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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 15384. 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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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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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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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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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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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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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

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

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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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

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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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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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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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

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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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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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

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: 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

PROCESS FOR PREPARATION OF 2-METHYL-2'-PHENYLPROPIONIC ACID DERIVATIVES AND NOVEL INTERMEDIATE COMPOUNDS

Номер: US20130116439A1
Принадлежит: YUHAN CORPORATION

The present invention relates to a process for preparing 2-methyl-2′-phenylpropionic acid derivatives showing antihistamine activity in more simplified way, intermediate compounds and their preparation processes used therefore. According to the present invention, pharmaceutically useful 2-methyl-2′-phenylpropionic acid derivatives can be prepared with high yield and purity on industrial scale. 1. A compound of the following Formula 1a:{'sub': 1', '1', '6, 'wherein Ris hydrogen or C-Clinear or branched alkyl.'} This application is a divisional of U.S. application Ser. No. 12/865,234 filed Jul. 29, 2010, which is a national phase application and claims priority to PCT Application No. PCT/KR2009/000668 filed Feb. 12, 2009 that claims priority to Korean Application No. 10-2008-0012656 filed Feb. 12, 2008 and Korean Application No. 10-2008-0090385 filed Sep. 12, 2008, all of which are incorporated herein by reference in their entireties.(a) Field of the InventionThe present invention relates to a process for preparing 2-methyl-2′-phenylpropionic acid derivatives, novel intermediate compounds and their preparation processes used therefore.(b) Description of the Related Art2-methyl-2′-phenylpropionic acid derivatives of the following Formula 1 show excellent antihistamine activity and antiallergic activity, and thus widely used in the field of pharmaceutics.wherein, A is oxygen or nitrogen; Ris hydrogen or C-Clinear or branched alkyl when A is oxygen, and Rtogether with A forms a 5 to 7-membered ring unsubstituted or substituted with C-Clinear or branched alkyl when A is nitrogen; Ris hydrogen or —CHCHOR′, provided that Ris —CHCHOR′ when A is nitrogen; and R′ is hydrogen, C-Clinear or branched alkyl, C-Ccyclic alkyl, or C-Calkenyl.Particularly, 2-methyl-2′-phenylpropionic acid derivatives exclusively have Hantihistamine activity. Thus, they show high selectivity without acting with other pharmaceutical receptors even at higher dose. Therefore, 2-methyl-2′-phenylpropionic ...

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16-05-2013 дата публикации

N-PHENYL-2-PYRIMIDINEAMINE DERIVATIVES

Номер: US20130121963A1
Принадлежит: CONCERT PHARMACEUTICALS INC.

This disclosure relates to novel N-phenyl-2-pyrimidineamines and pharmaceutically acceptable salts thereof. This disclosure also provides compositions comprising a compound of this disclosure and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering protein-tyrosine kinase inhibitors. 2. The compound of claim 1 , wherein each of Rand Ris independently selected from hydrogen and —CH.3. The compound of or claim 1 , wherein X is selected from a pharmaceutically acceptable salt of —POHand -A-R claim 1 , wherein A is a naturally occurring α-amino acid and Ris hydrogen.4. The compound of claim 3 , wherein X is a pharmaceutically acceptable salt of —POH.65. The compound of claim 3 , claim 3 , claim 3 , or claim 3 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.8. The composition of claim 7 , wherein the composition is formulated for pharmaceutical administration; and wherein the carrier is a pharmaceutically acceptable carrier.9. A method of inhibiting protein-tyrosine kinase activity in a cell claim 1 , comprising contacting the cell with a compound of claim 1 , or a pharmaceutically acceptable salt thereof.10. A method of treating a patient suffering from claim 8 , or susceptible to claim 8 , a disease selected from skin cancer claim 8 , renal disorders claim 8 , malaria claim 8 , arterial restenosis claim 8 , disorders of sexual function and reproduction claim 8 , eye disorders claim 8 , psoriasis claim 8 , diabetes type 1 and type 2 claim 8 , cerebral ischemia claim 8 , hematologic/blood cancer claim 8 , Multiple Sclerosis claim 8 , muscular dystrophy claim 8 , peripheral vascular disease claim 8 , neurological disorders claim 8 , fibrodysplasia claim 8 , viral hepatitis claim 8 , acne claim 8 , cardiovascular disorders claim 8 , chemical or biological agent exposure claim 8 , cystic fibrosis claim 8 , atherosclerosis claim 8 , urinary incontinence claim 8 , ...

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16-05-2013 дата публикации

Quinoxalinone derivatives as insulin secretion stimulators, methods for obtaining them and use thereof for the treatment of diabetes

Номер: US20130123257A1
Принадлежит: Merck Patent GmBH

The present invention relates to quinoxalinone derivatives of formula (I), wherein R1, R2, R3, R4, R5 and R6 are as defined in claim as insulin secretion stimulators. The invention also relates to the preparation and use of these quinoxalinone derivatives for the prophylaxis and/or treatment of diabetes and pathologies associated. 124.-. (canceled)26. A method according to claim 25 , wherein the compound induces insulin secretion in response to glucose concentration.27. A method according to claim 25 , for the treatment of diabetes.28. A method according to claim 27 , for the treatment of type II diabetes.29. A method according to claim 25 , for the treatment of dyslipidaemia or obesity30. A method according to claim 25 , for the treatment of diabetes related microvascular or macrovascular complications.31. A method according to claim 30 , wherein the complications include arterial hypertension claim 30 , atherosclerosis claim 30 , inflammatory processes claim 30 , microangiopathy claim 30 , macroangiopathy claim 30 , retinopathy or neuropathy.32. A method according to claim 25 , for the reducing hyperglycaemia.33. A method according to claim 25 , wherein R1 is: alkyl claim 25 , cycloalkyl claim 25 , cycloalkylalkyl claim 25 , heterocycloalkyl claim 25 , heterocycloalkylalkyl claim 25 , alkyloxyalkyl claim 25 , R7R8N-alkyl or alkylthioalkyl; wherein the heterocycloalkyl groups have one or more heteroatom selected from N claim 25 , O and S; and wherein each of these groups is optionally substituted by one or more groups selected from Y or Z.34. A method according to claim 25 , wherein R1 is: methyl claim 25 , ethyl claim 25 , butyl claim 25 , cyclopropyl or cyclopropylmethyl; wherein each of these groups is optionally substituted by one or more groups selected from Y or Z.35. A method according to claim 25 , wherein R1 is: 2 claim 25 ,2-difluoroethyl or 2 claim 25 ,2 claim 25 ,2-trifluoroethyl.36. A method according to claim 25 , wherein R6 is: alkyl claim 25 , aryl ...

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16-05-2013 дата публикации

COMPOUNDS THAT MODULATE INTRACELLULAR CALCIUM

Номер: US20130123265A1
Принадлежит: CalciMedica, Inc.

Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases, disorders or conditions that would benefit from inhibition of SOC channel activity. 2. The compound of claim 1 , wherein:{'sup': '1', 'Ris hydrogen, methyl, ethyl, n-propyl or iso-propyl.'}3. The compound of or claim 1 , wherein:{'sup': 4', '8, 'sub': 2', '3', '3', '1', '6', '1', '6', '1', '6', '3', '8', '1', '6, 'Ris a phenyl, optionally substituted with at least one substituent selected from F, Cl, Br, I, —CN, —NO, —CF, —OH, —OR, —OCF, C-Calkyl, C-C-fluoroalkyl, C-Cheteroalkyl, C-Ccycloalkyl, and C-Chaloalkyl.'}54. The compound of any of claim 1 , claim 1 , or claim 1 , wherein:{'sup': 4', '8', '9', '9', '9', '9', '9', '8', '9', '9', '9', '8', '9', '8', '9', '9', '8', '8, 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'Ris substituted with at least one substituent selected from —NHS(═O)R, —S(═O)N(R), —N(R)S(═O)N(R), —N(R), —N(R)C(═O)R, —N(R)C(═O)N(R), —N(R)C(═O)OR, —COR, —C(═O)R, —OC(═O)N(R), —CON(R), —SR, or —S(═O)R.'}6. The compound of claim 1 , wherein:{'sup': '4', 'Ris selected from phenyl; 2-fluorophenyl; 3-fluorophenyl; 4-fluorophenyl; 2-chlorophenyl; 3-chlorophenyl; 4-chlorophenyl; 2,4-dichlorophenyl; 2,3-dichlorophenyl; 3,4-dichlorophenyl; 3,5-dichlorophenyl; 2-bromophenyl; 3-bromophenyl; 4-bromophenyl; 2-iodophenyl; 3-iodophenyl; 4-iodophenyl; 2-methylphenyl; 3-methylphenyl; 4-methylphenyl; 2,4-dimethylphenyl; 2,3-dimethylphenyl; 3,4-dimethylphenyl; 3,5-dimethylphenyl; 2-trifluoromethylphenyl; 3-trifluoromethylphenyl;'}{'b': '4', 'and -trifluoromethylphenyl.'}76. The compound of - claims 1 , wherein:{'sup': 2', '8, 'sub': 2', '3', '3', '1', '6', '1', '6', '1', '6', '3', '8', '1', '6, 'Ris a phenyl, optionally substituted with at least one ...

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16-05-2013 дата публикации

SUBSTITUTED PIPERAZINYL-PYRROLIDINE COMPOUNDS USEFUL AS CHEMOKINE RECEPTOR ANTAGONISTS

Номер: US20130123270A1
Принадлежит: Millennium Pharmaceuticals, Inc.

The present invention relates to compounds useful as Chemokine Receptor antagonists. Compounds of general formula I are provided: 119.-. (canceled)21. (canceled)22. (canceled)23. The compound of claim 20 , wherein Ris —OH.24. The compound of claim 20 , wherein q is 0.25. The compound of claim 20 , wherein r is 0.26. The compound of claim 20 , wherein Cyis substituted with 1 or 2 occurrences of —R claim 20 , and each —Ris independently —Cl claim 20 , —F claim 20 , —CF claim 20 , —CH claim 20 , or —Br.27. The compound of claim 20 , wherein Cyis substituted with 1 occurrence of —R claim 20 , and —Ris —Cl.29. The compound of claim 20 , wherein Cyis phenyl substituted with 1 or 2 occurrences of —R claim 20 , and each —Ris independently —Cl claim 20 , —F claim 20 , —CF claim 20 , —CH claim 20 , or —Br.30. The compound of claim 20 , wherein Cyis phenyl substituted with 1 occurrence of —R claim 20 , and —Ris —Cl.31. (canceled)32. (canceled)33. The compound of claim 48 , wherein each Ris independently —Cl claim 48 , —Br claim 48 , —F claim 48 , —CH claim 48 , —CF claim 48 , —COOCH claim 48 , —CONH claim 48 , —NHCONH claim 48 , —NHCOOCH claim 48 , —NHCONHCH claim 48 , —CONHCH claim 48 , —C(CH)OH claim 48 , —OCH claim 48 , —OCHCH claim 48 , —CN claim 48 , -tetrazole claim 48 , —NO claim 48 , —N(CH) claim 48 , -or COOH.34. (canceled)35. A pharmaceutical composition comprising a therapeutically effective amount of compound of claim 47 , and a pharmaceutically acceptable carrier claim 47 , adjuvant claim 47 , or vehicle.36. The composition of claim 35 , comprising an additional therapeutic agent.3746.-. (canceled)49. The compound of claim 48 , wherein Cyis selected from 2-pyridyl (ii-a) claim 48 , pyrimidin-2-yl (iii-a) claim 48 , pyrimidin-4-yl (iii-b) claim 48 , quinolinyl (xxiv-a) claim 48 , or 4-quinaozlinyl (xxvi-a) 2-quinazolinyl (xLv-a) claim 48 , pyrido[2 claim 48 ,3-d]pyrimidinyl (xLvi-a) or pyrido[3 claim 48 ,4-d]pyrimidinyl (xLvii-a).50. The compound of claim 49 , ...

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16-05-2013 дата публикации

PHARMACOLOGICALLY ACTIVE COMPOUNDS CONTAINING SULFUR

Номер: US20130123504A1
Автор: Hackett John Allen
Принадлежит: JON PTY LIMITED

Disclosed herein is a method for the production of disulfide compounds of the formula I 2. A compound according to wherein Ris N-acetyl cysteine. This application is a divisional of U.S. patent application Ser. No. 12/093,917, filed Sep. 5, 2008, which is a U.S. PCT National Patent Application of PCT/AU2006/001727, filed Nov. 17, 2006, which claims the priority of Australian Patent Application No. 2005906409, filed Nov. 17, 2005, the entirety of which are herein incorporated by reference.This invention relates to pharmacologically active compounds containing sulfur which can be transformed to pharmacologically active di-sulfide compounds, and to methods for preparing the same in vitro or formulating to allow for in vivo formation of the di-sulfide compounds. The compounds according to this invention are preferably formed between a pharmaceutically active compound containing a thiol (sulfhydryl), sulfinyl, sulfonyl or sulfonamide group and a pharmacologically acceptable thiol compound.Sulfur in organic compounds plays a varied and critical role in biological systems. The simple sulfur containing amino acid cysteine is a significant protein building block. It participates in complex metal binding roles, binding to other sulfur groups, protein folding bonding and reduction-oxidation (REDOX) functions. Sulfur atoms are also an important part of amino acid building blocks of peptides, proteins, enzymes, membranes, nucleic acids and DNA.Many pharmaceutically active compounds (PACs) contain a thiol (sulfhydryl), sulfinyl (SO), sulfonyl (SO) or sulfonamide (SONR′R′ where R′ is hydrogen or alkyl) group which undergoes oxidation-reduction (REDOX) reactions with thiol (sulfhydryl), disulfide, sulfinyl or sulfonyl groups attached to proteins, enzymes (eg gastric H,K,ATPase), peptides (e.g. glutathione) or simple molecules (eg cysteine). The binding of the PAC to these groups is a reversible process influenced by a number of factors, including pH, presence of other oxidising and ...

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23-05-2013 дата публикации

SYNTHESIS AND REGIOSELECTIVE SUBSTITUTION OF 6-HALO- AND 6-ALKOXY NICOTINE DERIVATIVES

Номер: US20130131015A1
Принадлежит:

The present invention provides active compounds for modulating nicotinic acetylcholine receptors and methods of making the same. The methods of preparing the active compounds utilize different intermediate compounds. 110.-. (canceled)12. A compound of claim 11 , wherein Rand Rtogether form a fused ring.13. A compound of claim 11 , wherein Rand Rtogether form a fused ring.14. (canceled)15. A composition comprising a compound of in a pharmaceutically acceptable carrier. This patent application claims the benefit of U.S. Provisional Application No. 60/787,116, filed Mar. 29, 2006, the disclosure of which is hereby incorporated by reference in its entirety.The present invention concerns methods and intermediates useful for the synthesis of compounds active for modulating nicotinic acetylcholine receptors.Acetylcholine receptors are involved in the modulation of a variety of physiological and behavioral functions, including neuroendocrine function, respiration, mood, motor control and function, focus and attention, concentration, memory and cognition, and substance abuse. Ligands for acetylcholine receptors have been demonstrated to have effects on attention, cognition, appetite, substance abuse, memory, extrapyramidal function, cardiovascular function, pain and gastrointestinal motility and function. The distribution of acetylcholine receptors that bind nicotine, i.e., nicotinic acetylcholine receptors, are found in muscle, autonmic ganglia, the gastrointestinal tract and the cardiovascular system (see, e.g., U.S. Pat. No. 5,594,011).Acetylcholine receptors have been shown to be decreased, among other things, in the brains of patients suffering from Alzheimer's disease, and Parkinson's disease, as well as diseases associated with dementia, motor dysfunction and cognitive impairment. Such correlation between acetylcholine receptors and nervous system disorders suggest that compounds that modulate acetylcholine receptors will have beneficial therapeutic effects for many ...

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23-05-2013 дата публикации

USE OF DERIVATIVES OF INDOLES FOR THE TREATMENT OF CANCER

Номер: US20130131084A1

The present invention relates to the use of derivatives of indoles having a general formula (I) as follow: 120-. (canceled)24. The method according to claim 21 , wherein{'sub': '4', 'Rrepresents a nitrile or a carboxamide group, and'}{'sub': 5', '7, 'Rand Rrepresent a hydrogen atom.'}28. The method according to or claim 21 , wherein the compound of formula (I) or (II) is such that R claim 21 , Rand Rrepresent a hydrogen atom.29. The method according to or claim 21 , wherein the compound of formula (I) or (II) is such that Ris not a hydrogen atom.30. The method according to or claim 21 , wherein the compound of formula (I) or (II) is such that Ris not a hydrogen atom.31. The method according to anyone of or claim 21 , wherein said compound is selected fro the group consisting of:(Z)-2-(5-methoxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(5-ethoxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(5-isopropoxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(5-chloro-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(5-fluoro-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(4-methoxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-3-(6-fluoropyridin-3-yl)-2-(5-methoxy-1H-indol-3-yl)-acrylonitrile;(Z)-2-(6-methoxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(1H-indol-3-yl)-3-pyrimidin-5-yl-acrylonitrile;(Z)-2-(5-methoxy-1H-indol-3-yl)-3-pyrimidin-5-yl-acrylonitrile;(Z)-3-(1-cyano-2-(pyridin-3-yl)vinyl)-1H-indol-5-yl-acetate;(Z)-3-(1-cyano-2-(pyridin-3-yl)vinyl)-1H-indol-5-yl 2-methoxyacetate;(Z)-2-(5-benzyloxy-1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-2-(1H-indol-3-yl)-3-pyridin-3-yl-acrylonitrile;(Z)-3-(3,5-dimethoxy-phenyl)-2-(5-methoxy-1H-indol-3-yl)-acrylonitrile;(Z)-3-(3,5-dimethoxy-phenyl)-2-(1H-indol-3-yl)-acrylonitrile;(Z)-3-(4-chloro-phenyl)-2-(1H-indol-3-yl)-acrylonitrile;(Z)-2-(5-methoxy-1H-indol-3-yl)-3-pyridin-3-yl-propionitrile;(Z)-3-benzo[1,3]dioxol-5-yl-2-(1H-indol-3-yl)-acrylonitrile;(Z)-3-(1H-indol-3-yl)-2-pyridin-3-yl- ...

