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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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Форма поиска

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 18541. Отображено 100.
05-01-2012 дата публикации

New ccr2 receptor antagonists and uses thereof

Номер: US20120004252A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to novel antagonists for CCR2 (CC chemokine receptor 2) and their use for providing medicaments for treating conditions and diseases, especially pulmonary diseases like asthma and COPD.

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26-01-2012 дата публикации

Bridged compounds as hiv integrase inhibitors

Номер: US20120022045A1
Принадлежит: Individual

Compounds of Formula I are inhibitors of HIV integrase and inhibitors of HIV replication: the asterisk * in Q denotes the point of attachment to the rest of the compound; and n, L1, L2, X1, X2, χ3, Y, Z, R1, R2 and R3 are defined herein. The N compounds are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset or progression of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se (or as hydrates or solvates thereof) or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

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02-02-2012 дата публикации

Novel lipids and compositions for the delivery of therapeutics

Номер: US20120027796A1
Принадлежит: Alnylam Pharmaceuticals Inc

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structures: (Formula (I) or (XXXV)).

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08-03-2012 дата публикации

Carbazole and carboline kinase inhibitors

Номер: US20120058988A1
Принадлежит: Bristol Myers Squibb Co

The present invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof The Formula (I) compounds inhibit tyrosine kinase activity of Jak2, thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.

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15-03-2012 дата публикации

Compounds and their uses 708

Номер: US20120065214A1
Принадлежит: AstraZeneca AB

The present invention relates to pyrazinone derivatives of formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as herein defined; processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

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15-03-2012 дата публикации

Transfer Hydrogenation of Cyclopamine Analogs

Номер: US20120065400A1
Принадлежит: Infinity Pharmaceuticals Inc

Provided herein is a process for the transfer-hydrogenation of ketone analogs of members of the jervine type of Veratrum alkaloids, such as cyclopamine. Also provided herein are novel ruthenium transfer-hydrogenation catalysts.

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19-04-2012 дата публикации

Novel lipids and compositions for the delivery of therapeutics

Номер: US20120095075A1
Принадлежит: Alnylam Pharmaceuticals Inc

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure:

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10-05-2012 дата публикации

Compound inhibiting in vivo phosphorus transport and medicine containing the same

Номер: US20120115851A1
Принадлежит: Kyowa Hakko Kirin Co Ltd

An objective of the present invention is to provide compounds that can effectively suppress the concentration of phosphorus in serum to effectively prevent or treat diseases induced by an increase in concentration of phosphate in serum. The compounds according to the present invention are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof: wherein A represents an optionally substituted five- to nine-membered unsaturated carbocyclic moiety or a five- to nine-membered unsaturated heterocyclic moiety, and represents a single bond or a double bond, R 5 represents optionally substituted aryl or the like, Z represents —N═CHR 6 R 7 or the like, R 6 and R 7 represent H, optionally substituted alkyl, optionally substituted aryl or the like, R 101 and R 102 together form ═O, and R 103 and R 104 represent H, or R 101 and R 104 together from a bond, and R 102 and R 103 together form a bond.

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24-05-2012 дата публикации

5,6-dihydro-1h-pyridin-2-one compounds

Номер: US20120130068A1
Принадлежит: Anadys Pharmaceuticals Inc

The invention is directed to 5,6-dihydro-1H-pyridin-2-one compounds of Formula I wherein X is N, and A is and compounds used to synthesize the compounds of Formula I.

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07-06-2012 дата публикации

Synthesis of ttx intermediates

Номер: US20120142911A1

The present invention relates to the synthesis of intermediates which are useful in TTX synthesis and to the preparation thereof.

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14-06-2012 дата публикации

Chromene compound

Номер: US20120145974A1
Принадлежит: Tokuyama Corp

A chromene compound which contains a skeleton represented by the following formula (1) and has high color optical density at the time of exposure, double peak characteristic, little initial coloration, a practical fading speed and durability. (wherein R 1 is an electron donor group having a Hammett constant of less than 0, the ring including X is a hetero ring formed together with the 7-position and 8-position carbon atoms, and X is an oxygen atom, sulfur atom or group represented by ═NR 2 directly bonded to the 7-position carbon atom.)

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28-06-2012 дата публикации

Compounds and their use as BACE Inhibitors

Номер: US20120165347A1
Принадлежит: AstraZeneca AB

The present invention relates to compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI (“mild cognitive impairment”), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.

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12-07-2012 дата публикации

Lactam compounds useful as protein kinase inhibitors

Номер: US20120178739A1
Принадлежит: Millennium Pharmaceuticals Inc

The present invention provides novel compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

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12-07-2012 дата публикации

Pyrimidine derivatives and analogs, preparation method and use thereof

Номер: US20120178915A1
Автор: Lifeng Xu
Принадлежит: Individual

This invention relates with the arylheterocycle-fused pyrimidines, derivatives and analogs of formula I: or stereoisomers, tautoers, prodrugs, pharmaceutically acceptable salts, complex salts or solvates thereof, wherein: A-cycle is of 3-8 saturated or unsaturated arylheterocycles or aliheterocyclic, containing 1-4 heteroatoms, B-cycle 5-8 member saturated or unsaturated heterocycle containing 1-4 heteroatoms; X 1 , X 2 , X 3 , X 4 are, independently at each occurrence, C, O, S, Se, N and P elements; R 1 , R 2 , R 3 is a substituent containing alicyclic group, arylcycle group, heterocyclic group, adamantane alkyl, adamantane heterocycle, adamantane analogs, sugar group, hydroxyl group, amino acid group or a combination of the above substituents. This invention also relates with their preparative methods and applications.

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09-08-2012 дата публикации

Compounds for the treatment of hepatitis c

Номер: US20120201783A1
Принадлежит: Bristol Myers Squibb Co

The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

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23-08-2012 дата публикации

6,5-heterocyclic propargylic alcohol compounds and uses therefor

Номер: US20120214762A1
Принадлежит: Genentech Inc

The invention relates to novel compounds of Formula I: wherein A, Y, R 1 , R 2 and the subscript b each has the meaning as described herein and compounds of Formula I, and stereoisomers, geometric isomers, tautomers, solvates, metabolites, isotopes, pharmaceutically acceptable salts, or prodrugs thereof. Compounds of Formula I and pharmaceutical compositions thereof are useful in the treatment of disease and disorders in which undesired or over-activation of NF-kB signaling is observed.

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30-08-2012 дата публикации

Imidazopyrazine syk inhibitors

Номер: US20120220582A1
Принадлежит: Gilead Connecticut Inc

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample.

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08-11-2012 дата публикации

Inhibitors of Atypical Protein Kinase C and Their Use in Treating Hedgehog Pathway-Dependent Cancers

Номер: US20120283194A1
Принадлежит: Leland Stanford Junior University

Methods and compositions are provided for modulating Hedgehog (Hh) pathway signaling in a cell. Aspects of the methods include methods for inhibiting Hh pathway-promoted cancer proliferation and/or metastasis that is promoted by Hh pathway signaling, methods for treating cancers promoted by Hh pathway signaling, and methods for screening candidate agents for the ability to treat a cancer promoted by Hh pathway signaling. In addition, reagents and kits thereof that find use in practicing the subject methods are provided.

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21-02-2013 дата публикации

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

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

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

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07-03-2013 дата публикации

Synthesis of substituted pyrazoline carboxamidine derivatives

Номер: US20130060041A1

This invention relates to organic chemistry, in particular to processes for the preparation of pyrazoline carboxamidine derivatives of formula (I), known as potent 5-HT6 antagonists. The invention also relates to novel intermediates of these compounds. wherein the symbols have the meanings given in the description.

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21-03-2013 дата публикации

SUBSTITUTED HYDROXYETHYL AMINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE

Номер: US20130072483A1
Принадлежит: Amgen Inc.

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I 3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1a', '1b', '7, 'Rand Rtaken together with the carbon atom to which they are attached form a partially or fully saturated 4-, 5- or 6-membered ring of carbon atoms optionally including 1-2 heteroatoms selected from O, N, or S, the ring optionally substituted independently with 1-3 substituents of R; and'}{'sup': '1c', 'Ris H.'}4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein m is 1 and Ris a ring selected from phenyl claim 1 , pyridyl claim 1 , pyrimidyl claim 1 , pyridazinyl claim 1 , pyrazinyl claim 1 , triazinyl claim 1 , thiophenyl claim 1 , furyl claim 1 , pyrrolyl claim 1 , pyrazolyl claim 1 , imidazolyl claim 1 , triazolyl claim 1 , tetrazolyl claim 1 , thiazolyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , isothiazolyl claim 1 , thiadiazolyl claim 1 , oxadiazolyl claim 1 , pyrrolidinyl claim 1 , oxazolinyl claim 1 , isoxazolinyl claim 1 , thiazolinyl claim 1 , pyrazolinyl claim 1 , morpholinyl claim 1 , piperidinyl claim 1 , piperazinyl and pyranyl claim 1 , said ring optionally substituted with 1-5 substituents of R.6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': '1', 'Ais CH;'}{'sup': 2', '6, 'Ais CR;'}{'sup': 3', '4', '6', '3', '4, 'each of Aand A, independently, is CH or CRor N, provided no more than one of Aand Ais N;'}{'sup': 1a', '7, 'sub': 1-6', '2-6', '2-6', '1-6', '1-3', '1-6', '1-3', '1-6', '2', '1-3', '1-6', '1-3', '1-3', '1-3', '2-4', '1-3', '2-4', '1-3', '2-4', '1-3', '2-4', '1-3, 'Ris C-alkyl, Calkenyl, C-alkynyl, Calkyl-O—C-alkyl-, C-alkyl-S—C-alkyl-, C-alkyl ...

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21-03-2013 дата публикации

Chemical Compounds

Номер: US20130072690A1
Принадлежит: GlaxoSmithKline LLC

Disclosed are compounds of Formula III. Also disclosed are salts of the compounds, pharmaceutical composition comprising the compounds or salts, and methods for treating HCV infection by administration of the compounds or salts. 2. A compound according to wherein each X is identical.3. A compound according to wherein X is S or O.4. A compound according to wherein every CRR is CH.5. A compound according to wherein no more than two Rs in each spiro are methyl.6. A compound according to wherein each Ris isopropyl.7. A compound according to wherein each Ris methyl.8. A pharmaceutically acceptable salt of a compound according to .9. A salt according to wherein said salt is either a di-HCl salt or a sulfate salt.10. A salt according to wherein said salt is a sulfate salt.11. A salt according to claim 8 , wherein said salt is crystalline.12. A pharmaceutical composition comprising a compound according to .13. A pharmaceutical composition comprising a salt according . This application is filed as a continuation application of U.S. Ser. No. 12/936,545, filed Oct. 6, 2010, which is a National Phase Application of International Application No. PCT/US2010/046782 filed on Aug. 26, 2010, which claims priority from 61/239,855 filed on Sep. 4, 2009, 61/297,324 filed on Jan. 22, 2010 and 61/348,767 filed on May 27, 2010 in the United States.The present disclosure relates to antiviral compounds. In particular, the present disclosure relates to compounds useful for the treatment of hepatitis C virus (HCV) infection, crystalline salts of the compounds, pharmaceutical compositions comprising the compounds, and methods for treating HCV infection.Chronic infection with HCV is a major health problem associated with liver cirrhosis, hepatocellular carcinoma and liver failure. An estimated 170 million chronic carriers worldwide are at risk of developing liver disease. See, for example, Szabo, et al., 2003, 9:215-221, and Hoofnagle J H, 1997, 26:15S -20S. In the United States alone 2.7 ...

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04-04-2013 дата публикации

QUINOXALINE COMPOUND

Номер: US20130085134A1
Принадлежит: Astellas Pharma Inc.

Quinoxaline compounds of formula (I) have a PDE9-inhibiting action and are useful as an active ingredient for an agent for treating and/or preventing storage dysfunction, voiding dysfunction, and bladder/urethral diseases, and the like. 116-. (canceled)18. The method of claim 17 , wherein Ris hydrogen or lower alkyl and Ris a group of the formula (II) claim 17 , or Ris a group of the formula (II) and Ris hydrogen; halogen; or lower alkyl claim 17 , —O-lower alkyl or cycloalkyl claim 17 , each of which may be substituted with one or more substituents selected from the group consisting of —OH claim 17 , —O-lower alkyl claim 17 , —NH claim 17 , —NH-lower alkyl claim 17 , —N(lower alkyl) claim 17 , and a monocyclic nitrogen-containing hetero ring which may further be substituted with lower alkyl.19. The method of claim 17 , wherein{'sup': '1', 'Ris a group of the formula (II),'}{'sup': '2', 'sub': 2', '2, 'Ris halogen; cycloalkyl; or lower alkyl or —O-lower alkyl, each of which may be substituted with a substituent selected from the group consisting of —OH, —O-lower alkyl, —NH, —NH-lower alkyl, —N(lower alkyl)and a monocyclic nitrogen-containing hetero ring which may further be substituted with lower alkyl; and'}{'sup': 4', '5', '6, 'R, Rand Rare hydrogen atoms.'}20. The method of claim 19 , wherein{'sup': '3', 'sub': 2', '2', '2, 'Ris lower alkyl which is substituted with cycloalkyl and which may further be substituted with 1 to 3 substituents selected from the group consisting of —OH, oxo and halogen; lower alkyl which may be substituted with a monocyclic sulfur-containing saturated hetero ring; or cycloalkyl or a monocyclic saturated hetero ring, each of which may be substituted with 1 or 2 substituents selected from the group consisting of halogen, lower alkyl, —OH, oxo, —O-lower alkyl, —COOH, —CO—O-lower alkyl, —CO—O-lower alkenyl, lower alkynyl, —CO—O-lower alkylene-O-lower alkyl, —CO—O-lower alkylene-aryl, —CO—O-lower alkylene-O-aryl, —CO—NH, —CO—NH-lower alkyl, ...

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11-04-2013 дата публикации

Fluorescent dyes

Номер: US20130089853A1
Автор: Praveen Pande, Zaiguo Li
Принадлежит: Enzo Life Sciences Inc

Provided are various compounds comprising the formula Also provided are fluorescent dyes comprising the above compound. Additionally, a fluorescence energy transfer system is provided that comprises the above-described fluorescent dye and a second dye, wherein the second dye is capable of energy transfer with the fluorescent dye. Further provided is a kit for labeling a target molecule, where the kit comprises the above-described fluorescent dye with additional reagents useful for labeling the target molecule. Additionally provided is a target molecule labeled with the above-described fluorescent dye. A method of labeling a target molecule is also provided. The method comprises contacting reactive group Z of the above-described fluorescent dye with the target molecule such that reactive group Z reacts with the target molecule to form a covalent bond between reactive group Z and the target molecule. Also, another method of labeling a target molecule is provided. The method comprises contacting the above-described fluorescent dye, which further comprises a member of a binding pair, with the target molecule, where the target molecule comprises a second member of the binding pair.

