranuclear palsy claim 18 , Friedreich's Ataxia claim 18 , temporal lobe epilepsy claim 18 , stroke claim 18 , traumatic brain injury claim 18 , or a mitochondrial encephalopathy.20. The method of claim 18 , wherein said neurodegenerative disorder is Parkinson's disease. This ...

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29-08-2013 дата публикации

DIHYDROPTERIDINONES I

Номер: US20130225549A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to dihydropteridinones, their use as modulators of γ-secretase and to pharmaceutical compositions containing said compounds. In particular, the present invention relates to compounds which interfere with γ-secretase and/or its substrate and therefore modulate the formation of Aβ peptides. 4. A compound according to claim 1 , wherein{'sup': 'b', 'claim-text': {'sup': '6', 'a mono- or bicyclic heterocycle consisting, including the atoms to which ring D is attached to the core molecule, of 4 to 11 ring atoms, and wherein above mentioned heterocyclic groups, if they comprise a nitrogen atom, may optionally be substituted with Rat said nitrogen atom.'}, 'D is selected from the group Dconsisting of'}5. A compound according claim 1 , wherein{'sup': 'b', 'claim-text': {'sup': '7', '—(R)N—.'}, 'W is selected from the group Wconsisting of'}6. A compound according to claim 1 , wherein{'sup': 1', '1b, 'claim-text': {'sub': 1-8', '1-3', '1-3', '1-3', '1-3', '1-3', 'm, 'sup': 4', '5', '9', '9, 'claim-text': {'sub': 1-8', '1-3', '1-3', '1-3', '1-3', '1-3', '1-4', '3-6', '2', '1-4', '2', '1-4', '1-4', '1-4', '1-4', '2', '1-4', '1-4', '1-6, 'sup': 4', '5, 'claim-text': {'sub': 1-4', '3-6', '1-4', '2', '1-4', '1-4', '1-4', '1-4', '2', '1-4', '1-4', '1-6, 'wherein above mentioned C-alkyl-O—, C-cycloalkyl-O—, heterocyclyl-O—, (C-alkyl)N—, (C-alkyl)-C(O)—, (C-alkyl)-O—C(O)—, (C-alkyl)-HN—C(O)—, (C-alkyl)N—C(O)—, C-alkyl-O—C-alkyl- and C-alkyl- groups may optionally be substituted with 1 to 13 fluorine atoms.'}, 'wherein above mentioned C-alkyl-, carbocyclyl, carbocyclyl-C-alkyl-, C-linked heterocyclyl, heterocyclyl-C-alkyl-, aryl-C-alkyl-, heteroaryl, heteroaryl-C-alkyl- and RRN—C-alkyl- groups may optionally be substituted with 1 to 3 substituents independently selected from the group consisting of HO—, oxo, C-alkyl-O—, C-cycloalkyl-O—, heterocyclyl-O—, cyano, halogen, HN—, (C-alkyl)N—, (C-alkyl)-C(O)—, (C-alkyl)-O—C(O)—, (C-alkyl)-HN—C(O)—, (C-alkyl)N—C(O ...

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29-08-2013 дата публикации

FUSED TETRACYCLIC PYRIDO [4,3-B] INDOLE AND PYRIDO [3,4-B] INDOLE DERIVATIVES AND METHODS OF USE

Номер: US20130225558A1
Принадлежит:

This disclosure is directed to fused tetracyclic pyrido[4,3-b>]indole and pyrido[3,4-b]indole derivatives. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. 4. The compound of claim 3 , wherein Ris H or methyl.5. The compound of claim 3 , wherein each R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , Rand R claim 3 , where applicable claim 3 , is independently H claim 3 , hydroxyl claim 3 , substituted or unsubstituted C-Calkyl claim 3 , substituted or unsubstituted aryl claim 3 , substituted or unsubstituted heteroaryl claim 3 , substituted or unsubstituted heterocyclyl claim 3 , substituted or unsubstituted aralkyl claim 3 , or acylamino claim 3 , or Rand Rare taken together with the carbon to which they are attached to form a carbonyl moiety claim 3 , or Rand a vicinal R claim 3 , where applicable claim 3 , are taken together to form a bond.6. The compound of claim 3 , wherein at least one of R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , Rand Ris a group containing a cyclic moiety.7. The compound of claim 6 , wherein the group containing a cyclic moiety is selected from the group consisting of substituted or unsubstituted aryl claim 6 , substituted or unsubstituted heteroaryl claim 6 , substituted or unsubstituted cycloalkyl claim 6 , and substituted or unsubstituted heterocyclyl.8. The compound of claim 6 , wherein the group containing a cyclic moiety is a C-Calkyl claim 6 , or a C-Calkenyl claim 6 , substituted with a group selected from the group consisting of substituted or unsubstituted aryl claim 6 , substituted or unsubstituted heteroaryl claim 6 , substituted or unsubstituted cycloalkyl claim 6 , and substituted or unsubstituted ...