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23-05-2013 дата публикации

SALTS OF 3-(4-AMINO-1-OXO-1,3-DIHYDRO-ISOINDOL-2-YL)PIPERIDINE-2,6-DIONE AND DERIVATIVES THEREOF, OR POLYMORPHS OF SALTS, PROCESS FOR PREPARING SAME AND USE THEREOF

Номер: US20130131112A1
Автор: ZHANG Hesheng
Принадлежит:

The present invention provides a pharmaceutically acceptable strong acid salt of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)piperidine-2,6-dione, a solvate thereof, a process for preparing the same and use in the preparation of a medicament for treating diseases or physiological abnormities by inhibiting inflammatory factors or angiogenesis. The water-solubility of the pharmaceutically acceptable strong acid salts of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)piperidine-2,6-dione is quite higher than that of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)piperidine-2,6-dione. The present invention also provides polymorphs of a pharmaceutically acceptable strong acid salt of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)piperidine-2,6-dione and a solvate thereof. 2. The compound represented by formula (I) in polymorphic form according to claim 1 , wherein the strong acid is selected the group consisting of hydrochloric acid claim 1 , hydrobromic acid claim 1 , sulfuric acid claim 1 , nitric acid and substituted sulfonic acid.3. The compound represented by formula (I) in polymorphic form according to claim 2 , wherein the substituted sulfonic acid is selected the group consisting of methylsulfonic acid claim 2 , benzene sulfonic acid claim 2 , p-toluene sulfonic acid claim 2 , 1-naphthalenesulfonic acid claim 2 , 2-naphthalenesulfonic acid claim 2 , 1 claim 2 ,5-naphthalene disulfonic acid and pyridinesulfonic acid.16. A pharmaceutical composition comprising a therapeutically effective amount of the compound represented by formula (I) in polymorphic form according to .17. The pharmaceutical composition according to claim 16 , wherein the pharmaceutical composition is formed in a tablet claim 16 , a capsule claim 16 , a powder injection claim 16 , a solution formulation claim 16 , a freeze-dried powder injection claim 16 , an aerosol claim 16 , a spray claim 16 , a cream claim 16 , a paste claim 16 , eye drops claim 16 , ear drops or an implant.19. A method for treating ...

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23-05-2013 дата публикации

Process for Preparing Pyridyl-Substituted Pyrazoles

Номер: US20130131347A1
Принадлежит: Bayer Intellectual Property GmbH

The present invention relates to a process for preparing 1-pyridyl-substituted pyrazoles, comprising the reaction of acetyleneketones with pyridylhydrazine derivatives to give 1-pyridyl-substituted dihydro-1H-pyrazoles, the further reaction thereof with elimination of water to give 1-pyridyl-substituted trihalomethylpyrazoles, and the further processing thereof. 2. Process for preparing compounds of the formula (I) according to claim 1 , characterized in that{'sup': '1', 'sub': 1', '6, 'Ris (C-C)-alkoxy, halogen,'}{'sup': '2', 'sub': 1', '6', '1', '6, 'Ris (C-C)-alkoxy, aryl(C-C)-alkoxy, fluorine, chlorine, bromine, iodine,'}{'sup': '3', 'sub': 2', '1', '6', '1', '6', '1', '6', '1', '6, 'Ris halogen, CN, NO, (C-C)-alkyl, halo(C-C)-alkyl, (C-C)-alkoxy, halo(C-C)alkoxy,'}3. Process for preparing compounds of the formula (I) claim 1 , characterized in that the preparation of the compound of the formula (V) comprises steps (A) and (B) according to .5. Process for preparing compounds of the formula (I) according to claim 3 ,characterized in that the compounds of the formula (V)in whichX is halogen,{'sup': '4', 'sub': 1', '6', '3, 'Ris a protecting group selected from (C-C)-alkyl, aryl, benzyl, tetrahydropyran, (C═O)-alkyl, (C═O)—Oalkyl, Si(alkyl),'}{'sup': '3', 'sub': '2', 'Ris halogen, CN, NO, alkyl, cycloalkyl, haloalkyl, halocycloalkyl, alkoxy, haloalkoxy, alkylamino, dialkylamino, cycloalkylamino,'}are converted with addition of alcohol directly to the inventive compounds of the formula (I).6. Compounds of the formula (I) according to claim 1 , characterized in that{'sup': '1', 'Ris halogen,'}{'sup': '2', 'Ris fluorine, chlorine, bromine, iodine,'}{'sup': '3', 'sub': '2', 'Ris halogen, CN, NO, alkyl, cycloalkyl, haloalkyl, halocycloalkyl, alkoxy, haloalkoxy, alkylamino, dialkylamino, cycloalkylamino.'}7. Compounds of the formula (IV) according to claim 1 , characterized in thatX is halogen,{'sup': '3', 'Ris chlorine,'}{'sup': '4', 'Ris benzyl.'}8. Compounds of the ...

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23-05-2013 дата публикации

Process for producing amide compound

Номер: US20130131348A1
Принадлежит: Sumitomo Chemical Co Ltd

There is provided a process for producing an amide compound having an excellent harmful arthropod-controlling activity and represented by the formula (3): wherein R 1 , R 2 and R 3 independently represent a C1-C6 alkyl group optionally substituted with at least one halogen atom etc., R 4 , R 5 , R 6 and R 7 independently represent a halogen atom etc.

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23-05-2013 дата публикации

PROCESS FOR PRODUCING AMIDE COMPOUND

Номер: US20130131349A1
Принадлежит: Sumitomo Chemical Company, Limited

There is provided a process for producing an amide compound having an excellent harmful arthropod-controlling activity and represented by the formula (3): 2. The process according to claim 1 , wherein the quinone compound is a compound selected from the group consisting of 2 claim 1 ,3-dichloro-5 claim 1 ,6-dicyano-1 claim 1 ,4-benzoquinone claim 1 , tetrachloro-1 claim 1 ,2-benzoquinone claim 1 , and tetrachloro-1 claim 1 ,4-benzoquinone.3. The process according to claim 1 , wherein Rrepresents a methyl group or an ethyl group claim 1 , and Rrepresents a hydrogen atom claim 1 , a methyl group or an ethyl group.4. The process according to claim 1 , wherein Rand Reach represent a methyl group.5. The process according to claim 1 , wherein Rrepresents a methyl group and Rrepresents a hydrogen atom.6. The process according to claim 1 , wherein Rrepresents an ethyl group and Rrepresents a hydrogen atom. The present invention relates to a novel process for producing an amide compound, intermediated compounds thereof, and the like.To date, many compounds for controlling harmful arthropods have been developed and come into practical use. WO 01/70671 and WO 03/015518 disclose certain amide compounds having an arthropod-controlling activity.The present inventors studied intensively a process for producing an amide compound having an excellent controlling activity on harmful arthropods represented by the following formula (3):wherein Rrepresents a C1-C6 alkyl group optionally substituted with at least one halogen atom, Rrepresents a hydrogen atom, or a C1-C6 alkyl group optionally substituted with at least one halogen atom, Rrepresents a C1-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, a C3-C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least one halogen atom, Rrepresents a halogen atom, or a ...

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30-05-2013 дата публикации

NOVEL PYRROLIDINE DERIVATIVES

Номер: US20130137687A1
Принадлежит: Hoffmann-La Roche Inc.

The invention relates to a compound of formula (I) 2. The compound according to claim 1 , wherein Ris halophenylcycloalkyl or halopyridinylcycloalkyl.3. The compound according to claim 1 , wherein Ris selected from the group consisting of chlorophenylcyclopropyl claim 1 , chlorofluorophenylcyclopropyl claim 1 , bromophenylcyclopropyl claim 1 , bromofluorophenylcyclopropyl and chlorofluoropyridinylcyclopropyl.4. The compound according to claim 1 , wherein Rand Rare independently selected from hydrogen and alkyl.5. The compound according to claim 1 , wherein Rand Rare independently selected from the group consisting of hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl and butyl.6. The compound according to claim 1 , wherein R claim 1 , Rand Rare independently selected from the group consisting of halogen claim 1 , haloalkyl and haloalkoxy.7. The compound according to claim 1 , wherein R claim 1 , Rand Rare independently selected from the group consisting of hydrogen claim 1 , chloro claim 1 , trifluoromethyl and trifluoroethoxy.8. The compound according to claim 1 , wherein Ris chloro or trifluoromethyl.9. The compound according to claim 1 , wherein Ris hydrogen.10. The compound according to claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , chloro and trifluoroethoxy.11. The compound according to claim 1 , wherein one of Rand Ris hydrogen and the other one is alkyl or cycloalkyl.12. The compound according to claim 1 , wherein one of Rand Ris hydrogen and the other one is selected from the group consisting of ethyl claim 1 , propyl claim 1 , butyl and cyclopropyl.13. The compound according to selected from the group consisting of(2S,4R)-tert-butyl 2-((S)-1-(cyclopropylamino)-1,2-dioxopentan-3-ylcarbamoyl)-4-(2,4-dimethylphenylsulfonyl)pyrrolidine-1-carboxylate;(2S,4R)-tert-butyl 4-(4-chloro-2-methylphenylsulfonyl)-2-(S)-1-(cyclopropylamino)-1,2-dioxopentan-3-ylcarbamoyl)pyrrolidine-1-carboxylate;(2S,4R)—N—((S)-1-(cyclopropylamino)- ...

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30-05-2013 дата публикации

CONFORMATIONALLY RESTRICTED UREA INHIBITORS OF SOLUBLE EPOXIDE HYDROLASE

Номер: US20130137726A1

Inhibitors of the soluble epoxide hydrolase (sEH) are provided that incorporate multiple pharmacophores and are useful in the treatment of diseases. 3. The method in accordance with or , wherein Ris adamantyl.4. The method in accordance with or , wherein Ris cycloheptyl or cyclohexyl.5. The method in accordance with or , wherein L is a —C(O)—.6. The method in accordance with or , wherein Ris selected from the group consisting of hydrogen , C-Calkyl , and arylC-Calkyl.7. The method in accordance with or , wherein Ris C—Calkyl.8. A method in accordance with claim 2 , wherein said compound is selected from the group consisting of:N-(1-acetylpiperidin-4-yl)-N′-(adamant-1-yl)urea;N-(1-propionylpiperidin-4-yl)-N′-(adamant-1-yl)urea;N-(1-butyrylpiperidine-4-yl)-N′-(adamant-1-yl)urea;N-(1-benzoyl piperidin-4-yl)-N′-(adamant-1-yl)urea;4-[4-(3-adamantan-1-yl-ureido)-piperidin-1-yl]-4-oxo-butanoic acid methyl ester;5-[4-(3-adamantan-1-yl-ureido)-piperidin-1-yl]-5-oxo-pentanoic acid methyl ester;2-[4-(3-adamantan-1-yl-ureido)-piperidine-1-carbonyl]-benzoic acid methyl ester;3-[4-(3-adamantan-1-yl-ureido)-piperidine-1-carbonyl]-benzoic acid methyl ester;4-[4-(3-adamantan-1-yl-ureido)-piperidine-1-carbonyl]-benzoic acid methyl ester;1-(1-acetyl-piperidin-4-yl)-3-(4-trifluoromethoxyphenyl)urea;1-(1-trifluoromethylcarbonylpiperidin-4-yl)-3-(4-trifluoromethoxyphenyl)urea; and1-(1-acetyl-piperidin-4-yl)-3-cycloheptyl)urea;or a pharmaceutically acceptable salt thereof.9. The method in accordance with claim 8 , wherein said compound is selected from the group consisting of:N-(1-acetylpiperidin-4-yl)-N′-(adamant-1-yl)urea;N-(1-propionylpiperidin-4-yl)-N′-(adamant-1-yl)urea;N-(1-butyrylpiperidine-4-yl)-N′-(adamant-1-yl)urea; andN-(1-benzoylpiperidin-4-yl)-N′-(adamant-1-yl)ureaor a pharmaceutically acceptable salt thereof.10. The method in accordance with claim 8 , wherein said compound is N-(1-acetylpiperidin-4-yl)-N′-(adamant-1-yl)urea or a pharmaceutically acceptable salt thereof.11. ...

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30-05-2013 дата публикации

Compositions and Methods for the Treatment of Degenerative Diseases

Номер: US20130137728A1

Disclosed are compounds or pharmaceutically acceptable salts thereof, having the structure of formula I. Also disclosed are methods of preventing and/or treating degenerative disease in a subject, comprising administering to said subject a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof. Also disclosed are pharmaceutical compositions for preventing and/or treating de-generative disease in a subject comprising a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof. 170-. (canceled)73. The compound according to claim 72 , wherein Ris pyridyl.74. The compound according to claim 72 , wherein Ris phenyl.75. The compound according to claim 72 , wherein Ris phenyl.76. The compound according to claim 72 , wherein L′ claim 72 , is —CHNH— claim 72 , —CHCH— claim 72 , —C(O)NH— claim 72 , —CH(OH)CH— claim 72 , —C═C— claim 72 , —C═N— or —CHO—.78. The compound according to claim 77 , wherein Ris hydrogen claim 77 , hydroxyl or methoxyl.79. The compound according to claim 77 , wherein Ris pyridyl.80. The compound according to claim 77 , wherein Ris butyl claim 77 , —CH-phenyl claim 77 , —(CH)-phenyl or —CHC(O)OCHCH.81. The compound according to claim 77 , wherein Ris hydrogen or halogen.82. The compound according to claim 77 , wherein L′is —CHCH— claim 77 , —C═C— or —CHC(O)—.867185. A method of treating a retinal degenerative disease in a subject in need thereof claim 77 , comprising administering to said subject a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to any one of claims to .87. The method of wherein the retinal degenerative disease comprises retinitis pigmentosa.88. The method of wherein the retinal degenerative disease comprises age-related macular degeneration.897185. A method for preventing calcium-induced or oxidant-induced mitochondrial damage preventing or loss of mitochondrial respiratory ...

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06-06-2013 дата публикации

ARYL DIHYDROPYRIDINONE AND PIPERIDINONE MGAT2 INHIBITORS

Номер: US20130143843A1
Принадлежит:

The present invention provides compounds of Formula (I): 3. A compound according to claim 2 , wherein:{'sup': 11', '15, 'sub': '1-4', 'Rand Rare independently selected from the group consisting of: H, Calkyl and halo;'}{'sup': 12', '14, 'sub': 1-4', '1-4, 'Rand Rare independently selected from the group consisting of: H, halo, Calkyl and Calkoxy; and'}{'sup': 13', 'i', 'f', 'j', 'j', 'e, 'sub': 1-4', '1-4', '1-4', '1-4', '2', 'm', '3-4', '2', '1-4', '2', '1-4, 'Ris independently selected from the group consisting of: H, halo, Calkyl substituted with 0-1 R, Calkoxy, Chaloalkyl, Chaloalkoxy, —(CH)—Ccycloalkyl, CN, NRR, SR, NHCO(Calkyl), NHSO(Calkyl), and a 4- to 6-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NR, O, and S.'}11. A pharmaceutical composition claim 1 , comprising: a pharmaceutically acceptable carrier and a compound of claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof.12. A pharmaceutical composition claim 9 , comprising: a pharmaceutically acceptable carrier and a compound of claim 9 , or a stereoisomer claim 9 , a tautomer claim 9 , or a pharmaceutically acceptable salt thereof.13. A pharmaceutical composition claim 10 , comprising: a pharmaceutically acceptable carrier and a compound of any one of claim 10 , or a stereoisomer claim 10 , a tautomer claim 10 , or a pharmaceutically acceptable salt thereof.14. The pharmaceutical composition according to claim 11 , further comprising one or more other suitable therapeutic agents useful in the treatment of the aforementioned disorders including: anti-diabetic agents claim 11 , anti-hyperglycemic agents claim 11 , anti-hyperinsulinemic agents claim 11 , anti-retinopathic agents claim 11 , anti-neuropathic agents claim 11 , anti-nephropathic agents claim 11 , anti-atherosclerotic agents claim 11 , anti-ischemic agents claim 11 , anti-hypertensive agents claim 11 , anti-obesity agents claim 11 , anti-dyslipidemic ...

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06-06-2013 дата публикации

NOVEL PROLYLCARBOXYPEPTIDASE INHIBITORS

Номер: US20130143859A1
Принадлежит: Merck Sharp & Dohme Corp.

Compounds of structural formulas I-1 and I-2 are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders. 2. The compound of wherein Ris hydrogen; or a pharmaceutically acceptable salt thereof.6. The compound of wherein each Ris phenyl claim 5 , wherein phenyl is unsubstituted or substituted with one to three groups independently selected from R; or a pharmaceutically acceptable salt thereof.15. The compound of wherein Z is CR; or a pharmaceutically acceptable salt thereof.19. A pharmaceutical composition comprising a compound of in combination with a pharmaceutically acceptable carrier.20. A composition comprising a compound according to and a compound selected from simvastatin claim 1 , ezetimibe claim 1 , taranabant and sitagliptin; and a pharmaceutically acceptable carrier.2125-. (canceled)26. A method of treating a disorder claim 1 , condition or disease responsive to the inhibition of prolylcarboxypeptidase in a patient in need thereof comprising administration of a therapeutically effective amount of a compound according to .27. The method of wherein the disorder claim 26 , condition claim 26 , or disease is selected from the group consisting of: obesity claim 26 , diabetes claim 26 , metabolic syndrome claim 26 , a diabetes related disorder or an obesity related disorder.28. The method of wherein the disorder claim 27 , condition claim 27 , or disease is obesity. The present invention relates to compounds which are inhibitors of the prolylcarboxy-peptidase (PrCP) enzyme and the use of such compounds to control, prevent and/or treat conditions or diseases mediated by prolylcarboxypeptidase activity. The compounds of the present invention are useful for the control, prevention and treatment of ...

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06-06-2013 дата публикации

NEW BICYCLIC DIHYDROISOQUINOLINE-1-ONE DERIVATIVES

Номер: US20130143863A1
Принадлежит: Hoffmann-La Roche Inc.

The invention provides novel compounds having the general formula (I) 2. The compound according to claim 1 , wherein R claim 1 , R claim 1 , Rand Rare independently selected from the group consisting of H claim 1 , alkyl claim 1 , cycloalkyl claim 1 , cycloalkylalkyl claim 1 , haloalkyl claim 1 , halocycloalkyl claim 1 , hydroxyalkyl claim 1 , alkoxyalkyl claim 1 , haloalkoxyalkyl claim 1 , halocycloalkylalkyl claim 1 , substituted heterocycloalkyl claim 1 , substituted heterocycloalkylalkyl claim 1 , substituted arylalkyl and substituted heteroarylalkyl claim 1 , wherein substituted heterocycloalkyl claim 1 , substituted heterocycloalkylalkyl claim 1 , substituted arylalkyl and substituted heteroarylalkyl are substituted with RRand R.3. The compound according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , alkyl and arylalkyl substituted with R claim 1 , Rand R.4. The compound according to claim 1 , wherein Ris H or alkyl.5. The compound according to claim 1 , wherein Rand Rtogether with the carbon atom to which they are attached form a substituted cycloalkyl or a substituted heterocycloalkyl claim 1 , wherein substituted cycloalkyl and substituted heterocycloalkyl are substituted with R claim 1 , Rand R.6. The compound according to claim 1 , wherein Rand Rtogether with the carbon atom to which they are attached form a cycloalkyl substituted with R claim 1 , Rand R.7. The compound according to claim 1 , wherein Ris H or alkyl.8. The compound according to claim 1 , wherein Ris H.9. The compound according to claim 1 , wherein Ais CR.10. The compound according to claim 1 , wherein Ais CR.11. The compound according to claim 1 , wherein Ais CR.12. The compound according to claim 1 , wherein Ais CR.13. The compound according to claim 1 , wherein Ais CR.14. The compound according to claim 1 , wherein one of R claim 1 , R claim 1 , Rand Ris selected from the group consisting of halogen claim 1 , alkoxy and hydroxy and the others are each ...

