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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 44899. Отображено 100.
26-01-2012 дата публикации

Organic electronic device, compounds for same, and terminal

Номер: US20120018717A1
Принадлежит: Duksan Hi Metal Co Ltd

Disclosed are an organic electronic device and a compound thereof, and a terminal.

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26-01-2012 дата публикации

Enhancing Pilot Channel Transmission in TD-SCDMA Multicarrier Systems Using Secondary Carrier Frequencies

Номер: US20120020283A1
Принадлежит: Qualcomm Inc

Wireless communication in a multicarrier radio access network, such as a (TD-SCDMA) network, may be implemented where a user equipment (UE) maintains communication over various carrier frequencies in the multicarrier network. The UE will receive a downlink pilot channel transmitted on every subframe on a primary carrier frequency. The UE will also receive a downlink pilot channel transmitted on less than every subframe on a secondary carrier frequency The downlink pilot channel is sent in subframes on the secondary carrier frequencies using a particular period and offset to reduce or minimize interference.

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26-01-2012 дата публикации

Novel cyanopyrimidine derivative

Номер: US20120022077A1
Принадлежит: Otsuka Pharmaceutical Co Ltd

The present invention relates to a novel cyanopyrimidine compound and a pharmaceutical composition which have a safe and potent adenosine A2a receptor agonistic activity.

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02-02-2012 дата публикации

Synthesis of substituted-3-aminopyrazoles

Номер: US20120029204A1
Принадлежит: Schering Corp

The present invention discloses a process of preparing compound of formula (I): wherein A, M, and Z are as defined herein. An example of a compound of formula (I) is 3-amino-1-methyl-1H-1′H-4,4′-bispyrazole.

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16-02-2012 дата публикации

Insecticidal (1,3,5)-triazinyl phenyl hydrazones

Номер: US20120040837A1
Принадлежит: DOW AGROSCIENCES LLC

(1,3,5)-Triazinyl phenyl hydrazones are effective at controlling insects.

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22-03-2012 дата публикации

Aminopyrimidinamides As Pest Control Agents

Номер: US20120071496A1
Принадлежит: Bayer CropScience AG

The present application relates to novel aminopyrimidinamides, to processes for their preparation and to their use for controlling animal pests, especially arthropods, in particular insects.

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22-03-2012 дата публикации

Lenalidomide and Thalidomide Immunoassays

Номер: US20120071632A1
Принадлежит: Individual

Novel conjugates and immunogens derived from lenalidomide and antibodies generated by these immunogens are useful in immunoassays for the quantification and monitoring of thalidomide and lenalidomide in biological fluids.

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22-03-2012 дата публикации

Method for producing olmesartan medoxomil

Номер: US20120071665A1
Автор: Shigeo Yanagihara
Принадлежит: Daiichi Sankyo Co Ltd

A method for producing high-purity olmesartan medoxomil is provided in which a solvent containing water is used in steps of tritylation and DMDO esterification of olmesartan.

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29-03-2012 дата публикации

Methods for Synthesizing 3-(Substituted Dihydroisoindolinone-2-YL)-2, 6-Dioxopiperidine, and Intermediates Thereof

Номер: US20120077982A1

The present invention discloses methods for synthesizing 3-(substituted dihydroisoindolinone-2-yl)-2,6-dioxopiperidine and intermediates thereof, namely, the synthesis of compounds of the Formula (I), with each substitutional group defined in the patent specification. Owing to the advantages of high productivity, little influence to the environment and material accessibility, the methods of the present invention is suitable for industrial production.

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12-04-2012 дата публикации

Bicyclic Compounds and Methods of Making and Using Same

Номер: US20120088793A1
Принадлежит: Nanotherapeutics Inc

Disclosed herein are compounds that may be modulators of 5-HT receptors, and methods of making and using same.

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03-05-2012 дата публикации

Compound for an organic photoelectric device and organic photoelectric device including the same

Номер: US20120104941A1
Принадлежит: Cheil Industries Inc

A compound for an organic photoelectric device, an organic photoelectric device, and a display device, the compound being represented by the following Chemical Formula 3a, 3b, or 3c:

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14-06-2012 дата публикации

Multifunctional linkers and methods for the use thereof

Номер: US20120149653A1
Принадлежит: RGo Bioscience LLC

In accordance with the present invention, novel multifunctional compounds have been developed which have orthogonal reactive groups thereon, thereby facilitating preparation of compounds having multiple functional properties (e.g., a targeting moiety and a biologically active moiety). Such constructs are useful for a variety of applications, e.g., for the delivery of biologically compatible materials, and release thereof in active form. Therefore, in accordance with the present invention, there are provided multifunctional linkers of defined structure, as well as various derivatives thereof bearing one or more biologically active components thereon. Also provided in accordance with the present invention are methods for the preparation of such constructs, as well as various uses thereof.

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28-06-2012 дата публикации

Meptazinol carbamate prodrug salts

Номер: US20120165315A1
Принадлежит: SHIRE LLC

The present invention relates to salts of meptazinol carbamate prodrugs, and to their synthesis and use.

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05-07-2012 дата публикации

Acridine derivative and organic electroluminescence device including the same

Номер: US20120168730A1
Принадлежит: Doosan Corp

Disclosed are an acridine derivative and an organic electro-luminescence device including the same. Specifically, the disclosed acridine derivative compound has an aryl moiety or a heteroaryl moiety, linked to an acridine moiety and an amine moiety, and the disclosed organic electro-luminescence device including the acridine derivative compound requires a low operating voltage, shows high efficiency, and is enhanced in life-span.

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19-07-2012 дата публикации

Nitrogen-containing heterocyclic compound and salt thereof, and a fungicide for agricultural and horticultural use

Номер: US20120184732A1
Принадлежит: Nippon Soda Co Ltd

The present invention provides a nitrogen-containing heterocyclic compound represented by formula (I) and salt thereof, which is useful as an active ingredient of a fungicide for agricultural and horticultural use, having an assured effect and being safely usable.

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23-08-2012 дата публикации

Process for the resolution of omeprazole

Номер: US20120215003A1
Принадлежит: HETERO RESEARCH FOUNDATION

The present invention relates to process for the resolution of omeprazole. The present invention further provides a novel compound of enantiomers of omeprazole cyclic amine salt and a process for preparing it. The present invention also provides a solid of (R)- or (S)-omeprazole cyclic amine salt and a process for preparing it. The present invention also provides a process for the preparation of esomeprazole magnesium dihydrate substantially free of its trihydrate form. The present invention also provides a process for the preparation of recovery of chiral BINOL.

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06-09-2012 дата публикации

Nicotine haptens, immunoconjugates and their uses

Номер: US20120225087A1
Автор: Kim D. Janda
Принадлежит: Scripps Research Institute

The present invention provides novel nicotine hapten compounds and nicotine immunoconjugates which can be used for in vivo production of antibodies that specifically bind to nicotine. The invention also provides methods of using vaccines comprising the nicotine immunoconjugates in active or passive immunization protocols. The compositions and methods of the invention are useful for prevention and treatment of nicotine addiction.

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13-09-2012 дата публикации

Pharmaceutical, dietary supplement, and food grade salts of anatabine

Номер: US20120232115A1
Принадлежит: Rock Creek Pharmaceuticals Inc

Anatabine is obtained by reacting benzophenoneimine with 3-aminomethyl pyridine to form benzylhydrylidene-pyridin-3-yl-methyl-amine. The benzylhydrylidene-pyridin-3-yl-methyl-amine is treated with a non-nucleophilic base and a dielectrophile, such as cis-1,4-dichloro-2-butene, followed by acidification, then basification, to provide anatabine. The resulting anatabine is substantially free from contaminants and displays good stability. In an alternative embodiment, the benzylhydrylidene-pyridin-3-yl-methyl-amine may be used in the synthesis of other alkaloids such as anabasine, nornicotine, N-methylanabasine, and anabaseine.

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08-11-2012 дата публикации

Pyridinone hydroxycyclopentyl carboxamides: hiv integrase inhibitors with therapeutic applications

Номер: US20120282218A1

New chiral and achiral oxy-substituted cyclopentyl pyridinone diketocarboxamides and their derivatives and methods for their preparations are disclosed. The compounds include tautomers, regioisomers and geometric isomers. These complex carboxamides are designed as inhibitors of HIV replication through inhibition of HIV integrase. The compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents, especially other anti-HIV compounds (including other anti-HIV integrase agents), which can be used to create combination anti-HIV cocktails. Methods of treating AIDS and ARC and methods of treating or preventing infection by HIV are also described.

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08-11-2012 дата публикации

Substituted n-phenylpyrimidin-2-amine analogs as inhibitors of the axl kinase

Номер: US20120283261A1
Принадлежит: Individual

In one aspect, the invention relates to substituted N-phenylpyrimidin-2-amine analogs, derivatives thereof, and related compounds, which are useful as inhibitors of Axl kinase; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions for treating disorders associated with dysfunction of the Axl kinase. 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.

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29-11-2012 дата публикации

Material for organic electroluminescence devices and organic electroluminescence device using the material

Номер: US20120298975A1
Принадлежит: Idemitsu Kosan Co Ltd

A material for organic electroluminescence devices comprising a compound in which a heterocyclic group having nitrogen is bonded to an arylcarbazolyl group or a carbazolylalkylene group and an organic electroluminescence device comprising an anode, a cathode and an organic thin film layer comprising at least one layer and disposed between the anode and the cathode, wherein at least one layer in the organic thin film layer comprises the material for organic electroluminescence devices described above. The material can provide an organic electroluminescence device emitting bluish light with a high purity of color. The organic electroluminescence device uses the material.

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13-12-2012 дата публикации

Metal complex, and adsorbent, occlusion material and separator material made from same

Номер: US20120312164A1
Принадлежит: Kuraray Co Ltd

This invention provides a metal complex having a gas adsorption capability, a gas storing capability, and a gas separation capability. The present invention attained the above object by a metal complex comprising: a dicarboxylic acid compound (I) represented by the following General Formula (I), wherein R 1 , R 2 , R 3 , and R 4 are as defined in the specification; at least one metal ion selected from ions of a metal belonging to Group 2 and Groups 7 to 12 of the periodic table; and an organic ligand capable of bidentate binding to the metal ion, the organic ligand belonging to the D ∞h point group, having a longitudinal length of not less than 8.0 Å and less than 16.0 Å, and having 2 to 7 heteroatoms.

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13-12-2012 дата публикации

Phenyl-substituted 1,3,5-triazine compound, process for producing the same, and organic electroluminescent device containing the same as component

Номер: US20120313090A1

A phenyl-substituted 1,3,5-triazine compound represented by the general formula (1): wherein Ar 1 and Ar 2 independently represent substituted or unsubstituted phenyl, naphthyl or biphenylyl group; R 1 , R 2 and R 3 independently represent hydrogen atom or methyl group; X 1 and X 2 independently represent substituted or unsubstituted phenylene, naphthylene or pyridylene group; p and q independently represent an integer of 0 to 2; and Ar 3 and Ar 4 independently represent substituted or unsubstituted pyridyl or phenyl group. This compound is suitable for an organic electroluminescent device.

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20-12-2012 дата публикации

Condensed-cyclic compound and organic light emitting diode comprising the same

Номер: US20120319086A1
Принадлежит: Samsung Mobile Display Co Ltd

A condensed-cyclic compound and an organic light-emitting diode including the same.

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20-12-2012 дата публикации

Cytosine analogue, a method of preparation of a cytosine analogue, a dna methyltransferase 1 inhibitor, a method for dna methylation inhibition, the use of the analogue in the treatment of diseases associated with deviations from normal dna methylation

Номер: US20120322755A1
Принадлежит: INSTYTUT CHEMII BIOORGANICZNEJ PAN

This invention provides a cytosine analogue, a method of preparation of a cytosine analogue, a DNA rhethyltransferase 1 inhibitor, a method for DNA methylation inhibition, the use of the analogue in the treatment of diseases associated with deviations from normal DNA methylation. More precisely, the invention relates to various derivatives of cytosine, as well as methods of preparation of mono- and multi-1,4,5 and 6-substituted cytosines. In general, the solution relates to providing effective modulators of DNA methylation which could be used in prevention and treatment of diseases associated with DNA methylation level disorders.

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03-01-2013 дата публикации

Fluoro-substituted 2-aryl-3,5-dicyano-4-indazolyl-6-methyl-1,4-dihydropyridines and uses thereof

Номер: US20130005773A1
Принадлежит: Bayer Intellectual Property GmbH

The present invention relates to novel, fluoro-substituted 2-aryl-3,5-dicyano-4-(1H-indazol-5-yl)-6-methyl-1,4-dihydropyridine derivatives having protein tyrosine kinase inhibitory activity, to a process for the manufacture thereof and to the use thereof for the treatment of c-Met-mediated diseases or c-Met-mediated conditions, particularly Cancer and other proliferative disorders.

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31-01-2013 дата публикации

Agent for preventing or treating diseases accompanied by urinary pain

Номер: US20130030006A1
Принадлежит: Astellas Pharma Inc

[Problem] Provided is an agent for preventing or treating diseases accompanied by urinary pain. [Means for Solution] A pyridyl non-aromatic nitrogen-containing heterocyclic-1-carboxylate compound or a salt thereof was confirmed to have not only an action of increasing effective bladder capacity but also an analgesic action against bladder pain and testis pain, based on FAAH inhibitory action. Accordingly, the pyridyl non-aromatic nitrogen-containing heterocyclic-1-carboxylate compound or a salt thereof can be used for preventing or treating interstitial cystitis/bladder pain syndrome and/or chronic nonbacterial prostatitis/chronic pelvic pain syndrome.

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14-03-2013 дата публикации

RADIOLABELED COMPOUNDS AND METHODS THEREOF

Номер: US20130064770A1
Принадлежит: GE HEALTHCARE LIMITED

The present invention relates to radiodiagnostic compounds, methods of making those compounds, and methods of use thereof as imaging agents for preferably a HA serotonin 5-HT1A receptor for use in PET or SPECT, preferably PET. Compositions comprising an imaging-effective amount of radiolabeled compounds are also disclosed. The present invention also relates to non-radiolabeled compounds, methods of making those compounds, and methods of use thereof to treat various neurological and/or psychiatric disorders. 2. The compound of claim 1 , wherein the compound is radiolabeled.3. The compound of claim 1 , wherein the compound is not radiolabeled.4. The compound of claim 1 , wherein the compound comprises an F or a C atom.5. The compound of claim 1 , wherein an F or an C atom is attached directly to Ar.6. The compound of claim 1 , wherein a —OCHF group or —OCHgroup is directly attached to Ar claim 1 , wherein n is 1 to 4 and m is 2 to 8 claim 1 , respectively.7. The compound of claim 1 , wherein an F or an C atom is attached directly to Z or to a suitable group on Z.8. The compound of claim 1 , wherein an F or an C atom is attached directly to Lor Lor to a suitable group on Lor L.11. A composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a physiologically acceptable carrier or vehicle.12. A method for imaging one or more 5-HTreceptors in a subject in vivo claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, '(a) administering to the subject an imaging-effective amount of a compound of , or a pharmaceutically acceptable salt thereof; and'}{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, '(b) detecting the radioactive emission of the radiolabel on the compound of , or salt thereof, following its administration to the subject.'}13. The method of claim 12 , wherein the radioactive emission is detected using PET or SPECT.14. The method of claim 12 , wherein the radioactive emission is ...

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21-03-2013 дата публикации

TRIAZOLE COMPOUNDS THAT MODULATE HSP90 ACTIVITY

Номер: US20130072461A1
Принадлежит: Synta Pharmaceuticals Corp.

The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a composition comprising such a compound. 167-. (canceled)73. The compound of wherein R claim 72 , Rand Rare each independently —OH claim 72 , —SH claim 72 , —NHR claim 72 , —OC(O)NRR claim 72 , —SC(O)NRR claim 72 , —OC(O)R claim 72 , —SC(O)R claim 72 , —OC(O)OR claim 72 , —SC(O)OR claim 72 , —OS(O)R claim 72 , —S(O)OR claim 72 , —SS(O)R claim 72 , —OS(O)OR claim 72 , —SS(O)OR claim 72 , —OC(S)R claim 72 , —SC(S)R claim 72 , —OC(S)OR claim 72 , —SC(S)OR claim 72 , —OC(S)NRR claim 72 , —SC(S)NRR claim 72 , —OC(NR)R claim 72 , —SC(NR)R claim 72 , —OC(NR)OR claim 72 , —SC(NR)OR claim 72 , —OP(O)(OR)or —SP(O)(OR).74. A pharmaceutical composition claim 68 , comprising a pharmaceutically acceptable carrier and a compound of .75. The pharmaceutical composition of claim 74 , further comprising one or more additional therapeutic agents.76. A method of treating cancer in a mammal claim 68 , comprising administering to the mammal an effective amount of a compound of any one of .77. A method of treating cancer in a mammal claim 69 , comprising administering to the mammal an effective amount of a compound of any one of .78. A method of treating cancer in a mammal claim 70 , comprising administering to the mammal an effective amount of a compound of any one of .79. A method of treating cancer in a mammal claim 71 , comprising administering to the mammal an effective amount of a compound of any one of .80. A method of treating cancer in a mammal claim 72 , comprising administering to the mammal an effective amount of a compound of any one of .81. A ...

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21-03-2013 дата публикации

HETEROCYCLIC COMPOUNDS AND USES THEREOF IN THE TREATMENT OF SEXUAL DISORDERS

Номер: US20130072479A1
Принадлежит: ATIR Holding S.A.

Novel heterocyclic compounds, which exhibit a dopamine receptor (preferably a D4 receptor) agonistic activity, and/or a PDE5 inhibitory activity, processes of preparing same, pharmaceutical compositions containing same and uses thereof in the treatment of sexual disorders such as decreased libido, orgasm disorder and erectile dysfunction are disclosed. 2. The method of claim 1 , wherein R-Rand R-Rare selected from the group consisting of hydrogen and methyl.3. The method of claim 1 , wherein R claim 1 , Rand Rare each hydrogen.4. The method of claim 1 , wherein R-Rare each hydrogen.5. The method of claim 1 , wherein Ra is halide.6. The method of claim 1 , wherein Rb is selected from the group consisting of hydrogen and alkoxy.7. The method of claim 1 , wherein Rc is selected from the group consisting of hydrogen claim 1 , halide and alkyl.8. The method of claim 1 , wherein Rd is selected from the group consisting of hydrogen and alkyl.9. The method of claim 1 , wherein Ra-Rd are each hydrogen.11. The method of claim 1 , being for treating a condition in which activating a dopamine receptor is beneficial.12. The method of claim 11 , wherein said condition is a sexual disorder.13. The method of claim 1 , wherein said dopamine receptor is a D4 receptor claim 1 , the compound being characterized as a selective agonist of said D4 receptor. This application is a continuation of U.S. patent application Ser. No. 11/922,913 filed on Jun. 11, 2009, which is a National Phase of PCT Patent Application No. PCT/IL2007/000404 filed on Mar. 28, 2007, which claims the benefit of priority under 35 USC 119(e) of U.S. Provisional Patent Application Nos. 60/879,531 filed on Jan. 10, 2007 and 60/786,379 filed on Mar. 28, 2006. The contents of the above applications are all incorporated by reference as if fully set forth herein in their entirety.The present invention relates to the field of pharmacology and, more particularly, to heterocyclic compounds and their use in the treatment of ...