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29-08-2013 дата публикации

Substituted Imidazo[1,5-A]Quinoxalines As a PDE9 Inhibitor

Номер: US20130225572A1
Принадлежит:

The invention discloses quinoxaline derivatives or salts thereof having PDE9-inhibiting activity and being useful as treating agent of dysuria and the like, which are represented by the formula (I) 119-. (canceled)21. A compound according to claim 20 , in which Ais C and Ris hydrogen.22. A compound according to claim 20 , in which Ris Calkyl or Calkenyl which are optionally substituted with hydroxy claim 20 , halogen claim 20 , Calkoxy claim 20 , Chaloalkoxy having 1-9 halogen atoms claim 20 , carboxy claim 20 , Calkoxycarbonyl claim 20 , alkanoyl claim 20 , amino (wherein the amino may further be substituted with 1-2 substituents selected from Calkyl claim 20 , Calkenyl claim 20 , Calkynyl claim 20 , Chaloalkyl having 1-9 halogen atoms claim 20 , alkanoyl claim 20 , carbocyclic group and heterocyclic group) claim 20 , amido claim 20 , carbamoyl claim 20 , oxo claim 20 , carbocyclic group or heterocyclic group (wherein the carbocyclic group and heterocyclic group each may further be substituted with hydroxy claim 20 , halogen claim 20 , Calkyl claim 20 , Calkenyl claim 20 , Calkynyl claim 20 , Calkoxy claim 20 , carboxy claim 20 , Calkoxycarbonyl claim 20 , amino claim 20 , amido or carbamoyl); or saturated carbocyclic group which is optionally substituted with halogen claim 20 , hydroxy claim 20 , Calkyl claim 20 , Calkenyl claim 20 , Calkynyl claim 20 , Calkoxy (wherein the Calkyl claim 20 , Calkenyl claim 20 , Calkynyl and Calkoxy may further be substituted with halogen claim 20 , hydroxy claim 20 , Calkoxy claim 20 , Chaloalkoxy having 1-9 halogen atoms claim 20 , carboxy claim 20 , Calkoxycarbonyl claim 20 , alkanoyl claim 20 , amino claim 20 , amido claim 20 , carbamoyl claim 20 , carbocyclic group or heterocyclic group claim 20 , independently of each other) claim 20 , Chaloalkoxy having 1-9 halogen atoms claim 20 , carboxy claim 20 , Calkoxycarbonyl claim 20 , alkanoyl claim 20 , amino claim 20 , amido claim 20 , carbamoyl claim 20 , carbocyclic group or ...

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29-08-2013 дата публикации

DEXTROMETHORPHAN ANTITUSSIVE COMPOSITIONS

Номер: US20130225627A1
Принадлежит: Trinity Laboratories, Inc.

The invention provides orally administered antitussive pharmaceutical compositions comprising dextromethorphan, wherein the compositions are free of bromide, sodium and polistirex. 1. An antitussive composition , in dosage unit form , for oral administration comprising a safe and effective amount of dextromethorphan hydrochloride and one or more orally-acceptable pharmaceutical excipients , wherein the composition is essentially free of bromide , sodium and polistirex.2. The composition of wherein the composition comprises from about 1.0 mg to about 50 mg of dextromethorphan hydrochloride.3agave. The composition of wherein the composition is liquid and comprises -nectar claim 1 , wherein the pH of the composition is about 3 to about 6.5.4. The composition of wherein the composition is a solid dosage form.5. The composition of wherein the composition further comprises from about 100 mg to about 500 mg of acetaminophen.6. The composition of wherein the composition further comprises an antioxidant selected from the group consisting of quercetin claim 1 , hesperidin claim 1 , resveratrol claim 1 , myricetin and combinations thereof.7. The composition of wherein the composition further comprises from about 50 mg to about 200 mg of guaifene sin.8. The composition of wherein the composition further comprises from about 1 mg to about 5 mg of chiorpheniramine maleate.9. The composition of wherein the composition further comprises from about 2 mg to about 10 mg of phenylephrine hydrochloride.10. The composition of claim 1 , wherein the composition further comprises about 2 mg to about 10 mg of doxylamine succinate.11. The composition of claim 1 , wherein the composition is at a pH of about 3.4 to about 5.5 and comprises about 2.5 mg to about 30 mg of dextromethorphan per dose.12. A method of treating or preventing cough in a human in need thereof claim 1 , comprising orally administering to the human a safe and effective amount of the composition of . This application claims ...

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05-09-2013 дата публикации

Abuse-Resistant Oral Dosage Forms And Method Of Use Thereof

Номер: US20130230596A1
Автор: Mehta Atul M.
Принадлежит: Elite Laboratories, Inc.