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06-06-2013 дата публикации

NOVEL COMPOUNDS

Номер: US20130143870A1
Принадлежит:

This invention relates to compounds of formula I 3. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable adjuvant claim 1 , diluent and/or carrier.4. A method of treating schizophrenia claim 1 , schizoaffective disorder and substance induced psychotic disorder; cognitive disorders and dementias including age-associated learning and memory impairments or losses claim 1 , post stroke dementia claim 1 , deficits in concentration claim 1 , mild cognitive impairment claim 1 , the cognitive dysfunction in Alzheimers disease or the cognitive dysfunction of schizophrenia comprising administering to a patient a therapeutically effective amount of a compound according to . This invention relates to substituted pyrazoles and their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment.Glutamate is the primary excitatory amino acid in the mammalian central nervous system. Neurotransmission mediated by glutamate has been demonstrated to be critical in many physiological processes, such as synaptic plasticity, long term potentiation involved in both learning and memory as well as sensory perception (Riedel et al., Behav. Brain Res. 2003, 140:1-47). Furthermore, it has been demonstrated that an imbalance of glutamate neurotransmission plays a critical role in the pathophysiology of various neurological and psychiatric diseases.The excitatory neurotransmission of glutamate is mediated through at least two different classes of receptors, the ionotropic glutamate receptors (NMDA, AMPA and kainate) and the metabotropic glutamate receptors (mGluR). The ...

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06-06-2013 дата публикации

CRYSTALLINE FORMS OF THALIDOMIDE AND PROCESSES FOR THEIR PREPARATION

Номер: US20130143923A1
Принадлежит:

The present invention related to crystalline forms of thalidomide having a high polymorphic purity and to processes for their preparation. The present invention also relates to pharmaceutical preparations comprising the crystalline forms for the treatment of patients suffering from autoimmune, inflammatory or angiogenic disorders. 167-. (canceled)68. An anhydrous , crystalline α-form of thalidomide having a polymorphic purity greater than or equal to 95%.69. An anhydrous claim 68 , crystalline α-form of thalidomide according to :(i) having a polymorphic purity greater than or equal to 97%; and/or(ii) having a polymorphic purity greater than or equal to 99%; and/or(iii) having a polymorphic purity greater than or equal to 99.5%; and/or(iv) having a polymorphic purity greater than or equal to 99.9%; and/or(v) having a chemical purity greater than or equal to 99%; and/or(vi) having a chemical purity greater than or equal to 99.5%; and/or(vii) having a chemical purity greater than or equal to 99.8%; and/or(viii) containing less than or equal to 5% of crystalline β-form of thalidomide; and/or(ix) containing less than or equal to 3% of crystalline β-form of thalidomide; and/or(x) containing less than or equal to 1% of crystalline β-form of thalidomide; and/or(xi) containing less than or equal to 0.5% of crystalline β-form of thalidomide; and/or(xii) containing less than or equal to 0.1% of crystalline β-form of thalidomide.70. An anhydrous claim 68 , crystalline α-form of thalidomide having a chemical purity greater than or equal to 99%.71. An anhydrous claim 70 , crystalline α-form of thalidomide according to :(i) having a chemical purity greater than or equal to 99.5%; and/or(ii) having a chemical purity greater than or equal to 99.8%; and/or(iii) having a polymorphic purity greater than or equal to 95%; and/or(iv) having a polymorphic purity greater than or equal to 97%; and/or(v) having a polymorphic purity greater than or equal to 99%; and/or(vi) having a polymorphic ...

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06-06-2013 дата публикации

Human Adam-10 Inhibitors

Номер: US20130144056A1
Принадлежит: SYMPHONY EVOLUTION, INC.

The present invention provides compounds useful for inhibiting the ADAM-10 protein, with selectivity versus MMP-1. Such compounds are useful in the in vitro study of the role of ADAM-10 (and its inhibition) in biological processes. The present invention also comprises pharmaceutical compositions comprising one or more ADAM-10 inhibitors according to the invention in combination with a pharmaceutically acceptable carrier. Such compositions are useful for the treatment of cancer, arthritis, and diseases related to angiogenesis. Correspondingly, the invention also comprises methods of treating forms of cancer, arthritis, and diseases related to angiogenesis in which ADAM-10 plays a critical role. 2. The compound according to claim 1 , wherein Lis —C(O)— or —S(O)—.3. The compound according to claim 2 , wherein Lis —C(O)— and Ris —ORor —(CH)R claim 2 , —OC-Calkyl-mono-C-Calkyl amino claim 2 , —OC-Calkyl-di-C-Calkyl amino claim 2 , —OC-Calkyl-N-heterocyclyl claim 2 , —C-Calkyl-mono-C-Calkyl amino claim 2 , —C-Calkyl-di-C-Calkyl amino claim 2 , or —C-Calkyl-N-heterocyclyl.4. The compound according to claim 2 , wherein claim 2 , Ris C-C-alkoxy-C-C-alkoxy.5. The compound according to claim 2 , wherein Ris methoxyethoxy.6. The compound according to claim 3 , wherein Lis —S(O)— claim 3 , and Ris —NRR claim 3 , —(CH)R claim 3 , —C-Calkyl-mono-C-Calkyl amino claim 3 , —C-Calkyl-di-C-Calkyl amino claim 3 , or —C-Calkyl-N-heterocyclyl.7. The compound according to claim 3 , wherein Lis —O—.8. The compound according to claim 7 , wherein claim 7 , Ris phenoxyphenyl wherein each phenyl is optionally substituted with one or two Rsubstituents. In a more specific example claim 7 , the Rsubstituents are halo.9. The compound according to claim 8 , wherein the saturated or mono- or poly-unsaturated C-C-mono- or fused poly-cyclic hydrocarbyl containing one or two annular heteroatoms per ring is selected from the group consisting of morpholinyl claim 8 , piperazinyl claim 8 , homopiperazinyl ...

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06-06-2013 дата публикации

MICROBIOCIDAL HETEROCYCLES

Номер: US20130144064A1
Принадлежит: SYNGENTA CROP PROTECTION, LLC

The present invention relates to heterocyclic compounds of formula I which have microbiocidal activity, in particular fungicidal activity as well as methods of using the compounds of formula I to control microbes: 2. A compound according to claim 1 , wherein Ris C-Calkyl or phenyl optionally substituted with 1 to 3 substituents independently selected from C-Calkyl claim 1 , C-Chaloalkyl claim 1 , hydroxyl claim 1 , amino claim 1 , cyano and halogen. This application is a divisional of U.S. Ser. No. 13/390,023, filed on Feb. 10, 2012, which is a 371 of International Application No. PCT/EP2010/061464 filed Aug. 6, 2010, which claims priority from 09167741.9 filed Aug. 12, 2009; the contents of all above-named applications are incorporated herein by reference.The present invention relates to heterocycles, e.g. as active ingredients, which have microbiocidal activity, in particular fungicidal activity. The invention also relates to preparation of these heterocycles, to heterocyclic derivatives used as intermediates in the preparation of these heterocycles, to preparation of these intermediates, to agrochemical compositions which comprise at least one of the heterocycles, to preparation of these compositions and to use of the heterocycles or compositions in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, preferably fungi.Certain heterocycles for use as fungicides are described in WO 2007/014290, WO 2008/013622, WO 2008/013925, WO 2008/091580, WO 2008/091594 and WO 2009/055514.The present invention provides compounds of formula I:wherein A is x-C(RR)—C(═O)—, x-C(RR)—C(═S)—, x-O—C(═O)—, x-O—C(═S)—, x-N(R)—C(═O)—, x-N(R)—C(═S)—, x-C(RR)—SO— or x-N═C(R)— in each case x indicates the bond that is connected to R;Y, Y, Y, and Yare independently CRor N;n is 1 or 2; p is 1 or 2, providing that when n is 2, p is 1. Ris phenyl, pyridyl, imidazolyl, or pyrazolyl; ...

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13-06-2013 дата публикации

Tetrahydropyridinyl and Dihydropyrrolyl Compounds and the Use Thereof

Номер: US20130150377A1
Принадлежит:

The invention relates to tetrahydropyridinyl and dihydropyrrolyl compounds of Formula (I): and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein X, Y, Z, R, R, m, and n are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of calcium channels, and particularly N-type calcium channels. Compounds of the present invention are especially useful for treating pain. 166.-. (canceled)68. The method of claim 67 , wherein the N-type calcium channel is modulated.6973.-. (canceled)74. The method of claim 67 , wherein n is 1.79. The method of claim 67 , wherein n is 0.84. The method of claim 67 , wherein Hy is selected from the group consisting of pyridyl claim 67 , pyrimidinyl claim 67 , pyrazinyl claim 67 , pyrrolyl claim 67 , imidazolyl claim 67 , triazolyl claim 67 , thiazolyl claim 67 , oxazolyl claim 67 , isoxazolyl claim 67 , and 1 claim 67 ,2 claim 67 ,4-oxadiazolyl.85. The method of claim 84 , wherein Hy is selected from the group consisting of pyridin-2-yl claim 84 , pyridin-3-yl claim 84 , pyrimidin-2-yl claim 84 , pyrimidin-4-yl claim 84 , pyrazin-2-yl claim 84 , imidazol-2-yl claim 84 , imidazol-4-yl claim 84 , and oxazol-2-yl.86. The method of claim 85 , wherein Hy is pyridin-2-yl claim 85 , pyridin-3-yl claim 85 , pyrimidin-2-yl claim 85 , or oxazol-2-yl.87. The method of claim 67 , wherein Ris attached to a carbon atom adjacent to a nitrogen atom of said Hy ring.91. The method of claim 88 , wherein X is —CHR— and Rand Rboth are hydrogen.92. The method of claim 88 , wherein X is —CHR— and Rand Rtogether form a bridge —(CH)— and p is 2 claim 88 , 3 claim 88 , or 4.93. The method of claim 92 , wherein p is 2.94. The method of claim 88 , wherein X is —C(═O)— and Ris hydrogen.95. The method of claim 67 , wherein Ris —C(═W)NRR claim 67 , wherein W is O or NR claim 67 , Ris hydrogen or alkyl claim 67 , and Rand Rare each independently ...

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13-06-2013 дата публикации

Piperidinyl Pyrimidine Amides As KV7 Potassium Channel Openers

Номер: US20130150391A1
Принадлежит: PFIZER INC.

The present invention relates to compounds of Formula (I) as described herein or a pharmaceutically acceptable salt thereof, pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof and methods of treating, or manufacture of a medicament to treat, a disease, disorder, or condition of the central nervous system, including bipolar disorder, depressive disorders, anxiety disorders, cognitive disorders, pain disorders, urogentital disorder, and epilepsy, among the other diseases, disorders or conditions discussed herein as mono-therapy or in combination with another active pharmaceutical ingredient. 2. The compound of claim 1 , wherein R claim 1 , R claim 1 , and Rare each Calkoxy; wherein Ris Calkyl claim 1 , and wherein n and t are each 1 claim 1 , or a pharmaceutically acceptable salt thereof.3. The compound of claim 1 , wherein R claim 1 , R claim 1 , and Rare each methoxy; Ris —CH-t-butyl claim 1 , and n and t are each 1 claim 1 , or a pharmaceutically acceptable salt thereof.4. The compound that is N-(4 claim 1 ,6-dimethoxy-2-(4-methoxypiperidin-1-yl)pyrimidin-5-yl)-3 claim 1 ,3-dimethylbutanamide claim 1 , or a pharmaceutically acceptable salt thereof.5. A method for the treatment of a disease claim 1 , disorder claim 1 , or condition that is affected by the dampening of neuronal excitability characterized by the dysregulation of neuronal excitability in mammalian of the KCNQ family potassium ion channels claim 1 , comprising administering to a mammal in need thereof a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.6. The method of claim 5 , wherein the KCNQ channel is a KV7.2/KV7.3 channels.7. The method of claim 5 , wherein the disease claim 5 , disorder or condition is selected from cognitive disorders claim 5 , pain disorders claim 5 , and epilepsy.8. The method of claim 5 , wherein the disease claim 5 , disorder or condition is selected ...

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13-06-2013 дата публикации

NOVEL HYPOGLYCEMIC COMPOUNDS

Номер: US20130150578A1
Принадлежит: CADILA PHARMACEUTICALS LIMITED

The present invention relates to novel hypoglycemic compounds of formula (1) and pharmaceutically acceptable salts thereof. The invention relates to novel amino acid derivatives of the formula (1), wherein, A is amino acid B is peptide bond R—NH— wherein R is defined in the specification 2. The compound of formula 1 as claimed in wherein the amino acid is selected from amino acid analogues.3. The compound of formula 1 as claimed in wherein the amino acid is selected from glycine claim 1 , alanine claim 1 , valine claim 1 , histidine claim 1 , serine claim 1 , leucine claim 1 , isoleucine claim 1 , phenylalanine claim 1 , methionine claim 1 , tryptophan claim 1 , lysine claim 1 , glutamine claim 1 , glutamic acid claim 1 , serine claim 1 , proline claim 1 , cysteine claim 1 , tyrosine claim 1 , histidine claim 1 , arginine claim 1 , asparagines claim 1 , aspartic acid claim 1 , threonine or mixtures of amino acid thereof.4. An amino acid analogue of 2-({6-[(3R)-3-substituted-aminopiperidin-1-yl]-3-methyl-2 claim 1 ,4-dioxo-3 claim 1 ,4-dihydropyrimidin-1(2H)-yl}methyl)-benzonitrile and pharmaceutically acceptable salts thereof.5. An amino acid analogue of 1-[2-Amino-3 claim 1 ,3-bis-(4-fluoro-phenyl)-propionyl]-4-fluoro-pyrrolidine-2-carbonitrile and pharmaceutically acceptable salts thereof.6. An amino acid analogue of (2R)-4-oxo-4-[3-(trifluoromethyl)-5 claim 1 ,6-dihydro[1 claim 1 ,2 claim 1 ,4]triazolo[4 claim 1 ,3-a]pyrazin-7(8H)-yl]-1-(2 claim 1 ,4 claim 1 ,5-trifluorophenyl)butan-2-amine and pharmaceutically acceptable salts thereof.7. An amino acid analogue of 8-[(3R)-3-aminopiperidin-1-yl]-7-(but-2-yn-1-yl)-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]-3 claim 1 ,7-dihydro-1H-purine-2 claim 1 ,6-dione and pharmaceutically acceptable salts thereof.8. An amino acid analogue of (1S claim 1 ,3S claim 1 ,5S)-2-[(2S)-2-amino-2-(3-hydroxy-1-adamantyl)acetyl]-2-azabicyclo-[3.1.0]-hexane-3-carbonitrile and pharmaceutically acceptable salts thereof.9. An amino acid ...

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13-06-2013 дата публикации

Process for producing 1-triazole-2-butanol derivatives

Номер: US20130150586A1
Принадлежит: Kaken Pharmaceutical Co Ltd

An object is to provide a process for producing the compound of formula 1 in higher yield by the ring-opening addition reaction of epoxytriazole with amine under mild conditions without using a large excess of 4-methylenepiperidine. The process for producing (2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol or an acid addition salt thereof comprises reacting (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane with an acid addition salt of 4-methylenepiperidine in a reaction solvent in the presence of a hydroxide of an alkali metal or an alkaline earth metal selected from the group consisting of lithium, sodium, calcium, and strontium, or a hydrate thereof.

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20-06-2013 дата публикации

NICOTINE COMPOUNDS AND ANALOGS THEREOF, SYNTHETIC METHODS OF MAKING COMPOUNDS, AND METHODS OF USE

Номер: US20130157995A1
Принадлежит:

Embodiments of the present disclosure provide for compounds such as those shown in FIG. (compounds A, B, C, and D), 2′substituted nicotine compounds, azetidine compounds, ether linked nicotine compounds (FIG. , compounds E, F, G, and H), methods of synthesis of the compounds, methods of treatment of a condition using compounds A, B, C, D, 2′substituted nicotine compounds, azetidine compounds, or ether linked nicotine compounds, methods of selectively stimulating alpha7 nAChR and/or alpha4beta2 receptors, and the like. 135-. (canceled)37. The compound of claim 36 , wherein R4′ claim 36 , R5′ claim 36 , R6′ claim 36 , or R7′ is at the trans position.38. The compound of claim 36 , wherein R4′ claim 36 , R5′ claim 36 , R6′ claim 36 , or R7′ is at the cis position.39. The compound of claim 36 , wherein the alkyl group in each of the alkyl group claim 36 , the alkyl amino group claim 36 , and the alkyl group having a hydroxylic group claim 36 , has 1 or 2 carbons.40. A method claim 36 , comprising selectively stimulating alpha7 nAChR using R4′ claim 36 , R5′ claim 36 , R6′ or R7′ claim 36 , trans substituted compounds A claim 36 , B claim 36 , C claim 36 , and D and compound E claim 36 , F claim 36 , G claim 36 , and H claim 36 , respectively claim 36 , wherein compound A claim 36 , compound B claim 36 , compound C claim 36 , compound D claim 36 , compound E claim 36 , compound F claim 36 , compound G claim 36 , and compound H are described in claim 36 , wherein R4′ claim 36 , R5′ claim 36 , R6′ or R7′ are selected from a group selected from: an alkyl group having from 1 to 6 carbons claim 36 , an alkyl amino group having from 1 to 6 carbons claim 36 , an alkyl group having a hydroxylic group and having from 1 to 6 carbons claim 36 , and a methoxy group.41. A method comprising claim 36 , selectively stimulating alpha7 nAChR and alpha4beta2 receptors using R2′ substituted compound A claim 36 , compound B claim 36 , compound C claim 36 , and compound D claim 36 , ...

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27-06-2013 дата публикации

HETEROARYLS AND USES THEREOF

Номер: US20130165464A1
Принадлежит: Millennium Pharmaceuticals, Inc.