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21-03-2013 дата публикации

TRIAZOLE COMPOUNDS THAT MODULATE HSP90 ACTIVITY

Номер: US20130072489A1
Принадлежит: Synta Pharmaceuticals Corp.

The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to the use of a substituted triazole compound of the invention, or a composition comprising such a compound in the preparation of a medicament for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof. 1200-. (canceled)203. The method of or , wherein the proliferative disorder is cancer.204. The method of claim 203 , wherein the cancer is a c-kit associated cancer claim 203 , a Bcr-Abl associated cancer claim 203 , a FLT3 associated cancer claim 203 , an EGFR associated cancer claim 203 , or a non-Hodgkin's lymphoma.205. The method of claim 204 , wherein the non-Hodgkin's lymphoma is a B-cell non-Hodgkin's lymphoma.206. The method of claim 205 , wherein the B-cell non-Hodgkin's lymphoma is selected from the group consisting of Burkitt's lymphoma claim 205 , follicular lymphoma claim 205 , diffuse large B-cell lymphoma claim 205 , nodal marginal zone B-cell lymphoma claim 205 , plasma cell neoplasms claim 205 , small lymphocytic lymphoma/chronic lymphocytic leukemia claim 205 , mantle cell lymphoma claim 205 , and lymphoplamacytic lymphoma/Waldenstrom macroglobulinemia.207. The method of claim 204 , wherein the non-Hodgkin's lymphoma is a T-cell non-Hodgkin's lymphoma.208. The method of claim 207 , wherein the T-cell non-Hodgkin's lymphoma is selected from the group consisting of anaplastic large-cell lymphoma claim 207 , precursor-T-cell lymphoblastic leukemia/lymphoma claim 207 , unspecified peripheral T-cell lymphoma claim 207 , and angioimmunoblastic T-cell lymphoma. This application claims the benefit of U.S. Provisional Application No. 60/900,225, filed Feb. 8, 2007, and U.S. Provisional Application No. 60/993,709, filed Sep. 13, 2007, the entire teachings of which are incorporated herein by reference.Although tremendous advances have been made in elucidating the ...

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21-03-2013 дата публикации

FORMULATIONS CONTAINING PYRIDAZINE COMPOUNDS

Номер: US20130072496A1
Принадлежит: Northwestern University

The invention relates to chemical compounds, compositions and methods of making and using the same. In particular, the invention provides selected pyridazine compounds of the formula I wherein R1, R4, R5, R6, R7, R8, R9, R12, R13 ET R14 are independently hydrogen, hydroxyl, alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkoxy, alkenyloxy, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkoxy, aryl, aryloxy, arylalkoxy, aroyl, heteroaryl, heterocyclic, acyl, acyloxy, amino, imino, azido, thiol, thioallyl, thioalkoxy, thioaryl, nitro, cyano, halo, sulfate, sulfonyl, sulfinyl, sulfonyl, sultanate, sulfoxide, silyl, silyloxy, silylalkyl, silylthio, =0, ═S, phosphonate, ureido, carboxyl, carbonyl, carbamoyl, or carboxamide; and X is optionally substituted pyrimidinyl or pyridazinyl, an isomer, a pharmaceutically acceptable salt, or derivative thereof. The invention additional relates to compositions comprising the compounds, and methods of using the compounds and compositions for modulation of cellular pathways, for treatment or prevention of inflammatory diseases, for research, drug screening, and therapeutic applications. 126.-. (canceled)28. A method of claim 27 , wherein the dose of the compound is 0.1 to 100 mg/kg body weight of the subject.29. A method of claim 27 , wherein the dose of the compound is 0.1 to 50 mg/kg.30. A method of claim 27 , wherein the dose of the compound is 0.1 to 20 mg/kg.31. A method of claim 27 , wherein the traumatic brain injury is a closed head injury or a penetrating head injury.32. A method of claim 27 , wherein the traumatic brain injury is a closed head injury resulting from a hit to the head by a blunt object.33. A method of claim 27 , wherein the traumatic brain injury is whiplash.34. A method of claim 27 , wherein the traumatic brain injury is a penetrating head injury resulting from a bullet.35. A method of claim 27 , wherein the traumatic brain injury comprises secondary damage following an injury.36. A method of claim 35 , ...

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21-03-2013 дата публикации

Benzoimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine H4 receptor

Номер: US20130072510A1
Принадлежит: Janssen Pharmaceutica NV

Benzoimidazol-2-yl pyrimidines and pyrazines, pharmaceutical compositions and methods for Hreceptor activity modulation and for the treatment of disease states, disorders, and conditions mediated by Hreceptor activity, including allergy, asthma, autoimmune diseases, and pruritis. 1. A hydrated hemitartrate salt of a compound selected from:[5-(5-Fluoro-4-methyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(6-Fluoro-4-methyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-methyl-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Difluoro-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Cyclobutyl-5-(4,5-dimethyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Cyclobutyl-5-(4,6-dimethyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Methyl-5-(4-methyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-ethyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Cyclopropyl-5-(4,6-dimethyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4-Chloro-6-methyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[4-Ethyl-5-(5-fluoro-4-methyl-1H-benzoimidazol-2-yl)-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(4-Chloro-6-trifluoromethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine;[5-(1H-Benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine; and[5-(4,5-dimethyl-1H-benzoimidazol-2-yl)-4-propyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine. ...

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21-03-2013 дата публикации

BICYCLIC COMPOUNDS AS alpha4 beta2 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS

Номер: US20130072518A1
Принадлежит: Suven Life Science Limited

The present invention relates to novel bicyclic compounds of the formula (I), and their derivatives, prodrugs, tautomers, stereoisomers, polymorphs, solvates, hydrates, metabolites, N-oxides, pharmaceutically acceptable salts and compositions containing them. The present invention also relates to a process for the preparation of above said novel compounds, and their derivatives, prodrugs, tautomers, stereoisomers, polymorphs, solvates, hydrates, metabolites, N-oxides, pharmaceutically acceptable salts and compositions containing them. These compounds are useful in the treatment and prevention of various disorders that are related to αβnicotinic receptors. 117-. (canceled)19. The compound according to claim 18 , wherein Ris hydrogen or alkyl.20. The compound according to claim 18 , wherein Ris hydrogen claim 18 , hydroxy claim 18 , halogen claim 18 , amide claim 18 , amine claim 18 , carboxylic claim 18 , alkyl claim 18 , alkoxy or heterocyclyl.21. The compound according to claim 18 , which is selected from the group consisting of:3-(Pyridin-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane dihydrochloride;2-Methyl-3-(pyridin-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane;3-(2-Methylpyridin-3-yl-oxymethyl)-2-azabicyclo[3.1.0]hexane dihydrochloride;3-(2-Chloropyridin-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane dihydrochloride;3-(2-Chloropyridin-5-yloxymethyl)-2-azabicyclo[3.1.0]hexane dihydrochloride;3-(2-Fluoropyridin-5-yloxymethyl)-2-azabicyclo[3.1.0]hexane dihydrochloride;3-(5-Chloropyridin-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane dihydrochloride;3-(5-Bromopyridin-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane tartrate;3-(2-Fluoropyridin-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane tartrate;3-(2-Fluoropyridin-3-yloxymethyl)-2-methyl-2-azabicyclo[3.1.0]hexane tartrate;3-(2-Chloropyridin-3-yloxymethyl)-2-methyl-2-azabicyclo[3.1.0]hexane;2-Methyl-3-(2-methylpyridin-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane;2-Methyl-3-(2-methylpyridin-5-yloxymethyl)-2-azabicyclo[3.1.0]hexane;3-(2-Chloropyridin-5- ...

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21-03-2013 дата публикации

Compositions And Methods Of Synthesis Of Pyridinolypiperidine 5-HT1F Agonists

Номер: US20130072524A1
Принадлежит:

The present invention provides a novel polymorph of the hemisuccinate salt of 2,4,6-trifluoro-N-[6-(1-methyl-piperidine-4-carbonyl)-pyridin-2-yl]-benzamide (Form A) characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure. This polymorph is useful in pharmaceutical compositions, for example, for the treatment and prevention of migraine. The invention also provides a process for the synthesis of pyridinoylpiperidine compounds of Formula I in high yield and high purity. In particular, the provides a process for the preparation of 2,4,6-trifluoro-N-[6-(1-methyl-piperidine-4-carbonyl)-pyridin-2-yl]-benzamide, its hemisuccinate salt and polymorph (Form A). 1. A polymorph of the hemisuccinate salt of 2 ,4 ,6-trifluoro-N-[6-(1-methyl-piperidine-4-carbonyl)-pyridin-2-yl]-benzamide (Form A) characterized by an X-ray diffraction pattern is substantially similar to that set forth in .2. The polymorph according to claim 1 , wherein the X-ray diffraction pattern includes peaks at about 15.3 claim 1 , 16.4 claim 1 , 19.3 claim 1 , 22.1 claim 1 , 23.6 and 25.9 degrees 2θ using Cu—Kradiation.3. The polymorph according to claim 2 , wherein the X-ray diffraction includes one or more additional peaks set forth in Table 1.4. The polymorph according to claim 1 , further characterized by a Differential Scanning Calorimetry (DSC) thermogram having a single maximum value at about 199° C.5. The polymorph according to claim 1 , further characterized by having unit cell parameters at 150 Kelvin of about a=11.8 Å claim 1 , b=14.8 Å claim 1 , c=12.2 Å claim 1 , α=90° claim 1 , β=104.4 claim 1 , and γ angle=90°.6. The polymorph according to claim 1 , wherein the hemisuccinate salt of 2 claim 1 ,4 claim 1 ,6-trifluoro-N-[6-(1-methyl-piperidine-4-carbonyl)-pyridin-2-yl]-benzamide (Form A) is produced by recrystallization with ethanol.7. A pharmaceutical composition comprising the polymorph of and a pharmaceutically ...

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28-03-2013 дата публикации

Amine Substituted Methanesulfonamide Derivatives as Vanilloid Receptor Ligands

Номер: US20130079320A1
Принадлежит: GRUENENTHAL GmbH

The invention relates to amine substituted methanesulfonamide derivatives as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders. 2. The substituted compound according to claim 1 , wherein{'sup': 1', '2', '9', '10, 'sub': 2', '2, 'claim-text': [{'sup': '9', 'sub': 3', '2', '5, 'wherein Rrepresents H, CH, or CH, and'}, {'sup': '10', 'sub': 2', '3', '2', '5, 'wherein Rrepresents NH, CH, or CH,'}], 'one of residues Rand Rdenotes CH—N(R)—S(═O)—R,'}{'sup': 1', '2, 'sub': 3', '2', '2', '3', '3', '3, 'and the respective remaining residue of Rand Ris selected from the group consisting of H, F, Cl, Br, I, CH, CH—OH, CH—O—CH, CF, OH, and O—CH.'}3. The substituted compound according to claim 1 , wherein{'sup': 2', '9', '10, 'sub': 2', '2, 'claim-text': [{'sup': '9', 'sub': 3', '2', '5, 'wherein Rrepresents H, CH, or CH, and'}, {'sup': '10', 'sub': 2', '3', '2', '5, 'wherein Rrepresents NH, CH, or CH,'}], 'Rdenotes CH—N(R)—S(═O)—R,'}{'sup': '1', 'sub': 3', '2', '2', '3', '3', '3, 'and Ris selected from the group consisting of H, F, Cl, Br, I, CH, CH—OH, CH—O—CH, CF, OH, and O—CH.'}4. The substituted compound according to claim 1 , wherein{'sup': '3', 'sub': 3', '3', '3, 'Ris selected from the group consisting of H, F, Cl, CH, CF, OH and O—CH.'}5. The substituted compound according to claim 1 , whereinZ represents N and{'sup': '4a', 'Rrepresents H,'}or{'sup': '4b', 'claim-text': {'sup': '4b', 'sub': '3', 'wherein Rrepresents H or CH, and'}, 'Z represents C—R,'}{'sup': '4a', 'Rrepresents H.'}6. The substituted compound according to claim 1 , wherein{'sup': '5', 'Rrepresents H.'}7. The substituted compound according to claim 1 , whereinX represents N.8. The substituted compound according to claim 1 , wherein{'sup': '6', 'sub': '3', 'Rrepresents CF, tert.-Butyl or cyclopropyl.'}9. The substituted compound according to claim 1 , ...

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28-03-2013 дата публикации

PYRIDINE AND PYRIMIDINE DERIVATIVES AS PHOSPHODIESTERASE 10 INHIBITORS

Номер: US20130079325A1
Принадлежит:

Pyridine and pyrimidine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like. 6. The compound of wherein Y is NH claim 1 , N—CH claim 1 , NR claim 1 , or —C(═O).7. The compound of wherein Y is NH.8. The compound of wherein Y is —C(═O).9. The compound of wherein Y is —N—CH—CC—F.10. The compound of wherein Y is —CH—.11. The compound of wherein Y and Rform a 5- to 6-membered ring fused to the ring containing both said Y and R.12. The compound of wherein Xis N or C claim 1 , and each of X claim 1 , X claim 1 , and Xis C.13. The compound of wherein Xis N.14. The compound of wherein Xis C.15. The compound of wherein Z is NH claim 1 , N—Calk claim 1 , N-haloCalk claim 1 , S claim 1 , or —C═.16. The compound of wherein m is 0 or 1.17. The compound of wherein n is 0 or 1.18. The compound of wherein p is 0.19. The compound of wherein Ris selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , —OR claim 1 , Calk claim 1 , Chaloalk claim 1 , —C(═O)—O—R claim 1 , —C(═O)NRR claim 1 , —ORand —C(═O)NRR.20. The compound of wherein Ris selected from the group consisting of a saturated 4- claim 1 , 5- claim 1 , 6- claim 1 , or 7-membered monocyclic ring claim 1 , wherein each said ring contains 0 claim 1 , 1 claim 1 , 2 claim 1 , or 3 N atoms and 0 claim 1 , 1 claim 1 , or 2 O atoms claim 1 , and wherein each said ring is substituted by 0 claim 1 , 1 or 2 groups selected from F claim 1 , Cl claim 1 , Br claim 1 , Calk claim 1 , Chaloalk claim 1 , —OR claim 1 , —CN claim 1 , —C(═O)R claim 1 , —C(═O)OR claim 1 , and oxo.22. The compound of wherein Ris selected from the group consisting of a saturated claim 1 , partially-saturated or unsaturated 9- or 10-membered bicyclic ring claim 1 , ...

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28-03-2013 дата публикации

INDAZOLE-3-CARBOXAMIDES AND THEIR USE AS WNT/Beta-CATENIN SIGNALING PATHWAY INHIBITORS

Номер: US20130079329A1
Автор: Hood John, KC Sunil Kumar
Принадлежит:

Indazole-3-carboxamide compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole-3-carboxamide compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states. 2. The compound of wherein n is 0.3. The compound of wherein n is 1.4. The compound of wherein X is O.5. The compound of wherein R claim 1 , Rand Rare H.6. The compound of wherein Ris -heteroarylR.7. The compound of wherein the heteroaryl is 3-pyridyl.8. The compound of wherein the heteroaryl is 5-pyrimidinyl.9. The compound of wherein the heteroaryl is 4-pyridazinyl.10. The compound of wherein Ris one substituent and is selected from the group consisting of H and —N(R)C(═O)R.11. The compound of wherein Ris -heteroarylR.12. The compound of wherein the heteroaryl is 3-pyridyl.13. The compound of wherein the heteroaryl is 5-pyrimidinyl.14. The compound of wherein the heteroaryl is 4-pyridazinyl.15. The compound of wherein Ris one substituent and is selected from the group consisting of H claim 11 , halide claim 11 , —OCF claim 11 , —CF claim 11 , —(Calkyl)heterocyclylR claim 11 , —(Calkyl)N(R) claim 11 , —(Calkyl)N(R)SORand —N(R)C(═O)R.36. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable excipient.37. A method of treating a disorder or disease in which aberrant Wnt signaling is implicated in a patient claim 1 , the method ...

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28-03-2013 дата публикации

PHARMACEUTICALLY ACTIVE DISUBSTITUTED TRIAZINE DERIVATIVES

Номер: US20130079345A1
Принадлежит:

The present invention relates to disubstituted triazine derivatives and/or pharmaceutically acceptable salts thereof, the use of these derivatives as pharmaceutically active agents, especially for the prophylaxis and/or treatment of infectious diseases, including opportunistic diseases, immunological diseases, autoimmune diseases, cardiovascular diseases, cell proliferative diseases, inflammation, erectile dysfunction and stroke, and pharmaceutical compositions containing at least one of said disubstituted triazine derivatives and/or pharmaceutically acceptable salts thereof. Furthermore, the present invention relates to the use of said disubstituted triazine derivatives as inhibitors for a protein kinase. 6. The compound according to claim 1 , wherein the compound is selected from the group of compounds consisting of:3-[(4-(2-Methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethanesulfonamide,3-[(4-(4-Fluoro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(5-Fluoro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(6-Fluoro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(3,5-Difluoro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(4-Chloro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(5-Chloro-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(2-Methoxy-4-trifluoromethyl-phenyl)-1,3,5-triazin-2-yl)amino]benzene-methanesulfonamide,3-[(4-(2-Methoxy-5-trifluoromethyl-phenyl)-1,3,5-triazin-2-yl)amino]benzene-methanesulfonamide,3-[(4-(5-Hydroxymethyl-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzene-methanesulfonamide,3-[(4-(5-Formyl-2-methoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethane-sulfonamide,3-[(4-(2-Ethoxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethanesulfonamide,3-[(4-(2-Benzyloxyphenyl)-1,3,5-triazin-2-yl)amino]benzenemethanesulfonamide,1-(3-{[4-(2-phenoxyphenyl)-1,3,5-triazin-2-yl]amino}phenyl) ...