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11-04-2013 дата публикации

Heterocyclic compounds and their uses

Номер: US20130090323A1
Принадлежит: AMGEN INC

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

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18-04-2013 дата публикации

Di(arylamino)aryl compound

Номер: US20130096100A1
Принадлежит: Astellas Pharma Inc

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

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18-04-2013 дата публикации

LONG WAVELENGTH FLUOROGENIC INTRACELLULAR ION INDICATORS THAT ARE WELL RETAINED IN THE CYTOSOL

Номер: US20130096300A1
Автор: Gee Kyle, MARTIN Vladimir
Принадлежит: LIFE TECHNOLOGIES CORPORATION

Cell permeable metal ion indicator compounds and methods of their use and synthesis are described. The compound comprises a metal chelating moiety (M), a reporter molecule and two or more lipophilic groups (G) covalently bonded through a linker to the reporter molecule, wherein the lipophilic groups, when present in a live cell, are cleaved resulting in two or more negatively charged groups. 1. An intracellular ion indicator compound , wherein the compound comprises a metal chelating moiety (M) , a reporter molecule and two or more lipophilic groups (G) covalently bonded through a linker to the reporter molecule , wherein the lipophilic groups , when present in a live cell , are cleaved resulting in two or more negatively charged groups.245-. (canceled) The present invention provides intracellular ion indicator compounds capable of chelating and detecting metal ions in cells. The compounds generally comprise a metal chelating moiety (M), a reporter molecule and one or more lipophilic groups (G) covalently bonded to the reporter molecule, wherein the lipophilic groups, when present in a live cell, are cleaved resulting in one or more negatively charged groups.Metal ions such as calcium are involved in many cellular processes including signal transduction. Small variances in intracellular ion levels can have a major impact on cellular processes. Measurement of ion levels provides a very sensitive method for identifying various cellular activities.Several fluorescent calcium indicators known in art are employed in biological research and high throughput screening. Generally, long wavelength indicators, such as rhodamine-based compounds bear a positive charge. Positively charged molecules compartmentalize in cell mitochondria. Because calcium ion release in activated cells happens in the cytosol, positively charged indicators show a weak response to calcium ion influx. Alternatively, fluorescein-based indicators have also been described that avoid accumulation in the ...

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25-04-2013 дата публикации

NOVEL CYCLOPROPANE INDOLINONE DERIVATIVES

Номер: US20130102604A1
Принадлежит: Hoffmann-La Roche Inc.

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

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25-04-2013 дата публикации

PYRAZOLOPYRIMIDINE DERIVATIVE

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

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

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02-05-2013 дата публикации

METHODS OF USE OF CYCLOPAMINE ANALOGS

Номер: US20130108582A1
Принадлежит:

The invention provides methods for treating various conditions using derivatives of cyclopamine having the following formula: 121-. (canceled)23. The method of claim 22 , wherein Ris H claim 22 , —OR claim 22 , amino claim 22 , sulfonamido claim 22 , sulfamido claim 22 , OC(O)Ror N(R)C(O)R.24. The method of claim 22 , wherein Ris sulfonamido.25. The method of claim 22 , wherein Ris H or heterocycloalkyl.26. The method of claim 25 , wherein Ris H.27. The method of claim 22 , wherein Ris H.28. The method of claim 22 , wherein Ris H claim 22 , alkyl claim 22 , aralkyl claim 22 , —[(W)—C(O)N(R)]Ror —[(W)—N(R)C(O)]R.29. The method of claim 28 , wherein Ris H.30. The method of claim 22 , wherein said compound is epimerically pure.33. The method of claim 32 , wherein the cancer of the hematopoietic system is myeloma claim 32 , leukemia or lymphoma.34. The method of claim 33 , wherein the myeloma is multiple myeloma.35. The method of claim 33 , wherein the leukemia is acute lymphatic leukemia claim 33 , acute myelocytic leukemia claim 33 , chronic myelocytic leukemia or chronic lymphocytic leukemia.36. The method of claim 33 , wherein the lymphoma is non-Hodgkin's lymphoma.37. The method of claim 32 , wherein the cancer of the hematopoietic system is myelodysplastic syndrome.38. The method of claim 32 , wherein the compound is used in combination with one or more other chemotherapeutic agent claim 32 , anti-cancer agent or anti-cancer treatment.39. The method of claim 38 , wherein the chemotherapeutic agent is doxorubicin claim 38 , dexamethasone claim 38 , prednisolone claim 38 , chlorambucil claim 38 , methotrexate claim 38 , vinblastine claim 38 , bortezomib claim 38 , melphalan claim 38 , carmustine claim 38 , cyclophosphamide claim 38 , vincristine claim 38 , lenalidomide claim 38 , thalidomide claim 38 , cytarabine claim 38 , fludarabine or idarubicin.40. The method of claim 38 , wherein the other anti-cancer agent is a corticosteroid or an interferon.41. The method ...

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02-05-2013 дата публикации

METHODS OF USE FOR CYCLOPAMINE ANALOGS

Номер: US20130108583A1
Принадлежит:

The invention provides methods for treating various conditions using derivatives of cyclopamine having the following formula: 121-. (canceled)23. The method of claim 22 , wherein Ris H claim 22 , —OR claim 22 , amino claim 22 , sulfonamido claim 22 , sulfamido claim 22 , OC(O)Ror N(R)C(O)R.24. The method of claim 22 , wherein Ris sulfonamido.25. The method of claim 22 , wherein Ris H or heterocycloalkyl.26. The method of claim 25 , wherein Ris H.27. The method of claim 22 , wherein Ris H.28. The method of claim 22 , wherein Ris H claim 22 , alkyl claim 22 , aralkyl claim 22 , —[(W)—C(O)N(R)]Ror —[(W)—N(R)C(O)]R.29. The method of claim 28 , wherein Ris H.30. The method of claim 22 , wherein said compound is epimerically pure.33. The method of claim 32 , wherein the compound is used in combination with one or more other chemotherapeutic agent claim 32 , anti-cancer agent or anti-cancer treatment.34. The method of claim 33 , wherein the chemotherapeutic agent is doxorubicin claim 33 , dexamethasone claim 33 , prednisolone claim 33 , chlorambucil claim 33 , methotrexate claim 33 , vinblastine claim 33 , bortezomib claim 33 , melphalan claim 33 , carmustine claim 33 , cyclophosphamide claim 33 , vincristine claim 33 , lenalidomide claim 33 , thalidomide claim 33 , cytarabine claim 33 , fludarabine or idarubicin.35. The method of claim 33 , wherein the other anti-cancer agent is a corticosteroid or an interferon.36. The method of claim 33 , wherein the other anti-cancer treatment is radiation or surgery.37. The method of claim 32 , wherein the compound is administered locally to a tumor.38. The method of claim 32 , wherein the compound is administered systemically.39. The method of claim 32 , wherein the mode of administration of said compound is inhalation claim 32 , oral claim 32 , intravenous claim 32 , sublingual claim 32 , ocular claim 32 , transdermal claim 32 , rectal claim 32 , vaginal claim 32 , topical claim 32 , intramuscular claim 32 , intra-arterial claim 32 ...

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02-05-2013 дата публикации

TRIAZINE COMPOUNDS AS PI3 KINASE AND MTOR INHIBITORS

Номер: US20130109670A1
Принадлежит: PFIZER INC.

Compounds of formula I 156-. (canceled)60. The compound of claim 57 , or a pharmaceutically acceptable salt thereof claim 57 , wherein Ris NHR.61. The compound of claim 58 , or a pharmaceutically acceptable salt thereof claim 58 , wherein Ris NHR.62. The compound of claim 57 , or a pharmaceutically acceptable salt thereof claim 57 , wherein Ris optionally substituted phenyl or C-Cheteroaryl.63. The compound of claim 58 , or a pharmaceutically acceptable salt thereof claim 58 , wherein Ris optionally substituted phenyl or C-Cheteroaryl.64. The compound of claim 57 , or a pharmaceutically acceptable salt thereof claim 57 , wherein Ris phenyl substituted with —Y-Q.65. The compound of claim 58 , or a pharmaceutically acceptable salt thereof claim 58 , wherein Ris phenyl substituted with —Y-Q.66. The compound of claim 57 , or a pharmaceutically acceptable salt thereof claim 57 , wherein —Y— is C(O).67. The compound of claim 58 , or a pharmaceutically acceptable salt thereof claim 58 , wherein —Y— is C(O).68. The compound of claim 57 , or a pharmaceutically acceptable salt thereof claim 57 , wherein Q is 3-10 membered C-Cheterocyclyl claim 57 , substituted with di(C-Calkyl)amino-.69. The compound of claim 58 , or a pharmaceutically acceptable salt thereof claim 58 , wherein Q is 3-10 membered C-Cheterocyclyl claim 58 , substituted with di(C-Calkyl)amino-.76. A composition comprising a compound of and a pharmaceutically acceptable carrier.77. A composition comprising a compound of and a pharmaceutically acceptable carrier. This invention relates to 2,4,6-substituted [1,3,5]triazine compounds in which one substituent is an optionally substituted morpholino, tetrahydropyranyl or dihydropyranyl group, which inhibit PI3 kinase and mTOR, to processes for preparing them, to methods of treatment using them and to pharmaceutical compositions containing them.Phosphatidylinositol (hereinafter abbreviated as “PI”) is one of the phospholipids in cell membranes. In recent years it has ...

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02-05-2013 дата публикации

NOVEL COMPOUNDS

Номер: US20130109711A1
Принадлежит:

The invention relates to novel spirocyclic derivatives with affinity for Cav2.2 calcium channels and which are capable of interfering with Cav2.2 calcium channels; to processes for their preparation; to pharmaceutical compositions containing them; and to the use of such compounds in therapy for the treatment of pain. 2. A compound as defined in claim 1 , wherein n represents 1.3. A compound as defined in claim 1 , wherein R claim 1 , Rand Reach represent hydrogen and Rrepresents methyl claim 1 , ethoxy claim 1 , trifluoromethyl or trifluoromethoxy claim 1 , such as trifluoromethyl or trifluoromethoxy.4. A compound as defined in claim 1 , wherein R claim 1 , Rand Reach represent hydrogen and Rrepresents difluoromethoxy claim 1 , trifluoromethyl or trifluoromethoxy.5. A compound as defined in claim 1 , wherein Rand Reach represent hydrogen claim 1 , Rrepresents methyl or trifluoromethyl and Rrepresents chlorine claim 1 , bromine claim 1 , methyl claim 1 , trifluoromethyl or trifluoromethoxy.6. A compound as defined in claim 1 , wherein Rand Reach represent hydrogen claim 1 , Rrepresents methyl claim 1 , methoxy or trifluoromethyl and Rrepresents trifluoromethyl.7. A compound as defined in claim 1 , wherein Rand Reach represent hydrogen claim 1 , Rrepresents chlorine or trifluoromethyl and Rrepresents chlorine claim 1 , fluorine claim 1 , methyl or trifluoromethyl.8. A compound as defined in claim 1 , wherein Rand Reach represent hydrogen claim 1 , Rrepresents chlorine or trifluoromethyl and Rrepresents methyl or trifluoromethoxy.9. A compound as defined in claim 1 , wherein X represents—N(H)—, —N(Me)— or —O—, such as —N(H)— or —N(Me)—, in particular, —N(H)—.10. A compound or salt as defined in which is selected from:7-{[4-(Trifluoromethyl)phenyl]sulfonyl}-2,7-diazaspiro[4.5]decan-1-one (E1);2-Methyl-7-{[4-(trifluoromethyl)phenyl]sulfonyl}-2,7-diazaspiro[4.5]decan-1-one (E2);7-{[2-Chloro-4-(trifluoromethyl)phenyl]sulfonyl}-2,7-diazaspiro[4.5]decan-1-one (E3);7-{[2- ...

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09-05-2013 дата публикации

Hepatitis c virus inhibitors

Номер: US20130115194A1
Принадлежит: Theravance Inc

The invention provides compounds of formula (I): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.

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09-05-2013 дата публикации

3-aminopyrrolidine derivatives as modulators of chemokine receptors

Номер: US20130116230A1
Принадлежит: Incyte Corp

The present invention relates to 3-aminopyrrolidine derivatives of the formula I: (wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, Y and X are as defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of chemokine receptors and more specifically as a modulator of the CCR2 and/or CCR5 receptor. The compounds and compositions of the invention may bind to chemokine receptors, e.g., the CCR2 and/or CCR5 chemokine receptors, and are useful for treating diseases associated with chemokine, e.g., CCR2 and/or CCR5, activity, such as atherosclerosis, restenosis, lupus, organ transplant rejection and rheumatoid arthritis.

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09-05-2013 дата публикации

Cyclic n,n'-diarylthioureas and n,n'-diarylureas - androgen receptor antagonists, anticancer agent, method for preparation and use thereof

Номер: US20130116269A1

The present invention relates to novel cyclic N,N′-diarylureas and N,N′-diarylthioureas—androgen receptor antagonists, anti-cancer agent, pharmaceutical composition, medicament, and method for treatment of cancerous diseases, among them prostate cancer. Cyclic N,N′-diarylthioureas or N,N′-diarylureas of the general formula 1, their optical (R)- and (S)-isomers and pharmaceutically acceptable salts thereof exhibiting properties of androgen receptor antagonists have been proposed, wherein: X represents oxygen or sulfur; m=0 or 1; R1 represents C 1 -C 3 alkyl; R2 and R3 represent hydrogen; or R2 and R3 together with C-atom they are attached to form C═O group; R4 and R5 represent hydrogen; or R4 represents hydrogen, R5 represents methyl; or R4 represents methyl, R5 represents CH 2 R6 group in which R6 represents C 1 -C 3 alkoxycarbonyl, carboxyl, hydroxyl group optionally substituted with methyl or benzyl; or R4 and R5 together with C-atom they are attached to form 5- or 6-membered heterocycle comprising at least one oxygen atom or nitrogen atom optionally substituted with methyl; or R4 and R5 together with C-atom they are attached to form NH group.

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16-05-2013 дата публикации

Aryl- or Heteroaryl-Substituted Benzene Compounds

Номер: US20130123234A1
Принадлежит:

The present invention relates to aryl- or heteroaryl-substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes. 2. The method of claim 1 , wherein Ris C-Caryl or 5- or 6-membered heteroaryl claim 1 , each of which is optionally claim 1 , independently substituted with one or more -Q-T claim 1 , wherein Qis a bond or C-Calkyl linker claim 1 , and Tis H claim 1 , halo claim 1 , cyano claim 1 , —OR claim 1 , —NRR claim 1 , —(NRRR)A claim 1 , —C(O)NRR claim 1 , —NRC(O)R claim 1 , —S(O)R claim 1 , or R claim 1 , in which each of Rand R claim 1 , independently is H or R claim 1 , each of Rand R claim 1 , independently claim 1 , is C-Calkyl claim 1 , or Rand R claim 1 , together with the N atom to which they are attached claim 1 , form a 4 to 7-membered heterocycloalkyl ring having 0 or 1 additional heteroatom claim 1 , and each of R claim 1 , R claim 1 , and the 4 to 7-membered heterocycloalkyl ring formed by Rand R claim 1 , is optionally claim 1 , independently substituted with one or more -Q-T claim 1 , wherein Qis a bond or C-Calkyl linker and Tis selected from the group consisting of halo claim 1 , C-Calkyl claim 1 , 4 to 7-membered heterocycloalkyl claim 1 , OR claim 1 , —S(O)R claim 1 , and —NRR claim 1 , each of Rand Rindependently being H or C-Calkyl claim 1 , or -Q-Tis oxo; or any two neighboring -Q-T claim 1 , together with the atoms to which they are attached form a 5- or 6-membered ring optionally containing 1-4 heteroatoms selected from N claim 1 , O and S.5. The method of claim 4 , wherein Rand R claim 4 , together with the N atom to which they are attached claim 4 , form a 4 to 7-membered heterocycloalkyl ring having 0 or 1 additional heteroatoms to the N atom ...