An opioid-antagonist oral dosage form which does not release a therapeutically effective amount of the opioid antagonist when the oral dosage form is orally administered to a human being, but whereby a physical alteration of the oral dosage form results in a release of the therapeutically effective amount of the opioid antagonist. An embodiment of the oral dosage form includes an opioid-antagonist layer coated onto a biologically inert pellet, and a non-releasing membrane coated onto the opioid-antagonist layer. Optionally, the oral dosage form can also include an opioid agonist, such that a method of preventing the abuse of an oral dosage form of an opioid agonist is provided by forming the oral dosage form including an opioid agonist and an opioid antagonist. 1. A pellet comprising:a biologically inert pellet;an opioid-antagonist layer coated on the biologically inert pellet, wherein the opioid-antagonist layer comprises a therapeutically effective amount of an opioid antagonist; anda non-releasing membrane coated on the opioid-antagonist layer, wherein the non-releasing membrane comprises a water-retardant polymer that is a EUDRAGIT® NE 30D or NE 40D non-ionic poly(ethyl acrylate-co-methyl methacrylate), wherein the at least one water-retardant polymer constitutes about 42% to about 50% by weight of the solids content of the oral dosage form.2. The pellet of claim 1 , wherein the non-releasing membrane further comprises a lubricant.3. The pellet of claim 2 , wherein the lubricant comprises calcium stearate claim 2 , magnesium stearate claim 2 , zinc stearate claim 2 , stearic acid claim 2 , talc or a combination thereof.4. The pellet of claim 1 , wherein the opioid-antagonist layer further comprises a binder agent.5. The pellet of claim 4 , wherein the binder agent comprises a hydroxypropylmethyl cellulose claim 4 , hydroxyethyl cellulose claim 4 , hydroxypropyl cellulose claim 4 , methyl cellulose or polyvinyl pyrrolidone.6. The pellet of claim 1 , wherein the ...

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05-09-2013 дата публикации

Solid Forms of N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluorormethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihyroquinoline-3-carboxamide

Номер: US20130231368A1
Принадлежит: VERTEX PHARMACEUTICALS INCORPORATED

The present invention relates to solid state forms, for example, crystalline forms of N-(4-(7-azabicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide, pharmaceutical compositions thereof, and methods therewith. 126-. (canceled)27. A method of treating or lessening the severity of a disease in a patient , wherein said disease is selected from cystic fibrosis , asthma , smoke induced COPD , chronic bronchitis , rhinosinusitis , constipation , pancreatitis , pancreatic insufficiency , male infertility caused by congenital bilateral absence of the vas deferens (CBAVD) , mild pulmonary disease , idiopathic pancreatitis , allergic bronchopulmonary aspergillosis (ABPA) , liver disease , hereditary emphysema , hereditary hemochromatosis , coagulation-fibrinolysis deficiencies , such as protein C deficiency , Type 1 hereditary angioedema , lipid processing deficiencies , such as familial hypercholesterolemia , Type 1 chylomicronemia , abetalipoproteinemia , lysosomal storage diseases , such as I-cell disease/pseudo-Hurler , mucopolysaccharidoses , Sandhof/Tay-Sachs , Crigler-Najjar type II , polyendocrinopathy/hyperinsulemia , Diabetes mellitus , Laron dwarfism , myleoperoxidase deficiency , primary hypoparathyroidism , melanoma , glycanosis CDG type 1 , congenital hyperthyroidism , osteogenesis imperfecta , hereditary hypofibrinogenemia , ACT deficiency , Diabetes insipidus (DI) , neurophyseal DI , neprogenic DI , Charcot-Marie Tooth syndrome , Perlizaeus-Merzbacher disease , neurodegenerative diseases such as Alzheimer's disease , Parkinson's disease , amyotrophic lateral sclerosis , progressive supranuclear plasy , Pick's disease , several polyglutamine neurological disorders such as Huntington's , spinocerebullar ataxia type I , spinal and bulbar muscular atrophy , dentatorubal pallidoluysian , and myotonic dystrophy , as well as spongiform encephalopathies , such as hereditary Creutzfeldt-Jakob disease (due ...