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28-03-2013 дата публикации

5-AMINO-3,6-DIHYDRO-1H-PYRAZIN-2-ONE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE)

Номер: US20130079349A1
Принадлежит: Janssen Pharmaceutica NV

The present invention relates to novel 5-amino-3,6-dihydro-1H-pyrazin-2-one derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid. 3. The compound according to wherein{'sup': 1', '2', '1', '2, 'Rand Rare independently selected from the group consisting of hydrogen, fluoro, cyano, and trifluoromethyl; or Rand Rtaken together with the carbon atom to which they are attached may form a cyclopropyl ring;'}{'sup': '3', 'Ris methyl;'}{'sup': '4', 'Ris methyl;'}{'sup': 1', '2', '3', '4, 'X, X, X, Xare CH;'}{'sup': 6', '6, 'L is a bond or —N(R)CO—, wherein Ris hydrogen;'}Ar is homoaryl or heteroaryl;wherein homoaryl is phenyl or phenyl substituted with one or two substituents selected from chloro and cyano;heteroaryl is selected from the group consisting of pyridyl, pyrimidyl, and pyrazyl, each optionally substituted with one or two substituents selected from the group consisting of chloro, fluoro, cyano, methyl, and methoxy; oran addition salt or a solvate thereof.4. The compound according to wherein{'sup': 1', '2, 'R, Rare hydrogen;'}{'sup': 3', '4, 'R, Rare independently methyl or ethyl;'}{'sup': 1', '3, 'Xand Xare CH or CF;'}{'sup': 2', '4, 'Xand Xare CH;'}{'sup': 6', '6, 'L is a bond or —N(R)CO— wherein Ris hydrogen;'}Ar is heteroaryl;heteroaryl is selected from the group consisting of pyridyl, pyrimidinyl and pyrazyl, each optionally substituted with chloro, cyano, methyl, methoxy ...

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28-03-2013 дата публикации

PYRIDYL DERIVATIVES AND THEIR USE AS THERAPEUTIC AGENTS

Номер: US20130079354A1
Принадлежит: Xenon Pharmaceuticals Inc.

Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): 3. The method of wherein the mammal is a human.4. The method of wherein the disease or condition is selected from the group consisting of Type II diabetes claim 3 , impaired glucose tolerance claim 3 , insulin resistance claim 3 , obesity claim 3 , fatty liver claim 3 , non-alcoholic steatohepatitis claim 3 , acne claim 3 , dyslipidemia and metabolic syndrome and any combination of these.5. The method of wherein the disease or condition is Type II diabetes.6. The method of wherein the disease or condition is obesity.7. The method of wherein the disease or condition is metabolic syndrome.8. The method of wherein the disease or condition is fatty liver.9. The method of wherein the disease or condition is non-alcoholic steatohepatitis.11. The compound of wherein:{'sup': '1', 'sub': 1', '6, 'Ris hydrogen or C-Calkyl;'}{'sup': '2', 'sub': 7', '12', '3', '12', '7', '12', '2', '12', '3', '12', '3', '12', '4', '12', '13', '19', '3', '12', '3', '12, 'Ris selected from the group consisting of C-Calkyl, C-Calkenyl, C-Chydroxyalkyl, C-Calkoxyalkyl, C-Chydroxyalkenyl, C-Ccycloalkyl, C-Ccycloalkylalkyl, C-Caralkyl, C-Cheterocyclylalkyl, and C-Cheteroarylalkyl;'}{'sup': '3', 'sub': 3', '12', '3', '12', '3', '12', '3', '12', '3', '12', '3', '12', '3', '12', '4', '12', '7', '19', '3', '12', '3', '12', '1', '12', '3', '12, 'Ris selected from the group consisting of C-Calkyl, C-Calkenyl, C-Chydroxyalkyl, C-Chydroxyalkenyl, C-Calkoxy, C-Calkoxyalkyl, C-Ccycloalkyl, C-Ccycloalkylalkyl, aryl, C-Caralkyl, C-Cheterocyclyl, C-Cheterocyclylalkyl, C-Cheteroaryl and C-Cheteroarylalkyl;'}{'sup': 4', '5', '6, 'R, Rand Rare each hydrogen; and'}{'sup': 7', '7a', '8', '8a', '9', '9a', '10', '10a, 'R, R, R, R, R, R, R, and Rare each hydrogen.'}12. A method of treating a disease or condition mediated ...

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28-03-2013 дата публикации

NOVEL PIPERIDINO-DIHYDROTHIENOPYRIMIDINE SULFOXIDES AND THEIR USE FOR TREATING COPD AND ASTHMA

Номер: US20130079359A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The invention relates to novel piperidino-dihydrothienopyrimidine sulfoxides of formula I, 2. The compound of formula I according to claim 1 , wherein R is in the para-position of Ring A claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or an enantiomer or racemate thereof.3. The compound of formula I according to claim 1 , wherein Ring A is selected from the group consisting of phenyl claim 1 , pyridinyl and pyrimidinyl claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or an enantiomer or racemate thereof.4. The compound of formula I according to claim 2 , wherein Ring A is selected from the group consisting of phenyl claim 2 , pyridinyl and pyrimidinyl claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , or an enantiomer or racemate thereof.7. The compound according to claim 1 , wherein S* is in the R-configuration.8. The compound according to claim 1 , wherein S* is in the S-configuration.9. A crystalline anhydrous compound of formula III according to claim 6 , which shows a reflex peak in the X-ray powder diffraction diagram with a d-value of 4.62 Å.10. A crystalline anhydrous compound of formula III according to claim 6 , which shows reflex peaks in the X-ray powder diffraction diagram with d-values of 4.62 Å claim 6 , 6.82 Å claim 6 , and 10.09 Å.11. A crystalline anhydrous compound of formula III according to claim 6 , which shows reflex peaks in the X-ray powder diffraction diagram with d-values of 4.62 Å claim 6 , 4.17 Å claim 6 , and 3.66 Å.12. A crystalline anhydrous compound of formula III according to claim 6 , which shows reflex peaks in the X-ray powder diffraction diagram with d-values of 4.62 Å claim 6 , 6.82 Å claim 6 , 10.09 Å claim 6 , 3.93 Å claim 6 , and 4.94 Å.13. A crystalline anhydrous compound of formula III according to claim 6 , which shows reflex peaks in the X-ray powder diffraction diagram with d-values of 4.62 Å claim 6 , 4.17 Å claim 6 , 3.66 Å claim 6 , 3.73 Å claim 6 , and 18.47 Å.14. A ...

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28-03-2013 дата публикации

NOVEL IODO PYRIMIDINE DERIVATIVES USEFUL FOR THE TREATMENT OF MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF)-IMPLICATED DISEASES AND CONDITIONS

Номер: US20130079361A1
Принадлежит:

Compounds useful for the inhibition of macrophage migration inhibitory factor (MIF) are provided herein, having the Formula (I): wherein A is selected from the group consisting of aromatic or non-aromatic rings, bicyclic rings, polycyclic rings, alkenes or alkynes; B is H, OH, OR, SR, NH2, NHR, or alkyl; R is H or alkyl, and X and Y are independently N or CH, but one of X and Y must be N. Also provided are pharmaceutical compositions comprising a Formula I compound and methods for the treatment of MIF-implicated diseases or conditions, comprising administering a safe and effective amount of a Formula I compound. 2. The compound of selected from the group set forth in Table 1.3. The compound of claim 1 , wherein X and Y are both N.4. The compound of claim 3 , wherein B is H.5. The compound of claim 1 , wherein A is halo claim 1 , B is A claim 1 , and X and Y are both N.6. The compound of claim 1 , wherein X is N claim 1 , and Y is CH.7. The compound of claim 6 , wherein B is H.8. The compound of claim 1 , wherein X is CH claim 1 , and Y is N.9. The compound of claim 8 , wherein B is H.10. The compound of claim 1 , wherein A is selected from the group consisting of indole claim 1 , quinoline claim 1 , and naphthalene.11. The compound of claim 1 , wherein the compound is 4-Iodo-6-(2-fluorophenyl)pyrimidine or 4-Iodo-6-(3-aminocarbonylphenyl)pyrimidine.13. The pharmaceutical composition of claim 12 , wherein the compound is selected from the group set forth in Table 1.15. The method of claim 14 , wherein the MIF-implicated disease is selected from the group consisting of inflammatory disease and cancer.16. The method of claim 15 , wherein the inflammatory disease is selected from the group consisting of dermatitis claim 15 , arthritis claim 15 , rheumatoid arthritis claim 15 , insulin-dependent diabetes claim 15 , proliferative vascular disease claim 15 , acute respiratory distress syndrome claim 15 , sepsis claim 15 , septic shock claim 15 , psoriasis claim 15 , asthma ...

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28-03-2013 дата публикации

CYCLOPROPANE AMIDES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES

Номер: US20130079362A1
Принадлежит: DECIPHERA PHARMACEUTICALS, LLC

Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including, but not limited to, malignant melanomas, solid tumors, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, hepatic cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, chronic myelogenous leukemia, leukemias, papillary thyroid carcinoma, non-small cell lung cancer, mesothelioma, hypereosinophilia syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, diabetic retinopathy, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, and diseases caused by PDGFR-α kinase, PDGFR-β kinase, c-KIT kinase, cFMS kinase, c-MET kinase, and oncogenic forms, aberrant fusion proteins and polymorphs of any of the foregoing kinases. 12. A compound selected from the group consisting of N-(2 ,3-difluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-N′-(4-fluorophenyl)cyclopropane-1 ,1-dicarboxamide ,N-(3-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide,N-benzyl-N′-(2,3-difluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)cyclopropane-1,1-dicarboxamide,N-benzyl-N′-(3-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)cyclopropane-1,1-dicarboxamide,N-(3-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-N′-phenylcyclopropane-1,1-dicarboxamide,N-(3-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-N′-(3-(trifluoromethyl)phenyl)cyclopropane-1,1-dicarboxamide,N-(2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide,N-(3-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)phenyl)-N′-(4-methoxyphenyl)cyclopropane-1,1-dicarboxamide,N-(3-fluoro ...

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28-03-2013 дата публикации

N-Thio-anthranilamid compounds and their use as pesticides

Номер: US20130079513A1
Принадлежит: BASF SE

N-Thio-anthranilamid compounds of formula (I) wherein A is A 1 wherein the variables and the indices are as defined per the description, processes for preparing the compounds I, pesticidal compositions comprising compounds I, use of compounds I for the control of insects, acarids or nematodes, and methods for treating, controlling, preventing or protecting animals against infestation or infection by parasites by use of compounds of formula I.

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28-03-2013 дата публикации

DIHYDROETHIDINE ANALOGUES AND USES THEREOF

Номер: US20130079522A1
Принадлежит: WASHINGTON UNIVERSITY

Tracers for imaging distribution of reactive oxygen species (ROS) are disclosed. The tracers include radiolabeled dihydroethidine (DHE) analogues. Further disclosed are uses of the compounds, including methods of imaging tissue distribution of ROS in vivo by positron emission tomography (PET). Methods of synthesizing the compounds are also disclosed. 2. A radiolabeled compound or salt thereof in accordance with claim 1 , wherein the radioisotope is a positron-emitting radioisotope.3. A radiolabeled compound or salt thereof in accordance with claim 1 , wherein Ris H.4. A radiolabeled compound or salt thereof in accordance with claim 1 , wherein the compound or salt thereof comprises an CH.5. A radiolabeled compound or salt thereof in accordance with claim 1 , wherein Ris (CH)—CHand q is 0.6. A radiolabeled compound or salt thereof in accordance with claim 5 , wherein Ris CH.8. A radiolabeled compound or salt thereof in accordance with claim 1 , wherein Ris O—R claim 1 , Ris CH.9. A radiolabeled compound or salt thereof in accordance with claim 8 , wherein Ris O—R claim 8 , wherein Ris CH.11. A radiolabeled compound or salt thereof in accordance with claim 10 , wherein n is 1.12. A radiolabeled compound or salt thereof in accordance with claim 10 , wherein m is 2.13. A radiolabeled compound or salt thereof in accordance with claim 10 , wherein n is 1 and m is 2.15. A radiolabeled compound or salt thereof in accordance with claim 13 , wherein p is 2. The disclosed subject matter was developed in part with Government support under grant RC1AG036045 from the National Institutes of Health. The Government has certain rights in the invention.This application claims priority to U.S. Provisional Application Ser. No. 61/287,115 filed on Dec. 16, 2009, which is incorporated herein by reference in its entirety.The present teachings relate to the field of free radicals in biology and medicine.Free radicals play key roles in the pathogenesis of a large number of diseases and ...

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04-04-2013 дата публикации

INHIBITORS OF CATECHOL O-METHYL TRANSFERASE AND THEIR USE IN THE TREATMENT OF PSYCHOTIC DISORDERS

Номер: US20130084346A1
Принадлежит:

The present invention relates to 4-pyridinone compounds which are inhibitors of catechol O-methyltransferase (COMT), and are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which COMT enzyme is involved. The present invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which COMT is involved. 125-. (canceled)27. The compound according to wherein Y is phenyl claim 26 , indazolyl claim 26 , benzimidazolyl claim 26 , or pyridyl claim 26 , any of which is optionally substituted with 1 to 3 groups of R.28. The compound according to wherein Y is phenyl claim 26 , said phenyl optionally substituted with 1 to 3 groups of R.29. The compound according to wherein Y is benzimidazolyl claim 26 , said benzimidazolyl optionally substituted with 1 to 3 groups of R.30. The compound according to wherein Y is pyridyl claim 26 , said pyridyl optionally substituted with 1 to 3 groups of R.31. The compound according to wherein R claim 26 , A and X are hydrogen.32. The compound according to wherein Ris Calkyl claim 26 , said alkyl and alkenyl optionally substituted with 1 to 3 groups of halo claim 26 , OH claim 26 , O—Calkyl claim 26 , NRR claim 26 , CF claim 26 , Caryl claim 26 , Cheterocyclyl claim 26 , OCaryl claim 26 , Calkenyl claim 26 , Ccycloalkyl claim 26 , Calkynyl claim 26 , —C≡C—C6-10 aryl claim 26 , C(O)NRR claim 26 , NHSOCaryl claim 26 , COOR claim 26 , C(O)R claim 26 , cyano claim 26 , said aryl and heterocyclyl optionally substituted with 1 to 3 groups of Rand A and X are hydrogen.33. The compound according to wherein Ris Calkyl claim 27 , said alkyl and alkenyl optionally substituted with 1 to 3 groups of halo claim 27 , OH claim 27 , O—Calkyl claim 27 , NRR claim 27 , CF claim 27 , Caryl claim 27 , Cheterocyclyl claim 27 , OCaryl claim 27 , Calkenyl claim 27 , Ccycloalkyl claim 27 , Calkynyl claim 27 ...

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04-04-2013 дата публикации

Bicyclic Derivatives as Modulators of Ion Channels

Номер: US20130084639A1
Принадлежит: VERTEX PHARMACEUTICALS INCORPORATED

The present invention relates to bicyclic compounds useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders. 127-. (canceled)3036-. (canceled)38. The method according to claim 28 , wherein A is phenyl.39. The method according to claim 28 , wherein z is 0-2.40. The method according to claim 28 , wherein each Ris independently selected from R claim 28 , R claim 28 , or R.41. The method according to claim 28 , wherein each Ris independently selected from a hydrogen claim 28 , halo claim 28 , OR claim 28 , a C1-C6 aliphatic claim 28 , or an optionally substituted group independently selected from C3-C8 cycloaliphatic claim 28 , C6-C10 aryl claim 28 , C3-C8 heterocyclic claim 28 , or C5-C10 heteroaryl ring; wherein said cycloaliphatic claim 28 , said aryl claim 28 , said heterocyclic claim 28 , or said heteroaryl is optionally substituted with up to 3 substituents independently selected from R claim 28 , R claim 28 , R claim 28 , or R.42. The method according to claim 41 , wherein each Ris independently selected from hydrogen claim 41 , halo claim 41 , O(C1-C6 alkyl) claim 41 , C1-C6 alkyl claim 41 , C3-C8 cycloalkyl claim 41 , or phenyl.43. The method according to claim 28 , wherein Ris hydrogen.44. The method according to claim 28 , wherein Ris hydrogen.45. The method according to claim 28 , wherein Q is selected from a bond claim 28 , or a 1l-C6 straight or branched alkylidene chain claim 28 , wherein up to two methylene units of said alkylidene is independently replaced by O claim 28 , S claim 28 , OCO claim 28 , NH claim 28 , N(C1-C4 alkyl) claim 28 , or a spirocycloalkylene group.46. The method according to claim 45 , wherein Q is —X—(X)— claim 45 , wherein:{'sub': '2', 'sup': 1', '4', '5, 'Xis a bond or C1-C6 aliphatic, optionally substituted with up to two substituents independently selected from ...

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04-04-2013 дата публикации

HETEROCYCLIC COMPOUND AND H1 RECEPTOR ANTAGONIST

Номер: US20130085127A1
Принадлежит: ASKA Pharmaceutical Co., Ltd

A heterocyclic compound useful as an antiallergic agent is provided. 3. A heterocyclic compound or a salt thereof according to claim 1 , whereinthe ring A is a benzene ring or an aromatic 5- or 6-membered heterocyclic ring;the ring B is an aliphatic 4- to 10-membered heterocyclic ring;{'sup': '1', 'sub': '1-4', 'Ris a straight chain or branched chain Calkylene group;'}{'sup': 2a', '2b, 'sub': 1-6', '1-6', '1-6', '1-6, 'Rand Rare the same or different and each are a benzene ring which may have at least one substituent selected from the group consisting of a halogen atom, a Calkyl group, a haloCalkyl group, a Calkoxy group and a haloCalkoxy group;'}{'sub': 1-4', '1-4', '1-4, 'Z is a hydroxyl group; a Calkoxy group; an amino group; or an N-substituted amino group in which the nitrogen atom has at least one substituent selected from the group consisting of a Calkyl group and a Calkyl-carbonyl group; and'}when G is CH, X is an oxygen atom and n is 1; when G is N, n is 0.4. A heterocyclic compound or a salt thereof according to claim 1 , whereinthe ring A is an aromatic heterocyclic ring containing at least one hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom;the ring B is an aliphatic 5- or 6-membered heterocyclic ring;{'sup': '1', 'sub': '1-3', 'Ris a straight chain or branched chain Calkylene group;'}{'sup': 2a', '2b, 'sub': 1-3', '1-3', '1-3', '1-3, 'Rand Rare the same or different and each are a benzene ring which may have at least one substituent selected from the group consisting of a fluorine atom, a chlorine atom, a Calkyl group, a haloCalkyl group, a Calkoxy group and a haloCalkoxy group; and'}{'sub': 1-3', '1-3', '1-3, 'Z is a hydroxyl group; a Calkoxy group; an amino group; or an N-substituted amino group in which the nitrogen atom has at least one substituent selected from the group consisting of a Calkyl group and a Calkyl-carbonyl group.'}5. A heterocyclic compound or a salt thereof according to claim 1 , ...

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04-04-2013 дата публикации

HETEROCYCLIC COMPOUNDS AND THEIR USES

Номер: US20130085131A1
Принадлежит: Amgen Inc.

Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with pi 110δ activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer. 2. A method of treating rheumatoid arthritis claim 1 , ankylosing spondylitis claim 1 , osteoarthritis claim 1 , psoriatic arthritis claim 1 , psoriasis claim 1 , inflammatory diseases and autoimmune diseases claim 1 , inflammatory bowel disorders claim 1 , inflammatory eye disorders claim 1 , inflammatory or unstable bladder disorders claim 1 , skin complaints with inflammatory components claim 1 , chronic inflammatory conditions claim 1 , autoimmune diseases claim 1 , systemic lupus erythematosis (SLE) claim 1 , myestenia gravis claim 1 , rheumatoid arthritis claim 1 , acute disseminated encephalomyelitis claim 1 , idiopathic thrombocytopenic purpura claim 1 , multiples sclerosis claim 1 , Sjoegren's syndrome and autoimmune hemolytic anemia claim 1 , allergic conditions and hypersensitivity claim 1 , ...

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04-04-2013 дата публикации

NOVEL BENZAMIDE DERIVATIVES

Номер: US20130085160A1
Принадлежит:

The present invention provides a novel benzamide derivative or a pharmaceutically acceptable salt thereof, a method for preparing the same, and a 5-HTreceptor agonist containing the same as an active ingredient. Benzamide derivatives of the present invention have a superior affinity for 5-HTreceptors, a capability to reduce a gastric emptying time and a low toxicity, and consequently are therapeutically effective for the treatment of a variety of diseases associated with -HTreceptors. 2. The compound of formula 1 of claim 1 , wherein m represents an integer of 1 to 5; and Q represents a heteroaromatic ring or phenyl wherein the heteroaromatic ring or phenyl is independently substituted by 0 claim 1 , 1 claim 1 , 2 or 3 substituents selected from among C-Calkyl claim 1 , C-Calkoxy claim 1 , hydroxy and halogen claim 1 , wherein the heteroaromatic ring is a C-Caromatic ring or C-Cbicyclic aromatic ring independently containing 1 to 4 hetero atoms selected from among N claim 1 , O and S.3. The compound of formula 1 of that is selected from among the following compounds:N-((1-(3-(1,2,4-triazol-1-yl)propyl)piperidin-4-yl)methyl)-4-amino-5-chloro-2-methoxybenzamide,N-((1-(3-(tetrazol-1-yl)propyl)piperidin-4-yl)methyl)-4-amino-5-chloro-2-methoxybenzamide,N-((1-(3-(indol-1-yl)propyl)piperidin-4-yl)methyl)-4-amino-5-chloro-2-methoxybenzamide,N-((1-(3-(2-methylimidazol-1-yl)propyl)piperidin-4-yl)methyl)-4-amino-5-chloro-2-methoxybenzamide,N-((1-(5-(indol-1-yl)pentyl)piperidin-4-yl)methyl)-4-amino-5-chloro-2-methoxybenzamide,N-((1-(5-(1,2,3-triazol-1-yl)pentyl)piperidin-4-yl)methyl)-4-amino-5-chloro-2-methoxybenzamide,N-((1-(3-(1,2,3-triazol-1-yl)propyl)piperidin-4-yl)methyl)-4-amino-5-chloro-2-methoxybenzamide,N-((1-(3-(1,2,3-triazol-2-yl)propyl)piperidin-4-yl)methyl)-4-amino-5-chloro-2-methoxybenzamide,N-((1-(pyridin-3-ylmethyl)piperidin-4-yl)methyl)-4-amino-5-chloro-2-methoxybenzamide,N-((1((1-methylindol-3-yl)methyl)piperidin-4-yl)methyl)-4-amino-5-chloro-2- ...

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04-04-2013 дата публикации

PIPERIDINYL SUBSTITUTED 1,3-DIHYDRO-BENZOIMIDAZOL-2-YLIDENEAMINE DERIVATIVES

Номер: US20130085161A1
Принадлежит: NOVARTIS AG

The invention relates to new derivatives of formula (I), 7. The compound according to claim 1 ,or a salt thereof, wherein{'sup': '5', 'Rrepresents methyl, methoxy, acetylamino, chloro, cyano, or trifluoromethyl.'}8. A compound according to claim 1 , or a salt thereof claim 1 , wherein{'sup': '5', 'q represents 2, the substituents Rbeing located in the 2- and 5-position or'}{'sup': '5', 'q represents 1, the substituent Rbeing located in the 2- or 3-position.'}9. The compound according to claim 1 , or a salt thereof claim 1 , wherein{'sup': '1', 'Rrepresents halogen or'}{'sup': '1', 'Rrepresents, together with the phenyl ring, an unsubstituted or substituted indolyl, isoindolyl, indazolyl, benzimidazolyl, benztriazolyl, chinolinyl, isochinnolinyl, cinnolinyl, phtalazinyl, chazolinyl, chinoxalinyl, naphtalenyl, tetrahydro-naphtalenyl, indenyl, dihydroindenyl, the substituents being selected from the group consisting of halogen.'}10. The compound according to claim 1 , or a salt thereof claim 1 , wherein{'sup': '3', 'sub': 1-7', '1-7, 'Rrepresents hydrogen, Calkyl-carbonyl or Calkyloxy-carbonyl.'}11. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and one or more pharmaceutically acceptable carriers.12. The pharmaceutical composition of further comprising one or more therapeutically active agents claim 11 , selected from antiproliferative agents.1317-. (canceled)18. A method of modulating IGF-1R activity in a subject claim 1 , comprising the step of administering to a subject a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof.19. A method for the treatment of an IGF-1R mediated disorder or disease comprising the step of administering to a subject a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically ...

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04-04-2013 дата публикации

AMIDO COMPOUNDS AS RORyT MODULATORS AND USES THEREOF

Номер: US20130085162A1
Принадлежит:

Amido compounds are disclosed that have a formula represented by the following: 2. The method according to claim 1 , wherein each Rand Ris independently selected from H claim 1 , Me claim 1 , Et claim 1 , n-Pr claim 1 , i-Pr claim 1 , n-Bu claim 1 , t-Bu claim 1 , hydroxyethyl claim 1 , hydroxypropyl claim 1 , aminoethyl claim 1 , aminopropyl claim 1 , dimethylaminoethyl claim 1 , dimethylaminopropyl claim 1 , piperidinoethyl claim 1 , morpholinoethyl claim 1 , cyclopropylmethyl claim 1 , benzyl claim 1 , phenethyl claim 1 , furanylmethyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , and substituted and unsubstituted phenyl.3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. (canceled)14. The method according to claim 13 , wherein Cy is azetidinyl claim 13 , pyrrolidinyl claim 13 , piperidinyl claim 13 , piperizinyl claim 13 , morpholinyl claim 13 , tetrahydroquinolinyl claim 13 , indolinyl claim 13 , or azepinyl claim 13 , unsubstituted or substituted with alkyl claim 13 , substituted alkyl claim 13 , haloalkyl claim 13 , alkoxyalkyl claim 13 , hydroxyalkyl claim 13 , alkoxy claim 13 , hydroxyl claim 13 , CN claim 13 , substituted or unsubstituted aryl claim 13 , substituted or unsubstituted heteroaryl claim 13 , amido claim 13 , acyl claim 13 , aroyl claim 13 , or —CO-alkoxy.16. (canceled)17. (canceled)18. (canceled)21. (canceled)22. The method according to claim 19 , wherein each of Rand Ris independently OH claim 19 , substituted or unsubstituted alkyl claim 19 , substituted or unsubstituted alkoxy claim 19 , CN claim 19 , halo claim 19 , amido claim 19 , or haloalkyl.23. (canceled)24. (canceled)25. (canceled)26. (canceled)27. (canceled)28. The method according to claim 1 , wherein Rand Ris independently H claim 1 , CN claim 1 , or Me.29. (canceled)30. (canceled)31. (canceled)32. (canceled)33. The method according to claim 1 , wherein Ris H ...

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04-04-2013 дата публикации

Preparation of Pyridonecarboxylic Acid Antibacterials

Номер: US20130085281A1
Принадлежит: ABBOTT LABORATORIES

A process for making 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, and therapeutically acceptable salts thereof, and intermediates used in the process are disclosed. 2. The process of claim 1 , further comprising isolating the product of step (l).3. The process according to claim 1 , wherein the chlorinating agent is N-chlorosuccinimide claim 1 , thionyl chloride claim 1 , Cl claim 1 , ClO claim 1 , or 1 claim 1 ,3-dimethyl-5 claim 1 ,5-dichlorohydantoin claim 1 , with or without water claim 1 , and with or without an acid.4. The process according to claim 3 , wherein the chlorinating agent is N-chlorosuccinimide.5. The process according to claim 3 , wherein the chlorinating agent is thionyl chloride.6. The process according to claim 3 , wherein the chlorinating agent is Cl.7. The process according to claim 3 , wherein the chlorinating agent is ClO.8. The process according to claim 3 , wherein the chlorinating agent is 1 claim 3 ,3-dimethyl-5 claim 3 ,5-dichlorohydantoin.9. The process according to claim 3 , with an acid wherein the acid is sulfuric acid claim 3 , phosphoric acid claim 3 , trifluoroacetic acid claim 3 , or perchloric acid.10. The process according to claim 4 , with an acid wherein the acid is sulfuric acid claim 4 , phosphoric acid claim 4 , trifluoroacetic acid claim 4 , or perchloric acid.11. The process according to claim 5 , with an acid wherein the acid is sulfuric acid claim 5 , phosphoric acid claim 5 , trifluoroacetic acid claim 5 , or perchloric acid.12. The process according to claim 6 , with an acid wherein the acid is sulfuric acid claim 6 , phosphoric acid claim 6 , trifluoroacetic acid claim 6 , or perchloric acid.13. The process according to claim 7 , with an acid wherein the acid is sulfuric acid claim 7 , phosphoric acid claim 7 , trifluoroacetic acid claim 7 , or perchloric acid.14. The process according to claim 8 , with an acid wherein the acid is ...

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11-04-2013 дата публикации

Heterocyclic compounds and their uses

Номер: US20130090323A1
Принадлежит: AMGEN INC

Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110 activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.

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11-04-2013 дата публикации

NEW CCR2 RECEPTOR ANTAGONISTS, METHOD FOR PRODUCING THE SAME, AND USE THEREOF AS MEDICAMENTS

Номер: US20130090338A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to novel antagonists for CCR2 (CC chemokine receptor 2) and their use for providing medicaments for treating conditions and diseases, especially pulmonary diseases like asthma and COPD and pain diseases. 2. The compound of formula (I) according to claim 1 ,{'sub': 1', '1', '4', '3', '3', '6, 'wherein Ris a group selected from among —H, -halogen, —C-C-alkyl, —CF, —OCF, and —C-heteroaryl comprising a N atom;'}{'sub': 7', '1', '4', '3', '3', '6, 'wherein Ris a group selected from among —H, -halogen, —C-C-alkyl, —CF, —OCF, and —C-heteroaryl comprising a N atom; and'}{'sub': '4', 'wherein Rdenotes -hydrogen.'}3. The compound of formula (I) according to claim 1 ,{'sub': 7', '1', '4, 'wherein Rand Ron two neighbouring ring atoms together form a —C-alkenylene group, such that an annellated aromatic ring is formed, in which one or two carbon centers may optionally be replaced by 1 or 2 hetero atoms selected from N;'}{'sub': 4', '1', '3, 'wherein Ris a group selected from among -hydrogen, and —C-C-alkyl.'}4. The compound of formula (I) according to claim 1 , wherein A denotes N.5. The compound of formula (I) according to claim 1 , wherein A denotes C.6. The compound of formula (I) according to claim 1 , wherein Ris selected from among —H claim 1 , —C-C-alkyl claim 1 , and —O—C-C-alkyl.7. The compound of formula (I) according to claim 1 , wherein Ris selected from among -methyl claim 1 , and —OCH.8. The compound of formula (I) according to claim 1 , wherein Rdenotes -hydrogen.9. The compound of formula (I) according to claim 1 , wherein n is 2.10. The compound of formula (I) according to claim 1 , wherein G and E are N.11. The compound of formula (I) according to claim 1 ,{'sub': 5', '10', '10′, 'wherein Ris a group of the structure —N(R,R),'}{'sub': 10', '10′', '4, 'wherein Rand R, together form a —C-alkylene group such that a ring is formed,'}{'sub': 0', '3', '2', '1', '3, 'wherein such ring is optionally substituted with one or more groups ...

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11-04-2013 дата публикации

TETRAHYDROQUINOLINE AMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS

Номер: US20130090352A1
Принадлежит:

The present invention is directed to tetrahydroquinoline amide compounds of formula (I) (Formula should be inserted here) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis —O—.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis —CH—.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof wherein R is Cheterocyclyl optionally substituted with 1 to 3 groups of R.5. The compound of or a pharmaceutically acceptable salt thereof claim 4 , wherein the heterocyclyl is selected from the group consisting of optionally substituted pyridyl claim 4 , quinolinyl claim 4 , isoquinolinyl claim 4 , quinolizinyl claim 4 , quinoxalinyl claim 4 , quinazolinyl claim 4 , benzimidazolyl claim 4 , oxanyl claim 4 , pyranyl claim 4 , and napthrindinyl.6. The compound of or a pharmaceutically acceptable salt thereof claim 5 , wherein R is optionally substituted pyridyl.7. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein the Rsubstituent on R is selected from the group consisting of halogen claim 1 , hydroxy claim 1 , —O—Calkyl claim 1 , said alkyl optionally substituted with 1 to 3 groups of halo; —Calkyl claim 1 , said alkyl optionally substituted with 1 to 3 groups of halo; t-butoxycarbonyl claim 1 , —C(═O)—R claim 1 , —S(O)—R; Cheterocyclyl claim 1 , and Caryl claim 1 , said heterocyclyl and aryl optionally substituted with 1 to 3 groups of R.8. The compound of or a pharmaceutically acceptable salt thereof claim 7 , wherein Ris selected from the group ...

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11-04-2013 дата публикации

Pyrazolylaminopyridine derivatives useful as kinase inhibitors

Номер: US20130090358A1
Принадлежит: AstraZeneca AB

This invention relates to novel compounds having the formula (I): and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment for cancer.

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18-04-2013 дата публикации

USE OF ISOQUINOLONES FOR PREPARING DRUGS, NOVEL ISOQUINOLONES AND METHOD FOR SYNTHESISING SAME

Номер: US20130096083A1
Принадлежит:

The use of isoquinolones for preparing drugs, including novel isoquinolones as well as their synthesis method. In particular, isoquinolone derivatives used in the treatment of pathological angiogenesis, and more particularly of cancer. 136-. (canceled)38) A method for the prevention and treatment of mammals claim 37 , in particular humans claim 37 , suffering from pathological angiogenesis claim 37 , in particular retinopathies claim 37 , or benign or malignant (cancerous) tumours claim 37 , comprising administering to a mammal in need thereof an effective amount of at least one compound of general formula (I) according to .39) A method for the prevention and treatment of mammals claim 37 , in particular humans claim 37 , suffering from pathological angiogenesis claim 37 , in particular retinopathies claim 37 , or benign or malignant (cancerous) tumours claim 37 , comprising administering to a mammal in need thereof an effective amount of at least one compound of general formula (I) according to claim 37 , as a protein phosphatase 1 inhibitor claim 37 , vascular-disrupting agent and antiproliferative agent.40) A method for the prevention and treatment of mammals claim 37 , in particular humans claim 37 , suffering from pathological angiogenesis claim 37 , in particular retinopathies claim 37 , or benign or malignant (cancerous) tumours claim 37 , comprising administering to a mammal in need thereof an effective amount of at least one compound of general formula (I) according to claim 37 , as a tubulin polymerization inhibitor claim 37 , vascular-disrupting agent and antiproliferative agent.41) A method for the prevention and treatment of mammals claim 37 , in particular humans claim 37 , suffering from pathological angiogenesis claim 37 , in particular retinopathies claim 37 , or benign or malignant (cancerous) tumours claim 37 , comprising administering to a mammal in need thereof an effective amount of at least one compound of general formula (I) according to ...

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18-04-2013 дата публикации

SMALL-MOLECULE INHIBITORS OF THE ANDROGEN RECEPTOR

Номер: US20130096095A1

The present invention provides tetrahydropyrvinium (THP), derivatives thereof, benzoxazole compounds, and derivatives thereof. The present invention provides a method of using tetrahydropyrvinium (THP), derivatives thereof, benzoxazole compounds, and derivatives thereof. 121.-. (canceled)23. The method of claim 42 , wherein the salt forms comprise a counterion selected from the group consisting of pamoate claim 42 , chloride claim 42 , bromide claim 42 , succinate claim 42 , maleate and acetate.24. The method of claim 42 , wherein the salt forms comprise a counterion selected from the group consisting of pamoate claim 42 , chloride claim 42 , bromide claim 42 , succinate claim 42 , maleate and acetate.25. The method of claim 42 , wherein the method of inhibiting treats or prevents a disease selected from the group consisting of prostate cancer claim 42 , ovarian cancer claim 42 , hepatocellular carcinoma claim 42 , acne vulgaris claim 42 , endometriosis claim 42 , acanthosis nigricans claim 42 , hypertrichosis claim 42 , breast cancer claim 42 , precocious puberty claim 42 , polycystic ovary syndrome claim 42 , benign prostatic hyperplasia claim 42 , alopecia claim 42 , hirsutism and hypersexuality/paraphilia.26. The method of claim 25 , wherein the disease is prostate cancer.27. The method of claim 26 , wherein the disease is primary prostate cancer.28. The method of claim 26 , wherein the disease is hormone refractory prostate cancer.29. The method of claim 25 , wherein the administration is via topical claim 25 , oral claim 25 , intravenous claim 25 , intradermal claim 25 , intramuscular or parenteral administration.30. The method of claim 25 , wherein the disease is alopecia and the administration is topical.31. The method of claim 42 , wherein the compound of Formula I is administered with a course of hormonal therapy claim 42 , wherein the compound for hormonal therapy is selected from the group consisting of an anti-androgen and a LnRH agonist.32. The method ...

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18-04-2013 дата публикации

Di(arylamino)aryl compound

Номер: US20130096100A1
Принадлежит: Astellas Pharma Inc

The present invention provides a compound which is useful as an inhibitor against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins. As a result of extensive and intensive studies on compounds having an inhibitory effect against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins, the inventors of the present invention have found that the di(arylamino)aryl compound of the present invention has inhibitory activity against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins. This finding led to the completion of the present invention. The compound of the present invention can be used as a pharmaceutical composition for preventing and/or treating cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive cancer, EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive lung cancer, or EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive non-small cell lung cancer, etc.