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16-05-2013 дата публикации

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

Номер: US20130123236A1
Принадлежит: VANDERBILT UNIVERSITY

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

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16-05-2013 дата публикации

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

Номер: US20130123241A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to novel antagonists for CCR2 (CC chemokine receptor 2) of formula (I) wherein HET is a group selected from among formulas (IIa) (IIb) (IIc) (IId) and their use for providing medicaments for treating conditions and diseases, especially pulmonary diseases like asthma and COPD and pain diseases. 2. The compound of formula (I) according to claim 1 ,wherein HET is a group according to formula (IIa),{'sub': 1', '7', '6, 'wherein Ris —H, and wherein Ris —C-aryl,'}{'sub': 7', '3', '1', '6', '1', '6, 'and wherein the ring Ris optionally substituted with one or more groups selected from among —CF, —C-C-alkyl, —O—C-C-alkyl, and -halogen'}{'sub': '16', 'and wherein Ris -hydrogen;'}{'sub': 7', '1', '4, 'or wherein Rand Ron two neighbouring ring atoms together form a —C-alkenylene group, such that an annellated aromatic ring is formed, in which one carbon center may optionally be replaced by 1 nitrogen atom,'}{'sub': 1', '3', '3', '3, 'wherein the resulting annelated ring being optionally substituted by one or more groups selected from among —C-C-alkyl, —CN, —CF, —OCF, and -halogen,'}{'sub': '16', 'and wherein Ris a group selected from -hydrogen, and ═O;'}{'sub': 7', '1', '1, 'or wherein Rand Ron two neighbouring ring atoms together form a —C-alkylene group such that an annellated ring is formed,'}{'sub': 5', '10, 'wherein the resulting annelated ring being optionally substituted by a group of the structure —C-C-aryl,'}{'sub': '16', 'and wherein Ris -hydrogen;'}{'sub': 7', '5', '5', '4', '2', '1', '3', '1', '6', '3', '3', '5', '10, 'or wherein Ris a group selected from among spiro —C-cycloalkenyl, and spiro —C-heterocyclyl, wherein said spirocyclic ring being optionally substituted on two neighbouring ring atoms by a —C-alkenylene group, such that an annellated aromatic ring is formed, wherein the aromatic ring being optionally substituted by one or more groups selected from among —OH, —NH, —C-C-alkyl, —O—C-C-alkyl, —CN, —CF, —OCF, halogen, —C-C- ...

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16-05-2013 дата публикации

Crystalline (1r, 4r)-6'-fluoro-N,N-dimethyl-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano[3,4,b]indol]-4-amine

Номер: US20130123324A1
Принадлежит: GRUENENTHAL GmbH

Crystalline forms of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine, pharmaceutical compositions and medicaments comprising these crystalline modifications, the use of these modifications as well as a process for the enrichment of such crystalline modifications.

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23-05-2013 дата публикации

SPIROCYCLIC COMPOUNDS

Номер: US20130131041A1
Принадлежит: Merck Sharp & Dohme Corp.

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

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06-06-2013 дата публикации

Process for the Production of Seven-Membered Lactam Morphinans

Номер: US20130144053A1
Принадлежит: Mallinckrodt LLC

The present invention relates to improved processes for preparing lactam morphinans. The processes generally transform keto-morphinans to seven-membered lactam morphinans using a hydroxyamine sulfonic acid reagent and proceed in high yield and with good selectivity. 1. A process for the production of a seven-membered lactam morphinan , wherein the process comprises contacting a keto-morphinan with a hydroxyamine sulfonic acid to form the seven-membered lactam morphinan.2. The process of claim 1 , wherein the hydroxyamine sulfonic acid is hydroxyamine-O-sulfonic acid; and the keto-morphinan and the hydroxyamine sulfonic acid are present in a mole-to-mole ratio from about 1:1 to about 1:5.3. The process of claim 1 , wherein the contacting is performed in the presence of a proton donor; and the keto-morphinan and the proton donor are present in a mole-to-mole ratio from about 1:10 to about 1:80.4. The process of claim 1 , wherein the process is conducted at a temperature ranging from about 0° C. to about 50° C.5. The process of claim 1 , wherein the process further comprises addition of a proton acceptor; the proton acceptor is present in an aqueous solution; andthe aqueous solution comprises from about 20% to 60% v/v of the proton acceptor.6. The process of claim 1 , wherein a single regioisomer of the seven-membered lactam morphinan has a yield above about 75%.7. The process of claim 1 , wherein the seven-membered lactam morphinan is a (+)-morphinan or a (−)-morphinan.9. The process of claim 8 , wherein R claim 8 , R claim 8 , R claim 8 , R claim 8 , R claim 8 , Rand Rare hydrogen; Ris {—}OCH; and Ris methyl.10. The process of claim 8 , wherein R claim 8 , R claim 8 , R claim 8 , R claim 8 , R claim 8 , and Rare hydrogen; Ris hydroxyl; Ris hydroxyl; and Ris methyl claim 8 , cyclopropylmethyl claim 8 , or allyl.12. The process of claim 11 , wherein the compound comprising Formula (I) and the hydroxyamine sulfonic acid are present in a mole-to-mole ratio from about 1:1 ...

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13-06-2013 дата публикации

Solid forms of (1 r,4r)-6' -fluoro-(N, N-dimethyl)-4-phenyl-4' ,9'-dihydro-3'H-spiro[ cyclohexane-1,1 '-pyrano-[3,4,b]indol]-4-amine and sulfuric acid

Номер: US20130150589A1
Принадлежит: GRUENENTHAL GmbH

Solid forms of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4b]indol]-4-amine and sulfuric acid such as (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4b]indol]-4-amine sulfate or hemi-sulfate, particularly crystalline forms and/or amorphous forms thereof, pharmaceutical compositions and medicaments containing these solid forms, the use of these solid forms, and a process for obtaining such solid forms. 1. A solid form of (1r ,4r)-6′-fluoro-N ,N-dimethyl-4-phenyl-4′ ,9′-dihydro-3′H-spiro[cyclo-hexane-1 ,1′-pyrano[3 ,4 ,b]indol]-4-amine and sulfuric acid.2. The solid form according to claim 1 , which is a solid form of (1r claim 1 ,4r)-6′-fluoro-N claim 1 ,N-dimethyl-4-phenyl-4′ claim 1 ,9′-dihydro-3′H-spiro[cyclohexane-1 claim 1 ,1′-pyrano[3 claim 1 ,4 claim 1 ,b]indol]-4-amine sulfate or (1r claim 1 ,4r)-6′-fluoro-N claim 1 ,N-dimethyl-4-phenyl-4′ claim 1 ,9′-dihydro-3′H-spiro[cyclohexane-1 claim 1 ,1′-pyrano-[3 claim 1 ,4 claim 1 ,b]indol]-4-amine hemi-sulfate.3. The solid form according to claim 1 , which is an amorphous form.4. The solid form according to claim 1 , which is an a crystalline form.5. The crystalline form according to claim 4 , which has: 'and/or', 'at least one CuKα radiation X-ray diffraction peak selected from the group consisting of 9.7±1.0 (2Θ), 17.7±1.0 (2Θ), 18.2±1.0 (2Θ) and 25.7±1.0 (2Θ);'}{'sup': −1', '−1', '−1', '−1', '−1', '−1', '−1, 'at least one Raman band selected from the group consisting of 916±5 cm, 1002±5 cm, 1028±5 cm, 1569±5 cm, 1583±5 cm, 2980±5 cmand at 3076±5 cm.'}6. The crystalline form according to claim 4 , which is an ansolvate.7. The crystalline form according to which is a solvate.8. The crystalline form according to claim 4 , which has: {'sup': −1', '−1', '−1', '−1', '−1', '−1', '−1, 'claim-text': 'or', 'one or more Raman bands selected from the group consisting of 916±2 cm, 1002±2 cm, 1028±2 cm, 1571±2 cm, 1583±2 cm, 2983±2 cmand ...

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13-06-2013 дата публикации

Process for the preparation of (1r,4r)-6'-fluoro-(N,N-dimethyl- and N-methyl)-4-phenyl-4',9'-dihydro-3'H-spiro[cyclohexane-1,1'-pyrano-[3,4,b]indol]-4-amine

Номер: US20130150590A1
Принадлежит: GRUENENTHAL GmbH

A process for the preparation of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4b]indol]-4-amine and (1r,4r)-6′-fluoro-N-methyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4b]-indol]-4-amine or physiologically acceptable acid addition salts thereof.

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20-06-2013 дата публикации

Substituted Triazolopyridines

Номер: US20130156756A1
Принадлежит: Bayer Intellectual Property GmbH

The present invention relates to substituted triazolopyridine compounds of general formula (I): in which R, R, R, R, and Rare as given in the description and in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds, to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease of uncontrolled cell growth, proliferation and/or survival as well as to the use of intermediate compounds for the preparation of said compounds. 2. The compound according to claim 1 , wherein:{'sup': '1', 'claim-text': 'which is substituted, one or more times, identically or differently, with a substituent selected from:', 'Rrepresents an aryl or heteroaryl group'}{'sup': 6', '6', '6', '6', '6', '6', '6', '6', '6', '6', '7', '6', '6', '7', '7', '6', '7', '6', '7', '6', '6', '7', '6', '6', '6', '6', '7', '6', '6', '6', '7', '6', '7', '6', '6', '6', '7', '6', '7', '7', '6', '6', '7, 'sub': 2', 'n', '2', 'm', '1', '6', '2', 'n', '2', 'p', '1', '6', '1', '6', '1', '6', '1', '6', '2', '2', '2', '2', '2, 'claim-text': and', {'sup': 'xy', 'which is optionally substituted, one or more times, identically or differently, with a substituent Rselected from, {'sub': 1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'sup': 8', '7', '8', '8', '8', '7, 'halo-, hydroxyl-, cyano-, C-C-alkyl-, halo-C-C-alkyl-, C-C-alkoxy-, halo-C-C-alkoxy-, hydroxy-C-C-alkyl-, —N(H)C(═O)R, —N(R)C(═O)R, —C(═O)N(H)R, —C(═O)NRR;'}], 'R—(CH)(CHOH)(CH)—, R—(C-C-alkoxy)-, R—(CH)(CHOH)(CH)—O—, R—(C-C-alkoxy-C-C-alkyl)-, R—(C-C-alkoxy-C-C-alkyl)-O—, R—O—, —C(═O)R, —C(═O)O—R, —OC(═O)—R, —N(H)C(═O)R, —N(R)C(═O)R, —N(H)C(═O)NRR, —N(R)C(═O)NRR, —NRR, —C(═O)N(H)R, —C(═O)NRR, R—S—, R—S(═O)—, R—S(═O)—, —N(H)S(═O)R, —N(R)S(═O)R, —S(═O)N(H)R, —S(═O)NRR, —N(H)S(═O)R, —N(R)S(═O)R, —S(═O)N(H)R, —S(═O)NRR, —S(═O)(═NR)R, —S(═O)(═NR)R, —N═S(═O)(R)R;'}or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a ...

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20-06-2013 дата публикации

Aminopyrimidine derivatives as lrrk2 modulators

Номер: US20130157999A1
Принадлежит: Genentech Inc

Specific Compounds of formula I: or pharmaceutically acceptable salts thereof, wherein m, X, R 1 , R 2 , R 3 , R 5 , R 6 and R 7 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with LRRK2 receptor, such as Parkinson's disease.

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20-06-2013 дата публикации

POSITIVE ALLOSTERIC MODULATORS OF MGLUR2

Номер: US20130158002A1
Принадлежит:

The present invention is directed to 5-substituted 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide and 1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2,-dioxide derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved. 3. The compound according to wherein X is C.4. The compound according to wherein X is N.5. The compound according to wherein Y is methyl.6. The compound according to wherein Ris selected from the group consisting of: cyclopropylmethyl claim 2 , 2 claim 2 ,2-difluorocyclopropylmethyl claim 2 , cyclobutylmethyl claim 2 , 2 claim 2 ,2-dimethylpropyl and benzyl claim 2 , optionally substituted with methoxy or —OCF.8. The compound according to wherein Ris selected from the group consisting of: (1) —CN claim 7 , (2) halo claim 7 , (3) —CF claim 7 , (4) 1 claim 7 ,1-dioxidothiomorpholin-4-yl claim 7 , (5) morpholin-4-ylmethyl claim 7 , (6) —C(O)—O—Calkyl claim 7 , (7) Calkoxy claim 7 , (8) Calkyl claim 7 , optionally substituted with hydroxy claim 7 , (9) piperazinyl claim 7 , optionally substituted with —C(O)—O—Calkyl or isoxazolylcarbonyl claim 7 , and (10) piperidinyl claim 7 , optionally substituted with —C(O)—O—Calkyl or isoxazolylcarbonyl.10. The compound according to wherein Ris selected from the group consisting of: (1) —CN claim 9 , (2) halo claim 9 , (3) —CF claim 9 , (4) 1 claim 9 ,1-dioxidothiomorpholin-4-yl claim 9 , (5) morpholin-4-ylmethyl claim 9 , (6) —C(O)—O—Calkyl claim 9 , (7) Calkoxy claim 9 , (8) Calkyl claim 9 , optionally substituted with hydroxy claim 9 ...

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27-06-2013 дата публикации

Novel Thiazol-Carboximide Derivatives as PDK1 Inhibitors

Номер: US20130165450A1
Принадлежит:

This invention relates to certain thiazole carboxamide derivatives of Formula (I) as inhibitors of 3-phosphoinositide-dependent protein kinase (PDK-1). The compounds can be useful in inhibiting the proliferation of cancer cells, and other aberrant conditions where the PDK-1 signaling pathway is overstimulated. 3. The compound of claim 1 , wherein Aris a 6-membered aryl or heteroaryl.4. The compound of claim 1 , wherein Aris phenyl or pyridyl.7. The compound of claim 5 , wherein Ris NHor —CH—NH.10. The compound of claim 1 , wherein Aris pyrazolyl claim 1 , optionally substituted with one to three substituents selected from halo claim 1 , OH claim 1 , (CRR)OR claim 1 , COOR claim 1 , O—C-Calkyl claim 1 , NH claim 1 , CN claim 1 , C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , halo-C-Calkyl claim 1 , O-halo-C-Calkyl and S-halo-C-Calkyl.11. The compound of claim 1 , wherein —X—Z is —CH-pyridyl claim 1 , —CH-phenyl claim 1 , —CH—CH-phenyl or CH-thienyl claim 1 , wherein the pyridyl claim 1 , phenyl or thienyl is optionally substituted with fluoro.12. The compound of selected from the group consisting of:N-[5-amino-2-(3(R)-amino-1-piperidinyl)phenyl]-2-[1-[3-(dimethylamino)propyl]-1H-pyrazol-4-yl]-4-thiazolecarboxamide;N-[5-amino-2-(3(R)-amino-1-piperidinyl)phenyl]-2-[1-(2-thienylmethyl)-1H-pyrazol-4-yl]-4-thiazolecarboxamide;N-[5-amino-2-(3(R)-amino-1-piperidinyl)phenyl]-2-[1-(phenylmethyl)-1H-pyrazol-4-yl]-4-thiazolecarboxamide;N-[5-amino-2-(3(R)-amino-1-piperidinyl)phenyl]-2-[1-[2-(4-morpholinyl)ethyl]-1H-pyrazol-4-yl]-4-thiazolecarboxamide;1-[4-amino-2-[[[2-[1-(2-thienylmethyl)-1H-pyrazol-4-yl]-4-thiazolyl]carbonyl]amino]phenyl]-4-(methylamino)-4-piperidinecarboxamide;N-[2-[4-(aminomethyl)-1-piperidinyl]-3-fluorophenyl]-2-[1-(2-thienylmethyl)-1H-pyrazol-4-yl]-4-thiazolecarboxamide;N-[5-amino-2-(2,9-diazaspiro[5.5]undec-9-yl)phenyl]-2-[1-(2-thienylmethyl)-1H-pyrazol-4-yl]-4-thiazolecarboxamide;N-[5-amino-2-[4-(aminomethyl)-1-piperidinyl]phenyl]-2-[1-(2- ...