This invention provides compounds of formula IB: 3. The compound of claim 2 , provided that when HY is a non-fused group then HY is substituted with at least one occurrence of Ror R claim 2 , wherein Ror R is:{'sup': 11', '10a', '11', '11', '10a, 'sub': '2', '—N(R)C(O)R, —C(O)N(R), or —NRC(O)OR; or'}{'sub': 1', '1', '1', '1', '1', '3, 'sup': 10b', '11', '10b, '—V-T-R, wherein Vis —NR—, Tis a C-Calkylene chain, and Ris an optionally substituted 6- to 10-membered aryl ring or a 5- to 10-membered heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or'}{'sub': 1', '1, 'sup': 10c', '11', '10c, '—V—R, wherein Vis —NR—, and Ris a 5- to 10-membered heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.'}6. The compound of claim 5 , wherein Yis carbon claim 5 , Xis nitrogen claim 5 , Gis N(R) claim 5 , and Xand X claim 5 , are CH.7. The compound of claim 5 , wherein Yis carbon claim 5 , Xand Xare nitrogen claim 5 , Gis N(R) claim 5 , and Xis CH.8. The compound of claim 5 , wherein Yis carbon claim 5 , Xand Gare nitrogen claim 5 , Xis N(R) claim 5 , and Xis CH.9. The compound of claim 5 , wherein Yis carbon claim 5 , Xand Xare nitrogen claim 5 , Gis N(R) claim 5 , and Xis CH.10. The compound of claim 5 , wherein Yis carbon claim 5 , Gis N(R) claim 5 , Xis nitrogen claim 5 , and Xand XCH.11. The compound of claim 5 , wherein Yis carbon claim 5 , Gis nitrogen claim 5 , Xis N(R) claim 5 , and Xand Xare CH.12. The compound of claim 5 , wherein Yis carbon claim 5 , Xis nitrogen claim 5 , Xis N(R) claim 5 , and Xand Gare CH.13. The compound of claim 5 , wherein Yis carbon claim 5 , Xis nitrogen claim 5 , Gis N(R) claim 5 , and Xand X claim 5 , are CH.14. The compound of claim 5 , wherein Yis carbon claim 5 , Xis N(R) claim 5 , Gis nitrogen claim 5 , and Xand X claim 5 , are CH.15. The compound of claim 1 , wherein Ris Cy claim 1 , and Cy is an optionally substituted 5- to 6-membered heteroaryl or ...

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27-06-2013 дата публикации

HETEROARYLS AND USES THEREOF

Номер: US20130165472A1
Принадлежит: Millennium Pharmaceuticals, Inc.

This invention provides compounds of formula IA: 4. The compound of claim 3 , wherein Yis carbon claim 3 , Xis nitrogen claim 3 , Gis N(R) claim 3 , and Xand X claim 3 , are CH.5. The compound of claim 3 , wherein Yis carbon claim 3 , Xand Xare nitrogen claim 3 , Gis N(R) claim 3 , and Xis CH.6. The compound of claim 3 , wherein Yis carbon claim 3 , Xand Gare nitrogen claim 3 , Xis N(R) claim 3 , and Xis CH.7. The compound of claim 3 , wherein Yis carbon claim 3 , Xand Xare nitrogen claim 3 , Gis N(R) claim 3 , and Xis CH.8. The compound of claim 3 , wherein Yis carbon claim 3 , Gis N(R) claim 3 , Xis nitrogen claim 3 , and Xand XCH.9. The compound of claim 3 , wherein Yis carbon claim 3 , Gis nitrogen claim 3 , Xis N(R) claim 3 , and Xand Xare CH.10. The compound of claim 3 , wherein Yis carbon claim 3 , Xis nitrogen claim 3 , Xis N(R) claim 3 , and Xand Gare CH.11. The compound of claim 3 , wherein Yis carbon claim 3 , Xis nitrogen claim 3 , Gis N(R) claim 3 , and Xand X claim 3 , are CH.12. The compound of claim 3 , wherein Yis carbon claim 3 , Xis N(R) claim 3 , Gis nitrogen claim 3 , and Xand X claim 3 , are CH.13. The compound of claim 1 , wherein Ris Cy claim 1 , and Cy is an optionally substituted 5- to 6-membered heteroaryl or heterocyclyl ring.15. The compound of claim 1 , wherein Ris Cy claim 1 , and Cy is an optionally substituted 6-membered aryl ring.16. The compound of claim 1 , wherein Ris —CON(R) claim 1 , —C(O)OR claim 1 , —NHCOR claim 1 , or —CHOR.19. The compound of claim 1 , wherein Ris Caliphatic substituted with a 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.23. The compound of claim 22 , wherein R is hydrogen claim 22 , methyl claim 22 , or chloro.24. The compound of claim 22 , wherein R is methyl claim 22 , and Ris —NHCOR.25. The compound of claim 1 , wherein Ris —NHR claim 1 , wherein Ris an optionally substituted 5- to 10-membered heteroaryl having 1-5 heteroatoms ...

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27-06-2013 дата публикации

DEUTERIUM-ENRICHED HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS

Номер: US20130165475A1
Принадлежит: ASCEPION PHARMACEUTICALS, INC.

The present invention provides deuterium-enriched heteroaryl-containing urea compounds (I) and use of the same for treating conditions mediated by protein kinase such as 3. The compound of claim 2 , wherein L′ is a covalent bond.4. The compound of claim 2 , wherein Ar is Caryl or Cheteroaryl claim 2 , each of which is optionally substituted with one or more independent R.5. The compound of claim 4 , wherein Ar is substituted with one or more independent R; and at least one Ris deuterium-enriched Calkyl claim 4 , deuterium-enriched Ccycloalkyl claim 4 , deuterium-enriched Cheterocycloalkyl claim 4 , deuterium-enriched Calkyl-O— claim 4 , deuterium-enriched Ccycloalkyl-O— claim 4 , or deuterium-enriched Cheterocycloalkyl-O— claim 4 , each of which is optionally substituted with one or more independent Q.6. The compound of claim 2 , wherein L has 1 to 4 carbon atoms and is optionally deuterium-enriched and optionally substituted with one or more independent R.7. The compound of claim 6 , wherein L has 1 or 2 carbon atoms and is optionally deuterium-enriched and optionally substituted with one or more independent R.8. The compound of claim 7 , wherein L has one carbon atom and is optionally deuterium-enriched and optionally substituted with one or more independent R.9. The compound of claim 7 , wherein L is —CD- claim 7 , —CHD- claim 7 , or —CDCD-.10. The compound of claim 7 , wherein L is —CH—; Ar is Caryl or Cheteroaryl and substituted with one or more independent R; and at least one Ris deuterium-enriched Calkyl claim 7 , deuterium-enriched Ccycloalkyl claim 7 , deuterium-enriched Cheterocycloalkyl claim 7 , deuterium-enriched Calkyl-O— claim 7 , deuterium-enriched Ccycloalkyl-O— claim 7 , or deuterium-enriched Cheterocycloalkyl-O— claim 7 , each of which is optionally substituted with one or more independent Q.12. The compound of claim 11 , wherein A is A1-a claim 11 , A1-b claim 11 , A1-d claim 11 , A1-e claim 11 , A1-g claim 11 , A2-a claim 11 , A2-b claim 11 , A2 ...

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27-06-2013 дата публикации

HETEROARYLS AND USES THEREOF

Номер: US20130165483A1
Принадлежит: Millennium Pharmaceuticals, Inc.

This invention provides compounds of formula IB: 5. The compound of claim 4 , wherein Yis carbon claim 4 , Xis nitrogen claim 4 , Gis N(R) claim 4 , and Xand X claim 4 , are CH.6. The compound of claim 4 , wherein Yis carbon claim 4 , Xand Xare nitrogen claim 4 , Gis N(R) claim 4 , and Xis CH.7. The compound of claim 4 , wherein Yis carbon claim 4 , Xand Gare nitrogen claim 4 , Xis N(R) claim 4 , and Xis CH.8. The compound of claim 4 , wherein Yis carbon claim 4 , Xand Xare nitrogen claim 4 , Gis N(R) claim 4 , and Xis CH.9. The compound of claim 4 , wherein Yis carbon claim 4 , Gis N(R) claim 4 , Xis nitrogen claim 4 , and Xand XCH.10. The compound of claim 4 , wherein Yis carbon claim 4 , Gis nitrogen claim 4 , Xis N(R) claim 4 , and Xand Xare CH.11. The compound of claim 4 , wherein Yis carbon claim 4 , Xis nitrogen claim 4 , Xis N(R) claim 4 , and Xand Gare CH.12. The compound of claim 4 , wherein Yis carbon claim 4 , Xis nitrogen claim 4 , Gis N(R) claim 4 , and Xand X claim 4 , are CH.13. The compound of claim 4 , wherein Yis carbon claim 4 , Xis N(R) claim 4 , Gis nitrogen claim 4 , and Xand X claim 4 , are CH.14. The compound of claim 1 , wherein Ris Cy claim 1 , and Cy is an optionally substituted 5- to 6-membered heteroaryl or heterocyclyl ring.16. The compound of claim 1 , wherein Ris Cy claim 1 , and Cy is an optionally substituted 6-membered aryl ring.17. The compound of claim 1 , wherein Ris —CON(R) claim 1 , —C(O)OR claim 1 , —NHCOR claim 1 , or —CHOR.20. The compound of claim 1 , wherein Ris Caliphatic substituted with a 5-10-membered heteroaryl having 1-5 heteroatoms independently selected from nitrogen claim 1 , oxygen claim 1 , or sulfur.24. The compound of claim 23 , wherein R is hydrogen claim 23 , methyl claim 23 , or chloro.25. The compound of claim 23 , wherein Ris methyl claim 23 , and Ris —NHCOR.26. The compound of claim 1 , wherein Ris —NHR claim 1 , wherein Ris an optionally substituted 5- to 10-membered heteroaryl having 1-5 heteroatoms ...

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27-06-2013 дата публикации

Benzodithiophene organic semiconductive material and its preparation method and use

Номер: US20130165655A1

The present invention relates to optoelectronic materials field, and it discloses a benzodithiophene organic semiconductive material with the following structural formula (P): wherein, x+y=2; 1≦x<2, 0<y≦1; 1<n≦100; R 1 , R 2 are C 1 -C 20 alkyl; R 3 is selected from C 1 -C 20 alkyl; R 4 , R 5 are hydrogen, phenyl, C 1 -C 20 alkyl or phenyl substituted by C 1 -C 20 alkoxy. The present invention is also provided with preparation method and use of the benzodithiophene organic semiconductive material. The benzodithiophene containing bisphenyl siloles unit has good dissolution property, high carrier mobility, strong absorbance, wide optical absorption range, and improved utilization of sunlight, and its preparation process is simple, with high yield, and easy to operate and control.

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04-07-2013 дата публикации

FUSED PYRAZOLE DERIVATIVES AS NOVEL ERK INHIBITORS

Номер: US20130172341A1
Принадлежит:

Disclosed are the ERK inhibitors of Formula (I): (Formula (I)) and the pharmaceutically acceptable salts thereof. All substitutents are as defined herein. Also disclosed are methods of treating cancer using the compounds of Formula (I). 3. The compound of wherein Ris heteroaryl claim 1 , wherein said heteroaryl group is unsubstituted or substituted by one to three Rgroups claim 1 , or alternatively two Rcan optionally be taken together with the carbon atoms to which they are attached to form a five- or six-membered cycloalkyl claim 1 , cycloalkenyl claim 1 , heterocyclyl claim 1 , heterocyclenyl claim 1 , arl or heteroaryl.8. A pharmaceutical composition comprising at least one compound of and a pharmaceutically acceptable carrier.9. A method of treating or preventing cancer in a mammal in need of such treatment that is comprised of administering to said mammal a therapeutically effective amount of a compound of .10. A method of treating cancer or preventing cancer in accordance with wherein the cancer is selected from cancers of the brain claim 9 , genitourinary tract claim 9 , lymphatic system claim 9 , stomach claim 9 , larynx and lung.11. A method of treating or preventing cancer in accordance with wherein the cancer is selected from histiocytic lymphoma claim 10 , lung adenocarcinoma claim 10 , small cell lung cancers claim 10 , pancreatic cancer claim 10 , liver cancer claim 10 , gastric cancer claim 10 , colon cancer claim 10 , multiple myeloma claim 10 , gliobastomas and breast carcinoma.12. A method of using the compound according to for the preparation of a medicament useful in treating or preventing cancer in a mammal in need of such treatment.13. A method of using the compound according to for the preparation of a medicament useful in inhibiting ERK in a mammal in need of such treatment.14. A method of using the compound according to for the preparation of a medicament useful in preventing or modulating metastasis of cancer in a mammal in need of such ...

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04-07-2013 дата публикации

High enhancer-loading polyacrylate formulation for transdermal applications

Номер: US20130172428A1
Принадлежит: Alza Corp

A polyacrylate formulation suitable for delivery of drug to through a body surface of an individual. By loading the drug and permeation enhancers at a high concentration into a polyacrylate proadhesive that has inadequate adhesive properties for typical adhesive application on the skin, a formulation with desirable adhesive characteristics and effective therapeutic properties can be made. The proadhesive has higher glass transition temperature than typical pressure sensitive adhesives.

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04-07-2013 дата публикации

LENALIDOMIDE SOLVATES AND PROCESSES

Номер: US20130172563A1
Принадлежит:

The present application relates to lenalidomide salts and solvates, and processes for the preparation thereof. 120-. (canceled)22. The process of claim 21 , wherein the catalyst in step a) is selected from a metal catalyst or a chemical reducing agent.23. The process of claim 21 , wherein the reduction of formula II is carried out in the presence of a hydrogen source.24. The process of claim 21 , wherein the acid used in step a) is selected from an organic acid or an inorganic acid.25. The process of claim 21 , wherein the reduction of formula II is carried out in the presence of a solvent selected from water claim 21 , an alcohol solvent claim 21 , a ketone solvent claim 21 , dimethyl formamide claim 21 , N claim 21 ,N-dimethyl acetamide claim 21 , dimethyl sulfoxide or mixture thereof.26. The process of claim 21 , wherein an acid addition salt of lenalidomide of formula III is an alkyl- or aryl-sulfonate salt of lenalidomide.27. The process of claim 21 , wherein an acid addition salt of lenalidomide of formula III is a methanesulfonate salt of lenalidomide.28. The process of claim 21 , wherein the base used in step b) is selected from an organic base or an inorganic base.29. The process of claim 28 , wherein the base is an alkylamine.30. The process of claim 21 , further comprising converting N claim 21 ,N-dimethylformamide solvate of lenalidomide to lenalidomide.31. A process for preparing a N claim 21 ,N-dimethylformamide solvate of lenalidomide claim 21 , comprising:a) providing a solution of an acid addition salt of lenalidomide of formula III in a solvent comprising N,N-dimethylformamide;b) combining a base with the solution of step a);c) optionally, adding an anti-solvent; andd) isolating an N,N-dimethylformamide solvate of lenalidomide.32. The process of claim 31 , wherein an acid addition salt of lenalidomide of formula III is a methanesulfonate salt of lenalidomide.33. The process of claim 31 , wherein the solvent in step a) contains a co-solvent selected ...

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11-07-2013 дата публикации

ARYLETHYNYL DERIVATIVES

Номер: US20130178456A1
Принадлежит: Hoffmann-La Roche Inc.

The present invention relates to ethynyl compounds of formula I 2. The compound of claim 1 , selected from the group consisting of3-(3-fluoro-5-phenylethynyl-pyridin-2-yl)-5,5-dimethyl-oxazolidin-2-one;(5RS)-5-methoxymethyl-3-(5-phenylethynyl-pyridin-2-yl)-oxazolidin-2-one;(5R or 5S)-5-methoxymethyl-3-(5-phenylethynyl-pyridin-2-yl)-oxazolidin-2-one;(5S or 5R)-5-methoxymethyl-3-(5-phenylethynyl-pyridin-2-yl)-oxazolidin-2-one;5,5-dimethyl-3-(5-phenylethynyl-pyridin-2-yl)-oxazolidin-2-one;3-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-5,5-dimethyl-oxazolidin-2-one;5,5-dimethyl-3-(5-pyridin-3-ylethynyl-pyridin-2-yl)-oxazolidin-2-one;(5RS)-5-tert-butyl-3-(5-phenylethynyl-pyridin-2-yl)-oxazolidin-2-one;6-(5-phenylethynyl-pyridin-2-yl)-4-oxa-6-aza-spiro[2.4]heptan-5-one; and7-(5-phenylethynyl-pyridin-2-yl)-5-oxa-7-aza-spiro[3.4]octan-6-one.3. The compound of claim 1 , selected from the group consisting of3-(5-phenylethynyl-pyridin-2-yl)-1-oxa-3-aza-spiro[4.4]nonan-2-one;3-(5-phenylethynyl-pyridin-2-yl)-1-oxa-3-aza-spiro[4.5]decan-2-one;(5RS)-5-tert-butyl-5-methyl-3-(5-phenylethynyl-pyridin-2-yl)-oxazolidin-2-one;(3aRS,6aSR)-3-(5-phenylethynyl-pyridin-2-yl)-hexahydro-cyclopentaoxazol-2-one;(3aRS,6aSR)-3-(5-pyridin-3-ylethynyl-pyridin-2-yl)-hexahydro-cyclopentaoxazol-2-one;(3aRS,6aSR)-3-[5-(5-fluoro-pyridin-3-ylethynyl)-pyridin-2-yl]-hexahydro-cyclopentaoxazol-2-one;(RS)-4,5,5-trimethyl-3-(5-phenylethynyl-pyridin-2-yl)-oxazolidin-2-one;4,4,5,5-tetramethyl-3-(5-phenylethynyl-pyridin-2-yl)-oxazolidin-2-one;3-[5-(5-fluoro-pyridin-3-ylethynyl)-pyridin-2-yl]-5,5-dimethyl-oxazolidin-2-one; and5,5-dimethyl-3-(5-pyrimidin-5-ylethynyl-pyridin-2-yl)-oxazolidin-2-one.4. The compound of claim 1 , selected from the group consisting of5,5-dimethyl-3-[5-(1-methyl-1H-pyrazol-4-ylethynyl)-pyridin-2-yl]-oxazolidin-2-one;3-[5-(4-fluoro-phenylethynyl)-pyridin-2-yl]-5,5-dimethyl-oxazolidin-2-one;3-[5-(3,4-difluoro-phenylethynyl)-pyridin-2-yl]-5,5-dimethyl-oxazolidin-2-one;3-[5-(2,5-difluoro- ...

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11-07-2013 дата публикации

Inhibitors of Advanced Glycation End Products

Номер: US20130178480A1
Принадлежит: NephroGenex, Inc.