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18-04-2013 дата публикации

Isoquinolin-3-Ylurea Derivatives

Номер: US20130096119A1
Принадлежит:

The invention relates to isoquinolin-3-ylurea derivatives of formula (I) wherein Rrepresents (C-C)alkyl, (C-C)haloalkyl or cyclopropyl, Rrepresents H and the substituents Rand Rand Rhave the meanings disclosed in the specification; and to the salts of such compounds. These compounds are useful for the prevention or the treatment of bacterial infections. 4. The compound according to claim 1 , wherein Rrepresents (C-C)alkyl; or a salt thereof.5. The compound according to claim 1 , wherein Rrepresents ethyl; or a salt thereof.6. The compound according to claim 1 , wherein Rrepresents H; or a salt thereof.7. The compound according to claim 1 , wherein Rrepresents methyl; or a salt thereof.8. The compound according to claim 1 , wherein:{'sup': 3', '12', '14', '13', '12', '13', '14, 'sub': 1', '2', '1', '2', '1', '2', '1', '2', '1', '2', '1', '2, 'Rrepresents a group (B1) wherein either each of Band Brepresents H and Brepresents OH, halogen, acetyl, acetylamino, acetylaminomethyl, aminocarbonyl, dimethylaminocarbonyl, aminosulfonyl, (C-C)alkylsulfonyl, (C-C)alkoxy, (C-C)alkoxycarbonyl, cyano, amino-(C-C)alkyl or hydroxy-(C-C)alkyl, or each of Band Brepresents H and Brepresents acetyl, acetylamino, acetylaminomethyl, aminocarbonyl, dimethylaminocarbonyl, aminosulfonyl, (C-C)alkylsulfonyl, cyanomethyl or hydroxymethyl;'}{'sup': '3', 'sub': '2', 'Rrepresents a group (B2) wherein X represents CH;'}{'sup': '3', 'Rrepresents a group (B3);'}{'sup': '3', 'Rrepresents a group (B4);'}{'sup': '3', 'Rrepresents a group (B6); or'}{'sup': '3', 'Rrepresents quinolin-3-yl, imidazo[1,2-a]pyridin-6-yl, (thiazol-5-yl)carbonylamino, pyridin-3-ylcarbonylamino or pyridin-4-ylcarbonylamino;'}or a salt thereof.9. The compound according to claim 1 , wherein Rrepresents H; or a salt thereof.10. The compound according to claim 1 , wherein Rrepresents methyl; or a salt thereof.11. The compound according to claim 1 , wherein:{'sup': '2', 'Rrepresents halogen;'}{'sup': '2', 'Rrepresents a group (A1 ...

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18-04-2013 дата публикации

HETEROCYCLIC COMPOUNDS AND THEIR USES

Номер: US20130096134A1
Принадлежит: Amgen Inc.

Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with pi 105 activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelodysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer. 2. A method of treating rheumatoid arthritis claim 1 , ankylosing spondylitis claim 1 , osteoarthritis claim 1 , psoriatic arthritis claim 1 , psoriasis claim 1 , inflammatory diseases and autoimmune diseases claim 1 , inflammatory bowel disorders claim 1 , inflammatory eye disorders claim 1 , inflammatory or unstable bladder disorders claim 1 , skin complaints with inflammatory components claim 1 , chronic inflammatory conditions claim 1 , autoimmune diseases claim 1 , systemic lupus erythematosis (SLE) claim 1 , myestenia gravis claim 1 , rheumatoid arthritis claim 1 , acute disseminated encephalomyelitis claim 1 , idiopathic thrombocytopenic purpura claim 1 , multiples sclerosis claim 1 , Sjoegren's syndrome and autoimmune hemolytic anemia claim 1 , allergic conditions and hypersensitivity claim 1 , ...

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18-04-2013 дата публикации

Selected Inhibitors of Protein Tyrosine Kinase Activity

Номер: US20130096135A1
Принадлежит: METHYLGENE INC.

The present invention provides new compounds and methods for treating a disease responsive to inhibition of kinase activity, for example a disease responsive to inhibition of protein tyrosine kinase activity, for example a disease responsive to inhibition of protein tyrosine kinase activity of growth factor receptors, for example a disease responsive to inhibition of receptor type tyrosine kinase signaling, or for example, a disease responsive to inhibition of VEGF receptor signaling. 2. A composition comprising a compound according to and a pharmaceutically acceptable carrier.3. A method of treating an opthalmic disease claim 1 , condition or disorder claim 1 , the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to or a composition thereof claim 1 , wherein the ophthalmic disease claim 1 , disorder or condition is selected from the group consisting of (a) a disease claim 1 , disorder or condition caused by choroidal angiogenesis claim 1 , (b) diabetic retinopathy and (c) retinal oedema.4. The method according to claim 3 , wherein the ophthalmic disease claim 3 , disorder or condition is age-related macular degeneration. 1. Field of the InventionThis invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling and HGF receptor signaling. More particularly, the invention relates to compounds, compositions and methods for the inhibition of VEGF receptor signaling.2. Summary of the Related ArtTyrosine kinases may be classified as growth factor receptor (e.g. EGFR, PDGFR, FGFR and erbB2) or non-receptor (e.g. c-src and bcr-abl) kinases. The receptor type tyrosine kinases make up about 20 different subfamilies. The non-receptor type tyrosine kinases make ...

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18-04-2013 дата публикации

NOVEL SALTS OF 6-HETEROCYCLE SUBSTITUTED HEXAHYDROPHENANTHRIDINE DERIVATIVES

Номер: US20130096152A1
Принадлежит: NYCOMED GMBH

Disclosed herein are salts of 6-heteroaryl substituted hexahydrophenanthridine PDE4 inhibiting compounds, which can be used in the pharmaceutical industry for the production of pharmaceutical compositions. 113-. (canceled)14. A salt selected from the group consisting of5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one hydrochloride;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one methansulfonate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one citrate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one L-tartrate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one D-tartrate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one meso-tartrate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one D-malate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one L-malate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one fumarate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one maleinate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one 2-oxoglutarate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one oxalate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b-hexahydro-phenanthridin-6-yl)-1-methyl-1H-pyridin-2-one D-gluconate;5-((2R,4aR,10bR)-9-Ethoxy-2-hydroxy-8-methoxy-1,2,3,4,4a,10b- ...

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18-04-2013 дата публикации

Novel Dihydropyridin-2(1H)-One Compounds as S-Nitrosoglutathione Reductase Inhibitors and Neurokinin-3 Receptor Antagonists

Номер: US20130096161A1
Автор: Qiu Jian, Sun Xicheng
Принадлежит: N30 PHARMACEUTICALS, INC.

The present invention is directed to novel dihydropyridin-2(1H)-one compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors and/or Neurokinin-3 (NK3) receptor antagonists, pharmaceutical compositions comprising such compounds, and methods of making and using the same. 2. The compound of wherein Ris selected from the group consisting of hydroxyl claim 1 , carboxyl claim 1 , and tetrazol-5-yl.3. The compound of wherein R claim 1 , Rand Rare independently selected from the group consisting of hydrogen and methyl;{'sub': 3', '1', '6, 'Ris selected from the group consisting of hydrogen, nitro, cyano, carboxyl, carbamoyl, methylsulfonamido, fluoro, chloro, bromo, hydroxyl, methylsulfonyl, and methylsulfinyl, isoxazol-4-yl, C-Calkoxy, —C(NH)NHOH, sulfonic acid, and acetyl;'}{'sub': '4', 'Ris selected from the group consisting of hydroxyl, carboxyl, and tetrazol-5-yl;'}{'sub': 5', '2', '2', '2', '1', '6', '2', '2', '3', '2', '2', '3, 'Ris selected from the group consisting of hydrogen, hydroxyl, carboxyl, chloro, fluoro, cyano, —O(CH)NMe, C-Calkyl, —O(CH)OCH, —O(CH)OH, acetyl, CF, methoxy, ethoxy, isopropoxy, and n-propoxy; and'}{'sub': '6', 'Ris hydrogen.'}4. The compound of wherein Ris selected from the group consisting of hydrogen claim 3 , nitro claim 3 , and hydroxyl; Ris selected from the group consisting of hydroxyl claim 3 , carboxyl claim 3 , and tetrazol-5-yl; and Ris selected from the group consisting of hydrogen claim 3 , ethoxy claim 3 , fluoro claim 3 , and —O(CH)OH.5. The compound of wherein X is selected from the group consisting of aryl claim 1 , substituted aryl claim 1 , heteroaryl claim 1 , and substituted heteroaryl.6. The compound of wherein X is selected from the group consisting of phenyl claim 1 , substituted phenyl claim 1 , thiophen-yl claim 1 , substituted thiophen-yl claim 1 , thiazol-yl claim 1 , substituted thiazol-yl claim 1 , pyrazin-yl claim 1 , substituted pyrazin-yl claim 1 , pyridin-yl claim 1 , and substituted pyridin-yl ...

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18-04-2013 дата публикации

Nilotinib hcl crystalline forms

Номер: US20130096304A1
Принадлежит: Teva Pharmaceutical Industries LTD

Crystalline forms of Nilotinib HCl are described.

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18-04-2013 дата публикации

PROCESS FOR THE PREPARATION OF 5-SUBSTITUTED 1-ALKYLTETRAZOLYL OXIME DERIVATIVES

Номер: US20130096311A1
Принадлежит:

The present invention relates to a process for the preparation of 5-substituted 1-alkyltetrazolyl oxime derivatives. 3. Process according to claim 1 , characterized in that step (1) is carried out in the presence of a base.4. Process according to claim 3 , characterized in that the molar ratio of base to the oxime of the formula (II) used is 0.8-10.5. Process according to claim 1 , characterized in that step (1) is carried out in a solvent.6. Process according to claim 1 , characterized in that step (2) and (3) are carried out in the presence of a base.7. Process according to claim 6 , characterized in that the molar ratio of base to the compound of the formula (IV) used is 0.8-10.8. Process according to claim 1 , characterized in that the compound of the formula (V) obtained in step (2) is not isolated claim 1 , but is further reacted in situ. The present invention relates to a process for the preparation of 5-substituted 1-alkyltetrazolyl oxime derivatives.5-Substituted 1-alkyltetrazolyl oxime derivatives are important intermediate compounds in active ingredient manufacture or are already fungicidally effective compounds (see e.g. WO 2010/000841). It is already known that 5-substituted 1-alkyltetrazoles can be prepared by lithiation of 1-methyltetrazole at −70° C. (cf. 1971, 49, 2139-2142). However, the yield using the example of 5-benzoyl-1-methyltetrazole is only 41%. The 1-methyltetrazole used likewise has to be prepared in a multistage synthesis sequence. For an industrial reaction, the low temperatures and the expensive use of butyllithium are disadvantageous. Another process for the preparation of 5-benzoyl-1-methyltetrazole is known from 1963, 85, 2967-2976. Benzyl cyanide is reacted with ammonium azide to give 5-benzyltetrazole and then oxidized with chromium trioxide to give 5-benzoyltetrazole. The methylation to 5-benzoyl-1-methyltetrazole takes place with diazomethane. This synthesis route is likewise disadvantageous as regards safety and economical ...

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25-04-2013 дата публикации

TRANSITION METAL MEDIATED OXIDATION OF HETERO ATOMS IN ORGANIC MOLECULES COORDINATED TO TRANSITION METALS: OXIDATION OF COORDINATED BENZIMIDAZOLE TO OMEPRAZOLE

Номер: US20130101668A1
Принадлежит: Praktikatalyst Pharma LLC

The present invention is directed to a process for the catalytic oxidation of the thioether 5-methoxy-2-((4-methoxy-3,5-dimethyl-2-pyridinyl)methyl)methylthio)-1H-benzimidazole to its sulfoxide: 5-methoxy-2-((4-methoxy-3,5-dimethyl-2-pyridinyl) methyl) methylsulfinyl)-1H-benzimidazole comprising: reacting the thioether with: 1) a transition metal catalyst; and, 2) an oxygen source; wherein the thioether is oxidized to the sulfoxide commonly known as omeprazole and wherein one of either the R and S enantiomers is formed to an enantiomeric excess. 1. A composition of matter comprising a sulfoxide , 5-methoxy-2-((4-methoxy-3 ,5-dimethyl-2-pyridinyl)methyl)methylsulfinyl)-1H-benzimidazole , said sulfoxide having R and S enantiomers and further comprising a compound selected from the group consisting of a transition metal catalyst and an oxygen source wherein said transition metal catalyst is a transition metal complex comprising said sulfoxide and wherein said oxygen source is selected from the group consisting of peracids , hydrogen peroxide , dimethyldioxirane and molecular oxygen and has one of either the R and S enantiomers in an enantiomeric excess.2. A composition according to claim 1 , wherein the S enantiomer of the sulfoxide is present in a amount of from about 55% to about 99% of the combined weight of the enantiomers.3. A composition according to claim 1 , wherein the S enantiomer of the sulfoxide is present in a amount of from about 55% to about 95% of the combined weight of the enantiomers.4. A composition according to claim 1 , wherein the S enantiomer of the sulfoxide is present in a amount of from about 55% to about 90% of the combined weight of the enantiomers.5. A composition according to claim 1 , wherein the S enantiomer of the sulfoxide is present in an amount of from about 55% to about 85% of the combined weight of the enantiomers.6. The composition of wherein said transition metal complex comprises a ligand selected from the group consisting of ...

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25-04-2013 дата публикации

INDENOQUINOLONE COMPOUND, PREPARATION METHOD AND USE THEREOF

Номер: US20130102598A1
Принадлежит: SECOND MILITARY MEDICAL UNIVERSITY, PLA

An indenoquinolone compounds of Formula (A) is disclosed, wherein the definition of each group is described in the description. These compounds may specifically inhibit topoisomerase I, and they have good activities against many kinds of human tumor cells, such as lung cancer, colon cancer, breast cancer, liver cancer and the like. They can be used in the manufacture of antitumor drugs. The method for preparing the compound of formula (A), and pharmaceutical compositions containing such compounds and the use in the manufacture of antitumor drugs are also disclosed. 3. The compound according to claim 1 , wherein claim 1 , Rmay be located at one or two positions of 2- and 3-position; and/or Rmay be located at one or two positions of 8- and 9-position.4. The compound according to claim 1 , wherein claim 1 , Ris any one of the following groups: a) a hydrogen; b) a C1-8 straight-chain or branched alkyloxy; c) a halogen; and/or{'sub': '2', 'Ris any one of the following groups: a) a hydrogen; b) a C1-8 straight-chain or branched alkyloxy; c) a halogen; and/or'}{'sub': 3', '2', '4', '4', '5', '6', '5', '6, 'Ris —(CH)mR, wherein m is 1-4, and Rmay be a saturated or unsaturated 4-7 membered nitrogen-containing heterocycle, halogen, or NRR, wherein Ror Ris any one of the following groups: a) a hydrogen; b) a substituted or unsubstituted C1-8 straight-chain or branched alkyl.'}5. The compound according to claim 1 , wherein claim 1 , m in Ris 2-3 claim 1 , and Rmay be a saturated or unsaturated 5-6 membered nitrogen-containing heterocycle claim 1 , halogen claim 1 , or NRR claim 1 , wherein Ror Ris any one of the following groups: a) a hydrogen; b) a substituted or unsubstituted C1-8 straight-chain or branched alkyl.6. The compound according to claim 1 , wherein claim 1 , Ris halo-ethyl claim 1 , dimethylamino-ethyl claim 1 , diethylamino-ethyl claim 1 , piperidyl-ethyl claim 1 , morpholinyl-ethyl claim 1 , pyrrolidinyl-ethyl claim 1 , imidazolyl-ethyl claim 1 , dimethylamino- ...

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25-04-2013 дата публикации

NOVEL CYCLOPROPANE INDOLINONE DERIVATIVES

Номер: US20130102604A1
Принадлежит: Hoffmann-La Roche Inc.

The present invention relates to a compound of formula (I) 2. A compound according to claim 1 , wherein one of Rand Ris selected from hydrogen and alkyl and the other is selected from the group consisting of: pyridinyl claim 1 , halophenyl claim 1 , alkylsulfonylphenyl claim 1 , cyanophenyl and trifluoromethylphenyl.3. A compound according to claim 1 , wherein one of Rand Ris selected from hydrogen and isopropyl and the other is selected from the group consisting of: pyridinyl claim 1 , fluorophenyl claim 1 , chlorophenyl claim 1 , cyanophenyl claim 1 , methylsulfonylphenyl and trifluoromethylphenyl.4. A compound according to wherein Ris selected from the group consisting of: pyridinyl claim 1 , carboxypyridinyl claim 1 , tetrahydropyranyl claim 1 , dialkylamino claim 1 , morpholinyl claim 1 , alkylsulfonylpiperidinyl claim 1 , alkylpiperazinyl claim 1 , dialkylaminoalkylpiperazinyl claim 1 , dialkylaminopyrrolidinyl claim 1 , carboxyalkyl-1H-imidazolyl claim 1 , carboxy-1H-imidazolyl or substituted phenyl claim 1 , wherein substituted phenyl is phenyl substituted with one or two substituents independently selected from alkyl claim 1 , halogen claim 1 , carboxy claim 1 , alkylsulfonyl claim 1 , alkylaminocarbonyl claim 1 , alkylsulfonylaminocarbonyl claim 1 , piperidinylcarbonyl claim 1 , piperazinylcarbonyl claim 1 , morpholinylcarbonyl claim 1 , pyridinylpiperazinylcarbonyl claim 1 , alkylpiperazinylcarbonyl claim 1 , alkylsulfonylpiperazinylcarbonyl claim 1 , alkylpyrrolidinylalkylaminocarbonyl claim 1 , alkyl-1H-pyrazolylaminocarbonyl claim 1 , oxo-oxazolidinyl claim 1 , oxo-pyrrolidinyl and oxo-imidazolidinyl.5. A compound according to claim 1 , wherein Ris selected from the group consisting of: carboxypyridinyl claim 1 , carboxyalkyl-1H-imidazolyl claim 1 , carboxyphenyl and phenyl substituted with carboxy and oxo-oxazolidinyl.6. A compound according to claim 1 , wherein Ris selected from the group consisting of: hydrogen claim 1 , halogen and carboxy.7. A ...

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25-04-2013 дата публикации

BIPYRIDYL DERIVATIVES

Номер: US20130102608A1

The present invention relates to novel bipyridyl derivatives of formula (I) and to the use of such compounds in which the inhibition, regulation and/or modulation of signal transduction by ATP consuming proteins like kinases plays a role, particularly to inhibitors of TGF-beta receptor kinases, and to the use of such compounds for the treatment of kinase-induced diseases, in particular for the treatment of tumors. 2. Compound according to claim 1 , wherein{'sub': 1', '2', '3, 'sup': '3', 'W, W, Wdenote CR,'}or{'sub': 1', '2, 'sup': '3', 'W, Wdenote CR, and'}{'sub': '3', 'Wdenotes N,'}and the physiologically acceptable salts, solvates, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.3. Compound according to claim 1 , wherein{'sup': '1', 'sub': '3', 'Rdenotes monocyclic aryl having 5, 6, 7, 8, 9 or 10 C atoms, preferably phenyl, which can be independently substituted by at least one substituent selected from the group consisting of Y, Hal, CN, CFor OY,'}and the physiologically acceptable salts, solvates, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.4. Compound according to claim 1 , wherein{'sup': 2', '2', '2', '4, 'Rdenotes Ar, Hetor NY-Hetwhich can independently from each other be substituted by R,'}and the physiologically acceptable salts, solvates, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.5. Compound according claim 1 , wherein{'sup': 4', '3, 'sub': 3', 'n', 'n', 'n, 'Rdenotes A, CF, Hal, —(CYY)—OY, —(CYY)—NYY, (CYY)-Het,'}and the physiologically acceptable salts, solvates, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.6. Compound according to claim 1 , wherein{'sup': '3', 'sub': n', 'n', '2', '3', '2', '2', 'm, 'Hetdenotes a saturated monocyclic heterocycle having 4 or 5 C atoms and 1 or 2 N and/or O atoms, which can be independently substituted by at least one substituent selected from the group of Hal, A, —(CYY)—OY, —(CYY)—NYY, SY, ...