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04-07-2013 дата публикации

Heteroaryl amide derivatives

Номер: US20130172549A1
Принадлежит: H. Lundbeck A/S

Heteroaryl amide derivatives are provided, of the Formula: wherein variables are as described herein. Such compounds are ligands that may be used to modulate specific receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathological receptor activation in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for using such compounds to treat such disorders are provided, as are methods for using such ligands for receptor localization studies. 261-. (canceled) This application claims priority to U.S. Provisional Application 60/867,248, filed Nov. 27, 2006, which is hereby incorporated by reference in its entirety.This invention relates generally to heteroaryl amide derivatives that have useful pharmacological properties. The invention further relates to the use of such compounds for treating conditions related to P2Xreceptor activation, for identifying other agents that bind to P2Xreceptor, and as probes for the detection and localization of P2Xreceptors.Pain perception, or nociception, is mediated by the peripheral terminals of a group of specialized sensory neurons, termed “nociceptors.” A wide variety of physical and chemical stimuli induce activation of such neurons in mammals, leading to recognition of a potentially harmful stimulus. Inappropriate or excessive activation of nociceptors, however, can result in debilitating acute or chronic pain.Neuropathic pain, which typically results from damage to the nervous system, involves pain signal transmission in the absence of stimulus, pain from a normally innocuous stimulus (allodynia) and increased pain from a normally painful stimulus (hyperalgesia). In most instances, neuropathic pain is thought to occur because of sensitization in the peripheral and central nervous systems following initial damage to the peripheral system (e.g., via direct injury or systemic disease). Neuropathic pain is typically burning, ...

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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

Cannabinoid receptor modulators

Номер: US20130178457A1
Принадлежит: Lupin Ltd

Compounds of Formula (I) along with processes for their preparation that are useful for treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of cannabinoid (CB) receptors. Methods of treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of cannabinoid (CB) receptors of Formula (I).

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11-07-2013 дата публикации

COMPOUNDS FOR THE REDUCTION OF BETA-AMYLOID PRODUCTION

Номер: US20130178462A1
Принадлежит: BRISTOL-MYERS SQUIBB COMPANY

The present disclosure provides a series of compounds of the formula (I) 2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A is a five-membered heteroaromatic ring containing from one to three nitrogen atoms; wherein said heteroaromatic ring is optionally substituted with one group selected from halo and Calkyl.3. A compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein B is selected from phenyl and pyridinyl claim 2 , wherein the phenyl and pyridinyl are optionally substituted with one or two substituents independently selected from Calkoxy and halo.4. A compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein E is phenyl optionally substituted with one claim 3 , two claim 3 , or three substituents independently selected from Calkyl claim 3 , Calkoxy claim 3 , cyano claim 3 , halo claim 3 , haloCalkoxy claim 3 , and haloCalkyl.6. A compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris —NRR claim 5 , wherein Rand Rare independently selected from hydrogen claim 5 , CalkoxyCalkyl claim 5 , Calkyl claim 5 , Ccycloalkyl claim 5 , hydroxyCalkyl claim 5 , and trideuteromethyl claim 5 , wherein the alkyl part of the (Ccycloalkyl)Calkyl can be optionally substituted with a Calkoxy group.7. A compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris —NRR claim 5 , wherein Rand R claim 5 , together with the nitrogen atom to which they are attached claim 5 , form a four- to seven-membered monocyclic or bicyclic ring optionally containing one additional heteroatom selected from O and NR; wherein Ris selected from Calkyl claim 5 , and Calkoxycarbonyl; and wherein the ring is optionally substituted with one or two substituents independently selected from Calkoxy claim 5 , Calkyl claim 5 , halo claim 5 , haloCalkyl claim 5 , hydroxy claim 5 , —NRR claim 5 , oxo claim 5 , and spirocycle dioxolanyl; wherein Rand Rare ...

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18-07-2013 дата публикации

Hepatitis C Virus Inhibitors

Номер: US20130183269A1
Принадлежит: BRISTOL-MYERS SQUIBB COMPANY

The present disclosure is generally directed to antiviral compounds, and more specifically directed to combinations of compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such combinations, and methods for inhibiting the function of the NS5A protein. 1. A combination comprising an NS5A-targeting compound and an NS5A synergist , which , when administered , provides synergistic anti-HCV activity against variants that contain mutation(s) conferring resistance to the NS5A-targeting compound alone.2. The combination of which comprises two or more pharmaceutically acceptable carriers.3. The combination of wherein the NS5A-targeting compound and the NS5A synergist are combined in the same pharmaceutically acceptable carrier.19. A composition comprising a combination of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.20. The composition of further comprising one or two additional compounds having anti-HCV activity.21. The composition of wherein at least one of the additional compounds is an interferon or a ribavirin.22. The composition of wherein the interferon is selected from interferon alpha 2B claim 21 , pegylated interferon alpha claim 21 , pegylated interferon lambda claim 21 , consensus interferon claim 21 , interferon alpha 2A claim 21 , and lymphoblastoid interferon tau.23. The composition of wherein at least one of the additional compounds is effective to inhibit the function of a target selected from HCV protease claim 20 , HCV polymerase claim 20 , HCV helicase claim 20 , HCV NS4B protein claim 20 , HCV entry claim 20 , HCV assembly claim 20 , HCV egress claim 20 , HCV NS5A protein claim 20 , and IMPDH for the treatment of an HCV infection.24. A method of treating an HCV infection in a patient claim 1 , comprising administering to the patient a therapeutically effective amount of a combination of claim 1 , or a pharmaceutically ...

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18-07-2013 дата публикации

Therapeutic Agents

Номер: US20130184250A1
Принадлежит: AstraZeneca AB

Disclosed herein are azetidinyl compounds of formula I, 9. A compound according to selected from one or more of the following compounds:(3-(4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone;(+)-(3-(4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone;(−)-(3-(4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone;(3-(4-(5-oxa-2-azaspiro[3.4]octan-2-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone;(3-(4-(6-oxa-2-azaspiro[3.4]octan-2-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone;(3-(4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone;(+)-(3-(4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone;(−)-(3-(4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone;(3-(4-(6-oxa-2-azaspiro[3.4]octan-2-ylmethyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone;(3-(4-(5-oxa-2-azaspiro[3.4]octan-2-ylmethyl)phenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone;(3-(4-(6-oxa-2-azaspiro[3.4]octan-2-ylmethyl)-3-methylphenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone;(3-(4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)-3-methylphenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone;(+)-(3-(4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)-3-methylphenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone;(−)-(3-(4-(2-oxa-7-azaspiro[4.4]nonan-7-ylmethyl)-3-methylphenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone;(3-(4-(5-oxa-2-azaspiro[3.4]octan-2-ylmethyl)-3-methylphenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone;(3-(4-(2-oxa-5-azaspiro[3.4]octan-5-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone;( ...

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18-07-2013 дата публикации

TETRAHYDROPYRIDO-PYRIDINE AND TETRAHYDROPYRIDO-PYRIMIDINE COMPOUNDS AND USE THEREOF AS C5A RECEPTOR MODULATORS

Номер: US20130184253A1
Принадлежит: NOVARTIS AG

The present invention provides a compound of formula I: 3. A compound of claim 1 , in which Ris phenyl or 1H-pyrazolyl claim 1 , each of which is substituted with 1 or 2 independently selected C-Calkyl groups and 0 claim 1 , 1 or 2 additional substituents selected from the group consisting of halogen claim 1 , cyano claim 1 , C-Calkyl claim 1 , haloC-Calkyl claim 1 , C-Calkoxy claim 1 , cyclopropyl claim 1 , oxetanyl or 1-methyl-oxetanyl.4. The compound of claim 2 , in which Ris hydrogen or methyl;{'sup': 1e', '1a', '1e, 'Ris hydrogen, halogen, cyano, methyl or trifluoromethyl, wherein at least one of Rand Ris not hydrogen;'}{'sup': 3', '1f, 'Zis C(R);'}{'sup': '4', 'Zis N or CH;'}{'sup': '5', 'Zis N(H); and'}{'sup': '1f', 'Ris hydrogen or methyl.'}5. The compound of claim 1 , in which Ris 2 claim 1 ,6-dimethylphenyl claim 1 , 2 claim 1 ,6-diethylphenyl claim 1 , 3 claim 1 ,5-dimethyl-1H-indazol-4-yl claim 1 , 3 claim 1 ,5-dimethyl-1H-indol-4-yl claim 1 , 3 claim 1 ,5-dimethyl-1H-indol-4-yl claim 1 , 3 claim 1 ,5-dimethyl-1H-pyrazolo[3 claim 1 ,4-b]pyridin-4-yl claim 1 , or 5-trifluoromethyl-3H-pyrrolo[2 claim 1 ,3-b]pyridin-4-yl.6. The compound of claim 1 , in which Ris hydrogen.7. The compound of claim 1 , in which X is N.9. The compound of claim 1 , in which X is CH.10. The compound of claim 1 , in which Ris hydrogen or methyl.12. A compound of claim 1 , or a salt thereof claim 1 , in which Ris deuterium.13. A compound of claim 1 , or a salt thereof claim 1 , which compound is selected from the group consisting ofracemic 1-(2-(2,6-dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-2-methylpiperidin-4-ol;2-(2,6-dimethylphenyl)-4-(3,3-dimethylpiperidin-1-yl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine;(S)-2-(2,6-dimethylphenyl)-6-(3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(2-methylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine;2-(2,6-dimethylphenyl)-6-(3-isopropyl-1 ...

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18-07-2013 дата публикации

QUINAZOLINE DERIVATIVES SUBSTITUTED BY ANILINE, PREPARATION METHOD AND USE THEREOF

Номер: US20130184297A1
Автор: Dong Yanyan, Huang Zhenhua
Принадлежит: XUANZHU PHARMA CO., LTD.

The invention relates to quinazoline derivatives substituted by aniline which are represented by the below formula (I), pharmaceutical acceptable salts and stereoisomer thereof, wherein these groups of R, R, R, R, R, R, L and n have the meanings given in the specification. The invention also relates to preparation methods, pharmaceutical compositions, pharmaceutical preparation and the use for preparation of medicine of treating excessive hyperplasia and chronic obstructive pulmonary disease and uses for treating excessive hyperplasia and chronic obstructive pulmonary disease thereof. 2. A compound according to claim 1 , a pharmaceutically acceptable salt thereof or a stereoisomer thereof claim 1 , wherein{'sup': '1', 'sub': 1', '0-4', '0-4', '0-4', 'm', 'm', '3, 'Ris selected from the group consisting of the following groups that are unsubstituted or substituted by 1-2 Qsubstituents: a 6-10-membered saturated fused ring-Calkyl group, a 7-10-membered saturated spiro ring-Calkyl group or a 7-10-membered saturated bridged ring-Calkyl group, wherein 1-3 carbon atoms of the fused ring, the spiro ring or the bridged ring can be replaced with 1-3 hetero atoms and/or groups that can be identical or different and are selected from the group consisting of O, S(O), N(H), NCHand C(O), provided that after the replacement, O and C(O) in the ring are not adjacent to each other,'}{'sub': 1', '1-4', '1-4', '1-4', '1-4', '1-4', '1-4', '1-4', '1-4', '1-4', '3-6, 'Qis selected from the group consisting of halogen, hydroxyl, amino, carboxyl, cyano, a Calkyl group, a Calkoxyl group, a Calkylamino group, a di(Calkyl)amino group, a Calkylcarbonyloxy group, a Calkylacylamino group, a Calkylsulfonyl group, a Calkylsulfinyl group, Calkylsulfonylamino and Ccycloalkyl;'}{'sup': '2', 'sub': 1-4', '1-4', '2', '2', 'm, 'Ris selected from the group consisting of hydrogen, a Calkyl group or a Calkoxyl group that is unsubstituted or substituted by 1-2 Qsubstituents, a formyl group that is ...

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18-07-2013 дата публикации

PROCESS FOR PREPARATION OF NOVEL 42-O-(HETEROALKOXYALKYL) RAPAMICIN COMPOUNDS WITH ANTI-PROLIFERATIVE PROPERTIES

Номер: US20130184305A1
Принадлежит:

The invention discloses novel 42-0-(heteroalkoxyalkyl) rapamycin compounds of formula (1) and process for preparation thereof. These compounds are useful in the treatment of hyperproliferative vascular diseases such as restenosis and atherosclerosis Wherein, R denotes 3, 4 and 5 membered 3-hydroxy heteroalkoxyalkyl compounds selected from Tetrahydrofuran-3-ol, Oxetan-3-ol, Tetrahydropyran-3-ol, Tetrahydro-4- methyl furan-3-ol, Tetrahydro-2,5,5-trimethyl furan-3-ol, Tetrahydro-2,5-diethyl-2-methyl furan-3-ol, Tetrahydro-6-methoxy-2-methyl 2H-Pyran-3-ol and Tetrahydro-2,2-dimethyl-6-phenyl 2H-Pyran-3-ol. 2. The 42-O-(heteroalkoxyalkyl) rapamycin compounds of formula 1 according to claim 1 , wherein said compound is selected from the group consisting of:42-O-(tetrahydrofuran-3-yl) rapamycin (Merilimus-1);42-O-(oxetan-3-yl) rapamycin (Merilimus-2);42-O-(tetrahydropyran-3-yl) rapamycin (Merilimus-3);42-O-(4-methyl, tetrahydrofuran-3-yl) rapamycin;42-O-(2,5,5-trimethyl, tetrahydrofuran-3-yl) rapamycin;42-O-(2,5-diethyl-2-methyl, tetrahydrofuran-3-yl) rapamycin;42-O-(2H-Pyran-3-yl, tetrahydro-6-methoxy-2-methyl) rapamycin and42-O-(2H-Pyran-3-yl, tetrahydro-2,2-dimethyl-6-phenyl) rapamycin.3. The 42-O-(heteroalkoxyalkyl) rapamycin compounds of formula 1 according to claim 2 , wherein said compound is 42-O-(tetrahydrofuran-3-yl) rapamycin (Merilimus-1).4. The 42-O-(heteroalkoxyalkyl) rapamycin compounds of formula 1 according to claim 2 , wherein said compound is 42-O-(oxetan-3-yl) rapamycin (Merilimus-2).5. The 42-O-(heteroalkoxyalkyl) rapamycin compounds of formula 1 according to claim 2 , wherein said compound is 42-O-(tetrahydropyran-3-yl) rapamycin (Merilimus-3).6. A process for preparation of 42-O-(heteroalkoxyalkyl) rapamycin compounds represented by the general formula (1) comprising:a) reacting rapamycin with triflic anhydride in presence of an organic base and halogenated organic solvent to obtain triflate intermediate; andb) reacting the triflate intermediate with ...

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25-07-2013 дата публикации

BENZYL SULFONAMIDE DERIVATIVES AS RORC MODULATORS

Номер: US20130190288A1
Принадлежит: Genentech, Inc.