The present invention provides compounds of the formula, 2. The compound according to claim 1 , wherein X is N and G is hydrogen.3. The compound according to claim 2 , whereinB is aromatic; and{'sup': 1', '2', '3', '3, 'G, G, and Gare each independently O, N or CR.'}4. The compound according to claim 3 , wherein{'sup': '3', 'B is imidazolyl, oxazoyl, pyrazoyl, pyrroyl, or isoxazoyl wherein each carbon atom is substituted by R.'}5. The compound according to claim 4 , wherein{'sup': '3', 'B is imidazolyl wherein each carbon atom is substituted by R.'}6. The compound according to claim 5 , wherein{'sup': 3', 'Z3, 'claim-text': {'sup': Z3', 'Z3', 'Z3′, 'sub': 1', '6', '1', '6', '3', '8', '1', '6, 'claim-text': {'sup': 'Z3′', 'sub': 2', '1', '6', '1', '6', '3', '8, 'each R is independently -halogen, -cyano, —OR, —C(O)OR, —C(O)R, —C(O)NR, —(C-C)alkyl, —(C-C)haloalkyl, —(C-C)cycloalkyl, or -heterocycloalkyl.'}, 'Ris —H, —(C-C)alkyl, —(C-C)haloalkyl, —(C-C)cycloalkyl, —(C-C)alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein Ris optionally substituted with at least one R, wherein'}, 'each Ris independently R, wherein'}7. The compound according to claim 5 , wherein{'sup': 2', '6', 'Z6, 'sub': '2', 'claim-text': {'sup': Z3', 'Z6′', 'Z6′, 'sub': 1', '6', '1', '6', '3', '8', '1', '6, 'claim-text': {'sup': 'Z6′', 'sub': 1', '6', '1', '6, 'claim-text': {'sup': 'Z6′', 'wherein R is optionally substituted with one or more R′.'}, 'wherein each R is independently -halogen, —OR, —C(O)OR, —C(O)R, —(C-C)alkyl, or —(C-C)haloalkyl,'}, 'Ris —(C-C)alkyl, —(C-C)haloalkyl, —(C-C)cycloalkyl, —(C-C)alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein R is optionally substituted with at least one R,'}, 'Rand Rare each —H, -halogen, —NO, —CN, or —Rwherein'}8. The compound according to claim 5 , wherein{'sup': 'N′', 'sub': 1', '6', '1', '6', '1', '6', '3', '8', '3', '8', '1', '6', '1', '6, 'claim-text': {'sup': N′', 'N″', 'N″, 'sub': 2', '2', '1', '6', '3', '8', '1', '6, 'claim-text': {'sup ...

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18-07-2013 дата публикации

PIPERIDINYL-SUBSTITUTED LACTAMS AS GPR119 MODULATORS

Номер: US20130184257A1
Принадлежит:

Compounds of Formula (I) and pharmaceutically acceptable salts thereof in which X, X, L, R, R, R, Rand n have the meanings given in the specification, are modulators of GPR119 and are useful in the treatment or prevention of diseases such as such as, but not limited to, type 2 diabetes, diabetic complications, symptoms of diabetes, metabolic syndrome, obesity, dyslipidemia, and related conditions. 2. The compound according to claim 1 , wherein:{'sup': 1', '1, 'Xis CR;'}{'sup': 2', '2, 'Xis CR; and'}{'sup': 1', '2', '3', '4, 'sub': '3', 'R, R, Rand Rare independently selected from H, (1-6C)alkyl, CFand halogen.'}3. The compound of claim 2 , wherein:{'sup': 1', '2, 'Rand Rare independently selected from H, F and Cl; and'}{'sup': 3', '4, 'sub': '3', 'Rand Rare independently selected from H, Me, F, Cl and CF.'}4. The compound of claim 3 , wherein:{'sup': 1', '3, 'Rand Rare F; and'}{'sup': 2', '4, 'Rand Rare H.'}5. The compound of claim 3 , wherein:{'sup': 1', '4, 'Rand Rare H; and'}{'sup': 2', '3, 'Rand Rare F.'}6. The compound of claim 3 , wherein:{'sup': 1', '2', '4, 'R, Rand Rare H; and'}{'sup': '3', 'Ris F.'}7. The compound according to claim 1 , wherein:{'sup': '1', 'Xis N; and'}{'sup': 2', '2, 'Xis CR.'}8. The compound of claim 7 , wherein R claim 7 , Rand Rare independently selected from H claim 7 , halogen claim 7 , and (1-6C)alkyl.9. The compound of claim 8 , wherein R claim 8 , Rand Rare each H.10. The compound of claim 8 , wherein Rand Rare H and Ris Cl or F.11. The compound according to claim 1 , wherein:{'sup': 1', '1, 'Xis CR; and'}{'sup': '2', 'Xis N.'}12. The compound according to claim 11 , wherein R claim 11 , Rand Rare independently selected from H claim 11 , halogen claim 11 , and (1-6C)alkyl.13. The compound according to claim 12 , wherein each of R claim 12 , Rand Ris H.14. The compound according to claim 12 , wherein Rand Rare H and Ris Cl or F.15. The compound according to claim 1 , wherein Ris selected from (1-3C alkyl)sulfonyl claim 1 , (3-6C ...

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18-07-2013 дата публикации

Methods of Treating Traumatic Brain Injury Using Pro-Neurogenic Compounds

Номер: US20130184300A1

This invention relates generally to stimulating neurogenesis (e.g., post-natal neurogenesis, e.g., post-natal hippocampal neurogenesis) and protecting from neuron cell death. 2. The method of claim 1 , wherein when A is CRR claim 1 , the carbon attached to Rand Ris substituted with four different substituents claim 1 , and is (R) or (S) configured.3. The method of claim 2 , wherein the compound or salt is (+) (dextrorotatory) or (−) (levororotatory).4. The method of claim 1 , wherein the effective amount of the compound or salt stimulates neurogenesis.5. The method of claim 1 , wherein the effective amount of the compound or salt reduces neuron cell death.6. The method of claim 1 , wherein the compound is selected from:R-1-(3,6-Dibromo-9H-carbazol-9-yl)-3-(3-methoxyphenylamino)-propan-2-ol;S-1-(3,6-Dibromo-9H-carbazol-9-yl)-3-(3-methoxyphenylamino)-propan-2-ol;1-(3,6-dibromo-9H-carbazol-9-yl)-3-(2-iminopyridin-1(2H)-yl)propan-2-ol;1-(3,6-dibromo-9H-carbazol-9-yl)-3-(phenylthio)propan-2-ol;N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-hydroxypropyl)-N-(3-methoxyphenyl)acetamide;5-((3,6-dibromo-9H-carbazol-9-yl)methyl)-3-(3-methoxyphenyl)-oxazolidin-2-one;N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-3-methoxyaniline;1-(3,6-dibromo-9H-carbazol-9-yl)-3-(3-methoxyphenylamino)-propan-2-one;N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-methoxypropyl)-3-methoxyaniline;1-(3,6-Dimethyl-9H-carbazol-9-yl)-3-(3-methoxyphenylamino)propan-2-ol;1-(3-Bromo-6-methyl-9H-carbazol-9-yl)-3-(3-methoxyphenylamino)-propan-2-ol;1-(3,6-Dichloro-9H-carbazol-9-yl)-3-(3-methoxyphenylamino)propan-2-ol;1-(5-bromo-2,3-dimethyl-1H-indol-1-yl)-3-(phenylamino)propan-2-ol;1-(3,6-Dibromo-9H-pyrido[3,4-b]indol-9-yl)-3-(phenylamino)propan-2-ol;1-(3-Azidophenylamino)-3-(3,6-dibromo-9H-carbazol-9-yl)propan-2-ol;1,3-Bis(3,6-dibromo-9H-carbazol-9-yl)propan-2-ol;1-(9H-Carbazol-9-yl)-3-(3,6-dibromo-9H-carbazol-9-yl)propan-2-ol;3-(3,6-Dibromo-9H-carbazol-9-yl)-2-hydroxy-N-(3-methoxyphenyl)-propanamide;Ethyl 5-(2-Hydroxy- ...

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18-07-2013 дата публикации

METALLOENZYME INHIBITOR COMPOUNDS

Номер: US20130184309A1
Принадлежит: Viamet Pharmaceuticals, Inc.

The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes. 137-. (canceled)3942.-. (canceled)43. The method of claim 38 , wherein the disease or disorder is cancer claim 38 , cardiovascular disease claim 38 , inflammatory disease claim 38 , infectious disease claim 38 , metabolic disease claim 38 , ophthalmologic disease claim 38 , central nervous system (CNS) disease claim 38 , urologic disease claim 38 , or gastrointestinal disease.44. The method of claim 38 , wherein the disease or disorder is prostate cancer claim 38 , breast cancer claim 38 , androgen-dependent cancers claim 38 , estrogen-dependent cancers claim 38 , adrenal hyperplasia claim 38 , prostatic hypertrophy claim 38 , virilism claim 38 , hirsutism claim 38 , male pattern alopecia claim 38 , precocious puberty claim 38 , endometriosis claim 38 , uterus myoma claim 38 , uterine cancer claim 38 , mastopathy claim 38 , polycystic ovary syndrome claim 38 , infertility claim 38 , acne claim 38 , functional ovarian hyperandrogenism claim 38 , hyperandrogenism with chronic anovulation claim 38 , hyperandrogenemia claim 38 , premature adrenarche claim 38 , adrenal or androgen excess claim 38 , uterine fibroids claim 38 , inflammatory bowel disease claim 38 , psoriasis claim 38 , systemic fungal infection claim 38 , onychomycosis claim 38 , or cardiovascular disease.4552.-. (canceled)54. The composition of further comprising an additional therapeutic agent.55. The composition of further comprising an additional therapeutic agent that is an anti-cancer agent claim 53 , antifungal agent claim 53 , cardiovascular agent claim 53 , antiinflammatory agent claim 53 , chemotherapeutic agent claim 53 , an anti-angiogenesis agent claim 53 , cytotoxic agent claim 53 , an anti-proliferation agent claim 53 , metabolic disease agent claim 53 , ophthalmologic disease agent claim 53 , central nervous ...

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25-07-2013 дата публикации

COMPOUNDS FOR TREATING PROLIFERATIVE DISORDERS

Номер: US20130190325A1
Принадлежит: ITEK VENTURES PTY LTD

A compound of formula (I) or a pharmaceutically acceptable salt or solvate or physiologically hydrolysable, solubilising or immobilisable derivative thereof; wherein: any one or two of X., X2 and X3 is a N atom and the remaining two or one of X, Xand Xare independently CR; Y is selected from SOand SO; R, R, R, and Rand the one or two Rgroups are each independently selected from H and R, Ris selected from R, alkyl, aryl, heteroaryl and combinations of two or more thereof and combinations with one or more R, or Ris one or more moieties RSinking one or more alkyl, alkoxy, aryl, heteroaryl or Ror Rgroups or combinations thereof, directly or via a moiety selected from alkylene, arylene, heteroarylene or combinations thereof, wherein alkyl, aryl, heteroaryl groups or moieties thereof may be substituted with one or more groups R, or Ris selected from a group R; Ris selected from 0-, N—, NH—, N═C, CO—, C00-, CON—, CONH—, S0-, S0N—, S0NH—; Ris selected from halogen, NH, N0, CN, OH, COOH, CONH, C(═NH)NH, S0H, S0NH, S0CH, OCH, OCHCH, CF; Rand Rcomprise one or more solubilising moieties independently chosen from i) neutral hydrophilic groups, ii) ionisable organic acids, iii) ionisable organic bases, iv} chemical functions or moieties providing covalent or non-covalent attachment or binding to a solid phase or an immobile receptor and combinations thereof; R, Rand Rare each independently selected from H and R, or two of Rto Rare linked to form a cyclic ether or amine containing one or more additional oxygen or nitrogen atoms. The compound may be used for treating a condition mediated by one or more enzymes selected from AKT, Aurora kinase, BCR-ABL, CDK, FLT, GSK3, IKK, JAK, MAPK, PDGF, PI3K, PKA, PKB, PKC, PLK, Src and VEGF family enzymes, or for treating cancer or other proliferative disorder, or for inhibiting growth of cancer cells, or for inducing apoptosis of cancer cells, in a human or animal subject. 2. The compound of formula I or a pharmaceutically acceptable salt ...

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25-07-2013 дата публикации

THERAPEUTIC AGENT FOR NEUROLOGICAL DISEASES

Номер: US20130190363A1
Принадлежит:

An object of the present invention is to provide a pharmaceutical agent useful for treating and preventing neurological disease, having satisfactory solubility and oxidative stress-mediated cell death suppressive activity as well as capable of exhibiting excellent blood-brain barrier permeability. The present invention is directed to an acylaminoimidazole derivative represented by general formula (I) or a salt thereof, and a pharmaceutical and a therapeutic or preventive agent for neurological disease containing the same, as an active ingredient. 2. The acylaminoimidazole derivative or a salt thereof according to claim 1 , wherein Ris a group of formula (Ia) claim 1 , Ris a hydrogen atom and X is a nitrogen atom.3. The acylaminoimidazole derivative or a salt thereof according to claim 1 , wherein the acylaminoimidazole derivative is (2R)-2-(mesityloxy)-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl]propanamide.4. The acylaminoimidazole derivative or a salt thereof according to claim 1 , wherein the acylaminoimidazole derivative is 2-(mesitylamino)-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl]acetamide.5. The acylaminoimidazole derivative or a salt thereof according to claim 1 , wherein the acylaminoimidazole derivative is 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl]acetamide.6. A pharmaceutical comprising the acylaminoimidazole derivative or a salt thereof according to any one of to claim 1 , as an active ingredient.7. A therapeutic or preventive agent for neurological disease comprising the acylaminoimidazole derivative or a salt thereof according to any one of to claim 1 , as an active ingredient.8. An oxidative stress-mediated cell death suppressant comprising the acylaminoimidazole derivative or a salt thereof according to any one of to claim 1 , as an active ingredient.9. The therapeutic or preventive agent for neurological disease according to claim 7 , wherein the neurological disease is a neurodegenerative disease having cell degeneration due to oxidative ...

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01-08-2013 дата публикации

MORPHOLINO SUBSTITUTED UREA DERIVATIVES AS MTOR INHIBITORS

Номер: US20130196982A1
Принадлежит:

The invention relates to compounds of formula (I) 2. A compound of claim 1 , wherein Ris H; or Calkyl claim 1 , wherein Calkyl is optionally substituted with one or more R claim 1 , which are the same or different; or Ccycloalkyl claim 1 , wherein Ccycloalkyl is optionally substituted with one or more Rya claim 1 , which are the same or different.3. A compound of claim 1 , wherein Ris halogen; CN; OR; C(O)N(RR); or N(RR).4. A compound of claim 1 , wherein Ris halogen; CN; OR; or N(RR).5. A compound of claim 1 , wherein Ris halogen; CN; OR; N(RR); or Calkyl claim 1 , wherein Calkyl is optionally substituted with one or more halogen claim 1 , which are the same or different.6. A compound of claim 1 , wherein Ris T.7. A compound of claim 1 , wherein Tis unsubstituted or substituted with 1 or 2 R claim 1 , which are the same or different.8. A compound of claim 1 , wherein Ris halogen; CN; S(O)R; S(O)R; N(R)SOR; SON(RR); N(R)C(O)R; C(O)N(RR); CO(O)R; or CHR.9. A compound of claim 1 , wherein Ris H.10. A compound of claim 1 , wherein Ris methyl.11. A compound of claim 1 , wherein n is 0; n is 1 and Ris methyl; or n is 2 and the two Rare joined together with the morpholine ring to form an 8-oxa-3-azabicyclo[3.2.1]octan-3-yl ring.12. A compound of claim 1 , wherein Ris F.13. A compound of claim 1 , wherein m claim 1 , n are independently selected from the group consisting of 0; and 1.14. A compound of claim 1 , wherein Xis N.15. A compound of claim 1 , wherein Ris H.16. A compound of selected from the group consisting of1-cyclopropyl-3-(4-(2-morpholino-6-(pyridin-3-yl)pyrimidin-4-yl)phenyl)urea;(S)-1-ethyl-3-(4-(6-(5-fluoro-2-(methylsulfonyl)phenyl)-2-(3-methylmorpholino)pyrimidin-4-yl)phenyl)urea;(S)-1-cyclopropyl-3-(4-(4-(3-methylmorpholino)-6-(pyridin-3-yl)pyrimidin-2-yl)phenyl)urea;(S)-1-cyclopropyl-3-(4-(2-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)pyrimidin-4-yl)phenyl)urea;(S)-1-cyclopropyl-3-(4-(6-(3-methylmorpholino)-2-(3-(methylsulfonyl)phenyl)pyrimidin-4-yl ...

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01-08-2013 дата публикации

1',3'-DISUBSTITUTED-4-PHENYL-3,4,5,6-TETRAHYDRO-2H,1'H-[1,4']BIPYRIDINYL-2'-ONES

Номер: US20130197019A1
Принадлежит:

The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) 2. The method of wherein{'sup': '1', 'Ris 1-butyl, 2-methyl-1-propyl, 3-methyl-1-butyl, (cyclopropyl)methyl or 2-(cyclopropyl)-1-ethyl;'}{'sup': '3', 'Ris hydrogen, fluoro or cyano; and'}{'sub': '1-3', 'Ar is unsubstituted phenyl; or phenyl substituted with halo, trifluoromethyl, morpholinyl or hydroxyCalkyl;'}or a pharmaceutically acceptable salt or a solvate thereof.3. The method of wherein{'sup': '1', 'Ris 1-butyl, 3-methyl-1-butyl, (cyclopropyl)methyl or 2-(cyclopropyl)-1-ethyl;'}{'sup': '2', 'Ris chloro;'}{'sup': '3', 'Ris hydrogen or fluoro; and'}{'sub': '1-3', 'Ar is unsubstituted phenyl; or phenyl substituted with hydroxyCalkyl;'}or a pharmaceutically acceptable salt or a solvate thereof.4. The method of wherein said compound is selected from:3′-chloro-1′-cyclopropylmethyl-4-phenyl-3,4,5,6-tetrahydro-2H,1′H-[1,4′]bipyridinyl-2′-one;1′-butyl-3′-chloro-4-phenyl-3,4,5,6-tetrahydro-2H,1′H-[1,4′]bipyridinyl-2′-one;or a pharmaceutically acceptable salt or a solvate thereof.6. The method of wherein{'sup': '1', 'Ris 1-butyl, 2-methyl-1-propyl, 3-methyl-1-butyl, (cyclopropyl)methyl or 2-(cyclopropyl)-1-ethyl;'}{'sup': '3', 'Ris hydrogen, fluoro or cyano; and'}{'sub': '1-3', 'Ar is unsubstituted phenyl; or phenyl substituted with halo, trifluoromethyl, morpholinyl or hydroxyCalkyl;'}or a pharmaceutically acceptable salt or a solvate thereof.7. The method of wherein{'sup': '1', 'Ris 1-butyl, 3-methyl-1-butyl, (cyclopropyl)methyl or 2-(cyclopropyl)-1-ethyl;'}{'sup': '2', 'Ris chloro;'}{'sup': '3', 'Ris hydrogen or fluoro; and'}{'sub': '1-3', 'Ar is unsubstituted phenyl; or phenyl substituted with hydroxyCalkyl;'}or a pharmaceutically acceptable salt or a solvate thereof.8. The method of wherein said compound is selected from:3′-chloro-1′-cyclopropylmethyl-4-phenyl-3,4,5,6-tetrahydro-2H,1′H-[1,4′]bipyridinyl-2′-one;1′-butyl-3′-chloro-4-phenyl-3,4,5,6- ...