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25-04-2013 дата публикации

3-AMINO-5,6-DIHYDRO-1H-PYRAZIN-2-ONE DERIVATIVES USEFUL FOR THE TREATMENT OF ALZHEIMER'S DISEASE AND OTHER FORMS OF DEMENTIA

Номер: US20130102618A1
Принадлежит: Janssen Pharmaceutica NV

The present invention relates to novel 3-amino-5,6-dihydro-1H-pyrazin-2-one derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease or dementia associated with beta-amyloid. 2. The compound according to wherein{'sup': 1', '2, 'sub': '1-3', 'Rand Rare independently selected from Calkyl;'}{'sup': 1', '2', '3', '4', '3', '3, 'X, X, X, Xare independently C(R) wherein each Ris selected from hydrogen and halo;'}{'sup': 4', '4, 'L is a bond or —N(R)CO—, wherein Ris hydrogen;'}Ar is homoaryl or heteroaryl;{'sub': 1-3', '1-3, 'wherein homoaryl is phenyl or phenyl substituted with one or two substituents selected from the group consisting of halo, cyano, Calkyl, and Calkyloxy;'}{'sub': 1-3', '1-3, 'heteroaryl is selected from the group consisting of pyridyl, pyrimidyl, and pyrazyl, each optionally substituted with one or two substituents selected from the group consisting of halo, cyano, Calkyl, and Calkyloxy; or an addition salt thereof.'}3. The compound according to wherein{'sup': 1', '2, 'Rand Rare methyl;'}{'sup': 1', '2', '3', '4, 'X, X, X, Xare CH;'}{'sup': 4', '4, 'L is a bond or —N(R)CO—, wherein Ris hydrogen;'}Ar is homoaryl or heteroaryl;wherein homoaryl is phenyl or phenyl substituted with one or two substituents selected from chloro and cyano;heteroaryl is selected from the group consisting of pyridyl, pyrimidyl, and pyrazyl, each optionally substituted with one or two substituents selected from the group consisting of ...

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25-04-2013 дата публикации

Acridines As Inhibitors Of Haspin And DYRK Kinases

Номер: US20130102627A1
Принадлежит: THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

The present disclosure is directed to compounds of Formula I: which are inhibitors of Haspin kinase and DYRK kinases. The compounds of the present disclosure, and compositions thereof, are useful in the treatment of disease related to Haspin kinase and DYRK kinase expression and/or activity. 2. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein X is S or CH.3. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare each independently H claim 1 , Calkyl claim 1 , or Rand Rtogether with the N atom to which they are attached form a phthalimide group claim 1 , optionally substituted by halo claim 1 , OH claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , Chaloalkoxy claim 1 , —CN claim 1 , —C(O)NRR claim 1 , —S(O)R claim 1 , —S(O)NRR claim 1 , or —NRR.4. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rtogether with the N atom to which they are attached form an unsubstituted phthalimide group.5. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein X is S claim 1 , and Rand Rare both H.6. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare both Calkoxy.7. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris halo.8. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris chloro.9. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein n is 2.10. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein:{'sub': '2', 'X is S or CH;'}{'sup': 1', '2, 'Rand Rare each H;'}{'sup': 3', '5, 'Rand Rare each independently H, OH, methyl, methoxy, or chloro; and'}n is 2 or 3.11. The compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein:X is S;{'sup': 1', '2, 'Rand Rare each independently H or methyl;'}{'sup': 3', '5, ' ...

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25-04-2013 дата публикации

NOVEL MICROBIOCIDAL DIOXIME ETHER DERIVATIVES

Номер: US20130102631A1
Принадлежит: SYNGENTA CROP PROTECTION LLC

The present invention provides compounds of formula (I) wherein R, A, X, Y, Y, Y, G, G, Gand p are as defined in the claims. The invention further provides intermediates used in the preparation of these compounds, to compositions which comprise these compounds and to their use in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi. 2. A compound according to wherein Rrepresents hydrogen claim 1 , (C-Calkyl)OC claim 1 , C-Calkyl claim 1 , phenyl or pyridyl claim 1 , wherein the alkyl claim 1 , phenyl and pyridyl are optionally substituted by one or more groups independently selected from halogen claim 1 , CN claim 1 , C-Calkyl claim 1 , C-Chaloalkyl claim 1 , C-Ccycloalkyl and a 5- or 6-membered heterocycle containing one to three nitrogen atoms;{'sup': '1', 'Arepresents cycle A-2, A-4, or A-5;'}{'sup': 3', '6', '7', '8', '9', '11', '11', '12, 'sub': 1', '8', '3', '8', '2', '8', '2', '8', '1', '8', '1', '8', '1', '8', '2', '2', '2', '2', '1', '4', '1', '4', '1', '4', '1', '4, 'R, R, R, Rand Rindependently of one another represent hydrogen, halogen, CN, C-Calkyl, C-Ccycloalkyl, C-Calkenyl, C-Calkynyl, phenyl, a 5- or 6-membered heterocycle containing one to three nitrogen atoms, OR, SH, C-C-alkylthio, C-C-alkylsulphinyl, C-C-alkylsulphonyl, COR, CON(R), or wherein the alkyl, cycloalkyl, alkenyl, alkynyl, phenyl and heterocycle are optionally substituted by one or more groups independently selected from halogen, CN, NH, NO, OH, C-Calkyl, C-Chaloalkyl, C-Calkoxy and C-Chaloalkoxy;'}{'sup': 6', '7', '7', '8', '3', '8', '3', '9', '6', '7', '7', '8', '3', '8', '3', '9, 'sub': 2', '2', '1', '4', '1', '4', '1', '4', '1', '4, 'or Rand R, Rand R, Rand R, or Rand Rtogether with the fragment of the pyridyl ring to which they are attached may form a partially or fully unsaturated 5- to 7-membered carbocyclic ring, and wherein the ring formed by Rand R, Rand R, Rand R, or Rand Ris optionally ...

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25-04-2013 дата публикации

SUBSTITUTED HETEROCYCLIC COMPOUNDS AS ION CHANNEL MODULATORS

Номер: US20130102632A1
Принадлежит: Gilead Sciences, Inc.

The present invention relates to sodium channel inhibitors of Formula (I): 2. The compound of claim 1 , wherein Ris alkyl of 1-3 carbon atoms or phenyl optionally substituted by halo.3. The compound of claim 2 , wherein R claim 2 , Rand Rare independently chosen from hydrogen and halo.4. The compound of claim 3 , wherein Ris alkyl of 1-6 carbon atoms.5. The compound of claim 4 , wherein X is a covalent bond claim 4 , —C(O)O— claim 4 , or heteroaryl claim 4 , Y is methylene claim 4 , and Z is cycloalkyl or phenyl claim 4 , both of which are optionally substituted by halo or heteroaryl.6. The compound of claim 5 , wherein Rand Rare both methyl claim 5 , R claim 5 , R claim 5 , and Rare all hydrogen claim 5 , X is —C(O)O— claim 5 , Y is methylene claim 5 , and Z is 2-bromophenyl claim 5 , namely 2-bromobenzyl 2 claim 5 ,4-dimethylquinoline-3-carboxylate.7. The compound of claim 5 , wherein Ris methyl claim 5 , Ris phenyl claim 5 , R claim 5 , R claim 5 , and Rare all hydrogen claim 5 , X is —C(O)O— claim 5 , Y is methylene claim 5 , and Z is phenyl claim 5 , namely benzyl 2-methyl-4-phenylquinoline-3-carboxylate.8. The compound of claim 5 , wherein Rand Rare both methyl claim 5 , R claim 5 , R claim 5 , and Rare all hydrogen claim 5 , X is —C(O)O— claim 5 , Y is methylene claim 5 , and Z is 4-chlorophenyl claim 5 , namely 4-chlorobenzyl 2 claim 5 ,4-dimethylquinoline-3-carboxylate.9. The compound of claim 5 , wherein Rand Rare both methyl claim 5 , R claim 5 , R claim 5 , and Rare all hydrogen claim 5 , X is a covalent bond claim 5 , Y is 1 claim 5 ,3 claim 5 ,4-oxadiazole claim 5 , and Z is (4-chlorophenyl)propan-2-yl) claim 5 , namely 2-(2-(4-chlorophenyl)propan-2-yl)-5-(2 claim 5 ,4-dimethylquinolin-3-yl)-1 claim 5 ,3 claim 5 ,4-oxadiazole.10. The compound of claim 5 , wherein Ris methyl claim 5 , Ris phenyl claim 5 , Rand Rare hydrogen claim 5 , Ris 6-chloro claim 5 , X is —C(O)O— claim 5 , Y is methylene claim 5 , and Z is cyclopropyl claim 5 , namely ...

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25-04-2013 дата публикации

5-Lipoxygenase-Activating Protein (FLAP) Inhibitors

Номер: US20130102636A1
Принадлежит: Panmira Pharmaceuticals, Inc.

A method for treating a human comprises administering a therapeutically effective amount of 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid or a pharmaceutically acceptable salt or a pharmaceutically acceptable N-oxide thereof, to the human in need. 121-. (canceled)22. A method for treating inflammation in a human comprising administering a therapeutically effective amount of 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2 ,2-dimethyl-propionic acid or a pharmaceutically acceptable salt or a pharmaceutically acceptable N-oxide thereof , to the human in need.23. The method according to claim 22 , wherein 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2 claim 22 ,2-dimethyl-propionic acid is present in the form of a sodium salt.24. A method for treating respiratory disease in a human comprising administering a therapeutically effective amount of 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2 claim 22 ,2-dimethyl-propionic acid or a pharmaceutically acceptable salt or a pharmaceutically acceptable N-oxide thereof claim 22 , to the human in need.25. The method according to claim 24 , wherein the respiratory disease is asthma.26. The method according to claim 24 , wherein the respiratory disease is chronic obstructive pulmonary disease.27. The method according to claim 24 , wherein the respiratory disease is rhinitis.28. The method according to claim 24 , wherein 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2 claim 24 ,2-dimethyl-propionic acid is present in form of a sodium salt.29. The method according to claim 28 , wherein the respiratory disease is asthma.30. The method according to claim 28 , wherein the respiratory disease is chronic obstructive pulmonary disease.31. ...

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25-04-2013 дата публикации

METHOD OF MAKING COUPLED HETEROARYL COMPOUNDS VIA REARRANGEMENT OF HALOGENATED HETEROAROMATICS FOLLOWED BY OXIDATIVE COUPLING

Номер: US20130102785A1
Принадлежит: GEORGIA TECH RESEARCH CORPORATION

The inventions disclosed and described herein relate to new and efficient generic methods for making a wide variety of compounds having Formulas (I) and (II) as shown below (Formulas (I) and (II)) wherein HAr is an optionally substituted five or six membered heteroaryl ring, and Hal is a halogen, and Y is a bridging radical, such as S, Se, NRC(O), C(O)C(O), Si(R), SO, SO, PR, BR, C(R)or P(O)R. The synthetic methods employ a “Base-Catalyzed Halogen Dance” reaction to prepare a metallated compound comprising a five or six membered heteroaryl ring comprising a halogen atom, and then oxidatively coupling the reactive intermediate compound. The compounds of Formula (II) and/or oligomer or polymers comprising repeat units having Formula (II) can be useful for making semi-conducting materials, and/or electronic devices comprising those materials. 2. The method of wherein Hal is Br or I.3. The method of wherein HAr is an optionally substituted five membered heteroaryl ring.87. The method of any one of - wherein Ris a C-Caryl or heteroaryl optionally substituted by one to four ring substituents independently selected from halides claims 4 , alkyl claims 4 , alkynyl claims 4 , perfluoroalkyl claims 4 , alkoxide claims 4 , perfluoroalkoxide claims 4 , —Sn(R) claims 4 , —Si(R) claims 4 , —Si(OR)or —B(—OR)wherein each Ris an independently selected alkyl or aryl claims 4 , and each Ris an independently selected alkyl or aryl claims 4 , or the Rgroups together form an optionally substituted alkylene group to form a ring bridging the oxygen atoms.1110. The method of any one of - wherein the strongly basic compound is an alkyl lithium compound.1210. The method of any one of - wherein the strongly basic compound is a lithium dialkylamide compound.1310. The method of any one of - wherein the oxidizing agent is a Cu(II) salt.1410. The method of any one of - wherein the bishalo-bisheteroaryl compound is a 2 claims 1 ,2′-bishalo-1 claims 1 ,1′-bisheteroaryl compound.21. The method of ...

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25-04-2013 дата публикации

PROCESS FOR THE PREPARATION OF 5-SUBSTITUTED 1-ALKYLTETRAZOLYL OXIME DERIVATIVES

Номер: US20130102786A1
Принадлежит:

The present invention relates to a process for the preparation of 5-substituted 1-alkyltetrazolyl oxime derivatives. 3. Process according to one of claim 1 , characterized in that step (1) is carried out in the presence of a base.4. Process according to claim 3 , characterized in the molar ratio of base to the oxime of the formula (II) used is 0.8-10.5. Process according to claim 1 , characterized in that step (1) is carried out in a solvent.6. Process according to claim 1 , characterized in that step (2) is carried out in the presence of a base.7. Process according to claim 6 , characterized in that the molar ratio of base to the compound of the formula (IV) used is 0.8-10. The present invention relates to a process for the preparation of 5-substituted 1-alkyltetrazolyl oxime derivatives.5-Substituted 1-alkyltetrazolyl oxime derivatives are important intermediate compounds in active ingredient manufacture or are already fungicidally effective compounds (see e.g. WO 2010/000841). It is already known that 5-substituted 1-alkyltetrazoles can be prepared by lithiation of 1-methyltetrazole at −70° C. (cf. 1971, 49, 2139-2142). However, the yield using the example of 5-benzoyl-1-methyltetrazole is only 41%. The 1-methyltetrazole used likewise has to be prepared in a multistage synthesis sequence. For an industrial reaction, the low temperatures and the expensive use of butyllithium are disadvantageous. Another process for the preparation of 5-benzoyl-1-methyltetrazole is known from 1963, 85, 2967-2976. Benzyl cyanide is reacted with ammonium azide to give 5-benzyltetrazole and then oxidized with chromium trioxide to give 5-benzoyltetrazole. The methylation to 5-benzoyl-1-methyltetrazole takes place with diazomethane. This synthesis route is likewise disadvantageous as regards safety and economical aspects. The preparation of 1-cyclohexyl-5-acetyltetrazole by reacting acetyl chloride over cyclohexyl isocyanide with subsequent reaction with hydrazoic acid is also known (cf ...

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25-04-2013 дата публикации

NOVEL INDAZOLE DERIVATIVE OR SALT THEREOF AND PRODUCTION INTERMEDIATE THEREOF, AND ANTIOXIDANT USING SAME, AND USE OF INDAZOLE DERIVATIVE OR SALT THEREOF

Номер: US20130102787A1
Принадлежит:

A compound represented by formula (1) or salt thereof and a production intermediate thereof are created. The compound exhibited an excellent antioxidation action in a microsome lipid peroxidation measuring system using a rat liver microsome. Therefore, the compound or salt thereof is useful as an antioxidant. The present invention also provides use of a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof for production of an antioxidant. The present invention relates to a novel indazole derivative or salt thereof, and a production intermediate thereof. The present invention also relates to an antioxidant containing at least one of the indazole derivative or salt thereof as an active ingredient. Further, the present invention relates to use of such an indazole derivative or salt thereof, for production of an antioxidant.Recently, it has been revealed that generation of lipid peroxide in a biological body and radical reaction accompanying the same cause various adverse affects on the biological body through a membrane disorder, cell disorder or the like. In association with this, various attempts of application of an antioxidant or a lipid peroxide generation suppressing agent to a medicine have been made, and many studies for antioxidants are made.For example, as representative antioxidants, vitamin C, vitamin E, polyphenol and the like are used in foods and cosmetics. Also SOD (superoxide dismutase) or the like being an enzyme that brings active oxygen into an oxygen molecule and a hydrogen peroxide molecule is well known as an antioxidant. Further, edaravone is used as a therapeutic agent for preventing enlargement of an infarction site after cerebral infarction by its antioxidation action, and probucol or the like which is a therapeutic agent for hyperlipidemia is known to suppress oxidation of LDL (low density lipoprotein) and have an arteriosclerosis suppressing action. However, not many of these are practically satisfactory ...

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02-05-2013 дата публикации

Bile Acid Recycling Inhibitors for Treatment of Hypercholemia and Cholestatic Liver Disease

Номер: US20130108573A1
Принадлежит: Lumena Pharmaceuticals, Inc.

Provided herein are methods of treating or ameliorating hypercholemia or a cholestatic liver disease by administering to an individual in need thereof a therapeutically effective amount of an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising administering to an individual in need thereof a therapeutically effective amount of ASBTI or a pharmaceutically acceptable salt thereof. 1. A method for treating or ameliorating hypercholemia comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof.2. The method of claim 1 , wherein the method comprises decreasing at least 20% of serum bile acid or hepatic bile acid levels in the patient.3. The method of claim 1 , wherein less than 10% of the ASBTI is systemically absorbed.5. The method of claim 4 , wherein:q is 1;n is 2;{'sup': 'x', 'sub': 3', '2, 'Ris N(CH);'}{'sup': 7', '8, 'Rand Rare independently H;'}{'sup': 1', '2, 'Rand Ris alkyl;'}{'sup': 3', '4, 'Ris H, and Ris OH;'}{'sup': 5', '6', '9', '9', '9', '9', '9, 'sub': 2', '3', 'Z', 'Z, 'claim-text': wherein z is 1, 2 or 3; each L is independently a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted alkoxy, a substituted or unsubstituted aminoalkyl group, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted cycloalkyl, or a substituted or unsubstituted heterocycloalkyl; each K is a moiety that prevents systemic absorption;', {'sup': 15', '13', '13', '14', '13', '14', '13', '13', '13', '13', '13', '14', '13', ...