Compounds of the formula I: 2. The compound of claim 1 , wherein n is 0 or 1.3. The compound of claim 1 , wherein X claim 1 , X claim 1 , Xand Xare CR.4. The compound of claim 1 , wherein m is from 0 to 2 and each Ris independently: Calkyl; halo; Calkoxy; cyano; halo-Calkyl; or halo-Calkoxy.5. The compound of claim 1 , wherein Ris: Calkyl; Ccycloalkyl; or Ccycloalkyl-Calkyl; each of which may be optionally substituted one or more times with R.6. The compound of claim 1 , wherein Ris Ccycloalkyl.7. The compound of claim 1 , wherein Ris cyclobutyl.8. The compound of claim 1 , wherein Rand Rare hydrogen.9. The compound of claim 1 , wherein Rand Rare hydrogen.11. The compound of claim 1 , wherein Y is N.12. The compound of claim 1 , wherein Z is —CRR—.13. The compound of claim 1 , wherein Y is CH.14. The compound of claim 1 , wherein Z is —NR—.15. The compound of claim 1 , wherein p is 2.16. The compound of claim 1 , wherein q is 2.17. The compound of claim 1 , wherein each Ris indepently: hydrogen; Calkyl; or halo.18. The compound of claim 1 , wherein Rand Rare hydrogen.19. The compound of claim 1 , wherein Ris acetyl.22. The compound of claim 1 , wherein A is: pyrrolidin-1-yl; 4-hydroxy-piperidin-1-yl; 2-methoxy-ethylamino; morpholin-4-yl; 4-methyl-piperazin-1-yl; 2-hydroxy-ethylamino; 3-oxo-piperazin-1-yl; 2-dimethylamino-ethylamino; 4-(dimethylaminocarbonyl)-piperidin-1-yl; 4-methoxymethyl-piperidin-1-yl; 4-hydroxymethyl-piperidin-1-yl; 4-(aminocarbonyl)-piperidin-1-yl; 4-(dimethylamino)-piperidin-1-yl; 4-(cyanomethyl)-piperidin-1-yl; 3-hydroxy-pyrrolidin-1-yl; 4-(methanesulfonyl)-piperazin-1-yl; 4-acetyl-piperazin-1-yl; 4-methoxy-piperidin-1-yl; 3-hydroxy-piperidin-1-yl; 3-(aminocarbonyl)-pyrrolidin-1-yl; 1 claim 1 ,1-Dioxo-thiomorpholin-4-yl; 4-(methoxycarbonyl)-piperazin-1-yl; 4-(methylcarbonylamino)-piperidin-1-yl; 3-methanesulfonyl-pyrrolidin-1-yl; 3-hydroxy-azetidin-1-yl; 4-(ethoxycarbonyl)-piperazin-1-yl; 3-(aminocarbonyl)-azetidin-1-yl; 3-( ...

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25-07-2013 дата публикации

HETEROCYCLYL PYRAZOLOPYRIMIDINE ANALOGUES AS SELECTIVE JAK INHIBITORS

Номер: US20130190292A1
Принадлежит: CELLZOME LIMITED

The present invention relates to compounds of formula (I) 2. (canceled)3. A compound of claim 1 , wherein Ris T claim 1 , C(O)T claim 1 , Calkyl substituted with one or more T claim 1 , or N(R)T.4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. A compound of claim 1 , wherein R is H.10. A compound of claim 1 , wherein ring A is a pyrazole claim 1 , an oxazole or an isoxazole.11. (canceled)12. (canceled)13. A compound of claim 1 , wherein Ris ORor Calkyl claim 1 , which is optionally substituted with 1 or 2 R claim 1 , which are the same or different.14. (canceled)15. (canceled)16. A compound of claim 1 , wherein Ris halogen; CN; OR; C(O)N(RR); C(O)T claim 1 , wherein Tis an unsubstituted 4 to 7 membered heterocycle containing at least one ring nitrogen atom which is attached to C(O).17. (canceled)18. (canceled)19. (canceled)20. (canceled)22. (canceled)23. (canceled)24. A compound of claim 1 , wherein none or one of X claim 1 , X claim 1 , X claim 1 , X claim 1 , Xis N.25. (canceled)26. A compound of claim 1 , wherein one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , Ris Rand the others are independently selected from the group consisting of H; unsubstituted Calkyl; and halogen.27. (canceled)28. (canceled)29. A compound of claim 1 , wherein Tis a 4 to 7 membered heterocyclyl; or 7 to 11 membered heterobicyclyl.30. A compound of claim 29 , wherein Tis morpholinyl claim 29 , piperazinyl claim 29 , piperidinyl claim 29 , thiomorpholinyl-1 claim 29 ,1-dioxide claim 29 , tetrahydro-2H-pyranyl claim 29 , azetidinyl claim 29 , oxetane claim 29 , or pyrrolidine claim 29 , and wherein Tis optionally substituted with one or more R claim 29 , which are the same or different.31. (canceled)32. (canceled)33. (canceled)34. (canceled)35. (canceled)36. (canceled)37. (canceled)38. (canceled)39. (canceled)40. (canceled)41. (canceled)42. (canceled)43. (canceled)45. A compound of selected from the group consisting of(R)—N-(1-methyl-1H-pyrazol-4-yl)-1-((6-(3- ...

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01-08-2013 дата публикации

Compounds for the treatment and prophylaxis of respiratory syncytial virus disease

Номер: US20130196974A1
Принадлежит: Hoffmann La Roche Inc

A compound of formula (I) as well as pharmaceutically acceptable salt thereof, wherein R 1 to R 10 , A, Q, X and Y are as defined in the specification and claims, and their use as a pharmaceutical for the treatment or prophylaxis of respiratory syncytial virus disease.

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01-08-2013 дата публикации

1',3'-disubstituted-4-pheny-3,4,5,6-tetrahydro-2h,1'h-[1,4']bipyridinyl-2'-ones

Номер: US20130196992A1

The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors—subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

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01-08-2013 дата публикации

SPIRO-CYCLIC AMINE DERIVATIVES AS S1P MODULATORS

Номер: US20130196998A1
Принадлежит: AbbVie B.V.

The present invention relates to spiro-cyclic amine derivatives of the formula (I) 2. The compound of claim 1 , wherein R3 is selected from —(CH)—OH claim 1 , —CH—COOH claim 1 , —(CH)—COOH claim 1 , —(CH)—COOH claim 1 , —CH—CHCH—COOH claim 1 , —CH—C(CH)—COOH claim 1 , —CHCH—CH—COOH claim 1 , —CH—CF—COOH claim 1 , —CO—CH—COOH claim 1 , 1 claim 1 ,3-cyclobutylene-COOH claim 1 , —(CH)—POH claim 1 , —(CH)—POH claim 1 , —(CH)—OPOH claim 1 , —(CH)—OPOH claim 1 , —CH-tetrazol-5-yl claim 1 , —(CH)-tetrazol-5-yl claim 1 , and —(CH)-tetrazol-5-yl;and Q is a bond.3. The compound of claim 1 , wherein R2 is selected from H claim 1 , methyl claim 1 , chloro claim 1 , and fluoro claim 1 , and Z is selected from CH and CR2.4. The compound of claim 1 , wherein —W—T— is selected from —CH—O— claim 1 , —O—CH— claim 1 , —O—CH—CH— claim 1 , and —CO—O—; and R5 is H.5. The compound of claim 1 , wherein Y is selected from a bond claim 1 , —O— claim 1 , —CO— claim 1 , —CH═CH— claim 1 , —C(CF)═CH— claim 1 , —C≡C— claim 1 , and a trans-cyclopropylene; and n is an integer from 0 to 6.6. The compound of claim 1 , wherein R1 is selected froma group selected from (1-4C)alkyl, cyclohexyl, cyclohexenyl, and biphenyl, wherein the group is optionally substituted with at least one halogen atom,a phenyl optionally substituted with one, two or three substituents independently selected from halogen, (1-4C)alkyl, trifluoromethyl, (1-4C)alkoxy, trifluoromethoxy, and cyclopropyl optionally substituted with phenyl, thienyl, pyridyl, tetrahydropyranyl, each optionally substituted with halogen, (1-4C)alkyl, cyclopropyl or phenyl optionally substituted with halogen, anda group selected from indolyl, dihydrobenzofuranyl, and benzdioxanyl, wherein the croup is optionally substituted with a substituent selected from a halogen atom and (1-4C)alkyl.7. The compound of claim 1 , wherein R1 is selected from phenyl claim 1 , optionally substituted with at least one substituent independently selected from a halogen atom ...

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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

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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15-08-2013 дата публикации

Compounds and Their Use as BACE Inhibitors

Номер: US20130210837A1
Принадлежит: AstraZeneca Intellectual Property

The present invention relates to compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI (“mild cognitive impairment”), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration. 125-. (canceled)27. A compound according to or a pharmaceutically acceptable salt thereof claim 26 , wherein Ris Calkyl.28. A compound according to or a pharmaceutically acceptable salt thereof claim 27 , wherein Ris methyl or ethyl.29. A compound according to or a pharmaceutically acceptable salt thereof claim 26 , wherein Ris aryl claim 26 , heteroaryl claim 26 , Calkynyl claim 26 , halogen claim 26 , NHC(O)Ror ORwherein:{'sub': '2-6', 'sup': '7', 'said aryl, heteroaryl, or Calkynyl is optionally substituted with one to three R.'}30. A compound according to or a pharmaceutically acceptable salt thereof claim 26 , wherein Rand Rare independently hydrogen or heterocyclyl wherein:{'sub': '1-6', 'sup': '8', 'said heterocyclyl is optionally substituted with one or two substituents independently selected from Calkyl or OR.'}31. A compound according to or a pharmaceutically acceptable salt thereof claim 26 , wherein Rand R claim 26 , together with the carbon to which they are attached claim 26 , form a ring B claim 26 , wherein ring B is:{'sub': '1-6', 'sup': '8', 'a 3-14 membered cycloalkyl or heterocyclyl monocyclic ring, ...

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15-08-2013 дата публикации

METHOD FOR STEREOSELECTIVE SYNTHESIS OF BICYCLIC HETEROCYCLIC COMPOUNDS

Номер: US20130211081A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The invention relates to a method for the stereoselective preparation of a compound of formula (5), optionally in the form of the tautomers thereof, The invention relates to a method for the stereoselective preparation of a compound of formula (5), optionally in the form of the tautomers thereof,Compounds of formula (5), optionally in the form of the tautomers thereof, are valuable intermediates in methods for the stereoselective preparation of the compound of formula (I), optionally in the form of the tautomers thereof, and optionally the pharmacologically acceptable acid addition salts thereof,which compound has valuable pharmacological properties, particularly an inhibiting action on signal transduction mediated by tyrosine kinases, and for the treatment of diseases, particularly tumoral diseases, benign prostatic hyperplasia and diseases of the lungs and respiratory tract.Quinazoline derivatives are known from the prior art as active substances for example for the treatment of tumoral diseases and also diseases of the lungs and airways. Methods for preparing quinazoline derivatives are described in WO2003082290 and WO2007068552. WO2009098061 and WO2011015526 disclose methods of preparing the compound (I).The problem of the present invention is to provide an alternative stereoselective synthesis process for preparing the compound of formula (I) or an advantageous method of preparing important intermediates of this synthesis.The present invention solves the problem stated above by means of the method of synthesis described hereinafter.The invention relates to a process for the stereoselective preparation of the compound of formula (5), optionally in the form of the tautomers thereof,In a preferred process the reaction steps (C) and (D) are preceded by further reaction steps (A) and (B),Also preferred is a process for the stereoselective preparation of the compound of formula (5), optionally in the form of the tautomers thereof,The invention further relates to an ...

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22-08-2013 дата публикации

NOVEL COMPOUNDS USEFUL FOR THE TREATMENT OF DEGENERATIVE AND INFLAMMATORY DISEASES

Номер: US20130217664A1
Принадлежит:

Novel imidazolopyridines according to Formula I, able to inhibit JAK are disclosed, these compounds may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons. 2. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris Me or Et.5. A compound or pharmaceutically acceptable salt according to claim 4 , wherein Ris Calkyl.6. A compound or pharmaceutically acceptable salt according to claim 4 ,{'sup': '2', 'sub': '1-4', 'wherein Ris Calkyl.'}7. A compound or pharmaceutically acceptable salt according to claim 4 , wherein the compound is according to Formula VId claim 4 , VIe claim 4 , or VIf claim 4 , and Ris H claim 4 , Me or Et.8. A compound or pharmaceutically acceptable salt according to claim 1 , wherein Ris 4-7 membered heterocycloalkenyl comprising 1 double bond claim 1 , and comprising 1 or 2 heteroatoms independently selected from N claim 1 , O claim 1 , and S claim 1 , substituted with one or more groups independently selected from R.11. A compound or pharmaceutically acceptable salt according to claim 9 , wherein Lis —C(═O)— claim 9 , —C(═O)O— claim 9 , —O— claim 9 , or SO—.12. A compound or pharmaceutically acceptable salt according to claim 9 , wherein Ris Me claim 9 , Et claim 9 , n-Pr claim 9 , i-Pr claim 9 , or t-Bu.13. A compound or pharmaceutically acceptable salt according to claim 9 , wherein Ris —CH—CN claim 9 , —CH—CH—CN claim 9 , —CH—CH—OH—C(OH)H—CH claim 9 , —C(OH)H—CF claim 9 , —CHF claim 9 , —CH—CF claim 9 , —CH—CMe-OH claim 9 , —CMeH—OMe claim 9 , —CH—OH claim 9 , CMe-OH claim 9 , —CH—OMe claim 9 , —CH—C(═O)t-Bu claim 9 , ...

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22-08-2013 дата публикации

NOVEL 3-HYDROXYISOTHIAZOLE 1-OXIDE DERIVATIVES

Номер: US20130217690A1
Автор: Ohkouchi Munetaka
Принадлежит: MOCHIDA PHARMACEUTICAL CO., LTD.

[Object] 3. The compound according to claim 2 , wherein any one of q and s is 1 or more claim 2 ,or a pharmaceutically acceptable salt of the compound, or a pharmaceutically acceptable solvate of the salt or a pharmaceutically acceptable solvate of the compound.4. The compound according to claim 3 , wherein any one of q and s is 1 or more and Ris a group optionally selected from a halogen atom claim 3 , a cyano group claim 3 , a Calkyl group (the Calkyl group is substituted with 1 to 5 halogen atom(s) claim 3 , 1 to 5 —OH claim 3 , or 1 to 5 Calkoxy group(s)) claim 3 , a Calkoxy group (the Calkoxy group is substituted with 1 to 5 halogen atom(s)) claim 3 , a Calkenyl group claim 3 , a Calkanoyl group claim 3 , a —S(O)R(i is an integer of 0 to 2) group claim 3 , a —CONRRgroup claim 3 , and a —NRRgroup claim 3 ,or a pharmaceutically acceptable salt of the compound, or a pharmaceutically acceptable solvate of the salt or a pharmaceutically acceptable solvate of the compound.5. The compound according to claim 4 , wherein any one of q and s is 1 or more;{'sup': 8', 'a, 'sub': 1-6', '1-6', '1-6', 'i, 'Ris a Calkoxy group (the Calkoxy group is substituted with 1 to 5 —OH, 1 to 5 Calkoxy group(s), or 1 to 5 —S(O)R(i is an integer of 0 to 2) group(s)); and'}{'sup': 9', 'a', 'b1', 'c1, 'sub': 1-6', '1-6', '1-6', '1-6', 'i, 'Ris a group optionally selected from a halogen atom, a cyano group, a Calkyl group (the Calkyl group is substituted with 1 to 5 halogen atom(s) or 1 to 5 —OH), a Calkoxy group (the Calkoxy group is substituted with 1 to 5 halogen atom(s)), a —S(O)R(i is an integer of 0 to 2) group, and a —NRRgroup,'}or a pharmaceutically acceptable salt of the compound, or a pharmaceutically acceptable solvate of the salt or a pharmaceutically acceptable solvate of the compound.7. The compound according to claim 6 , wherein any one of q and s is 1 or more claim 6 ,or a pharmaceutically acceptable salt of the compound, or a pharmaceutically acceptable solvate of the salt or ...