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05-09-2013 дата публикации

SELECTIVE BROMINATION OF PERYLENE DIIMIDES AND DERIVATIVES THEREOF UNDER MILD CONDITIONS

Номер: US20130231481A1
Принадлежит: YED RESEARCH AND DEVELOPMENT CO.LTD

The present invention is directed to novel process for the preparation of regioselective perylenediimides derivatives, specifically mono and dibrominated derivatives. 2. The compound of claim 1 , wherein said metal or metal ion comprises Pd claim 1 , Pt claim 1 , Fe claim 1 , Cu claim 1 , Ag claim 1 , Rh claim 1 , Ir claim 1 , Ru or Os.3. The compound of claim 1 , wherein said metal or metal ion is coordinated to a chelating group. This application is a Divisional application from United-States application Serial No. 12/599,292 filed Jun. 22, 2010, which is a National Phase application from International Application Number PCT/IL2008/000621 filed May 6, 2008 which claims the benefit of U.S. Ser. No. 60/924,327 filed May 9, 2007, each of which is hereby incorporated by reference in its entirety.The present invention is directed to novel processes for the regioselective preparation of perylenediimides derivatives, specifically mono and dibrominated derivatives.Perylene-diimides (PDIs) are outstanding versatile organic chromophores. They demonstrate exceptional thermal and photochemical stability, strongly absorb visible light, and show high fluorescence quantum yields. PDIs have been utilized as industrial dyes, electronic materials, sensors, photovoltaics, and building blocks for light-harvesting and artificial photosynthetic systems Importantly, photophysical and redox properties of PDIs can be conveniently modified through substitution in the aromatic core at the positions 1, 6, 7, and 12 (bay region). Substitutions at bay positions and expansion of the PDI core are usually carried out starting from the halogenated derivatives, particularly brominated PDIs. These are almost exclusively synthesized through bromination of perylene dianhydride (PDA) in concentrated HSOupon heating, followed by imidation with amines. Usually this bromination procedure affords a mixture of di-, tri- and tetrabrominated PDIs. The dibromoperylene diimides contain 1,7 (major) and 1,6 ( ...

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05-09-2013 дата публикации

CRYSTAL OF 6,7-UNSATURATED-7-CARBAMOYL MORPHINAN DERIVATIVE AND METHOD FOR PRODUCING THE SAME

Номер: US20130231485A1
Принадлежит:

Stable crystalline forms of a compound represented by the formula (IA): 3. The crystal of the p-toluenesulfonic acid salt according to claim 2 , wherein the crystal has peaks in diffraction angles (2θ) of: 7.8°±0.2° claim 2 , 10.6°±0.2° claim 2 , 15.6°±0.2° claim 2 , 17.8°±0.2° and 21.5°±0.2° in an X-ray powder diffraction spectrum.4. The crystal of the p-toluenesulfonic acid salt according to claim 2 , wherein the crystal has peaks in diffraction angles (2θ) of: 7.8°±0.2° claim 2 , 10.6°±0.2° claim 2 , 15.6°±0.2° claim 2 , 17.8°±0.2° claim 2 , 18.6°±0.2° claim 2 , 20.4°±0.2° claim 2 , 21.5°±0.2° claim 2 , 21.9°±0.2° claim 2 , 23.6°±0.2° and 25.5°±0.2° in an X-ray powder diffraction spectrum.5. The crystal of the p-toluenesulfonic acid salt according to claim 2 , wherein an X-ray powder diffraction spectrum of the crystal is substantially identical with .6. A form I crystal of the p-toluenesulfonic acid salt hydrate according to claim 2 , wherein the crystal has peaks in diffraction angles (2θ) of: 12.9°±0.2° claim 2 , 17.6°±0.2° claim 2 , 22.4°±0.2° claim 2 , 25.4°±0.2° and 28.7°±0.2° in an X-ray powder diffraction spectrum.7. The form I crystal of the p-toluenesulfonic acid salt hydrate according to claim 2 , wherein the crystal has peaks in diffraction angles (2θ) of: 6.6°±0.2° claim 2 , 8.9°±0.2° claim 2 , 11.4°±0.2° claim 2 , 12.9°±0.2° claim 2 , 14.0°±0.2° claim 2 , 15.0°±0.2° claim 2 , 17.6°±0.2° claim 2 , 18.2°±0.2° claim 2 , 22.4°±0.2° claim 2 , 25.4°±0.2° and 28.7°±0.2° in an X-ray powder diffraction spectrum.8. The form I crystal of the p-toluenesulfonic acid salt hydrate according to claim 2 , wherein an X-ray powder diffraction spectrum of the crystal is substantially identical with .9. A form II crystal of the p-toluenesulfonic acid salt hydrate according to claim 2 , wherein the crystal has peaks in diffraction angles (2θ) of: 8.8°±0.2° claim 2 , 17.5°±0.2° claim 2 , 21.9°±0.2° claim 2 , 23.7°±0.2° and 26.1°±0.2° in an X-ray powder diffraction ...