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02-05-2013 дата публикации

Chemical Compounds

Номер: US20130109667A1
Принадлежит:

The invention relates to new sulfonamide Nav1.7 inhibitors and pharmaceutically acceptable salts thereof, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. Nav 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain. 1. A compound selected from:5-Chloro-4-[4-chloro-2-(2-piperazin-1-ylpyrimidin-4-yl)phenoxy]-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide;5-Chloro-4-[4-chloro-2-(2-piperazin-1-ylpyrimidin-4-yl)phenoxy]-2-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide;5-Chloro-2-fluoro-4-[5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,3-thiazol-4-ylbenzenesulfonamide;5-Chloro-2-fluoro-4-[4-fluoro-2-pyridazin-4-yl-5-(trifluoromethyl)phenoxy]-N-1,3-thiazol-4-ylbenzenesulfonamide;4-[2-(2-Aminopyridin-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-(5-fluoropyrimidin-2-yl)benzenesulfonamide;4-[2-(2-Aminopyridin-4-yl)-4-(trifluoromethyl)phenoxy]-5-chloro-2-fluoro-N-(5-fluoropyrimidin-2-yl)benzenesulfonamide;4-[2-(2-Aminopyridin-4-yl)-4-fluorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide;4-[2-(3-Amino-1H-pyrazol-4-yl)-4-(trifluoromethoxy)phenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide;4-[2-(2-Aminopyridin-4-yl)-4-chlorophenoxy]-3-chloro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide;4-[2-(2-Aminopyridin-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide;4-[2-(5-Amino-1H-pyrazol-4-yl)-4-fluorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide;5-Chloro-2-fluoro-4-[2-pyridazin-4-yl-4-(trifluoromethoxy)phenoxy]-N-1,3-thiazol-4-ylbenzenesulfonamide;4-[2-(1-Azetidin-3-yl-1H-pyrazol-5-yl)-5-chloro-2-fluoro-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-5-ylbenzenesulfonamide;5-Chloro-2-fluoro-4-{4-trifluoromethyl-2-[1-(1-methylazetidin-3-yl)-1H-pyrazol-5-yl]phenoxy}-N-1,3,4-thiadiazol-ylbenzenesulfonamide;3-Cyano-4-[2-(3-methylpyridazin-4-yl)-4-(trifluoromethyl)phenoxy]-N-1, ...

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02-05-2013 дата публикации

GRP94 INHIBITORS

Номер: US20130109684A1
Принадлежит: University of Kansas

The present disclosure provides a series of compounds which exhibit isoform selective inhibition of GRP94, a homologue of Hsp90 that is localized to the endoplasmic recticulum. Through GRP94 inhibition, these compounds are likely to manifest anti-cancer, anti-inflammatory, anti-metastasis, and immunosuppressive activities, as well as utility in the treatment of neurodegenerative diseases, and diabetes. 4. The compound or pharmaceutically acceptable salt according to whereinV is N;X is CH;Y is CH; andZ is N.5. The compound or pharmaceutically acceptable salt according to wherein Ris F claim 1 , Cl claim 1 , Br claim 1 , or I.6. The compound or pharmaceutically acceptable salt according to wherein Ris Cl;{'sup': '2', 'Ris OH; and'}{'sup': '3', 'Ris OH.'}13. A pharmaceutical composition comprising a compound or salt according to and a pharmaceutically acceptable carrier.14. A method of treating or preventing a GRP94 related disorder in a patient in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a compound or salt according to claim 1 , and a pharmaceutically acceptable carrier or excipient to the patient.15. The method according to claim 14 , wherein the GRP94 related disorder is selected from the group consisting of cancer claim 14 , metastasis claim 14 , an inflammatory disorder claim 14 , a neurodegenerative disorder claim 14 , and diabetes. This application claims the benefit of priority to U.S. Provisional Application Ser. No. 61/473,343, filed Apr. 8, 2011, which is hereby incorporated herein by reference.This invention was made with Government support under National Institutes of Health (NIH) Grant Nos. AG18001, GM077480, DK053058 and CA109265, awarded by the National Cancer Institute. The Government has certain rights in this invention.1. Field of the InventionThe present disclosure provides a series of compounds which exhibit isoform selective inhibition of Glucose-related protein 94 (Grp94), ...

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02-05-2013 дата публикации

ISOINDOLONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS

Номер: US20130109686A1
Принадлежит:

The present invention is directed to isoindolone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor. 2. The compound of wherein W is pyridyl claim 1 , and pharmaceutically acceptable salts thereof.3. The compound of wherein W is phenyl claim 1 , and pharmaceutically acceptable salts thereof.4. The compound of wherein R is Ccycloalkyl optionally substituted with 1 to 3 groups of R claim 1 , and pharmaceutically acceptable salts thereof.5. The compound according to wherein R is cyclohexyl or cyclohexenyl claim 4 , both optionally substituted with 1 to 3 groups of R claim 4 , and pharmaceutically acceptable salts thereof.6. The compound of wherein R is (CHR)Cheterocycle claim 1 , optionally substituted with 1 to 3 groups of R claim 1 , and pharmaceutically acceptable salts thereof.7. The compound according to wherein R is pyranyl claim 6 , tetrahydropyranyl claim 6 , or pyridyl claim 6 , all optionally substituted with 1 to 3 groups of R claim 6 , and pharmaceutically acceptable salts thereof.8. The compound according to wherein R is (CHR)Caryl claim 1 , optionally substituted with 1 to 3 groups of R claim 1 , and pharmaceutically acceptable salts thereof.9. The compound according to wherein R is phenyl optionally substituted with 1 to 3 groups of R claim 8 , and pharmaceutically acceptable salts thereof.15. A compound of formula (I) of which is found in Table 1 as well as those listed immediately below:2-[(1S,2S)-2-Hydroxycyclohexyl]-5-(4-methoxybenzyl)-1,2-dihydro-3H-benzo[e]isoindol-3-one;2-[(1S,2S)-2-Hydroxycyclohexyl]-5-[(6-methylpyridin-3-yl)methyl]-1,2-dihydro-3H-benzo[e]isoindol-3-one,2-[(1S ...

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02-05-2013 дата публикации

POLYCYCLIC HETEROARYL SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS

Номер: US20130109695A1
Принадлежит: Rigel Pharmaceuticals, Inc.

Polycyclic heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl activity are also disclosed. 2. The method of wherein the disease or condition is selected from rheumatoid arthritis claim 1 , vascular disease claim 1 , vascular injury claim 1 , psoriasis claim 1 , visual impairment due to macular degeneration claim 1 , diabetic retinopathy claim 1 , retinopathy of prematurity claim 1 , kidney disease claim 1 , osteoarthritis and cataracts.3. The method of wherein a manifestation of the disease or condition is solid tumor formation in the mammal.4. The method of wherein the disease or condition is selected from breast carcinoma claim 3 , renal carcinoma claim 3 , endometrial carcinoma claim 3 , ovarian carcinoma claim 3 , thyroid carcinoma claim 3 , non-small cell lung carcinoma and uveal melanoma.5. The method of wherein a manifestation of the disease or condition is liquid tumor formation in the mammal.6. The method of wherein the disease or condition is myeloid leukemia or lymphoma.7. The method of wherein the disease or condition is endometriosis.8. The method of wherein the disease or condition is metastasis to the liver.9. The method of wherein the disease or condition is a cell proliferative disorder.10. The method of wherein the cell proliferative disorder is selected from renal cell carcinoma claim 9 , clear cell carcinoma of kidney claim 9 , renal cell adenocarcinoma claim 9 , invasive ductal carcinoma claim 9 , invasive lobular carcinoma claim 9 , ductal carcinoma claim 9 , lobular carcinoma in situ claim 9 , metastatic breast cancer claim 9 , basal cell carcinoma claim 9 , squamous cell carcinoma claim 9 , malignant melanoma claim 9 , Karposi's sarcoma claim 9 , small cell lung carcinoma claim 9 , non-small cell lung carcinoma claim 9 ...

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02-05-2013 дата публикации

FAAH Inhibitors

Номер: US20130109721A1
Принадлежит: Ironwood Pharmaceuticals, Inc.

The present disclosure relates to N-benzyl pyrrole compounds of formula (I) useful as inhibitors of the enzyme Fatty Acid Amide Hydrolase (FAAH). The disclosure also provides pharmaceutically acceptable compositions comprising the compounds of the disclosure and methods of using the compositions in the treatment or prevention of various disorders. 2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein ring B is an optionally substituted ring selected from the group consisting of phenyl claim 1 , pyridine claim 1 , pyrimidine claim 1 , pyrazine claim 1 , pyridazine claim 1 , pyrrole claim 1 , imidazole claim 1 , pyrazole claim 1 , furan claim 1 , thiophene claim 1 , triazole claim 1 , tetrazole claim 1 , thiazole claim 1 , oxathiazole and oxazole.3. The compound according to claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein ring B is an optionally substituted pyridine or an optionally substituted phenyl.45.-. (canceled)6. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein n is selected from the group consisting of 0 and 1.7. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Jis independently selected from the group consisting of halogen claim 1 , Calkyl claim 1 , cyclopropyl claim 1 , cyclopropyloxy claim 1 , Chaloalkyl claim 1 , Calkoxy and Chaloalkoxy.8. The compound according to claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein each Jis independently selected from the group consisting of halogen claim 7 , methyl claim 7 , ethyl claim 7 , propyl claim 7 , isopropyl claim 7 , trifluoromethyl claim 7 , methoxy claim 7 , trifluoromethoxy claim 7 , ethoxy claim 7 , propyloxy and isopropyloxy.10. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein p is selected from the group consisting of 0 claim 1 , 1 and 2.11. The compound ...

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02-05-2013 дата публикации

TELOMERASE INHIBITORS AND A METHOD FOR THE PREPARATION THEREOF

Номер: US20130109861A1

The invention relates to the field of organic and medicinal chemistry, and molecular biology, and concerns a method for the preparation of a new class of telomerase-inhibiting compounds, which can be utilized for studying telomerases and catalytic sub-units of telomerases, and reverse transcriptases, and foe studying and treating neoplastic and viral diseases. Telomerase-inhibiting coordination compounds of derivatives of imidazol-4-one are characterized by general formula 2. The coordination compounds according to claim 1 , wherein said substituent A is an unsubstituted or monosubstituted claim 1 , or disubstituted aryl substituent claim 1 , wherein substituents in the aryl group are selected from the group consisting of halogens and alkyl substituents.3. The coordination compounds according to claim 1 , wherein said substituent A is an unsubstituted or monosubstituted claim 1 , or disubstituted condensed aryl substituent claim 1 , wherein substituents in the condensed aryl group is selected from the group consisting of halogens and alkyl groups.4. The coordination compounds according to claim 1 , wherein said substituent A is selected from the group consisting of phenyl CH— claim 1 , 3-chloro-4-fluorophenyl 3-Cl-4-F—CH— claim 1 , 4-carbethoxyphenyl 4-CHO(O)CCH— claim 1 , methyl CH— claim 1 , allyl CH═CHCH— claim 1 , 2-antranyl claim 1 , propyl CH—.5. The coordination compounds according to claim 1 , wherein said substituent B is selected from the groups consisting of 1 claim 1 ,2-ethandiyl—(CH)— claim 1 , 1 claim 1 ,3-propanediyl—(CH)— claim 1 , 1 claim 1 ,4-buthanediyl—(CH)— claim 1 , 1 claim 1 ,6-hexanediyl—(CH)— claim 1 , 1 claim 1 ,10-decanediyl—(CH)—.6. The coordination compounds according to claim 1 , wherein said substituent C is selected from the group consisting of 2-quinolyl claim 1 , 2-pyridyl claim 1 , 1-methyl-2-imidazolyl claim 1 , 4-methyl-5-imidazolyl claim 1 , 5-imidazolyl claim 1 , 2-imidazolyl claim 1 , 1 claim 1 ,5-dimethyl-3-pyrazolyl claim 1 ...

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09-05-2013 дата публикации

Organic light-emitting device, method of manufacturing the same, and flat panel display device including the same

Номер: US20130112949A1
Принадлежит: Samsung Display Co Ltd

An organic light-emitting device including: a substrate; a first electrode; a second electrode; an emission layer between the first electrode and the second electrode; and an electron transport layer between the emission layer and the second electrode, wherein the emission layer includes a blue emission layer, the electron transport layer includes a unit that includes a first single layer including a first material, a first mixed layer on the first single layer and including the first material and a second material, a second single layer on the first mixed layer and including the second material, a second mixed layer on the second single layer and including the first and second materials, and a third single layer on the second mixed layer and including the first material, wherein the first mixed layer has a thickness that is larger than that of the second mixed layer.

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09-05-2013 дата публикации

HETEROCYCLIC RING COMPOUND

Номер: US20130116214A1
Принадлежит:

The present invention provides a compound having a muscle cell or adipocyte differentiation regulating action, useful for the prophylaxis or treatment of diseases such as diabetes, obesity, dyslipidemia and the like, and the like, and having superior efficacy. 2. The compound or salt of claim 1 , wherein Lis a Calkenylene group.3. The compound or salt of claim 1 , wherein Lis a Calkylene group.4. The compound or salt of claim 1 , wherein A is a benzene ring optionally substituted by 1 to 3 substituents selected from a Calkoxy group and a halogen atom.5. The compound or salt of claim 1 , wherein Y is a bond or —O—.6. The compound or salt of claim 1 , wherein Ris{'sub': '1-6', '(1) imidazolyl, oxadiazolyl or morpholinyl, each of which is optionally substituted by 1 to 3 Calkyl groups,'}{'sub': '1-6', '(2) benzimidazolyl optionally substituted by 1 to 3 Calkyl groups,'}{'sub': 3', '2', '2', '5', '2, 'is (3) —PO(OCH)or —PO(OCH)or'}{'sub': 2', '3, '(4) —S(O)CH.'}7. The compound or salt of claim 1 , wherein Ris imidazol-1-yl claim 1 , benzimidazol-1-yl claim 1 , 1 claim 1 ,3 claim 1 ,4-oxadiazol-2-yl or morpholin-4-yl claim 1 , each of which is optionally substituted by Calkyl group(s).10. (2E)-3-[4-(4-Fluorophenyl)pyridin-3-yl]-N-{4-[2-(1 claim 1 ,3 claim 1 ,4-oxadiazol-2-yl)ethyl]phenyl}prop-2-enamide or a salt thereof.11. (2E)-3-[4-(4-Fluorophenyl)pyrimidin-5-yl]-N-{4-[2-(1 claim 1 ,3 claim 1 ,4-oxadiazol-2-yl)ethyl]phenyl}prop-2-enamide or a salt thereof.12. A medicament comprising the compound or salt of .13. The medicament of claim 12 , which is a muscle cell or adipocyte differentiation regulating agent.14. The medicament of claim 12 , which is an agent for the prophylaxis or treatment of a muscle cell or adipocyte differentiation-associated disease.15. The medicament of claim 12 , which is an agent for the prophylaxis or treatment of diabetes claim 12 , obesity or dyslipidemia.16. A method for the prophylaxis or treatment of diabetes claim 1 , obesity or ...

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09-05-2013 дата публикации

THIAZOLES AND PYRAZOLES USEFUL AS KINASE INHIBITORS

Номер: US20130116228A1
Принадлежит: VERTEX PHARMACEUTICALS INCORPORATED

The present invention relates to compounds useful as inhibitors of Aurora protein kinases. The invention also provides pharmaceutically acceptable compositions comprising those compounds and methods of using the compounds and compositions in the treatment of various disease, conditions, and disorders. The invention also provides processes for preparing compounds of the invention. 2. (canceled)3. (canceled)4. The compound of claim 1 , wherein Xis N.5. The compound of claim 1 , wherein Xis CH.6. The compound of claim 1 , wherein Xis N.7. The compound of claim 1 , wherein Xis CH.9. The compound of selected from a compound of formula I-a.11. The compound of claim 10 , wherein Q is —S—.12. The compound of claim 10 , wherein Q is —O—.13. The compound of any one of or claim 10 , wherein Ris H or Calkyl.14. The compound of any one of or claim 10 , wherein Ris H.15. The compound of claim 1 , wherein Ring D is a 5-6 membered monocyclic aryl or heteroaryl ring; and Ring D is fused with Ring D′.16. The compound of claim 1 , wherein Ring D-D′ is an 8-12 membered bicyclic aryl or heteroaryl containing 1-5 heteroatoms selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.1722-. (canceled)23. The compound of claim 1 , wherein Ring D is a 5-6 membered monocyclic aryl or heteroaryl ring; and wherein D is not fused with D′.24. The compound of claim 23 , wherein Ring D is a 6-membered monocyclic aryl or heteroaryl ring.25. The compound of claim 24 , wherein Ring D is phenyl or pyridyl.26. The compound of claim 25 , wherein Ring D is phenyl.2730-. (canceled)31. The compound of claim 1 , wherein Ris —Z—R.32. The compound of claim 31 , wherein Ris absent.33. The compound of claim 31 , wherein Z is a Calkylidene chain wherein 1-2 methylene units of Z is optionally replaced by O claim 31 , —N(R)— claim 31 , or S.3433. The compound of any one of - claims 31 , wherein Ris an optionally substituted azetidine.3536-. (canceled)3646-. (canceled) This application is a continuation ...

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09-05-2013 дата публикации

NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A

Номер: US20130116229A1
Принадлежит:

The present invention relates to compounds which are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders. 2. The compound of claim 1 , where Ris selected from the group consisting of halogen claim 1 , CN claim 1 , OH claim 1 , C-C-alkyl claim 1 , fluorinated C-C-alkyl claim 1 , C-C-alkoxy claim 1 , fluorinated C-C-alkoxy claim 1 , C-C-cycloalkyl claim 1 , fluorinated C-C-cycloalkyl claim 1 , N(R)(R) claim 1 , C-C-alkyl-N(R)(R) claim 1 , C(O)O—R claim 1 , C(O)N(R)(R) claim 1 , N(R)S(O)(R) and S(O)N(R)(R).3. The compound of claim 1 , where Xis C—H.4. The compound of claim 1 , where Xis N.5. The compound of claim 1 , where Xis C—R.6. The compound of claim 1 , where Xis N.7. The compound of claim 1 , where Y is O.8. The compound of claim 1 , where Ris C-C-alkyl claim 1 , C-C-cycloalkyl or C-C-cycloalkylmethyl.9. The compound of claim 8 , where Ris a radical of the formula CHRR claim 8 , where Ris selected from the group consisting of hydrogen and C-C-alkyl and where Ris selected from the group consisting of C-C-alkyl.10. The compound of claim 1 , where Ris a moiety Z—Ar.11. The compound of claim 1 , where Ris a radical of the formula CRRR.12. The compound of claim 11 , where{'sup': 21', '22', 'g', 'h', 'h', 'g, 'sub': '2', 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'Rand Rtogether with the carbon atom, to which they are bound form a saturated 5- to 7-membered carbocyclic ring or a saturated 5- to 7-membered heterocyclic ring which has 1, 2 or 3 heteroatoms or heteroatom containing groups selected from the group of O, N, S, SO and SOas ring members, where the carbocyclic ring and the heterocyclic ring may be unsubstituted or may be substituted by 1, 2 or 3 identical or different ...