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29-08-2013 дата публикации

PYRAZOLOQUINOLINE COMPOUND

Номер: US20130225553A1
Принадлежит: Astellas Pharma Inc.

The present inventors have investigated a compound which has a PDE9-inhibiting action and is useful as an active ingredient for an agent for treating and/or preventing storage dysfunction, voiding dysfunction, bladder/urethral diseases, and the like, and thus, have found that a pyrazoloquinoline compound has a PDE9-inhibiting action, thereby completing the present invention. 3. The compound or a salt thereof as set forth in claim 1 , wherein{'sup': 1', '2, 'one of Rand Ris hydrogen, halogen, halogeno-lower alkyl, lower alkyl, —O-lower alkyl, or lower alkylene-O-lower alkyl,'}and the other is a group of the formula (II),{'sup': '3', 'Ris lower alkylene-(cycloalkyl which may be substituted with halogen or —O-lower alkyl); lower alkylene-oxygen-containing saturated hetero ring; cycloalkyl which may be substituted with halogen or —O-lower alkyl; an oxygen-containing saturated hetero ring; or a monocyclic nitrogen-containing saturated hetero ring which may be substituted with lower alkyl, lower alkylene-aryl, or —CO-lower alkylene-O-lower alkyl,'}{'sup': 4', '5, 'Rand Rare hydrogen,'}{'sup': '6', 'Ris hydrogen or lower alkyl,'}{'sup': a', 'b, 'sub': 2', '1, 'one of Rand Ris hydrogen, and the other is lower alkyl which may be substituted; cycloalkyl which may be substituted with a hetero ring which may be substituted with a group selected from a group G; or a hetero ring which may be substituted with lower alkylene-(aryl which may be substituted with a group selected from a group G), or'}{'sup': a', 'b, 'sub': 2', '1, 'Rand Rare combined with the adjacent nitrogen atom to form a monocyclic nitrogen-containing hetero ring which may be substituted, or a polycyclic nitrogen-containing hetero ring which may be substituted with a group selected from the group consisting of halogen; —O-lower alkyl; a hetero ring which may be substituted with a group selected from a group G; lower alkylene-(aryl which may be substituted with a group selected from a group G; lower alkyl; and ...

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29-08-2013 дата публикации

PYRIDO[3,2-d]PYRIMIDINE PI3K DELTA INHIBITOR COMPOUNDS AND METHODS OF USE

Номер: US20130225557A1
Принадлежит: Genentech, Inc.

Formula I compounds, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological disorders, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 4. The compound of wherein Ris 1H-indazol-4-yl and n is 0.5. The compound of selected from2-(1-((2-(2-methyl-1H-benzo[d]imidazol-1-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol;2-(1-((2-(2-cyclopropyl-1H-benzo[d]imidazol-1-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol;2-(1-((2-(2-methylbenzofuran-3-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol;2-ethyl-1-(6-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-4-morpholinopyrido[3,2-d]pyrimidin-2-yl)-1H-indazol-3(2H)-one;2-(1-((2-(5-fluoro-1H-indol-4-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol;(2-(5-fluoro-1H-indol-4-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methanol;2-(1-((2-(1H-indol-4-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol;2-(1-((2-(1H-indazol-4-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol;4-(2-(5-fluoro-1H-indol-4-yl)-6-(3-(tetrahydro-2H-pyran-4-yl)azetidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-yl)morpholine;2-(1-((2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol;4-(2-(2-isopropyl-1H-benzo[d]imidazol-1-yl)-6-43-(tetrahydro-2H-pyran-4-yl)azetidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-yl)morpholine;(S)-2-(1-((2-(2-(1-methoxyethyl)-1H-benzo[d]imidazol-1-yl)-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-4-yl)propan-2-ol;(R)-2-(1-((2-(2-(1-methoxyethyl)-1H- ...

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29-08-2013 дата публикации

PYRROLOTRIAZINE DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS AND DISEASES ASSOCIATED WITH ANGIOGENESIS

Номер: US20130225809A1
Принадлежит: Bayer HealthCare LLC

This invention relates to pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and the use of those compounds and compositions for the prevention and/or treatment of hyper-proliferative disorders and diseases associated with angiogenesis. 1. A compound of formula (I)wherein{'sup': '1', 'claim-text': [{'sub': 1', '4', '1', '4', '1', '3, 'claim-text': {'sub': 1', '3', '1', '3, '(C-C)alkoxy can be optionally substituted with (C-C)alkylamino,'}, '(C-C)alkyl, wherein (C-C)alkyl can be substituted with 0, 1, 2 or 3 halogen, 0 or 1 heterocyclyl, or 0 or 1 (C-C)alkoxy, wherein'}, {'sub': 1', '3', '1', '3', '1', '3, '(C-C)alkoxy, wherein (C-C)alkoxy can be optionally substituted with (C-C)alkylamino,'}, 'halogen,', 'trifluoromethyl,', 'trifluoromethoxy,', {'sub': 3', '6, '(C-C)cycloalkyl,'}, 'phenyl optionally substituted with 1 or 2 halogen,, 'wherein aryl and heteroaryl can be optionally substituted with 0, 1, 2, 3 or 4 substituents independently selected from the group consisting of'}, 'Ris selected from the group consisting of aryl, benzyl, and heteroaryl,'} [ nitro,', 'cyano,', {'sub': 1', '3, '(C-C)alkylthio,'}, 'trifluoromethylthio,', {'sub': 1', '3, '(C-C)alkylcarbonyl,'}, {'sub': 1', '6, '(C-C)alkoxycarbonyl, and'}, {'sub': 1', '6', '1', '6, 'phenoxy, wherein phenoxy can optionally be substituted with 0, 1 or 2 substituents independently selected from the group consisting of (C-C)alkyl, (C-C)alkoxy, trifluoromethoxy, and halogen,'}]}, 'and', {'sub': 1', '3', '1', '3, 'wherein benzyl can be substituted with 0, 1, 2 or 3 groups selected from halogen, (C-C)alkyl, and (C-C)alkoxy;'}]}{'sup': '2', 'sub': 1', '4', '1', '4, 'Ris selected from the group consisting of hydrogen, halogen, (C-C)alkyl and (C-C)alkoxy;'}{'sup': '3', 'claim-text': carboxyl,', 'formyl,', {'sub': 1', '6', '1', '6, '(C-C)alkylcarbonyl optionally substituted with 0, 1, 2, or 3 groups selected from fluorine, chlorine, hydroxy, (C-C)alkoxy, and heterocycle,'}, {'sub': 3', ' ...

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05-09-2013 дата публикации

2-SUBSTITUTED-ETHYNYLTHIAZOLE DERIVATIVES AND USES OF SAME

Номер: US20130231321A1
Принадлежит: H. Lundbeck A/S

The present invention provides 2-substituted-ethynylthiazole derivatives of formula (I): 2) (canceled)3) (canceled)4) The compound of claim 1 , wherein Ris an alkyl claim 1 , cycloalkyl claim 1 , aryl or heteroaryl.6) The compound of claim 1 , wherein Ris hydrogen or fluorine.9) A pharmaceutical composition comprising at least one compound of and at least one pharmaceutically acceptable carrier or excipient.10) The pharmaceutical composition of claim 9 , wherein the composition improves cognitive functioning in a human.11) The pharmaceutical composition of claim 9 , wherein the composition is for use in a human who has been diagnosed with a cognitive impairment.12) The pharmaceutical composition of claim 9 , wherein the composition is for use in a human who has first-episode schizophrenia13) A method of improving cognitive functioning claim 1 , comprising administering an effective amount of a compound of to a human in need thereof.14) The method according to claim 13 , wherein the human suffers from cognitive dysfunction.15) The method of claim 14 , wherein the cognitive dysfunction presents in connection with a disease or disorder selected from the group consisting of psychosis claim 14 , schizophrenia claim 14 , a disease involving a psychotic symptom claim 14 , schizophreniform disorder claim 14 , schizoaffective disorder claim 14 , delusional disorder claim 14 , brief psychotic disorder claim 14 , shared psychotic disorder claim 14 , substance-induced psychotic disorder claim 14 , an affective disorder claim 14 , ADHD claim 14 , or a combination thereof.16) The method according to claim 15 , wherein the affective disorder is depression claim 15 , mania claim 15 , or bipolar disorder.17) The method according to claim 15 , wherein the disease or disorder is schizophrenia.18) The method according to claim 15 , wherein the disease or disorder is ADHD.19) The method according to claim 15 , wherein the method further comprises reducing a cognitive symptom in a ...

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12-09-2013 дата публикации

IMIDAZOPYRIZINE SYK INHIBITORS

Номер: US20130237521A1
Принадлежит: Gilead Connecticut, Inc.

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample. 132-. (canceled)34. The method according to claim 33 , wherein the patient is a human.35. The method according to claim 33 , wherein the effective amount of said at least one chemical entity is administered to the patient intravenously claim 33 , intramuscularly claim 33 , parenterally claim 33 , or orally.36. (canceled)37. The method according to claim 33 , wherein the disease responsive to inhibition of Syk activity is cancer.38. The method according to claim 37 , wherein the disease responsive to inhibition of Syk activity is B-cell lymphoma or leukemia.39. The method according to claim 33 , wherein the disease responsive to inhibition of Syk activity is rheumatoid arthritis claim 33 , allergic rhinitis claim 33 , chronic obstructive pulmonary disease (COPD) claim 33 , adult respiratory distress syndrome (ARDs) claim 33 , an allergy-induced inflammatory disease claim 33 , multiple sclerosis claim 33 , autoimmune disease claim 33 , inflammatory disease claim 33 , acute inflammatory reaction claim 33 , allergic disorder claim 33 , or polycystic kidney disease.4052-. (canceled)53. The method according to claim 33 , wherein the disease responsive to inhibition of Syk activity is B-cell lymphoma claim 33 , Hodgkin's lymphoma claim 33 , non-Hodgkin's lymphoma claim 33 , hairy cell leukemia claim 33 , multiple myeloma claim 33 , chronic myelogenous leukemia claim 33 , acute myelogenous leukemia claim 33 , chronic lymphocytic leukemia claim 33 , or acute lymphocytic leukemia.54. The method according to claim 33 ...

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12-09-2013 дата публикации

Synthesis of polycyclic alkaloids

Номер: US20130237524A1
Принадлежит: Rigel Pharmaceuticals Inc

Disclosed embodiments concern polycyclic alkaloid compounds and methods for their use and synthesis. Particular embodiments concern polycyclic alkaloids having a fused, six-membered ring, while other embodiments concern polycyclic alkaloids having a fused, five-membered ring. Methods for making the polycyclic alkaloids are disclosed, as well as methods for their use as prophylactics or treatments for certain diseases. Also disclosed are pharmaceutical compositions comprising the polycyclic alkaloids and their use.

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19-09-2013 дата публикации

Triazolopyridine Compounds

Номер: US20130245002A1
Принадлежит: NOVARTIS AG

The invention relates to compounds of formula (I) and salts thereof: 2. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris selected from{'sub': 1', '2, 'sup': 1', '1, '(i) optionally substituted —(C-C)alkyl-heterocyclyl, under the proviso that Ris optionally substituted pyrazole, and'}{'sup': '1', '(ii) optionally substituted heterocyclyl.'}3. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris pyrazolyl claim 1 , optionally substituted by (C-C)alkyl claim 1 , said (C-C)alkyl being optionally substituted by one OH group.4. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein{'sup': 1', '9', '10, 'claim-text': [{'sup': '9', 'sub': 1', '4, 'Ris hydrogen or (C-C)alkyl; and,'}, {'sup': '10', 'sub': 1', '4', '1', '4, 'Ris hydrogen or (C-C)alkyl, said (C-C)alkyl being optionally substituted by one OH group; and'}], 'Ris —CR═N—O—R, wherein'}{'sup': 3', '1, 'Ris optionally substituted heterocyclyl.'}5. A compound or pharmaceutically acceptable salt thereof according to claim 4 , wherein{'sup': 1', '9', '10, 'claim-text': [{'sup': '9', 'sub': 1', '2, 'Ris (C-C)alkyl; and,'}, {'sup': '10', 'sub': 1', '2', '1', '2, 'Ris hydrogen or (C-C)alkyl, said (C-C)alkyl being optionally substituted by one OH group.'}], 'Ris —CR═N—O—R, wherein'}6. A compound or pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris -methyl-heterocyclyl claim 2 , wherein heterocyclylis a 5 or 6 membered saturated N-heterocyclic ring which is attached via the N-atom and optionally comprises one additional ring heteroatom selected from N and O in a position other than adjacent to the linking N atom claim 2 , wherein any additional ring N-atom is substituted with an (C-C)alkyl group.7. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris heterocyclyl claim 1 , wherein heterocyclylis a 4 claim 1 , 5 claim 1 , 6 claim 1 , or 7 membered saturated ...

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19-09-2013 дата публикации

4-AZA-2, 3-DIDEHYDROPODOPHYLLOTOXIN COMPOUNDS AND PROCESS FOR THE PREPARATION THEREOF

Номер: US20130245048A1

The present invention provides 4-Aza-2,3-didehydropodophyllotoxin compound of general formula A (4a-4z and 4aa-4ae) as useful potential antitumour agents against human cancer cell lines. The present invention further provides a process for the synthesis of 4-Aza-2,3-didehydropodophyllotoxin compounds (4a-4z and 4aa-4ae). 2. The compound as claimed in claim 1 , are selected from;2,4-dimethoxy-5-(3,4,5-trimethoxyphenyl)-5,6,8,9-tetrahydrofuro[3′,4′:5,6]pyrido[2,3-d]pyrimidin-6-one (4a);5-(4-hydroxy-3-methoxyphenyl)-2,4-dimethoxy-5,6,8,9-tetrahydrofuro[3′,4′:5,6]pyrido[2,3-d]pyrimidin-6-one (4b);5-(3-hydroxy-4-methoxyphenyl)-2,4-dimethoxy-5,6,8,9-tetrahydrofuro[3′,4′:5,6]pyrido[2,3-d]pyrimidin-6-one (4e);5-(4-fluoro-3-methoxyphenyl)-2,4-dimethoxy-5,6,8,9-tetrahydrofuro[3′,4′:5,6]pyrido[2,3-d]pyrimidin-6-one (4d);3-(4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-4,5,7,8 tetrahydrofuro[3′,4′:5,6]pyrido[3,2-d]isoxazol-5-one (4aa);4-(3-hydroxy-4-methoxyphenyl)-3-(4-methoxyphenyl)-4,5,7,8-tetrahydrofuro[3′,4′:5,6]pyrido[3,2-d]isoxazol-5-one (4ab);3-(4-chlorophenyl)-4-(3,4,5-trimethoxyphenyl)-4,5,7,8-tetrahydrofuro[3′,4′:5,6]pyrido[3,2-d]isoxazol-5-one (4ae);3-(4-chlorophenyl)-4-(3-hydroxy-4-methoxyphenyl)-4,5,7,8-tetrahydrofuro[3′,4′:5,6]pyrido[3,2-d]isoxazol-5-one (4ad),4. The compound as claimed in claim 1 , wherein said compounds exhibit in vitro anticancer activity against human cancer cell lines selected from the group consisting of colon (Colo205) claim 1 , lung (Hop-62 claim 1 , A549) claim 1 , cervix (SiHa) claim 1 , prostate (PC3) claim 1 , oral (KB claim 1 , DWD claim 1 , Gurav) claim 1 , Ovarian (A-2780) and breast (MCF7 claim 1 , Zr-75-1).5. The compounds as claimed in claim 2 , wherein the concentration of the compound used for in vitro activity against breast cancer cell lines for GIis in the range of 0.1 to 2.9 μm at an exposure period of at least 48 hrs.6. The compounds as claimed in claim 2 , wherein the concentration of the compound used for in vitro activity ...