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12-09-2013 дата публикации

SILICONE COATED IMPLANT

Номер: US20130236524A1
Принадлежит: AXXIA PHARMACEUTICALS, LLC

Implants for delivery of therapeutic agents such as opioids, and the manufacture and uses of such implants are provided. In particular, subcutaneous drug delivery systems having a biocompatible thermoplastic elastomeric polymer matrix, a therapeutic agent embedded homogeneously in said matrix, and a biocompatible drug impermeable cross-linked silicone polymer coating said matrix and methods of making the same are provided. 1. A subcutaneous delivery system comprising:(i) a biocompatible thermoplastic elastomer matrix,(ii) a therapeutic agent dispersed homogeneously in said matrix, and(iii) a biocompatible therapeutic agent impermeable silicone polymer coating said matrix,wherein said delivery system has a geometry such that there is an external coated wall and an internal uncoated wall forming an opening for release of said therapeutic agent, and the distance between the uncoated wall and the coated wall opposite the uncoated wall is substantially constant throughout the delivery system.2. A subcutaneous delivery system as in claim 1 , wherein said delivery system is cylindrical in shape.3. A subcutaneous delivery system as in claim 1 , wherein said matrix is a polyurethane matrix.4. A subcutaneous delivery system as in claim 3 , wherein said urethane matrix has an isocyanate as a hard segment claim 3 , and a PEG claim 3 , PPG or PTMEG glycol soft segment.5. A subcutaneous delivery system as in claim 1 , wherein said matrix is a copolyester matrix.6. A subcutaneous delivery system as in claim 5 , wherein said copolyester matrix has a polyester as a hard segment claim 5 , and a PEG claim 5 , PPG or PTMEG glycol soft segment.7. A subcutaneous delivery system as in claim 1 , wherein said matrix is a polyether block amide matrix.8. A subcutaneous delivery system as in claim 7 , wherein said polyether block amide matrix has a polyamide as a hard segment claim 7 , and a PEG claim 7 , PPG or PTMEG soft segment.9. A subcutaneous delivery system as in claim 4 , wherein the ...

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12-09-2013 дата публикации

BENZODIAZEPINE DERIVATIVES, COMPOSITIONS AND METHODS FOR TREATING COGNITIVE IMPAIRMENT

Номер: US20130237530A1
Автор: III John A., Lowe
Принадлежит: AGENEBIO, INC.

This invention relates to benzodiazepine derivatives, compositions comprising therapeutically effective amounts of those benzodiazepine derivatives and methods of using those derivatives or compositions in treating central nervous system (CNS) disorders with cognitive impairment that are responsive to agonists of α5 subunit containing GABAreceptor, e.g., age-related cognitive impairment, Mild Cognitive Impairment (MCI), dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia and cancer-therapy-related cognitive impairment. 3. The compound according to claim 1 , wherein Y is —C(R)═.4. The compound according to claim 3 , wherein Ris —H.5. The compound according to or claim 3 , wherein X and the two carbon atoms designated by α and β together form a phenyl ring claim 3 , optionally substituted with m occurrences of R.6. The compound according to or claim 3 , wherein m is an integer selected from 1-4 claim 3 , and at least one Ris —OR claim 3 , wherein R is (C1-C12)-aliphatic- substituted with 0-5 R′.7. The compound according to claim 6 , wherein R is unsubstituted (C1-C4)-aliphatic-.8. The compound according to claim 7 , wherein R is methyl.9. The compound according to or claim 7 , wherein m is an integer selected from 1-4 claim 7 , and at least one Ris (C1-C12)-aliphatic- substituted with 0-5 R′.10. The compound according to claim 9 , wherein said at least one Ris substituted with at least one —OH.11. The compound according to or claim 9 , wherein m is an integer selected from 1-3 claim 9 , and at least one Ris halogen.12. The compound according to claim 11 , wherein said at least one Ris Cl— or Br—.13. The compound according to or claim 11 , wherein Ris (C1-C12)-aliphatic-substituted with 0-5 R′.14. The compound according to claim 13 , wherein Ris (C1-C4)-aliphatic-.15. The compound according to claim 14 , wherein Ris methyl claim 14 , ethyl or isopropyl.16. The compound according to or claim 14 , wherein Ris (C1-C12)- ...

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12-09-2013 дата публикации

CDK Inhibitors

Номер: US20130237533A1
Принадлежит: G1 THERAPEUTICS, INC.