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01-08-2013 дата публикации

COMPOSITION AND METHODS FOR TREATING GLIOBLASTOMA

Номер: US20130197026A1
Автор: KLINE Toni, Stella Nephi

The disclosure provides methods of treating glioblastoma, methods of screening for compounds that treat glioblastoma, and pharmaceutical compositions useful the treatment of glioblastoma. 2. The compound according to claim 1 , wherein X is CH.3. The compound according to claim 1 , wherein Ris C-Calkyl or C-Calkoxy.4. The compound according to claim 3 , wherein Ris methyl or methoxy.5. The compound according to claim 1 , wherein Ris H.6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. The compound according to claim 1 , wherein Rand Rtaken together with the atoms to which they are attached form a 6-membered heterocyclyl optionally substituted with one to four R.12. The compound according to claim 1 , wherein Rand Rare each independently H claim 1 , C-Calkoxy claim 1 , C-Chaloalkoxy claim 1 , halogen claim 1 , or —OH.13. (canceled)15. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to and one or more pharmaceutically acceptable diluents claim 1 , preservatives claim 1 , solubilizers claim 1 , emulsifiers claim 1 , adjuvants claim 1 , excipients claim 1 , or carriers.16. A method of treating or inhibiting glioblastoma claim 1 , acognition disorder claim 1 , schizophrenia claim 1 , Alzheimer's disease and dementia claim 1 , Parkinson's disease claim 1 , depression claim 1 , multiple sclerosis claim 1 , amyotrophic lateral sclerosis (ALS) claim 1 , Huntington's disease claim 1 , Fronto temporal dementia claim 1 , parkinsonism linked to chromosome 17 claim 1 , and prion diseases claim 1 , comprising administering to the subject an effective amount of a compound according to .17. The method according to claim 16 , wherein the method is for treating or inhibiting glioblastoma.1832-. (canceled)34. A method of screening for therapeutic agents useful in the treatment of glioblastomas in a subject comprising the steps of:contacting a test compound with a GPR124 polypeptide or a fragment thereof;measuring a ...

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01-08-2013 дата публикации

1, 2, 4-TRIAZOLONE DERIVATIVE

Номер: US20130197217A1
Принадлежит: TAISHO PHARMACEUTICAL CO., LTD

The present invention provides a 1,2,4-triazolone derivative represented by Formula (1A) having an antagonistic activity on the arginine-vasopressin 1b receptor or a pharmaceutically acceptable salt thereof and provides a pharmaceutical composition comprising the compound or the salt as an active ingredient, in particular, a therapeutic or preventive agent exhibiting favorable pharmacokinetics in a disease such as mood disorder, anxiety disorder, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorder, hypertension, gastrointestinal disease, drug addiction, epilepsy, cerebral infarction, cerebral ischemia, cerebral edema, head injury, inflammation, immune-related disease, or alopecia. 4. The 1 claim 1 ,2 claim 1 ,4-triazolone derivative or pharmaceutically acceptable salt thereof according to claim 1 , wherein{'sup': '1', 'sub': '1-5', 'Ris a Calkyl;'}{'sup': '2', 'Ris a hydrogen atom; and'}{'sup': '3', 'sub': 1-5', '1-5, 'Ris phenyl or pyridyl (the phenyl or pyridyl is optionally substituted by one or two groups selected from the group consisting of Calkyl, Calkoxy, halogen atoms, cyano, hydroxy, trifluoromethyl, difluoromethoxy, and trifluoromethoxy).'}5. The 1 claim 1 ,2 claim 1 ,4-triazolone derivative or pharmaceutically acceptable salt thereof according to claim 1 , wherein{'sub': '1-5', 'A is phenylene, pyridinediyl, or pyrimidinediyl (the phenylene, pyridinediyl, and pyrimidinediyl are optionally substituted by one or two groups selected from halogen atoms and Calkoxy).'}6. The 1 claim 1 ,2 claim 1 ,4-triazolone derivative or pharmaceutically acceptable salt thereof according to claim 1 , wherein{'sub': '1-5', 'A is phenylene or pyridinediyl (the phenylene and pyridinediyl are optionally substituted by one or two groups selected from halogen atoms and Calkoxy).'}8. The 1 claim 1 ,2 claim 1 ,4-triazolone derivative or pharmaceutically acceptable salt thereof according to claim 1 , whereinX is a single bond;n is an integer ...

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08-08-2013 дата публикации

PYRROLIDINE COMPOUNDS

Номер: US20130203728A1
Принадлежит: Hoffmann-La Roche Inc.

The present application relates to compounds of formula 2. The compound of claim 1 , wherein Ris aryl substituted by halogen.3. The compound of claim 2 , wherein aryl is phenyl.5. The compound of claim 1 , selected from the group consisting ofrac-{(3S,4R)-4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-ethyl-carbamic acid 4-fluoro-phenyl ester;rac-{(3S,4R)-4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-isopropyl-carbamic acid 4-fluoro-phenyl ester;rac-{(3S,4R)-4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-isobutyl-carbamic acid 4-fluoro-phenyl ester;rac-{(3S,4R)-4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-cyclopropyl-carbamic acid 4-fluoro-phenyl ester;{(3S,4R)-4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-ethyl-carbamic acid 4-fluoro-phenyl ester;{(3R,4S)-4-(3,4-Dichloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-ethyl-carbamic acid 4-fluoro-phenyl ester;{(3R,4S)-4-(4-Chloro-phenyl)-1-[1-(5-cyano-pyrimidin-2-yl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-ethyl-carbamic acid 4-fluoro-phenyl ester;[(3R,4S)-1-(5′-Acetyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carbonyl)-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester;[(3R,4S)-4-(4-Chloro-phenyl)-1-(4′-cyano-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carbonyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester;[(3R,4S)-4-(4-Chloro-phenyl)-1-(5′-methanesulfonyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carbonyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester;{(3R,4S)-4-(4-Chloro-phenyl)-1-[1-(5-cyano-pyrazin-2-yl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-ethyl-carbamic acid 4-fluoro-phenyl ester; and{(3R,4S)-4-(4-Chloro-phenyl)-1-[1-(6-cyano-pyridazin-3-yl)- ...

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15-08-2013 дата публикации

SOLUBLE GUANYLATE CYCLASE ACTIVATORS

Номер: US20130210798A1
Принадлежит:

This inventions relates to compounds having the structure Formula I and pharmaceutically acceptable salts thereof which are soluble guanylate cyclase activators. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver. 4. The compound of selected form the group consisting of:1-[6-(4-Chloro-3′-methyl-4′-{[1-(2,2,2-trifluoroethyl)azetidin-3-yl]methoxy}biphenyl-2-yl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid;1-(6-[4-chloro-4′-(4-cyclopropylpiperidin-1-yl)biphenyl-2-yl]pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid;1-{6-[4-chloro-4′-(4,4-difluorocyclohexyl)biphenyl-2-yl]pyridin-2-yl}-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid;1-{6-[4′-(4-cyclopropylpiperidin-1-yl)-4-methylbiphenyl-2-yl]pyridin-2-yl}-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid;1-(6-{4-chloro-4′-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]biphenyl-2-yl}pyridin-2-yl)-5-(trifluoromethyl)-1-pyrazole-4-carboxylic acid;1-[2′-{4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenyl}-5′-(trifluoromethyl)-2,3′-bipyridin-6-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid;1-[6-(4-chloro-4′-{4-[(2,2-difluorocyclopropyl)methyl]piperazin-1-yl}biphenyl-2-yl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid;1-(6-{4-chloro-4′-[1-(methoxycarbonyl)piperidin-4-yl]biphenyl-2-yl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid;1-(6-{4-chloro-4′-[1-(ethoxycarbonyl)piperidin-4-yl]biphenyl-2-yl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid;1-(6-{4-chloro-4′-[1-(dimethylcarbamoyl)piperidin-4-yl]-3′-methylbiphenyl-2-yl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid;1-(6-{(4- ...

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15-08-2013 дата публикации

Methods for Treating Obesity

Номер: US20130210821A1
Автор: Vath James E.
Принадлежит:

The disclosure provides for methods of treating obesity and related disorders. Pharmaceutical compositions and methods of using, e.g. in the treatment of obesity are provided. 3. The method of claim 2 , wherein Ris H claim 2 , nitro claim 2 , Cl claim 2 , Br claim 2 , or SOH.4. The method of claim 2 , wherein Ris H or an optionally substituted alkyl.5. The method of claim 4 , wherein Ris methyl which is optionally substituted by one or more of phenyl claim 4 , naphthyl claim 4 , anthracenyl claim 4 , fluorenyl claim 4 , indenyl claim 4 , azulenyl; pyridyl claim 4 , 1-oxo-pyridyl claim 4 , furanyl claim 4 , benzo[1 claim 4 ,3]dioxolyl claim 4 , benzo[1 claim 4 ,4]dioxinyl claim 4 , thienyl claim 4 , pyrrolyl claim 4 , oxazolyl claim 4 , imidazolyl claim 4 , thiazolyl claim 4 , isoxazolyl claim 4 , quinolinyl claim 4 , pyrazolyl claim 4 , isothiazolyl claim 4 , pyridazinyl claim 4 , pyrimidinyl claim 4 , pyrazinyl claim 4 , triazinyl claim 4 , triazolyl claim 4 , thiadiazolyl claim 4 , isoquinolinyl claim 4 , indazolyl claim 4 , benzoxazolyl claim 4 , benzofuryl claim 4 , indolizinyl claim 4 , imidazopyridyl claim 4 , tetrazolyl claim 4 , benzimidazolyl claim 4 , benzothiazolyl claim 4 , benzothiadiazolyl claim 4 , benzoxadiazolyl claim 4 , indolyl claim 4 , tetrahydroindolyl claim 4 , azaindolyl claim 4 , indazolyl claim 4 , imidazopyridyl claim 4 , quinazolinyl claim 4 , purinyl claim 4 , pyrrolo[2 claim 4 ,3]pyrimidinyl claim 4 , pyrazolo[3 claim 4 ,4] pyrimidinyl claim 4 , benzo(b)thienyl; cyclopropyl claim 4 , cyclobutyl claim 4 , cyclopentyl claim 4 , cyclohexyl claim 4 , cycloheptyl claim 4 , aziridinyl claim 4 , oxiranyl claim 4 , azetidinyl claim 4 , oxetanyl; piperidinyl claim 4 , piperazinyl claim 4 , 2-oxopiperazinyl claim 4 , 2-oxopiperidinyl claim 4 , 2-oxo pyrrolidinyl claim 4 , 4-piperidonyl claim 4 , tetrahydropyranyl claim 4 , oxazolidinyl claim 4 , 2-oxo-oxazolidinyl claim 4 , tetrahydrothiopyranyl claim 4 , tetrahydrothiopyranyl sulfone claim 4 , ...

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22-08-2013 дата публикации

DERIVATIVES OF PYRAZOLOPHENYL-BENZENESULFONAMIDE COMPOUNDS AND USE THEREOF AS ANTITUMOR AGENTS

Номер: US20130217715A1
Принадлежит:

Substituted pyrazolophenyl-benzenesulfonamide compounds of formula (I) are described, wherein m, R1, R2, R3, and R4 are defined in the description, which modulate the activity of protein kinases, These compounds find utility in treating diseases caused by deregulated protein kinase activity, such as cancer and cell proliferative disorders. 3. A compound according to claim 1 , wherein m is an integer from 0 to 3.4. A compound according to claim 2 , wherein m is 0 claim 2 , 1 or 2.5. A compound according to claim 4 , wherein R1 is selected from the group consisting of: trifluoromethyl claim 4 , halogen claim 4 , cyano claim 4 , OR5 claim 4 , NR6R7 claim 4 , COOR10 claim 4 , CONR11R12 claim 4 , or an optionally substituted group selected from (C-C)alkyl claim 4 , (C-C)cycloalkyl or heterocyclyl.6. A compound according to claim 4 , wherein R1 is an optionally substituted group selected from (C-C)cycloalkyl or heterocyclyl.7. A compound according to claim 1 , wherein R1 is hydrogen.8. A compound according to claim 4 , wherein R2 and R3 are independently chosen from hydrogen and halogen.11. A compound selected from:1) 2,5-difluoro-N-{2-fluoro-3-[1-(1-isopropyl-piperidin-4-yl)-4-pyridin-4-yl-1H-pyrazol-3-yl]-phenyl}-benzenesulfonamide;2) N-{3-[1-(1-cyclopropyl-piperidin-4-yl)-4-pyridin-4-yl-1H-pyrazol-3-yl]-2-fluoro-phenyl}-2,5-difluoro-benzenesulfonamide;3) N-{3-[4-(2-amino-pyrimidin-4-yl)-1-ethyl-1H-pyrazol-3-yl]-2-fluoro-phenyl}-2,5-difluoro-benzenesulfonamide;4) N-{3-[4-(2-amino-pyridin-4-yl)-1-ethyl-1H-pyrazol-3-yl]-2-fluoro-phenyl}-2,5-difluoro-benzenesulfonamide;5) 2,5-difluoro-N-{2-fluoro-3-[1-(1-methyl-piperidin-4-yl)-4-pyridin-4-yl-1H-pyrazol-3-yl]-phenyl}-benzenesulfonamide;6) N-{3-[4-(2-amino-pyrimidin-4-yl)-1-(1-methyl-piperidin-4-yl)-1H-pyrazol-3-yl]-2-fluoro-phenyl}-2,5-difluoro-benzenesulfonamide;7) 2,5-difluoro-N-{2-fluoro-3-[1-(2-fluoro-ethyl)-4-pyridin-4-yl-1H-pyrazol-3-yl]-phenyl}-benzenesulfonamide;8) 2,5-difluoro-N-{2-fluoro-3-[1-(1-methyl-piperidin-4 ...

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29-08-2013 дата публикации

F, G, H, I and K Crystal Forms of Imatinib Mesylate

Номер: US20130224288A1
Автор: Mutz Michael
Принадлежит:

The invention relates to the F-crystal form, G-crystal form, H-crystal form, I-crystal form and K-crystal form of the methanesulfonic acid addition salt of 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide, certain processes for their preparation, pharmaceutical compositions containing these crystal forms, their use in diagnostic methods or for the therapeutic treatment of warm-blooded animals, and their use as an intermediate or for the preparation of pharmaceutical preparations for use in diagnostic methods or for the therapeutic treatment of warm-blooded animals, especially humans. 148-. (canceled)50. The crystalline form according to claim 49 , which shows on X-ray diffraction a peak at an angle of refraction 2theta of 37.9°.51. The crystalline form according to claim 49 , which is characterized by an X-ray diffraction peak at an angle of refraction 2theta of 21.0°.52. The crystalline form of the methanesulfonic acid addition salt of a compound of formula I according to claim 49 , which shows in an X-ray diffraction diagram lines at the following angles of refraction 2theta: 12.1° claim 49 , 14.1° claim 49 , 18.2° claim 49 , 18.4° claim 49 , 21.0° claim 49 , 23.4° and 28.4°.53. The crystalline form according to claim 49 , which is present in essentially pure form.56. The composition according to comprising additionally at least one distinct form of the methanesulfonic acid addition salt of a compound of formula I selected from the amorphous form claim 55 , the α-crystal form claim 55 , the β-crystal form and the H1-crystal form.57. A pharmaceutical composition comprising a crystalline form of the methanesulfonic acid addition salt of a compound of formula I according to claim 49 , optionally together with pharmaceutically acceptable carrier.58. The pharmaceutical composition according to comprising additionally at least one distinct form of the methanesulfonic acid addition salt of a compound of formula I ...

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29-08-2013 дата публикации

METHODS OF MODULATING THE ACTIVITY OF THE MC5 RECEPTOR AND TREATMENT OF CONDITIONS RELATED TO THIS RECEPTOR

Номер: US20130225563A1
Принадлежит: MIMETICA PTY LTD

The present invention provides compounds of Formula (I) that are useful for modulating the biological activity of the melanocortin-5 receptor (MC5R). Compounds of this invention can be used to treat diseases and/or conditions in which downregulation of MC5R is beneficial. Such diseases and/or conditions include, but are not limited to, acne, seborrhea, seborrheic dermatitis, cancer, and inflammatory diseases. 3. A method according to wherein Ris NRR; Rand Rare each independently H or C-Calkyl; Rand Rare each independently H claim 2 , methyl claim 2 , trifluoromethyl claim 2 , ethyl claim 2 , 2 claim 2 ,2 claim 2 ,2-trifluoroethyl claim 2 , isopropyl claim 2 , isopropenyl claim 2 , propyl claim 2 , 2-ethyl-propyl claim 2 , 3 claim 2 ,3-dimethyl-propyl claim 2 , butyl claim 2 , 2-methylbutyl claim 2 , isobutyl claim 2 , 3 claim 2 ,3-dimethyl-butyl claim 2 , 2-ethyl-butyl claim 2 , pentyl claim 2 , 2-methyl-pentyl claim 2 , optionally substituted phenyl or optionally substituted C-Cheteroaryl wherein the C-Cheteroaryl is thiophene claim 2 , furan claim 2 , pyrrole claim 2 , imidazole claim 2 , pyrazole claim 2 , pyridine claim 2 , pyrazine claim 2 , or tetrazole; Ris H; Rand Rare each independently H or C-Calkyl; or a pharmaceutically acceptable salt thereof.4. A method according to wherein each optional substituent is independently selected from the group consisting of F claim 3 , Cl claim 3 , Br claim 3 , I claim 3 , CH claim 3 , CHCH claim 3 , OH claim 3 , OCH claim 3 , CF claim 3 , OCF claim 3 , NO claim 3 , NH claim 3 , and CN; or a pharmaceutically acceptable salt thereof.5. A method according to wherein X is —C(═O)—; Y is CH; Z is —(CH)—; Ris H; Ris H; r is 1; q is 1 claim 4 , 2 claim 4 , 3 claim 4 , or 4; or a pharmaceutically acceptable salt thereof.6. A method according to wherein Ris H claim 5 , —C(═NH)NH claim 5 , —C(═NH)N(CH) claim 5 , —C(═NH)NHCH(CH) claim 5 , —C(═O)CH claim 5 , —C(═O)cyclohexyl claim 5 , CH claim 5 , CHCH claim 5 , CHCHCH claim 5 , CH(CH ...