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26-09-2013 дата публикации

MACROCYCLIC DERIVATIVES FOR THE TREATMENT OF DISEASES

Номер: US20130252961A1
Принадлежит: PFIZER INC.

The invention relates to compounds of formula (Φ) 2. The compound of claim 1 , wherein X is —(CRR)C(O)N(R)(CRR)— claim 1 , or a pharmaceutically acceptable salt thereof.3. The compound of claim 2 , wherein m is 0 claim 2 , n is 1 claim 2 , q is 0 claim 2 , and r is 0 claim 2 , or a pharmaceutically acceptable salt thereof.4. The compound of claim 1 , wherein Z is CH claim 1 , or a pharmaceutically acceptable salt thereof.5. The compound of claim 4 , wherein Y is CH claim 4 , or a pharmaceutically acceptable salt thereof.6. The compound of claim 4 , wherein Y is N claim 4 , or a pharmaceutically acceptable salt thereof.7. The compound of claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , C-Calkyl claim 1 , and C-Ccycloalkyl claim 1 , or a pharmaceutically acceptable salt thereof.8. The compound of claim 1 , wherein each Ris independently selected from the group consisting of C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , —S(O)R claim 1 , —S(O)NRR claim 1 , —OR claim 1 , —O(CRR)(CRR)OR claim 1 , —O(CRR)(CRR)Rand —CN; wherein each hydrogen on said C-Calkyl and C-Ccycloalkyl may be independently optionally substituted by halogen claim 1 , —OH claim 1 , —NH claim 1 , —S(O)R claim 1 , —S(O)NRR claim 1 , —S(O)OR claim 1 , —NO claim 1 , —OR claim 1 , —CN claim 1 , —C(O)R claim 1 , —OC(O)R claim 1 , —NRC(O)R claim 1 , —C(O)OR claim 1 , —C(═NR)NRR claim 1 , —NRC(O)NRR claim 1 , —NRS(O)Ror —C(O)NRR claim 1 , or a pharmaceutically acceptable salt thereof.9. The compound of claim 1 , wherein A is a ring selected from the group consisting of phenyl claim 1 , pyridine claim 1 , pyrimidine claim 1 , pyridazine claim 1 , pyrazine claim 1 , triazine claim 1 , pyrazole claim 1 , imidazole claim 1 , triazole claim 1 , tetrazole claim 1 , thiazole claim 1 , isothiazole claim 1 , oxazole and isoxazole claim 1 , or a pharmaceutically acceptable salt thereof.10. The compound of claim 1 , wherein Rand Rare each independently selected from the group consisting of ...

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26-09-2013 дата публикации

SPIRO-OXINDOLE COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS

Номер: US20130252962A1
Принадлежит:

This invention is directed to spiro-oxindole compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain. 13.-. (canceled)5. The compound of selected from:1′-(pyridin-2-ylmethyl)spiro[furo[2,3-g]quinoxaline-8,3′-indol]-2′(1′H)-one;1-(diphenylmethyl)spiro[indole-3,3′-thieno[2,3-f][1]benzofuran]-2(1′H)-one;1-(diphenylmethyl)spiro[indole-3,3′-thieno[2,3-f][1]benzofuran]-2(1′H)-one 5,5′-dioxide;spiro[indole-3,3′-thieno[2,3-f][1]benzofuran]-2(1′H)-one 5,5′-dioxide; or1-(pyridin-2-ylmethyl)spiro[indole-3,3′-thieno[2,3-f][1]benzofuran]-2(1′H)-one 5,5′-dioxide.1′-(4-methoxybenzyl)-3-methylspiro[furo[2,3-f][1,2]benzisoxazole-7,3′-indol]-2′(1′H)-one;5-(benzyloxy)-1′-[(5-chloro-2-thienyl)methyl]spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;1′-(diphenylmethyl)-6-methoxy-5-methylspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-bromo-1′-(diphenylmethyl)spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;1′-(diphenylmethyl)-5,6-dimethylspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-(benzyloxy)-1′-(diphenylmethyl)spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;1′-(diphenylmethyl)-5-fluoro-6-methoxyspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;1′-(diphenylmethyl)-5-fluorospiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;1′-(diphenylmethyl)-6-methoxyspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-(benzyloxy)-1′-(3-methylbutyl)spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-bromo-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[1-benzofuran-3,3′-indol]-2′(1H)-one;5-bromo-1-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-methoxy-5-methylspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6-bromospiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;5,6-dimethylspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;5-fluoro-6-methoxyspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;5-fluoro-spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one;6- ...

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26-09-2013 дата публикации

CYCLIC N,N'-DIARYLTHIOUREA - ANDROGEN RECEPTOR ANTAGONIST, ANTI BREAST CANCER COMPOSITION AND USE THEREOF

Номер: US20130252992A1
Принадлежит:

The present invention relates to novel cyclic N,N′-diarylurea-androgen receptor antagonist, anti-cancer agent, pharmaceutical composition, medicament, and method for treatment of breast cancer disease. 4. The composition of in the form of a tablet claim 1 , a capsule claim 1 , or an injection placed in a pharmaceutically acceptable package.5. A method for treating a breast cancer in a subject comprising administering an effective dose of a pharmaceutical composition according to to a subject in need thereof. This application is a continuation-in-part of U.S. application Ser. No. 13/811,282 filed Jan. 21, 2013, which claims benefit of priority to the International application PCT/RU2011/000476 filed Jul. 1, 2011, which claims benefit of foreign priority to the Russian Federation application RU 2010130618 of Jul. 22, 2010. The priority applications are hereby incorporated by reference in their entirety.The invention relates to novel cyclic N,N′-diarylthioureas and N,N′-diarylureas-androgen receptor antagonists, anticancer agent, pharmaceutical composition, medicament and method for treatment of cancer including prostate cancer.There are known androgen receptor antagonists which are—1,3-diaryl-5,5-dimethyl-2-thioxoimidazolidin-4-ones I, 5,7-diaryl-6-thioxo-5,7-diazaspiro[3,4]octan-8-ones II and 1,3-diaryl-2-thioxo-1,3-diazaspiro[4,4]nonan-4-ones III exhibiting anticancer activity [WO2006124118, WO2007127010]. Amongst these compounds the most promoted is 4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl]-2-fluoro-N-methylbenzamide MDV3100 (androgen receptor antagonist with IC=36 nM), which is now in the III phase of clinical trials as medicament for prostate cancer treatment [2009, 31(6), 609].Searching for highly effective anticancer medicaments exhibiting enhanced activity and reduced toxicity, is still one of the main directions in the development of novel pharmacological remedies for cancer treatment, including prostate cancer. In ...

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26-09-2013 дата публикации

HETEROARYLOXYHETEROCYCLYL COMPOUNDS AS PDE10 INHIBITORS

Номер: US20130253186A1
Принадлежит: Amgen Inc.

Heteroaryloxyheterocyclyl compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, Huntington's Disease, bipolar disorder, obsessive-compulsive disorder, and the like. 11H-Benzo[d]imidazol-2-yl)(4-(3-(pyridine-4-yl)pyrazin-2-yloxy)piperidin-1-yl)methanone;1-(4-(3-(1-(1H-Benzo[d]imidazol-2-carbonyl)piperidin-4-yloxy)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone;1-(4-(3-(1-(1H-benzo[d]imidazole-2-carbonyl)piperidin-4-yloxy)pyrazin-2-yl)piperidin-1-yl)ethanone;1-(4-(3-(1-(1H-benzo[d]imidazole-2-carbonyl)azetidin-3-yloxy)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone;1-(4-(3-(1-(1H-benzo[d]imidazole-2-carbonyl)azetidin-3-yloxy)pyrazin-2-yl)piperidin-1-yl)ethanone;1-(4-(3-(1-(1H-pyrrole-2-carbonyl)azetidin-3-yloxy)pyrazin-2-yl)piperidin-1-yl)ethanone;1-(3-(2-(1-picolinoylazetidin-3-yloxy)pyridin-3-yl)piperidin-1-yl)ethanone;(R) and (S)-1-(3-(2-(1-(1H-benzo[d]imidazole-2-carbonyl)azetidin-3-yloxy)pyridin-3-yl)piperidin-1-yl)ethanone;(1H-benzo[d]imidazol-2-yl)(3-(pyrazin-2-yloxy)azetidin-1-yl)methanone;(1H-benzo[d]imidazol-2-yl)(3-((3-chloropyrazin-2-yl)oxy)azetidin-1-yl)methanone;(R) and (S)-1-(3-(2-(1-(1H-benzo[d]imidazole-2-carbonyl)azetidin-3-yloxy)pyridin-3-yl)piperidin-1-yl)-2-methylpropan-1-one;(1H-benzo[d]imidazol-2-yl)(3-((3-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-yl)oxy)azetidin-1-yl)methanone;benzyl 3-((3-chloropyrazin-2-yl)oxy)azetidine-1-carboxylate;tert-butyl 3-((3-((1r,4r)-4-hydroxycyclohexyl)pyridin-2-yl)oxy)azetidine-1-carboxylate;(1H-benzo[d]imidazol-2-yl)(3-(3-(tetrahydro-2H-pyran-4-yl)pyridin-2-yloxy)azetidin-1-yl)methanone;(1H-benzo[d]imidazol-2-yl)(3-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)azetidin-1-yl)methanone;benzyl 3-((3-(1-acetyl-4-hydroxypiperidin-4-yl)pyrazin-2-yl)oxy)azetidine-1-carboxylate;(1H-benzo[d]imidazol-2-yl)(3-((3- ...

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03-10-2013 дата публикации

METHODS OF USE OF DIAZACARBAZOLES FOR TREATING CANCER

Номер: US20130261104A1
Принадлежит: Genentech, Inc.

Methods of use of compounds of formula (I) for treating cancer: 2. The method of claim 1 , wherein the compounds of formula (I) are those wherein X is CR.3. The method of claim 1 , wherein the compounds of formula (I) are those wherein Ris H.4. The method of claim 1 , wherein the compounds of formula (I) are those wherein Y is CR.5. The method of claim 1 , wherein the compounds of formula (I) are those wherein Ris H.6. The method of claim 1 , wherein the compounds of formula (I) are those wherein Z is CR.7. The method of claim 1 , wherein the compounds of formula (I) are those wherein Ris H.8. The method of claim 1 , wherein the compounds of formula (I) are those wherein Ris Br.9. The method of claim 1 , wherein the compounds of formula (I) are those wherein Ris H.10. The method of claim 1 , wherein the compounds of formula (I) are those wherein Ris R.11. The method of claim 1 , wherein the compounds of formula (I) are those wherein Ris C-Calkyl claim 1 , C-Calkynyl claim 1 , Caryl claim 1 , or 5-6 membered monocyclic or 8-10-membered bicyclic heteroaryl having 1 to 2 ring atoms selected from N claim 1 , O and S; and wherein each member of Ris independently substituted with one to two Rgroups.12. The method of claim 1 , wherein the compounds of formula (I) are those wherein Ris isopropyl claim 1 , propynyl claim 1 , phenyl claim 1 , pyrazolyl claim 1 , furanyl claim 1 , thienyl claim 1 , pyridyl claim 1 , imidazolyl claim 1 , pyrimidinyl claim 1 , benzothienyl claim 1 , thiazolyl claim 1 , tetrahydrothienopyridinyl claim 1 , tetrahydrothiazolopyridinyl claim 1 , isothiazolyl claim 1 , tetrahydropyridinyl claim 1 , tetrahydroisoquinolinyl claim 1 , triazolyl claim 1 , dihydrobenzodioxinyl claim 1 , dihydroindolyl claim 1 , oxazolyl claim 1 , or tetrahydrobenzothienyl claim 1 , wherein each member of Ris independently substituted with one to two Rgroups.13. The method of claim 1 , wherein the compounds of formula (I) are those wherein Ris halo claim 1 , R claim 1 , — ...

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10-10-2013 дата публикации

IMIDAZOPYRAZINE SYK INHIBITORS

Номер: US20130267496A1
Принадлежит: Gilead Connecticut, Inc.

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample. 110-. (canceled)121: A pharmaceutical composition comprising at least one chemical entity of claim , together with at least one pharmaceutically acceptable vehicle chosen from carriers , adjuvants , and excipients.131: A method for treating a patient having a disease responsive to the inhibition of Syk activity , comprising administering to the patient an effective amount of at least one chemical entity according to claim . This application is a Continuation-in-Part of U.S. patent application Ser. No. 12/632,140, filed Dec. 7, 2009, which claims the benefit of provisional U.S. Patent Application 61/120,587, filed Dec. 8, 2008, provisional U.S. Patent Application No. 61/140,514, filed Dec. 23, 2008, and provisional U.S. Patent Application No. 61/240,979, filed Sep. 9, 2009. The contents of the above patent applications are incorporated by reference herein in their entirety.Provided herein are certain imidazopyrazines, compositions, and methods of their manufacture and use.Protein kinases, the largest family of human enzymes, encompass well over 500 proteins. Spleen Tyrosine Kinase (Syk) is a member of the Syk family of tyrosine kinases, and is a regulator of early B-cell development as well as mature B-cell activation, signaling, and survival.Syk is a non-receptor tyrosine kinase that plays critical roles in immunoreceptor- and integrin-mediated signaling in a variety of cell types, including B cells, macrophages, monocytes, mast cells, eosinophils, basophils, neutrophils, dendritic cells, T cells, natural ...

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17-10-2013 дата публикации

Compound for organic light-emitting diode and organic light-emitting diode including the same

Номер: US20130270524A1
Принадлежит: Samsung Display Co Ltd

A compound represented by Formula 1 below may be used in an organic light emitting diode.

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17-10-2013 дата публикации

Chemical Compounds

Номер: US20130274304A1
Принадлежит:

Disclosed are compounds of Formula III. Also disclosed are salts of the compounds, pharmaceutical composition comprising the compounds or salts, and methods for treating HCV infection by administration of the compounds or salts. 3. The method of wherein said salt is either a di-HCl salt or a sulfate salt.4. The method of wherein said salt is a sulfate salt.5. The method of wherein said salt is either a di-HCl salt or a sulfate salt.6. The method of wherein said salt is a sulfate salt. This application is filed as a continuation application of U.S. Ser. No. 13/677,358, filed on Nov. 15, 2012, which is a continuation application of U.S. Ser. No. 12/936,545, filed Oct. 6, 2010 (now U.S. Pat. No. 8,344,155), which is a National Phase Application of International Application No. PCT/US2010/046782 filed on Aug. 26, 2010, which claims priority from 61/239,855 filed on Sep. 4, 2009, 61/297,324 filed on Jan. 22, 2010 and 61/348,767 filed on May 27, 2010 in the United States, all of which are incorporated by reference herein in their entireties.The present disclosure relates to antiviral compounds. In particular, the present disclosure relates to compounds useful for the treatment of hepatitis C virus (HCV) infection, crystalline salts of the compounds, pharmaceutical compositions comprising the compounds, and methods for treating HCV infection.Chronic infection with HCV is a major health problem associated with liver cirrhosis, hepatocellular carcinoma and liver failure. An estimated 170 million chronic carriers worldwide are at risk of developing liver disease. See, for example, Szabo, et al., 2003, 9:215-221, and Hoofnagle J H, 1997, 26:15S-20S. In the United States alone 2.7 million are chronically infected with HCV, and the number of HCV-related deaths in 2000 was estimated between 8,000 and 10,000, a number that is expected to increase significantly over the next years. Infection by HCV is insidious in a high proportion of chronically infected (and infectious) carriers ...