Compounds of formulae I, II or III, and pharmaceutically acceptable salts thereof, are useful as CDK inhibitors. 2. The compound of claim 1 , wherein Ris hydrogen or C-Calkyl.3. The compound of having the formula selected from the structures shown in .14. The compound of claim 1 , wherein both of X are N.15. The compound of claim 1 , wherein Ris selected from the structures of .16. The compound of claim 1 , wherein Ris -(alkylene)-heterocyclo claim 1 , -(alkylene)-NRR claim 1 , -(alkylene)-C(O)—NRR claim 1 , -(alkylene)-C(O)—O-alkyl or -(alkylene)-ORany of which may be optionally independently substituted with one or more Rgroups as allowed by valance claim 1 , and wherein two Rgroups bound to the same or adjacent atom may optionally combine to form a ring.21. The compound of claim 17 , wherein each Ris only optionally substituted by C-Calkyl claim 17 , halogen or hydroxy.22. The compound of claim 18 , wherein each Ris only optionally substituted by C-Calkyl claim 18 , halogen or hydroxy.23. The compound of claim 19 , wherein each Ris only optionally substituted by C-Calkyl claim 19 , halogen or hydroxy.24. The compound of claim 20 , wherein each Ris only optionally substituted by C-Calkyl claim 20 , halogen or hydroxy.27. The compound of claim 1 , wherein Ris not further substituted.28. The compound of claim 17 , wherein R* is alkylene claim 17 , -(alkylene)m-O-(alkylene)m- claim 17 , -(alkylene)m-C(O)-(alkylene)m- claim 17 , -(alkylene)m-S(O)2-(alkylene)m- and or -(alkylene)m-NH-(alkylene)m- wherein each m is independently 0 or 1 claim 17 , and wherein any alkylene is not further substituted.29. The compound of claim 18 , wherein R* is alkylene claim 18 , -(alkylene)m-O-(alkylene)m- claim 18 , -(alkylene)m-C(O)-(alkylene)m- claim 18 , -(alkylene)m-S(O)2-(alkylene)m- and or -(alkylene)m-NH-(alkylene)m- wherein each m is independently 0 or 1 claim 18 , and wherein any alkylene is not further substituted.30. The compound of claim 19 , wherein R* is alkylene claim 19 ...

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12-09-2013 дата публикации

CDK INHIBITORS

Номер: US20130237534A1
Принадлежит: G1 THERAPEUTICS, INC.

Compounds of formulae I, II or III, and pharmaceutically acceptable salts thereof, are useful as CDK inhibitors. 2. The compound of claim 1 , wherein Ris hydrogen or C-Calkyl.3. (canceled)4. The compound of claim 1 , wherein Ris selected from any one of the structures of .5. The compound of claim 1 , wherein Ris -(alkylene)-heterocyclo claim 1 , -(alkylene)-NRR claim 1 , -(alkylene)-C(O)—NRR claim 1 , -(alkylene)-C(O)—O-alkyl or -(alkylene)-ORany of which may be optionally independently substituted with one or more Rgroups as allowed by valance claim 1 , and wherein two Rgroups bound to the same or adjacent atom may optionally combine to form a ring.10. The compound of claim 6 , wherein each Ris only optionally substituted by C-Calkyl claim 6 , halogen or hydroxy.11. The compound of claim 7 , wherein each Ris only optionally substituted by C-Calkyl claim 7 , halogen or hydroxy.12. The compound of claim 8 , wherein each Ris only optionally substituted by C-Calkyl claim 8 , halogen or hydroxy.13. The compound of claim 9 , wherein each Ris only optionally substituted by C-Calkyl claim 9 , halogen or hydroxy.16. The compound of claim 1 , wherein Ris not further substituted.17. The compound of claim 6 , wherein R* is an alkylene claim 6 , -(alkylene)-O-(alkylene)- claim 6 , -(alkylene)-C(O)-(alkylene)- claim 6 , -(alkylene)-S(O)-(alkylene)- or -(alkylene)-NH-(alkylene)- wherein each m is independently 0 or 1 claim 6 , and wherein any alkylene is not further substituted.18. The compound of claim 7 , wherein R* is an alkylene claim 7 , -(alkylene)-O-(alkylene)- claim 7 , -(alkylene)-C(O)-(alkylene)- claim 7 , -(alkylene)-S(O)-(alkylene)- or -(alkylene)-NH-(alkylene)- wherein each m is independently 0 or 1 claim 7 , and wherein any alkylene is not further substituted.19. The compound of claim 8 , wherein R* is an alkylene claim 8 , -(alkylene)-O-(alkylene)- claim 8 , -(alkylene)-C(O)-(alkylene)- claim 8 , -(alkylene)-S(O)-(alkylene)- or -(alkylene)-NH-(alkylene)- wherein ...

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12-09-2013 дата публикации

Cdk inhibitors

Номер: US20130237544A1
Принадлежит: G1 Therapeutics Inc

Compounds of formulae I, II or III, and pharmaceutically acceptable salts thereof, are useful as CDK inhibitors.