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29-08-2013 дата публикации

MANUFACTURING PROCESS FOR PYRIMIDINE DERIVATIVES

Номер: US20130225571A1
Принадлежит: NOVARTIS AG

The invention relates to new crystalline forms of processes for manufacturing a compound of formula 5, 147-. (canceled)49. A hemihydrate of Compound A according to in polymorph Form H claim 48 , wherein the hemihydrate shows on X-ray diffraction a peak at an angle of diffraction 2theta of 19.2+/−0.3° and 18.7+/−0.3°.50. A crystalline form of compound A according to in polymorph Form A anhydrous claim 48 , wherein the crystalline form of Compound A shows on X-ray diffraction a peak at an angle of diffraction 2theta of 14.8+/−0.3° and 10.2+/−0.3°.51. A monohydrate of the monohydrochloride salt of Compound A according to in polymorph Form Ha claim 48 , wherein the monohydrate shows on X-ray diffraction a peak at an angle of diffraction 2theta of 9.3°+/−0.3° and 15.8+/−0.3°.52. A monohydrochloride salt of Compound A according to in polymorph Form A claim 48 , wherein said monohydrochloride salt shows on X-ray diffraction a peak at an angle of diffraction 2theta of 9.9°+/−0.3° and 20.0°+/−0.3°.53. A monohydrochloride salt of Compound A according to in polymorph Form B claim 48 , wherein said monohydrochloride salt shows on X-ray diffraction a peak at an angle of diffraction 2theta of 18.7°+/−0.3° and 21.8°+/−0.3°.54. A solvate of the monohydrochloride salt of Compound A according to in the form of polymorph Form S claim 48 , wherein said solvate of the monohydrochloride salt of Compound A shows on X-ray diffraction a peak at an angle of diffraction 2theta of 16.6°+/−0.3° and 28.4°+/−0.3°.55. A solvate of the monohydrochloride salt of Compound A according to in the form of polymorph Form S claim 48 , wherein said solvate of the monohydrochloride salt of Compound A shows on X-ray diffraction a peak at an angle of diffraction 2theta of 19.8°+/−0.3° and 17.5°±/−0.3°.56. A solvate of the monohydrochloride salt of Compound A according to the form of polymorph Form S claim 48 , wherein said solvate of the monohydrochloride salt of Compound A shows on X-ray diffraction a peak at ...

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29-08-2013 дата публикации

SUBSTITUTED 2-HYDROXY-4-(2-(PHENYLSULFONAMIDO)ACETAMIDO)BENZOIC ACID ANALOGS AS INHIBITORS OF STAT PROTEIN

Номер: US20130225621A1
Принадлежит:

In one aspect, the invention relates to substituted 2-hydroxy-4-(2-(phenylsulfonamido)acetamido)benzoic acid analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 5. The compound of claim 1 , wherein the compound exhibits inhibition of STAT with an ICof less than about 300 μM.6. The compound of claim 1 , wherein the compound exhibits inhibition with an Kof less than about 300 μM.7. A pharmaceutical composition comprising a therapeutically effective amount of a compound of and a pharmaceutically acceptable carrier.12. The method of claim 8 , wherein the mammal has been diagnosed with a need for treatment of the disorder prior to the administering step.13. The method of claim 8 , wherein the disorder is selected from psoriasis and pulmonary arterial hypertension.14. The method of claim 8 , wherein the disorder is a disease of uncontrolled cellular proliferation.15. The method of claim 14 , wherein the disease of uncontrolled cellular proliferation is a cancer selected from cancers of the head claim 14 , neck claim 14 , pancreas claim 14 , brain claim 14 , colon claim 14 , rectum claim 14 , skin claim 14 , ovary claim 14 , kidney claim 14 , prostate claim 14 , breast claim 14 , lung claim 14 , colon claim 14 , uterus claim 14 , and liver.18. The method of claim 16 , wherein the mammal has been diagnosed with a need for treatment of the disorder prior to the administering step.19. The method of claim 16 , wherein the disorder is a disease of uncontrolled cellular proliferation.20. The method of claim 19 , ...

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29-08-2013 дата публикации

IMIDAZOLE DERIVATIVES AND PREPARATION METHOD AND USE THEREOF

Номер: US20130225638A1
Автор: Li Jin
Принадлежит: BEIJING ORBIEPHARM CO., LTD

Disclosed are imidazole derivatives as represented by formula (I), and preparation method and use thereof. The compounds can inhibit cyclooxygenase and treat diseases mediated by cyclooxygenase. 2. The compound of claim 1 , or its pharmaceutically acceptable salt claim 1 , solvate claim 1 , isomer or prodrug claim 1 , wherein:when X═N, Y═C or Y═N, X═C atom,{'sup': '1', 'sub': '1-5', 'the substituent group Rrepresents hydrogen atom, Calkyl, halogen or cyano group;'}{'sup': 2', '4', '4', '4', '6', '4', '5', '5', '5', '4', '6', '4, 'sub': 1-8', '0-8', '0-8', '2', '2', '2, 'the substituent group Rrepresents aryl or heteroaryl substituted independently by one or more groups which are selected from a group consisting of halogen, Calkyl, ROCalkyl, RSCalkyl, cyano group, nitro group, —NRR, —NRSOR, —SOR, —SOR, —SONRRand —CONRR;'}{'sup': 3', '7', '7', '7, 'sub': '2', 'the substituent group Rrepresents —SOR, —SORor —SRgroup;'}{'sup': '4', 'sub': 1-8', '1-8', '0-8', '1-8', '1-8, 'the substituent group Rrepresents hydrogen atom, Calkyl, Chaloalkyl or aryl Calkyl, wherein the aryl is optionally substituted by one or more groups selected from Calkyl, halogen, Chaloalkyl, cyano group and nitro group;'}{'sup': '5', 'sub': 1-8', '1-8, 'the substituent group Rrepresents Calkyl or Chaloalkyl;'}{'sup': '6', 'sub': 1-8', '0-8', '1-8', '1-8, 'the substituent group Rrepresents hydrogen atom, Calky or aryl Calkyl, wherein the aryl is optionally substituted by one or more groups selected from Calkyl, halogen, Chaloalkyl, cyano group and nitro group;'}the aryl is phenyl or naphthyl; the heteroaryl is pyridine, pyrazine, pyrimidine or pyridazine; and{'sup': '7', 'sub': 2', '1-8', '1-8, 'the substituent group Rrepresents —NH, Calky or Chaloalkyl.'}3. The compound of claim 2 , or its pharmaceutically acceptable salt claim 2 , solvate claim 2 , isomer or prodrug claim 2 , wherein:{'sup': '1', 'sub': '1-5', 'the substituent group Rrepresents hydrogen atom, Calkyl or halogen;'}{'sup': 2', '4', '4', ...

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29-08-2013 дата публикации

USE OF AZIDES IN SYNTHESIS

Номер: US20130225819A1
Принадлежит: Massachusetts Institute of Technology

Described herein are inventive methods for synthesis of tetrazoles. In some embodiments, the method involves the use of a flow reactor. The methods provided herein are capable at being carried out in short reaction times, with high yields, with minimal side reactions, and/or with minimal chance of explosions caused by the presence of azides. 4. The method of claim 1 , wherein the reacting is carried out in the presence of a catalyst.5. The method of claim 4 , wherein the catalyst is ZrBr.6. The method of claim 4 , wherein the catalyst is provided in an amount of about 0.5 equiv claim 4 , about 0.75 equiv claim 4 , about 1 equiv claim 4 , about 1.5 equiv claim 4 , about 2 equiv claim 4 , about 3 equiv claim 4 , about 4 equiv claim 4 , or about 5 equiv. of the compound of formula (I).7. The method of claim 1 , wherein the reacting is carried out in a flow reactor.8. The method of claim 1 , wherein the azide source is NaN.9. The method of claim 1 , wherein the ratio of the azide source to a compound about formula (I) is about 1:1 claim 1 , about 1.05:1 claim 1 , about 1.1:1 claim 1 , about 1.2:1 claim 1 , about 1.3:1 claim 1 , about 1.4:1 claim 1 , about 1.5:1 claim 1 , about 2:1 claim 1 , about 3:1 claim 1 , or about 4:1.10. The method of claim 1 , wherein the conditions comprise reacting at a temperature of about 150° C. claim 1 , about 160° C. claim 1 , about 170° C. claim 1 , about 180° C. claim 1 , about 190° C. claim 1 , about 200° C. claim 1 , about 210° C. claim 1 , about 220° C. claim 1 , or about 230° C.11. The method of claim 1 , wherein the conditions comprise reacting at a temperature between about 150° C. and about 220° C.12. The method of claim 1 , wherein the conditions comprise reacting in a solution comprising water and a polar aprotic solvent.13. The method of claim 12 , wherein the ratio of water to polar aprotic solvent is between about 1:9 and about 9:1.14. The method of claim 1 , wherein the reaction is carried out under conditions suitable for ...

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29-08-2013 дата публикации

SYNTHESIS OF THIOHYDANTOINS

Номер: US20130225821A1

A novel synthesis of the anti-androgen, A52, which has been found to be useful in the treatment of prostate cancer, is provided. A52 as well as structurally related analogs may be prepared via the inventive route. This new synthetic scheme may be used to prepare kilogram scale quantities of pure A52. 2. The method of claim 1 , wherein the step of coupling comprises irradiating the reaction mixture with microwaves.3. The method of claim 1 , wherein the step of coupling comprises acid hydrolysis of an imidohydantoin intermediate.4. The method of claim 1 , wherein the step of coupling comprises adding thiophosgene to the reaction mixture in DMF and heating overnight at approximately 60° C.5. The method of claim 4 , wherein the step of coupling comprises acid hydrolysis of an imidohydantoin intermediate.7. The method of claim 6 , wherein the step of coupling comprises irradiating the reaction mixture with microwaves.11. The method of claim 10 , wherein the step of coupling comprises thiophosgene.12. The method of claim 11 , wherein the step of coupling is performed in N claim 11 ,N-dimethylacetamide as the solvent.13. The method of claim 12 , wherein the step of coupling is performed at approximately 60° C.14. The method of claim 11 , wherein the step of coupling further comprises acid hydrolysis of an imidohydantoin intermediate. The present application claims priority under 35 U.S.C. §120 to and is a continuation of U.S. patent application, U.S. Ser. No. 12/450,423, filed Apr. 5, 2010, which claims priority to and is a national stage filing under 35 U.S.C. §371 of international PCT application, PCT/US2008/058429, filed Mar. 27, 2008, which claims priority under 35 U.S.C. §119(e) to U.S. provisional patent applications, U.S. Ser. No. 60/908,280, filed Mar. 27, 2007, and U.S. Ser. No. 60/909,195, filed Mar. 30, 2007, each of which is incorporated herein by reference.This invention was made with U.S. Government support under grant number P01 129243 awarded by the ...

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05-09-2013 дата публикации

SMALL MOLECULE INHIBITORS OF EBOLA AND LASSA FEVER VIRUSES AND METHODS OF USE

Номер: US20130231332A1
Принадлежит:

The present invention relates to compositions and methods for the treatment of infection by enveloped viruses, such as Ebola and Lassa fever viruses. 1. (canceled)3. (canceled)5. (canceled)9. The method of claim 7 , wherein the viral infection is an Ebola infection.10. The method of claim 7 , wherein the viral infection is a Lassa fever infection. This application claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 61/379,138, filed Sep. 1, 2010, the contents of which are hereby incorporated by reference.This invention was made with government support under AI057159 awarded by the National Institutes of Health. The government has certain rights in the invention.Ebolaviruses (EboV) are enveloped negative-sense RNA viruses that cause sporadic outbreaks of rapidly fatal zoonotic infection. EboV is transmitted by close contact and virus levels increase by 75-fold/day for several days after initial infection. The clinical symptoms are manifestations of the massive production of pro-inflammatory cytokines, including interferon-α and TNF-α in response to infection. The endothelial cell dysfunction associated with “cytokine storm” results in capillary leak, hypovolemic shock, disseminated intravascular coagulation and inadequate perfusion of major organs. In many outbreaks, the mortality rate from EboV infection exceeds 75% in 14 days. Current therapy is supportive; there is no effective anti-EboV vaccine or therapy. The unpredictable onset, ease of transmission, rapidity of progression, high mortality, and bio-terrorism potential have created a high level of public concern about EboV. Therefore, development of anti-EboV drugs is a high priority.Recent studies have identified promising drug targets. Previously, it was found that stepwise proteolytic cleavage of EboV envelope glycoprotein GP by the lysosomal cysteine proteases cathepsin L (Cat L) and cathepsin B (Cat B) is required for infection; and therefore, inhibitors of Cat L and Cat B are ...

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05-09-2013 дата публикации

1-[(4-hydroxypiperidin-4-yl)methyl]pyridin-2(1H)-one derivatives, preparation methods and uses thereof

Номер: US20130231369A1

Provided are N-[(4-hydroxypiperidin-4-yl)methyl]pyridin-2(1H)-one derivatives represented by formula I, stereoisomers, pharmaceutically acceptable salts or solvates thereof. 2. The compound of claim 1 , a tautomer thereof claim 1 , a racemate or optical isomer thereof claim 1 , or a pharmaceutically acceptable salt or a solvate thereof claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R′each independently is H claim 1 , halogen (F claim 1 , Cl claim 1 , Br claim 1 , I) claim 1 , C-Calkyl claim 1 , substituted C-Calkyl claim 1 , C-Calkenyl claim 1 , substituted C-Calkenyl claim 1 , phenyl claim 1 , substituted phenyl claim 1 , heteroaryl claim 1 , substituted heteroaryl claim 1 , C-Calkoxy claim 1 , C-Caryloxy claim 1 , substituted C-Caryloxy claim 1 , C-Calkylamino claim 1 , C-Carylamino claim 1 , substituted arylamino claim 1 , di-(C-Calkyl)amino claim 1 , di-(C-Caryl)amino claim 1 , di-(substituted C-Caryl)amino claim 1 , Chydrocarbylacyloxy claim 1 , Carylacyloxy claim 1 , Chydrocarbylamido claim 1 , Carylamido claim 1 , carboxy claim 1 , Chydrocarbyloxyformyl claim 1 , Caryloxyformyl claim 1 , carbamoyl claim 1 , Chydrocarbylaminoformyl claim 1 , or Carylaminoformyl; wherein the heteroaryl ring is a monocyclic or fused cyclic aromatic hydrocarbyl having 1-3 heteratoms selected from the group consisting of N claim 1 , O or S claim 1 , the substituent of each substituted group is selected from the group consisting of halogen claim 1 , hydroxy claim 1 , cyano claim 1 , nitro claim 1 , Calkyl claim 1 , Calkoxy claim 1 , Calkylthio claim 1 , mono- claim 1 , di- or tri-halogenated Calkyl claim 1 , amino claim 1 , Calkylamino claim 1 , Chydrocarbylacyloxy claim 1 , Chydrocarbylamido claim 1 , Carylacyloxy or Carylamido; wherein Rcan represent 1-3 substituents which can be at o- claim 1 , m- or p-position of benzene ring; Rcan represent 1-3 substituents; wherein Rrepresents at most 3 substituents which can be at 3- claim 1 , 4- claim 1 , 5- or 6-position when Y is ...

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05-09-2013 дата публикации

Small Molecule Inhibitors Of P-type ATPases

Номер: US20130231372A1
Автор: Matsui Mary, Yarosh Daniel
Принадлежит:

Small, low molecular weight compounds of the formula I and/or the formula II, as defined herein, which inhibit Cu-ATPases, ATP7A and ATP7B. Compositions and methods therefore, are provided. 2. The small molecule inhibitor of ATP7A or ATP7B claim 1 , according to claim 1 , which is selected from the group consisting of omeprazole claim 1 , 5- or 6-methoxy-2-{[(4-methoxy-3 claim 1 ,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole; esomeprazole claim 1 , S-5-methoxy-2-{(4-methoxy-3 claim 1 ,5 dimethylpyridin-2-yl)methylsufinyl]-3H-benzoimidazole; lansoprazole claim 1 , 2-{[3-methyl-4-(2 claim 1 ,2 claim 1 ,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl-1H-benzo(d)imidazole; pantoprazole claim 1 , RS-6-(difluoromethoxy))-2-[(3 claim 1 ,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo(d)imidazole; rabeprazole (pariprazole) claim 1 , 2-([4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl)-1H-benzo(d)imidazole claim 1 , leminoprazole claim 1 , 2-((o-(isobutylmethylamino)benzyl)sulfinyl)benzimidazole; and timoprazole claim 1 , 2-(pyridine-2-ylmethylsulfinyl)-1H-benzimidazole.3. The small molecule inhibitor of ATP7A or ATP7B according to claim 2 , which comprises omeprazole claim 2 , 5- or 6-methoxy-2-{[(4-methoxy-3 claim 2 ,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole.6. The small molecule inhibitor of ATP7A or ATP7B according to claim 1 , which is selected from the group consisting of SCH-28080; soraprazan [(7R claim 1 ,8R claim 1 ,9R)-2 claim 1 ,3-dimethyl-8-hydroxy-7(2-methoxyethoxy)-9-phenyl-7 claim 1 ,8 claim 1 ,9 claim 1 ,10-tetrahydro-imidazo-[1 claim 1 ,2-h][1 claim 1 ,7]-naphthyridine] claim 1 , pumaprazole 8-(2-methoxycarbonylamino-6-benzulamino)-2 claim 1 ,3-dimethylimidazo-[1 claim 1 ,2-a)pyridine-D claim 1 ,L-hemimalate claim 1 , AR-H047108 claim 1 , (8-[(2-ethyl-6-methylbenzyl)amino]2 claim 1 ,3-dimethylimidazo[1 claim 1 ,2-a]pyridine-6-carboxamide; dapiprazole claim 1 , 3-{2-[4-(2-methylphenyl)piperazin-1-yl]ethyl}-5 claim 1 ,6 claim ...

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12-09-2013 дата публикации

PHENICOL ANTIBACTERIALS

Номер: US20130237502A1
Принадлежит:

The present invention provides novel phenicol derivatives, their use for the treatment of infections in mammals, pharmaceutical composition containing these novel compounds, and methods for the preparation of these compounds. 2. A compound of wherein W is H claim 1 , —PO(OH) claim 1 , or —CHOPO(OH).3. A compound of wherein W is H.4. A compound of wherein X and Y are chloride; and Z is H.5. A compound of wherein X and Y are fluoride; and Z is H.6. A compound of wherein the Het moiety is a 5- or 6-membered cyclic ring system having from one to three hetero atoms selected from N claim 1 , O claim 1 , and S claim 1 , optionally substituted with R.7. A compound of wherein Het moiety is pyridinyl claim 6 , thiophenyl claim 6 , thiazolyl claim 6 , thiadiazolyl claim 6 , imidazolyl claim 6 , oxadiazolyl claim 6 , pyrimidinyl claim 6 , pyrazinyl claim 6 , isoxazole claim 6 , isothiazole claim 6 , or pyridazine.8. A compound of wherein Het moiety is pyridinyl or thiazolyl.9. A compound of wherein said Rand Rare independently H or Rand Rare taken together with the nitrogen to which they are attached form a 4- to 6-membered heterocyclic ring moiety optionally having an additional one to two hetero atoms selected from the group consisting from N claim 1 , S and O claim 1 , wherein the heterocyclic ring is optionally substituted with R.10. A compound of wherein Rand Rare each H.11. A compound of wherein Rand Rare independently H or Calkyl or Rand Rare taken together to form a Ccycloalkyl.12. A compound of wherein Rand Rare taken together to form a cyclopropyl.13. A compound of wherein W is H claim 1 , —PO(OH) claim 1 , or —CHOPO(OH); Het moiety is a 5- or 6-membered cyclic ring system having from one to three hetero atoms selected from N claim 1 , O claim 1 , and S claim 1 , optionally substituted with R; Rand Rare each H; —Rand Rare independently H or Calkyl or Rand Rare taken together to form a cyclopropyl; and X claim 1 , Y and Z are independently H claim 1 , chloride or ...