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09-05-2013 дата публикации

TYROSINE KINASE INHIBITORS

Номер: US20130116231A1
Принадлежит:

The present invention relates to 1,4-dihydropyridazinone derivatives, that are useful for treating cellular proliferative diseases, for treating disorders associated with MET activity, and for inhibiting the receptor tyrosine kinase MET. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals. 2. The compound of wherein Ris heteroaryl claim 1 , wherein said heteroaryl group is optionally substituted with one to three groups independently selected from the group consisting of halo claim 1 , cyano or Calkyl; or a pharmaceutically acceptable salt thereof.3. The compound of wherein Ris heteroaryl claim 2 , wherein said heteroaryl group is optionally substituted with Calkyl claim 2 , or a pharmaceutically acceptable salt thereof.4. The compound of wherein Ris hydrogen claim 2 , R is hydrogen claim 2 , Ris hydrogen and R is hydrogen claim 2 , or a pharmaceutically acceptable salt thereof.5. The compound of wherein Ris heteroaryl or phenyl claim 1 , wherein said heteroaryl and phenyl groups are optionally substituted with one to three groups independently selected from the group consisting of halo claim 1 , oxo claim 1 , Calkyl claim 1 , (Calkyl)OR claim 1 , OR claim 1 , R claim 1 , OR claim 1 , O(Calkyl)OR claim 1 , O(Calkyl)R claim 1 , (C═O)R claim 1 , (C═O)OR claim 1 , (C═O)NHR claim 1 , (C═O)R claim 1 , NHR claim 1 , NH(C═O)OR claim 1 , NH(C═O)R claim 1 , NH(C═O)O(Calkyl)ORand NO;or a pharmaceutically acceptable salt thereof.6. The compound of wherein Ris quinolinyl claim 5 , wherein said quinolinyl is optionally substituted with one to three groups independently selected from the group consisting of halo claim 5 , oxo claim 5 , Calkyl claim 5 , (Calkyl)OR claim 5 , OR claim 5 , R claim 5 , OR claim 5 , O(Calkyl)OR claim 5 , O(Calkyl)R claim 5 , (C═O)R claim 5 , (C═O)OR claim 5 , (C═O)NHR claim 5 , (C═O)R claim 5 , NHR claim 5 , NH(C═O)OR claim 5 , NH(C═O)R claim 5 , NH(C═O)O(Calkyl)ORand NO; or a ...

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09-05-2013 дата публикации

NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A

Номер: US20130116233A1
Принадлежит:

The present invention relates to novel compounds of the formula I which are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders. 3. The compound of claim 1 , where Xis selected from O claim 1 , S claim 1 , —X═C(R)— claim 1 , where C(R) is bound to the carbon atom which carries R.4. The compound of claim 1 , where A is selected from A claim 1 , A claim 1 , Aand A.5. The compound of claim 1 , where Xis C—R.6. The compound of claim 5 , where Ris hydrogen or Y-Cyc.7. The compound of claim 1 , where Xis N.8. The compound of claim 1 , where Xis CH.9. The compound of claim 1 , where Xis S.10. The compound of claim 1 , where Xis O.11. The compound of claim 1 , where Xis C(R)═C(R).12. The compound of claim 1 , where Xis N═(CR).13. The compound of claim 11 , where Ris hydrogen or Y-Cyc3.14. The compound of claim 1 , where Xis N═C(R).15. The compound of claim 11 , where Ris hydrogen.16. The compound of claim 1 , where Ris a radical Y-Cyc.17. The compound of claim 1 , where Ris selected from the group consisting of hydrogen claim 1 , fluorine claim 1 , C-C-alkyl claim 1 , C-C-fluoroalkyl claim 1 , C-C-alkoxy claim 1 , C-C-fluoroalkoxy claim 1 , cyclopropyl claim 1 , optionally substituted by 1 claim 1 , 2 or 3 methyl groups claim 1 , and fluorinated cyclopropyl.18. The compound of claim 17 , where Ris hydrogen.19. The compound of claim 1 , where A is A.20. The compound of claim 19 , where R claim 19 , Rare selected from hydrogen and fluorine.21. The compound of claim 19 , where Rand Rare claim 19 , independently of each other claim 19 , selected from the group consisting of hydrogen claim 19 , fluorine and methyl.22. The compound of claim 1 , where A is A.23. The compound of claim 1 , where A is ...

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09-05-2013 дата публикации

8-FLUOROPHTHALAZIN-1(2H)-ONE COMPOUNDS

Номер: US20130116246A1
Принадлежит: Genentech, Inc.

8-Fluorophthalazin-1(2h)-one compounds of Formula II where one or two of X, X, and Xare N, are provided, including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula II for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 2. The compound of wherein Ris —(C-Cheteroaryl)-(C-Cheterocyclyl).3. The compound of wherein Ris —(C-Cheteroaryl)-(C-Cheterocyclyl) and where heteroaryl is optionally substituted pyridinyl and heterocyclyl is optionally substituted piperazinyl.4. The compound of wherein Ris C-Cheteroaryl.5. The compound of wherein Ris selected from:pyrimidinyl,6,7-dihydro-4H-thiazolo[5,4-c]pyridin-2-yl,5-(morpholine-4-carbonyl)-2-pyridyl,pyrazolyl,thiazolyl,6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-2-yl,oxazolyl,isoxazolyl,imidazolyl,5-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-yl,1,2,3-triazolyl,4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine,pyrazinyl, and5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-yl.7. The compound of wherein Xis N claim 1 , Xis CR claim 1 , and Xis CR.8. The compound of wherein Xis CR claim 1 , Xis N claim 1 , and Xis CR.9. The compound of wherein Xis CR claim 1 , Xis CR claim 1 , and Xis N.10. The compound of selected from: Xand Xare N claim 1 , Xand Xare N claim 1 , or Xand Xare N.11. The compound of wherein Xis CR claim 1 , and Ris F.12. The compound of wherein Xand Xare CH.13. The compound of wherein Ris —CHOH.16. The compound of wherein Ris —CH claim 14 , and n is 1 or 2.17. The compound of wherein Ris oxetan-3-yl.18. The compound of wherein Yis CH.19. The compound of wherein Yis CH.20. The compound of wherein Zis CH.21. The compound of wherein Zis CH.22. The compound of selected from Table 123. The compound of selected from Table 224. A pharmaceutical composition comprised of a ...

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09-05-2013 дата публикации

IRE-1alpha INHIBITORS

Номер: US20130116247A1
Принадлежит: MANNKIND CORPORATION

Compounds which directly inhibit IRE-1α activity in vitro, prodrugs, and pharmaceutically acceptable salts there-of. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response or with regulated IRE1-dependent decay (RIDD) and can be used as single agents or in combination therapies. 114-. (canceled)16. A product comprising a compound of , wherein the product is selected from the group consisting of (a) a pharmaceutical composition comprising the compound of and a pharmaceutically acceptable vehicle; and (b) a complex comprising IRE-1α and the compound of .17. A method of inhibiting IRE-1α activity claim 15 , comprising contacting IRE-1α with a compound of or a prodrug or pharmaceutically acceptable salt thereof.18. The method of wherein the IRE-1α activity is selected from the group consisting of cleavage of RNA claim 17 , cleavage of mRNA claim 17 , RNA splicing claim 17 , and mRNA splicing.19. The method of wherein the IRE-1α activity is cleavage of mRNA and wherein the mRNA is selected from the group consisting of Blos1 mRNA claim 18 , DGAT2 mRNA claim 18 , CD59 mRNA claim 18 , and IRE-1α mRNA.20. The method of claim 18 , wherein the IRE-1α activity is inhibited to treat a disorder associated with the unfolded protein response claim 18 , comprising administering to a patient in need thereof the compound of or the prodrug or pharmaceutically acceptable salt thereof.21. The method of further comprising administering a therapeutic agent that induces or up-regulates IRE-1α expression.2202. The method of claim further comprising administering a therapeutic agent which is less effective when IRE-1α is expressed.23. The method of claim 20 , further comprising administering to the patient a proteasome inhibitor.24. The method of claim 20 , wherein the IRE-1α activity is inhibited to treat a disorder associated with a target of regulated IRE 1-dependent decay (RIDD) claim 20 , comprising administering to a patient in need ...

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09-05-2013 дата публикации

Novel HSP90 Inhibitor

Номер: US20130116252A1
Принадлежит: Nippon Kayaku Co Ltd

Disclosed is a triazole derivative(s) represented by the general formula (1) below or a pharmacologically acceptable salt(s) thereof. Also disclosed are a prodrug(s) of such a triazole derivative(s) and an HSP90 inhibitor(s) containing any one of them as an active constituent. (1) (In the formula, X represents a halogen atom, an optionally substituted alkyl group, an optionally substituted alkynyl group or the like; Y represents a mercapto group, a hydroxyl group, an optionally substituted sulfonyl group, an optionally substituted amino group or the like; and R represents an optionally substituted aryl or alkyl group or the like.)

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09-05-2013 дата публикации

Novel HSP90 Inhibitor

Номер: US20130116253A1
Автор: Tomura Arihiro
Принадлежит: Nippon Kayaku Kabushiki Kaisha

Disclosed is a triazole derivative(s) represented by the general formula (1) below or a pharmacologically acceptable salt(s) thereof. Also disclosed are a prodrug(s) of such a triazole derivative(s) and an HSP90 inhibitor(s) containing any one of them as an active constituent. (1) (In the formula, X represents a halogen atom, an optionally substituted alkyl group, an optionally substituted alkynyl group or the like; Y represents a mercapto group, a hydroxyl group, an optionally substituted sulfonyl group, an optionally substituted amino group or the like; and R represents an optionally substituted aryl or alkyl group or the like.) 2. The method of claim 1 , wherein the compound is not3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(3-trifluoromethyl-phenyl)-5-carbamoyloxy-[1,2,4]triazole;3-(2,4-Dihydroxy-5-ethyl-phenyl)-4-(1-methyl-indol-4-yl)-5-carbamoyloxy-[1,2,4]triazole;3-(2,4-Dihydroxy-5-methoxy-phenyl)-4-(8-methoxy-quinolin-5-yl)-5-carbamoyloxy-[1,2,4]triazole;3-(2-Hydroxy-4-ethoxycarbonyoxy-5-methoxy-phenyl)-4-(1-isopropyl-benzoimidazol-4-yl)-5-hydroxy-[1,2,4]triazole;3-(2-Hydroxy-4-ethoxycarbonyoxy-5-ethyl-phenyl)-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(naphthalin-2-yl)-5-hydroxy-[1,2,4]triazole;3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-chloro-phenyl]-4-(quinolin-5-yl)-5-mercapto-[1,2,4]triazole;3-[2-Hydroxy-4-(dimethyl-carbamoyoxy)-5-ethyl-phenyl]-4-(2,3-difluoro-phenyl)-5-mercapto-[1,2,4]triazole; or3-[2-Hydroxy-4-isobutyryloxy-5-ethyl-phenyl]-4-(1-methyl-benzo-imidazol-4-yl)-5-hydroxy-[1,2,4]triazole.3. The method of claim 1 , wherein when Y is —OH or —SH claim 1 , Rand Rare selected from the group consisting of an acyl group claim 1 , a carbamoyl group claim 1 , an alkoxycarbonyl group claim 1 , and an alkoxymethyl group.4. The method of claim 1 , wherein Rand Rare the same.5. The method of claim 1 , wherein R is an optionally substituted carbocyclic aryl group.6. The method of claim 1 , wherein R is an ...

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09-05-2013 дата публикации

ANDROGEN RECEPTOR MODULATORS AND USES THEREOF

Номер: US20130116258A1
Принадлежит: ARAGON PHARMACEUTICALS, INC.

Described herein are compounds that are androgen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such androgen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon androgen receptors. 2. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , or N-oxide thereof claim 1 , wherein:{'sup': '1', 'sub': 3', '6, 'both Rare taken together with the carbon atom to which they are attached to form a C-Ccycloalkyl;'}or{'sup': '1', 'sub': 1', '4, 'each Ris independently C-Calkyl;'}X is S;ring B is phenyl;{'sup': '4', 'sub': 1', '6', '1', '6', '1', '6, 'Ris H, halogen, —CN, —OH, C-Cfluoroalkyl, C-Cfluoroalkoxy, or C-Calkoxy;'}{'sup': 5', '9', '9', '10', '10', '9', '10', '9', '9', '9', '1', '2', '6, 'sub': 2', '2', '2', '2', '2', '2', '2', '1', '10', '1', '10', '1', '10', '1', '10', '1', '10', '3', '10', '2', '10, 'claim-text': [{'sup': '1', 'sub': 2', '2, 'Lis absent, —O—, —S—, —S(O)—, —S(O)—, —NH—, —C(═O)—, —C(═O)NH—, or —S(═O)NH—;'}, {'sup': '2', 'sub': 1', '6', '1', '6', '1', '6, 'Lis C-Calkylene, C-Cfluoroalkylene or C-Cheteroalkylene;'}, {'sup': 6', '9', '9', '10', '10', '9', '9', '9, 'sub': 2', '2', '2', '2', '2', '2', '3', '10', '2', '10, 'Ris —CN, —NO, —OH, —OR, —SR, —S(═O)R, —S(═O)R, —S(═O)N(R), —COR, —C(═O)N(R), substituted or unsubstituted C-Ccycloalkyl, substituted or unsubstituted C-Cheterocycloalkyl, substituted or unsubstituted monocyclic heteroaryl, substituted or unsubstituted bicyclic heteroaryl, or substituted or unsubstituted aryl.'}], 'Ris halogen, —CN, —NO, —OH, —OR, —SR, —S(═O)R, —S(═O)R, —S(═O)N(R), —C(═O)R, —COR, —N(R), —C(═O)N(R), C-Calkyl, C-Cfluoroalkyl, C-Cfluoroalkoxy, C-Calkoxy, C-Cheteroalkyl, substituted or unsubstituted C-Ccycloalkyl, substituted or unsubstituted C-Cheterocycloalkyl, substituted or unsubstituted phenyl, substituted or ...

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09-05-2013 дата публикации

Novel Hetaryl (thio)carboxamide Compounds for Controlling Invertebrate Pests

Номер: US20130116264A1
Принадлежит: BASF SE

The present invention relates to hetaryl (thio)carboxamide compounds of formula I, to the tautomers and N-oxides thereof and to the salts thereof: 115-. (canceled)17. The compound of wherein X is oxygen.18. The compound of claim 16 , wherein Rselected from the group consisting of C-C-alkyl claim 16 , C-C-haloalkyl claim 16 , C-C-alkenyl claim 16 , C-C-alkynyl claim 16 , C-C-alkylene-CN claim 16 , C-C-alkylene-OR claim 16 , phenyl-C-C-alkyl claim 16 , C-C-cycloalkyl-C-C-alkyl claim 16 , 5- or 6-membered saturated heterocyclyl-C-C-alkyl claim 16 , and 5- or 6-membered hetaryl-C-C-alkyl claim 16 , where the cycloalkyl ring and the heterocyclyl ring in C-C-cycloalkyl-C-C-alkyl and heterocyclyl-C-C-alkyl claim 16 , respectively claim 16 , is unsubstituted or carry 1 claim 16 , 2 claim 16 , 3 claim 16 , 4 or 5 claim 16 , in particular 1 claim 16 , 2 or 3 claim 16 , identical or different substituents R claim 16 , and where the phenyl ring and the hetaryl ring in phenyl-C-C-alkyl and hetaryl-C-C-alkyl claim 16 , respectively claim 16 , is unsubstituted or carry 1 claim 16 , 2 claim 16 , 3 claim 16 , 4 or 5 identical or different substituents R.20. The compound of claim 19 , wherein A is a radical A2.21. The compound of claim 19 , wherein A is a radical A1.22. The compound of claim 19 , wherein A is a radical A3.23. The compound of claim 19 , wherein A is selected from the group consisting of the radicals A4 claim 19 , A5 claim 19 , A6 and A7.24. The compound of claim 19 , wherein Z is NRwith Rbeing selected from the group consisting of C-C-alkyl claim 19 , C-C-haloalkyl claim 19 , heterocyclyl-C-C-alkyl claim 19 , C-C-alkoxy-C-C-alkyl claim 19 , C-C-alkylene-CN claim 19 , C-C-cycloalkyl claim 19 , C-C-cycloalkyl-C-C-alkyl claim 19 , where the cycloalkyl moiety is in the last two mentioned radicals is unsubstituted or carries 1 or 2 radicals selected from the group consisting of halogen claim 19 , CN and C-C-haloalkyl.25. The compound of claim 24 , wherein A is a radical A2 ...

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09-05-2013 дата публикации

Substituted indole derivatives

Номер: US20130116283A1
Принадлежит: Grünenthal GmbH

Substituted indole derivatives, processes for the preparation thereof, medicinal products and pharmaceutical compositions containing these compounds and the use of substituted indole derivatives to treat pain and other conditions and for other medical purposes. 3. Substituted indole derivative according to claim 1 , wherein A denotes CHand B denotes CHor C═O.4. Substituted indole derivative according to claim 1 , wherein X stands for indolyl claim 1 , which is unsubstituted or mono- or polysubstituted with one or more substituents independently selected from the group consisting of F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , CN claim 1 , CH claim 1 , CH claim 1 , CH claim 1 , NH claim 1 , NO claim 1 , SH claim 1 , CF claim 1 , OH claim 1 , OCH claim 1 , OCH claim 1 , N(CH)and phenyl claim 1 , which phenyl is itself unsubstituted or mono- or polysubstituted with one or more substituents independently selected from the group consisting of F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , CN claim 1 , CH claim 1 , CH claim 1 , NH claim 1 , NO claim 1 , SH claim 1 , CF claim 1 , OH claim 1 , OCH claim 1 , OCHand N(CH).5. Substituted indole derivative according to claim 1 , wherein{'sup': 1', '2, 'Rand Rindependently denote methyl or H.'}6. Substituted indole derivative according to claim 1 , wherein{'sup': '3', 'sub': 3', '2', '5', '2', '2', '3', '3', '2', '5', '3', '2, 'Rstands for phenyl, benzyl, phenethyl, thienyl, pyridyl, thiazolyl, imidazolyl, 1,2,4-triazolyl, benzimidazolyl or benzyl, each of which is unsubstituted or mono- or polysubstituted with one or more substituents independently selected from the group consisting of F, Cl, Br, CN, CH, CH, NH, NO, SH, CF, OH, OCH, OCHor N(CH); and ethyl,'}{'sub': 3', '2', '5, 'n-propyl, 2-propyl, allyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, cyclopentyl or cyclohexyl, each of which is unsubstituted or mono- or polysubstituted with one or more substituents independently ...

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