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12-09-2013 дата публикации

Stability of Hydromorphone Hydrochloride Solutions

Номер: US20130237558A1
Принадлежит: Mallinckrodt LLC

The present invention relates generally to a sterile hydromorphone hydrochloride solution that is substantially free of buffer. 1. A pharmaceutical composition comprising a sterile aqueous solution of hydromorphone hydrochloride , wherein said composition is substantially free of buffer.2. The composition as recited in claim 1 , wherein said composition contains less than 1.0% pseudo-hydromorphone.3. The composition as recited in claim 2 , wherein said composition contains less than 0.1% pseudo -hydromorphone.4. The composition as recited in claim 1 , wherein said composition contains less than 0.2% hydromorphone N-oxide.5. The composition as recited in claim 4 , wherein said composition is substantially free of hydromorphone N-oxide.6. The composition as recited in claim 1 , wherein said composition is substantially free of dihydromorphone.7. The composition as recited in claim 1 , wherein said composition is substantially free of 6-β-tetrahydrooripavine.8. The composition as recited in claim 1 , wherein said composition is substantially free of particulates.9. The composition as recited in claim 1 , wherein said composition is suitable for intrathecal delivery.10. The composition as recited in claim 1 , wherein said composition is stable at 25° C. and 60% relative humidity for at least 3 months.11. The composition as recited in claim 1 , wherein said composition is stable at 30° C. and 65% relative humidity for at least 3 months.12. The composition as recited in claim 1 , wherein said composition is stable at 40° C. and 75% relative humidity for at least 3 months.13. The composition as recited in claim 1 , wherein said composition is not terminally sterilized.14. The composition as recited in claim 1 , having a liquid drug formulation wherein the concentration of hydromorphone hydrochloride is about 10.0 mg/mL.15. The composition as recited in claim 1 , having a liquid drug formulation wherein the concentration of hydromorphone hydrochloride is about 2.0 mg/mL.16. ...

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19-09-2013 дата публикации

Substituted Heterocyclic Compounds

Номер: US20130244999A1
Принадлежит: INCYTE CORPORATION

The present invention relates to substituted heterocyclic compounds of Formula I: 2. The compound of claim 1 , or pharmaceutically acceptable salt or N-oxide or quaternary ammonium salt thereof claim 1 , wherein the ring formed by Rand Rtogether with the N atom to which they are attached is a 5-7 membered heterocycloalkyl group substituted with 0 claim 1 , 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , or 5 R claim 1 , and wherein each of the ring-forming atoms of the 5-7 membered heterocycloalkyl group is C or N.3. The compound of claim 1 , or pharmaceutically acceptable salt or N-oxide or quaternary ammonium salt thereof claim 1 , wherein the ring formed by Rand Rtogether with the N atom to which they are attached is a pyrrolidine ring claim 1 , a piperidine ring claim 1 , or a piperazine ring claim 1 , each substituted with 0 claim 1 , 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , or 5 R.4. The compound of claim 1 , or pharmaceutically acceptable salt or N-oxide or quaternary ammonium salt thereof claim 1 , wherein:{'sup': 3', '4', '5, 'the ring formed by Rand Rtogether with the N atom to which they are attached is substituted with 0, 1, 2, or 3 R; and'}{'sup': '5', 'sub': 1-6', '1-6', '2', '1-4', '1-4', '2', '1-6', '1-6', '2', '1-4', '1-4, 'each Ris independently selected from Calkyl, Chaloalkyl, NH, NH(Calkyl), and N(Calkyl), wherein each of the Calkyl and Chaloalkyl is substituted with 0 or 1 substituent selected from NH, NH(Calkyl), and N(Calkyl).'}8. The compound of claim 1 , or pharmaceutically acceptable salt or N-oxide or quaternary ammonium salt thereof claim 1 , wherein two adjacent Rtogether with the two atoms to which they are attached form a fused aryl group substituted with 0 claim 1 , 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 claim 1 , or 5 —W—X—W—X—Y—Z.9. The compound of claim 1 , or pharmaceutically acceptable salt or N-oxide or quaternary ammonium salt thereof claim 1 , wherein two adjacent Rtogether with the two atoms to which they are attached ...

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19-09-2013 дата публикации

USE OF BINDERS FOR MANUFACTURING STORAGE STABLE FORMULATIONS

Номер: US20130245054A1
Принадлежит:

The present invention relates to storage stable prolonged release pharmaceutical dosage forms comprising oxycodone or a pharmaceutically acceptable salt thereof and naloxone or a pharmaceutically acceptable salt thereof, the manufacture thereof as well as their use for administration to human beings. 1138.-. (canceled)139. An oral prolonged release pharmaceutical composition comprising:at least one prolonged release material;oxycodone or a pharmaceutically acceptable salt thereof in an amount equivalent to 1 to 15 mg of oxycodone HCl;naloxone or a pharmaceutically acceptable salt thereof in an amount equivalent to 0.5 to 7.5 mg of naloxone HCl; anda binder selected from hydroxypropyl cellulose, co-povidone, hydroxypropylmethyl cellulose, polyvinyl pyrrolidone vinyl alcohol (PVPVA), microcrystalline cellulose, polyethylene glycols (PEGs), gelatin, starch, glycerol esters of fatty acids, and combinations thereof.140. The composition of claim 139 , wherein the binder includes hydroxypropyl cellulose.141. The composition of claim 139 , wherein the composition does not include povidone.142. The composition of claim 139 , wherein the composition comprises the binder in an amount of about 1% to about 10% by weight.143. The composition of claim 142 , wherein the composition comprises the binder in an amount of about 3% to about 4% by weight.144. The composition of claim 139 , wherein the composition comprises oxycodone or a pharmaceutically acceptable salt thereof in an amount equivalent to 1 to 9 mg of oxycodone HCl and naloxone or a pharmaceutically acceptable salt thereof in an amount equivalent to 0.5 to 4.5 mg of naloxone HCl.145. The composition of claim 139 , wherein the composition comprisesoxycodone or a pharmaceutically acceptable salt thereof in an amount equivalent to 1 mg of oxycodone HCl and naloxone or a pharmaceutically acceptable salt thereof in an amount equivalent to 0.5 mg of naloxone HCl,oxycodone or a pharmaceutically acceptable salt thereof in an ...