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12-09-2013 дата публикации

PYRROLIDINONE CARBOXAMIDE DERIVATIVES

Номер: US20130237514A1
Принадлежит: ChemoCentryx, Inc.

Pyrrolidinone carboxamide compounds are provided that are useful for inhibiting the binding of ligands to the ChemR23 receptor. 3. A compound of claim 1 , wherein Ris methyl.4. A compound of claim 1 , wherein Ris methyl claim 1 , and Ris H or Calkyl.5. A compound of claim 1 , wherein Ris H or Calkyl claim 1 , Ris methyl claim 1 , and Ris H or Calkyl.6. A compound of claim 1 , wherein Ris CF.7. A compound of claim 1 , wherein Ris methyl and Ris CF.9. A compound of claim 8 , wherein Ris selected from the group consisting of —NRRand RRN—Calkyl.10. A compound of claim 9 , wherein Ris RRN—Calkyl.11. A compound of claim 9 , wherein Ris —NRR.12. A compound of claim 8 , wherein Rand Rare each methyl.13. A compound of claim 12 , wherein Ris selected from the group consisting of CF claim 12 , CN and cyclopropyl.14. A compound of claim 8 , wherein Ris mono- or di-(Calkyl)amino-Calkyl claim 8 , and Ris methyl.15. A compound of claim 14 , wherein Ris di(Calkyl)aminomethyl.16. A compound of claim 8 , wherein Rand Rare each methyl.18. A compound of claim 17 , wherein Ris H claim 17 , and Rand Rare each methyl.19. A compound of claim 18 , wherein Ris CF.21. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.221111111111111111111111111111111. The pharmaceutical composition of claim 21 , wherein the compound is a compound provided in claim 21 , B claim 21 , C claim 21 , D claim 21 , E claim 21 , F claim 21 , G claim 21 , H claim 21 , I claim 21 , J claim 21 , K claim 21 , L claim 21 , M claim 21 , N claim 21 , O claim 21 , P claim 21 , Q claim 21 , R claim 21 , S claim 21 , T claim 21 , U claim 21 , V claim 21 , W claim 21 , X claim 21 , Y claim 21 , Z claim 21 , AA claim 21 , BB claim 21 , CC claim 21 , DD claim 21 , EE and FF.23. A method of treating a disease or disorder in a mammal claim 1 , said method comprising administering to said subject a therapeutically effective amount of a compound of claim 1 , for a period of time ...

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12-09-2013 дата публикации

LACTAM DERIVATIVES USEFUL AS OREXIN RECEPTOR ANTAGONISTS

Номер: US20130237525A1
Принадлежит: ACTELION PHARMACEUTICALS LTD.

The present invention relates to lactam derivatives of formula (I) 3. The compound according to ; wherein Rrepresents Aror Ar—X—Ar—* wherein the asterisk indicates the bond that is attached to the rest of the molecule; wherein{'sup': '1', 'claim-text': [ [{'sub': 1-4', '1-4', '3-6', '1-3', '1-3', '1-3', '1-4', '3-6', '1-4', '1-4', '1-4, '(C)alkyl, (C)alkoxy, (C)cycloalkyl, halogen, cyano, (C)fluoroalkyl, (C)fluoroalkoxy, (C)fluoroalkyl-thio-, (C)alkyl-sulfonyl, (C)cycloalkyl-(C)alkoxy, (C)alkoxy-(C)alkoxy; and'}, {'sup': 4', '5', '4', '5', '4', '5, 'sub': '1-4', '—NRR, wherein Rand Rare independently selected from hydrogen, (C)alkyl, or, Rand Rtogether with the nitrogen atom to which they'}, 'are attached form a saturated 5-, 6-, or 7-membered ring optionally containing an oxygen atom;, 'substituted with one, two, or three substituents, wherein the substituents are independently selected from the group consisting of, {'sub': '1-3', 'or said aryl or heteroaryl is fused to a non-aromatic 5- or 6-membered ring, wherein said ring optionally contains one or two heteroatoms independently selected from oxygen and nitrogen; wherein said ring is optionally substituted with one or two substituents independently selected from (C)alkyl, oxo, and halogen;'}, 'or, in the specific case wherein said aryl is naphthyl, or said heteroaryl is a bicyclic or tricyclic ring, said aryl or heteroaryl may additionally be unsubstituted;, 'Arrepresents aryl or heteroaryl, wherein the aryl or heteroaryl independently is{'sup': '2', 'claim-text': {'sub': 1-4', '1-4', '3-6', '1-3', '1-3', '1-3', '1-4', '3-6', '1-4', '1-4', '1-4, '(C)alkyl, (C)alkoxy, (C)cycloalkyl, halogen, cyano, (C)fluoroalkyl, (C)fluoroalkoxy, (C)fluoroalkyl-thio-, (C)alkyl-sulfonyl, (C)cycloalkyl-(C)alkoxy, (C)alkoxy-(C)alkoxy;'}, 'unsubstituted, or substituted with one, or two substituents, wherein the substituents are independently selected from the group consisting of, 'Arrepresents phenyl or 5- or 6-membered heteroaryl; ...

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12-09-2013 дата публикации

Optically Active Cyclic Alcohol Compound And Method For Preparing The Same

Номер: US20130237708A1
Принадлежит: MITSUBISHI TANABE PHARMA CORPORATION

The present invention relates to a method for preparing an optically active cyclic alcohol compound represented by general formula [I]: 2. The method according to claim 1 , wherein the asymmetric reduction is conducted in the presence of an optically active oxazaborolidine compound claim 1 , and a boron hydride compound.6. The method according to claim 1 , wherein the asymmetric reduction is conducted in the presence of an asymmetric transition metal complex obtained from a transition metal compound and an asymmetric ligand claim 1 , and a hydrogen donor.7. The method according to claim 6 , wherein the transition metal compound is tetrachlorobis(benzene)diruthenium claim 6 , tetrachlorobis(p-cymene)diruthenium claim 6 , tetrachlorobis(hexamethylbenzene)diruthenium claim 6 , tetrachlorobis(mesitylene)diruthenium claim 6 , tetrachlorobis(ethyl benzoate)diruthenium claim 6 , tetrabromobis(benzene)diruthenium claim 6 , tetrabromobis(p-cymene)diruthenium claim 6 , tetrabromobis(mesitylene)diruthenium claim 6 , tetraiodobis(benzene)diruthenium claim 6 , tetraiodobis(p-cymene)diruthenium or tetraiodobis(mesitylene)diruthenium.10. The method according to claim 6 , wherein the asymmetric ligand is (S claim 6 ,S)— or (R claim 6 ,R)—N-tosyl-1 claim 6 ,2-diphenylethylenediamine; (S claim 6 ,S)— or (R claim 6 ,R)—N-methyl-N′-tosyl-1 claim 6 ,2-diphenylethylenediamine; (S claim 6 ,S)— or (R claim 6 ,R)—N-p-methoxyphenylsulfonyl-1 claim 6 ,2-diphenylethylenediamine; (S claim 6 ,S)— or (R claim 6 ,R)—N-p-chlorophenylsulfonyl-1 claim 6 ,2-diphenylethylenediamine; (S claim 6 ,S)— or (R claim 6 ,R)—N-p-mesitylsulfonyl-1 claim 6 ,2-diphenylethylenediamine; or (S claim 6 ,S)— or (R claim 6 ,R)—N-(2 claim 6 ,4 claim 6 ,6-tri-isopropylphenyl)sulfonyl-1 claim 6 ,2-diphenylethylenediamine.11. The method according to claim 6 , wherein the hydrogen donor is a lower alkanol having a hydrogen atom(s) at its α-position.14. The non-racemic cyclic alcohol compound according to claim 12 , wherein R ...

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19-09-2013 дата публикации

TRIAZOLES AS INHIBITORS OF FATTY ACID SYNTHASE

Номер: US20130243727A1
Принадлежит: INFINITY PHARMACEUTICALS, INC.

Provided herein are triazole FASN inhibitors of the formula (I): 2. The method of claim 1 , wherein X is selected from hydrogen claim 1 , —CN claim 1 , —CHO claim 1 , —C(═O)R claim 1 , —C(═O)N(R) claim 1 , —COH claim 1 , —COR claim 1 , —C(═NR)OR claim 1 , —C(═NR)N(R) claim 1 , —C(═S)N(R) claim 1 , —C(═O)SR claim 1 , —C(═S)SR claim 1 , Cperhaloalkyl claim 1 , Caryl claim 1 , and 5-14 membered heteroaryl.3. The method of claim 2 , wherein X is —CN.4. The method of claim 1 , wherein Ris selected from Caryl and 5-14 membered heteroaryl.5. The method of claim 4 , wherein Ris Caryl.7. The method of claim 6 , wherein each of RR claim 6 , R claim 6 , Rand Ris independently selected from hydrogen claim 6 , halogen claim 6 , —CN claim 6 , —OR claim 6 , —N(R) claim 6 , —COH claim 6 , —COR claim 6 , —C(═O)N(R) claim 6 , —SOR claim 6 , Calkyl claim 6 , Calkynyl claim 6 , 3-14 membered heterocyclyl claim 6 , and Caryl; or one or more of Rand R claim 6 , Rand R claim 6 , Rand Ror Rand Rare joined to form a 5-14 membered heteroaryl ring.8. The method of claim 7 , wherein each of R claim 7 , R claim 7 , R claim 7 , Rand Ris independently selected from hydrogen claim 7 , halogen claim 7 , —OR claim 7 , Calkyl claim 7 , and —C(═O)N(R); or Rand Rare joined to form a 5-14 membered heteroaryl ring.10. The method of claim 9 , wherein each of Rand Ris independently halogen.11. The method of claim 10 , wherein each of Rand Ris independently selected from fluoro and chloro.12. The method of claim 1 , wherein Rand Rtogether with the nitrogen (N) atom to which each is attached are joined to form a 5-14 membered carbocyclyl claim 1 , heterocyclyl claim 1 , aryl or heteroaryl ring.14. The method of claim 13 , wherein Rand Rare joined to form a Ccarbocyclyl claim 13 , 3-14 membered heterocyclyl claim 13 , Caryl or 5-14 membered heteroaryl ring.15. The method of claim 14 , wherein Rand Rare joined to form a Ccarbocyclyl.16. The method of claim 15 , wherein Q is CRR.17. The method of claim 16 , ...

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19-09-2013 дата публикации

CARBOXAMIDE COMPOUNDS AND THEIR USE AS CALPAIN INHIBITORS

Номер: US20130245003A1
Принадлежит: Abbott GmbH & Co. KG

The present invention relates to novel carboxamide compounds and their use for the manufacture of a medicament. The carboxamide compounds are inhibitors of calpain (calcium dependant cysteine proteases). The invention therefore also relates to the use of these carboxamide compounds for treating a disorder associated with an elevated calpain activity. 140-. (canceled)42. The carboxamide compound as claimed in claim 41 , in which m is 0 or 1 and claim 41 , when m=1 claim 41 , R* is selected from OH claim 41 , F claim 41 , Cl claim 41 , CN claim 41 , CF claim 41 , C-C-alkyl which is unsubstituted or may have 1 claim 41 , 2 or 3 substituents R claim 41 , or C-C-haloalkyl claim 41 , C-C-alkoxy claim 41 , C-C-haloalkoxy and C-C-cycloalkyl.43. The carboxamide compound as claimed in claim 41 , in which X is a C(═O)—NRRradical.45. The carboxamide compound as claimed in claim 44 , in which X is C(O)—NH.46. The carboxamide compound as claimed in claim 41 , in which Ris selected from C-C-alkyl which may be partly or completely halogenated and/or have 1 claim 41 , 2 or 3 substituents R claim 41 , C-C-cycloalkyl-C-C-alkyl claim 41 , where the cycloalkyl moiety may have 1 claim 41 , 2 claim 41 , 3 or 4 radicals R claim 41 , phenyl-C-C-alkyl and hetaryl-C-C-alkyl claim 41 , where phenyl and hetaryl in the last 2 radicals mentioned may be unsubstituted or carry 1 claim 41 , 2 claim 41 , 3 or 4 identical or different radicals R.47. The carboxamide compound as claimed in claim 41 , in which Ris selected from OH claim 41 , F claim 41 , Cl claim 41 , NH claim 41 , CN claim 41 , CF claim 41 , —CHF claim 41 , O—CF claim 41 , O—CHF claim 41 , O—CHF claim 41 , C-C-alkyl claim 41 , C-C-cycloalkyl claim 41 , C-C-alkylamino claim 41 , C-C-dialkylamino claim 41 , pyrrolidinyl claim 41 , piperidinyl claim 41 , morpholinyl claim 41 , imidazolyl claim 41 , C-C-alkoxy claim 41 , C-C-alkoxy-C-C-alkyl claim 41 , CONRR claim 41 , SONRR claim 41 , —NH—SO—R claim 41 , —(CH)—NRR claim 41 , NH—CO—R claim ...

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19-09-2013 дата публикации

COMPOUNDS THAT MODULATE INTRACELLULAR CALCIUM

Номер: US20130245063A1
Принадлежит: CalciMedica, Inc.

Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity. 118.-. (canceled)22. The compound of wherein Lis —CHN(H)—.23. The compound of wherein Ris phenyl.24. The compound of wherein Ris phenyl substituted with at least one Rselected from F claim 23 , Cl claim 23 , Br claim 23 , I claim 23 , —CN claim 23 , —OH claim 23 , —CF claim 23 , —OCF claim 23 , —OR claim 23 , —N(R) claim 23 , and C-Calkyl.25. The compound of wherein Ris selected from —CF claim 24 , —OCF claim 24 , —OR claim 24 , C-Calkyl claim 24 , and C-Ccycloalkyl.26. The compound of wherein Ris C-Calkyl.27. The compound of wherein Ris —CFand Ris —CH.28. The compound of wherein Ris C-Chaloalkyl.29. The compound of wherein Ris —CFand Ris —CF.30. The compound of wherein Ris phenyl substituted with at least 2 substituents.31. The compound of wherein Ris phenyl substituted with at least 3 substituents.32. The compound of wherein Ris heteroaryl.33. The compound of wherein heteroaryl is selected from thienyl claim 32 , thianthrenyl claim 32 , furyl claim 32 , pyranyl claim 32 , thiadiazolyl claim 32 , benzothiadiazolyl claim 32 , isobenzofuranyl claim 32 , chromenyl claim 32 , xanthenyl claim 32 , phenoxathiinyl claim 32 , pyrrolyl claim 32 , imidazolyl claim 32 , pyrazolyl claim 32 , isothiazolyl claim 32 , isoxazolyl claim 32 , pyridyl claim 32 , pyrazinyl claim 32 , pyrimidinyl claim 32 , pyridazinyl claim 32 , pyrazolo-pyrimidinyl claim 32 , triazolo-pyrimidinyl claim 32 , imidazo-pyrimidinyl claim 32 , indolizinyl claim 32 , isoindolyl claim 32 , 3H-indolyl claim 32 , indolyl claim 32 , indazolyl claim 32 , purinyl claim 32 , 4H-quinolizinyl claim 32 , isoquinolyl claim 32 , quinolyl claim 32 , ...

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19-09-2013 дата публикации

DEUTERIUM-ENRICHED LENALIDOMIDE

Номер: US20130245067A1
Автор: Czarnik Anthony W.
Принадлежит: DEUTERIA PHARMACEUTICALS, INC.

The present application describes deuterium-enriched lenalidomide, pharmaceutically acceptable salt forms thereof, and methods of treating using the same. 2. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R-Ris selected from at least 8% claim 1 , at least 15% claim 1 , at least 23% claim 1 , at least 31% claim 1 , at least 38% claim 1 , at least 46% claim 1 , at least 54% claim 1 , at least 62% claim 1 , at least 69% claim 1 , at least 77% claim 1 , at least 85% claim 1 , at least 92% claim 1 , and 100%.3. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R-Ris selected from at least 33% claim 1 , at least 67% claim 1 , and 100%.4. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in Rand R-Ris selected from at least 33% claim 1 , at least 67% claim 1 , and 100%.5. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R claim 1 , R claim 1 , and R-Ris selected from at least 17% claim 1 , at least 33% claim 1 , at least 50% claim 1 , at least 67% claim 1 , at least 83% claim 1 , and 100%.6. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R-Ris selected from at least 33% claim 1 , at least 67% claim 1 , and 100%.7. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R-Ris selected from at least 50% and 100%.8. A deuterium-enriched compound of claim 1 , wherein the abundance of deuterium in R-Ris selected from at least 25% claim 1 , at least 50% claim 1 , at least 75% claim 1 , and 100%.9. A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 1-7 of Table 1.10. A deuterium-enriched compound of claim 1 , wherein the compound is selected from compounds 8-14 of Table 2.12. An isolated deuterium-enriched compound of claim 11 , wherein the abundance of deuterium in R-Ris selected from at least 8% claim 11 , at least 15% claim 11 , at least 23% claim 11 , at ...

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26-09-2013 дата публикации

(AZA)INDOLE DERIVATIVE AND USE THEREOF FOR MEDICAL PURPOSES

Номер: US20130252955A1
Принадлежит: KISSEI PHARMACEUTICAL CO., LTD.

The present invention provides compounds useful as agents for the prevention or treatment of a disease associated with abnormal serum uric acid level which has a uricosuric activity or the like. The present invention relates to (aza)indole derivatives represented by the following general formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of serum uric acid level, prodrugs thereof, or salts thereof. In the formula (I), T represents nitro or cyano and the like; ring J represents aryl or heteroaryl and the like; Q represents carboxy or 5-tetazolyl and the like; Y represents H, OH, NH, halogen, nitro, alkyl, alkoxy and the like; X, Xand Xindependently represent CRor N; Rand Rindependently represent halogen, cyano, haloalkyl, A-D-E-G, —N(-D-E-G)and the like, in the formula, A represents a single bond, O, S and the like; D and G independently represent optionally substituted alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene and the like; E represents a single bond, O, S, COO, SOand the like. 2. An (aza)indole derivative as claimed in claim 1 , wherein X claim 1 , Xand Xindependently represent CRwith the proviso that when two or more Rexist claim 1 , these Rare optionally the same or different from each other claim 1 , or a prodrug thereof claim 1 , or a pharmaceutically acceptable salt thereof.3. An (aza)indole derivative as claimed in claim 1 , wherein T represents cyano claim 1 , or a prodrug thereof claim 1 , or a pharmaceutically acceptable salt thereof.4. An (aza)indole derivative as claimed in claim 1 , wherein Q represents carboxy claim 1 , or a prodrug thereof claim 1 , or a pharmaceutically acceptable salt thereof.5. An (aza)indole derivative as claimed in claim 1 , wherein Y represents a hydrogen atom claim 1 , hydroxy or a halogen atom claim 1 , or a prodrug thereof claim 1 , or a pharmaceutically acceptable salt thereof.6. An (aza)indole ...

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