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26-09-2013 дата публикации

ABUSE-PROOFED ORAL DOSAGE FORM

Номер: US20130251643A1
Принадлежит:

The present invention relates to an abuse-proofed, oral dosage form with controlled opioid-release for once daily administration, characterised in that it comprises at least one opioid with potential for abuse (A), at least one synthetic or natural polymer (C), optionally delayed-release matrix auxiliary substances, physiologically acceptable auxiliary substances (B), optionally a wax (D) and optionally at least one delayed-release coating, component (C) or (D) in each case exhibiting a breaking strength of at least 500 N, preferably of at least 1000 N. 1. An abuse-proofed oral dosage form with controlled opioid release for once daily administration , comprising at least one opioid with potential for abuse (A) and/or one of the physiologically acceptable compounds thereof , polyethylene oxide having a molecular weight of 0.5 million to 15 million (C) , optionally delayed release auxiliary substances , optionally physiologically acceptable auxiliary substances (B) , optionally a wax (D) and optionally at least one delayed-release coating , said abuse-proofed oral dosage form exhibiting a breaking strength of at least 500 N.2. A dosage form according to claim 1 , wherein the opioid is at least one opioid selected from the group consisting of oxycodone claim 1 , hydromorphone claim 1 , morphine claim 1 , tramadol claim 1 , the stereoisomers thereof claim 1 , the enantiomers thereof claim 1 , the diastereomers thereof in any desired mixtures and the physiologically acceptable compounds thereof.3. The dosage form of claim 2 , wherein said physiologically acceptable compounds thereof are salts claim 2 , solvates claim 2 , esters or ethers.4. A dosage form according to claim 1 , wherein said at least one opioid is selected from the group consisting of (2R claim 1 ,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methyl-pentan-3-ol claim 1 , (1RS claim 1 ,3RS claim 1 ,6RS)-6-dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexane-1 claim 1 ,3-diol claim 1 , (1RS claim 1 ,2RS)-3-(2- ...

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26-09-2013 дата публикации

TAMPER-RESISTANT ORAL OPIOID AGONIST FORMULATIONS

Номер: US20130251789A1
Принадлежит: Purdue Pharma L.P.

Disclosed is an oral dosage form comprising: (i) an opioid agonist in releasable form and (ii) a sequestered opioid antagonist which is not released when the dosage form is administered orally intact. 161-. (canceled)62. An oral dosage form comprising:(i) an opioid agonist and(ii) multiparticulates comprising an opioid antagonist in a substantially non-releasable form, which, when administered intact, release at least 0.025 mg, but less than 0.25 mg, of the opioid antagonist at 1 hour, and, when administered after tampering, 0.25 mg or more of the opioid antagonist at 1 hour, based on an in-vitro dissolution in 900 ml of Simulated Gastric Fluid using a USP Type II (paddle) apparatus at 75 rpm at 37° C.,wherein the opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof, and the opioid agonist is coated on the surface of the multiparticulates, or the mulitiparticulates and the opioid agonist are included in the dosage form as separate pellets.63. The dosage form of claim 62 , wherein the substantially non-releasable form comprises multiparticulates of the opioid antagonist individually coated with a material which substantially prevents the release of the opioid antagonist from the multiparticulates which are administered intact.64. The dosage form of claim 62 , wherein the substantially non-releasable form comprises multiparticulates comprising the opioid antagonist dispersed in a matrix comprising a material which substantially prevents the release of the opioid antagonist from the multiparticulates which are administered intact.65. The dosage form of claim 64 , wherein the material comprises an acrylic polymer.66. The dosage form of claim 62 , wherein the substantially non-releasable form comprises multiparticulates comprising inert beads coated with the opioid antagonist and overcoated with a material which substantially prevents the release of the opioid antagonist from the multiparticulates which are administered intact.67. The dosage form ...

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