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17-10-2013 дата публикации

Arylethynyl Derivatives

Номер: US20130274464A1
Принадлежит:

The present invention relates to ethynyl compounds of formula I

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17-10-2013 дата публикации

ASYMMETRIC SYNTHESES FOR SPIRO-OXINDOLE COMPOUNDS USEFUL AS THERAPEUTIC AGENTS

Номер: US20130274483A1
Принадлежит:

This invention is directed to asymmetric syntheses of certain spiro-oxindole derivatives, which are useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain. 15. The method of wherein the phase transfer catalyst is a quaternary ammonium salt of quinidine or a quaternary ammonium salt of cinchonine.64. The method of wherein the phase transfer catalyst is a quaternary ammonium salt of quinidine or a quaternary ammonium salt of cinchonine. This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 61/623,336, filed Apr. 12, 2012. This application is incorporated herein by reference in its entirety.The present invention is directed to improved methods of preparing certain spiro-oxindole compounds as well as various intermediates involved therein. In particular, this invention is directed to asymmetric syntheses of certain spiro-oxindole compounds, and their pharmaceutically acceptable salts, which are useful in treating sodium channel-mediated diseases or conditions, such as pain, as well as other diseases and conditions associated with the mediation of sodium channels.Sodium channels play a diverse set of roles in maintaining normal and pathological states, including the long recognized role that voltage gated sodium channels play in the generation of abnormal neuronal activity and neuropathic or pathological pain. Damage to peripheral nerves following trauma or disease can result in changes to sodium channel activity and the development of abnormal afferent activity including ectopic discharges from axotomised afferents and spontaneous activity of sensitized intact nociceptors. These changes can produce long-lasting abnormal hypersensitivity to normally innocuous stimuli, or allodynia. Examples of neuropathic pain include, but are not limited to, post-herpetic neuralgia, trigeminal neuralgia, diabetic neuropathy, chronic lower back pain, phantom limb pain, and pain resulting ...

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24-10-2013 дата публикации

INHIBITORS OF FOCAL ADHESION KINASE

Номер: US20130281443A1
Принадлежит: The Scripps Research Institute

The invention provides inhibitors of focal adhesion kinase, an enzyme involved in the attachment of the cytoskeleton of a cell to an extracellular matrix, which has been implicated in processes such as cell migration, cell proliferation, and cell survival. The inhibitors are derivatives of a 5-substituted 2,4-diaminopyridine wherein the substituents are as defined herein. The invention also provides a method of using the inhibitors in treatment of cancer, and methods of preparation of the inhibitors by use of coupling reactions. 140.-. (canceled)42. The compound of wherein X is a bond.43. The compound of wherein Y comprises in at least one occurrence a 5 or 6-membered heterocyclyl or heteroaryl which is substituted with 0-3 Y substituents.44. The compound of wherein Ror Ror both comprises a phenyl group substituted with 0-3 Y groups.45. The compound of wherein Rcomprises a morpholino-substituted phenyl group substituted with 0-2 additional Y groups.46. The compound of wherein Ris trifluoromethyl.47. The compound of wherein Ris nitro.48. The compound of wherein Ris fluoro.49. The compound of wherein Ris chloro.50. The compound of wherein Ris cyano.52. A method of inhibiting focal adhesion kinase claim 41 , in vitro or in vivo claim 41 , comprising contacting a compound selected from or at an effective concentration with the focal adhesion kinase.53. A method of treating cancer in a mammal that is mediated by abnormal focal adhesion kinase activities claim 41 , comprising administration of the compound of or in a dosage claim 41 , at a frequency claim 41 , and for a duration to produce a beneficial effect on the mammal.54. A pharmaceutical composition comprising a compound of or and a suitable excipient.56. The method of wherein the zero-valent transition metal complex is a zero-valent palladium complex claim 55 , wherein Z is halo claim 55 , or both.57. The method of wherein the zero-valent palladium complex comprises Pd(dba).58. The method of further comprising the ...

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24-10-2013 дата публикации

NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS

Номер: US20130281482A1

The invention provides novel nicotinic acetylcholine receptor agonists, for example, phantasmidine and derivatives thereof, for example a compound of formula (I). Also disclosed are methods of treating disorders responsive to nicotinic acetylcholine receptor agonists such as Alzheimer's disease, schizophrenia, Myasthenia Gravis, Tourette's syndrome, Parkinson's disease, epilepsy, pain, and cognitive dysfunction by treatment with the nicotinic acetylcholine for agonists. 1. Phantasmidine , or phantasmidine in isolated or purified form , an enantiomer thereof , stereoisomer thereof , racemic mixtures thereof , or a pharmaceutically acceptable salt thereof.3. The compound claim 2 , enantiomer thereof claim 2 , stereoisomer thereof claim 2 , racemic mixtures thereof claim 2 , or salt of claim 2 , wherein the compound has Formula I.4. The compound claim 3 , enantiomer thereof claim 3 , stereoisomer thereof claim 3 , racemic mixtures thereof claim 3 , or salt of claim 3 , wherein m is 1 claim 3 , n is 0 claim 3 , p is 2 claim 3 , W is a bond claim 3 , and Z is 0.5. The compound claim 4 , enantiomer thereof claim 4 , stereoisomer thereof claim 4 , racemic mixtures thereof claim 4 , or salt of claim 4 , wherein Ris selected from the group consisting of hydrogen claim 4 , C-Calkyl claim 4 , C-Calkenyl claim 4 , C-Calkynyl claim 4 , C-Ccycloalkyl claim 4 , C-Ccycloalkenyl claim 4 , C-Carylalkyl claim 4 , C-Caryl claim 4 , heterocyclyl claim 4 , heteroaryl claim 4 , and RCO.6. The compound claim 4 , enantiomer thereof claim 4 , stereoisomer thereof claim 4 , racemic mixtures thereof claim 4 , or salt of claim 4 , wherein Ris selected from the group consisting of hydrogen claim 4 , C-Calkyl claim 4 , C-Calkenyl claim 4 , C-Calkynyl claim 4 , and RCO.7. The compound claim 6 , enantiomer thereof claim 6 , stereoisomer thereof claim 6 , racemic mixtures thereof claim 6 , or salt of claim 6 , wherein Ris hydrogen or C-Calkyl.8. The compound claim 7 , enantiomer thereof claim 7 , ...

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24-10-2013 дата публикации

Isoxazolo-pyridine derivatives

Номер: US20130281690A1
Принадлежит: Hoffmann La Roche Inc, Roche Palo Alto LLC

The present invention is concerned with isoxazole-pyridine derivatives of formula I wherein X, R 1 to R 6 are as described herein. The compounds are active on the GABA A α5 receptor binding site and useful for the treatment of cognitive disorders, such as Alzheimer's disease.

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31-10-2013 дата публикации

NOVEL PHENAZINE DERIVATIVES AND THEIR USES

Номер: US20130289030A1
Принадлежит:

The present invention is directed to novel compounds of formula I 2. The compound according to and pharmaceutically acceptable salts and solvates thereof claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , and Rare each H.11. A pharmaceutical composition comprising a compound according to or a pharmaceutically acceptable salt or solvate thereof and at least one pharmaceutically acceptable carrier claim 1 , diluent claim 1 , excipient and/or adjuvant.12. Medicament comprising a compound according to or a pharmaceutically acceptable salt or solvate thereof.1316-. (canceled)17. A method of treating cancer comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof.18. A method of treating an angiogenic disorder comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof.19. A method of treating an inflammatory claim 1 , immune or infectious disease comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof.20. A method for birth control claim 1 , comprising administering to a patient in need thereof a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof. The present invention relates to novel phenazine derivatives including their pharmaceutically acceptable salts and solvates, which are useful as anti-angiogenic and/or anti-tumor agents, in particular under hypoxic conditions.Angiogenesis is a highly regulated process, whereby new blood vessels form from preexisting ones (Folkman J. Nat. Rev. Drug Discov. 2007; 6: 273-86). In adult mammals, physiologic angiogenesis is largely limited to the ovaries, uterus, and placenta, with the turnover rate of vascular endothelial ...

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31-10-2013 дата публикации

IAP BINDING COMPOUNDS

Номер: US20130289075A1
Принадлежит:

IAP binding molecules and compositions including these are disclosed. The IAP binding molecules interact with IAPB (inhibitor of apoptosis proteins) in cells and may be used to modify apoptosis in cells treated with such molecules. Embodiments of these compounds have a Kof less than 0.1 micromolar. Methods of using these IAP binding molecules for therapeutic, diagnostic, and assay purposed are also disclosed. 5. The compound of or a pharmaceutically acceptable salt thereof where Ais H claim 1 , methyl claim 1 , or ethyl and where Ris H; Ris methyl or ethyl.6. The compound of or a pharmaceutically acceptable salt thereof where Y is an alkyl group of 1 to 10 carbon atoms claim 1 , a branched alkyl group of 1 to 10 carbon atoms claim 1 , an alkynyl group claim 1 , a cycloalkyl group of 3 to 7 carbon atoms claim 1 , or optionally substituted versions of these groups.7. The compound of or a pharmaceutically acceptable salt thereof where Zand Zare independently an H claim 1 , hydroxy claim 1 , amino claim 1 , alkylamino claim 1 , dialkylamino claim 1 , alkoxy claim 1 , aryloxy claim 1 , or heteroaryloxy.8. The compound of or a pharmaceutically acceptable salt thereof where M is an alkyl or an alkylene of 1 to 5 carbon atoms.13. A method of treating cancerous cells comprising administering to the cells an IAP binding compound of .14. A method of treating cells comprising:{'claim-ref': {'@idref': 'CLM-00011', 'claim 11'}, 'administering to cells that have a proliferation disorder, wherein the disorder is selected from the group consisting of a cancer or an autoimmune disorder, an amount of the IAP binding compound of or a pharmaceutically acceptable salt thereof that reduces the cellular proliferation disorder in the sample of cells.'}15. A method of treating cells comprising:{'claim-ref': {'@idref': 'CLM-00012', 'claim 12'}, 'administering to cells that have a proliferation disorder, wherein the disorder is selected from the group consisting of a cancer or an autoimmune ...

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07-11-2013 дата публикации

QUINOLINES AND AZA-QUINOLINES AS CRTH2 RECEPTOR MODULATORS

Номер: US20130296300A1
Принадлежит:

The invention provides certain quinolines and aza-quinolines of the Formula (I), and their pharmaceutically acceptable salts, wherein E, J, J, J, R, R, R, R, R, R, R, X, Y, b, n, and q are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions associated with uncontrolled or inappropriate stimulation of CRTHfunction. 3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein E is —N(R)(R).4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein{'sup': '6a', 'claim-text': {'sup': 6b', 'AH', 'HC, 'Ris -Q-Ror -Q-R; or'}, '(i) Ris H and'}{'sup': 6a', '6b', '6H, '(ii) Rand Rtogether with the N atom to which they are attached form R.'}5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein{'sup': '6a', 'Ris H and'}{'sup': 6b', 'AH', 'HC, 'Ris -Q-Ror -Q-R.'}7. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein Rand Rtogether with the N atom to which they are attached form R.13. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein the compound is selected from the group consisting of:(1) 2-phenyl-6-[[[[4-(trifluoromethoxy)phenyl]methyl]amino]carbonyl]-3-quinolinepentanoic acid;(1D 6-[[[(3-chlorophenyl)methyl]amino]carbonyl]-2-phenyl-3-quinolinepentanoic acid;(1E) 6-[[[(4-methylphenyl)methyl]amino]carbonyl]-2-phenyl-3-quinolinepentanoic acid;(1L) 2-phenyl-6-[(3(R)-phenyl-1-piperidinyl)carbonyl]-3-quinolinepentanoic acid;(1T) 2-phenyl-6-[[(1(S)-phenylethyl)amino]carbonyl]-3-quinolinepentanoic acid;(1AD) 6-[[[1(R)-(4-chlorophenyl)ethyl]amino]carbonyl]-2-phenyl-3-quinolinepentanoic acid;(1AE) 6-[[[1(S)-(4-chlorophenyl)ethyl]amino]carbonyl]-2-phenyl-3-quinolinepentanoic acid;(1AF) 6-[[[1(R)-(4-chlorophenyl)-2,2,2-trifluoroethyl]amino]carbonyl]-2-phenyl-3-quinolinepentanoic acid;(1AG) 6-[[[1(S ...

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14-11-2013 дата публикации

Inhibitors of Hepatitis C Virus

Номер: US20130302282A1
Автор: Li Leping, Zhong Min
Принадлежит: PRESIDIO PHARMACEUTICALS, INC.

A class of compounds that inhibit Hepatitis C Virus (HCV) is disclosed, along with compositions containing the compound, and methods of using the composition for treating individuals infected with HCV. 2. The compound of claim 1 , having an inhibitory activity with respect to HCV claim 1 , as measured by the concentration of the compound effective to produce a half-maximal inhibition of HCV1b replication (EC) in a 1b_Huh-Luc/Neo-ET cell line in culture claim 1 , of 1 mM or less.7. The compound of claim 6 , selected from the group consisting of compounds identified by ID NOS: B89 claim 6 , B96 claim 6 , B97 claim 6 , B125 claim 6 , B126 claim 6 , and B129.9. The compound of claim 5 , wherein Ris phenyl substituted with one or more Rsubstituents.10. The compound of claim 5 , where Ris 4-phenoxyphenyl and the phenoxy group is substituted with one or more Rsubstituents.15. The compound of claim 14 , having an inhibitory activity with respect to HCV claim 14 , as measured by the concentration of the compound effective to produce a half-maximal inhibition of HCV1b replication (EC) in a 1b_Huh-Luc/Neo-ET cell line in culture claim 14 , of 100 nM or less.17. The compound of claim 16 , selected from the group consisting of compounds identified by ID NOS: B5 claim 16 , B15 claim 16 , B20 claim 16 , B33 claim 16 , B35 claim 16 , B45 claim 16 , B67 claim 16 , B85 claim 16 , B92 claim 16 , B94 claim 16 , B107 claim 16 , B118 claim 16 , B120 claim 16 , B121 claim 16 , B127 claim 16 , B128 claim 16 , B130 claim 16 , B131 claim 16 , B132 claim 16 , B138 claim 16 , B139 claim 16 , B145 claim 16 , B148 claim 16 , B158 claim 16 , B163 claim 16 , B168 claim 16 , B169 claim 16 , B171 claim 16 , B187 claim 16 , B190 claim 16 , B191 claim 16 , B192 claim 16 , B196 claim 16 , B197 claim 16 , B198 claim 16 , B201 claim 16 , B207 claim 16 , B208 claim 16 , B212 claim 16 , B214 claim 16 , B218 claim 16 , B221 claim 16 , B226 claim 16 , B232 claim 16 , B233 claim 16 , B236 claim 16 , B237 ...

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14-11-2013 дата публикации

SUBSTITUTED HETERO-BIARYL COMPOUNDS AND THEIR USES

Номер: US20130303507A1
Принадлежит: NOVARTIS AG

The present invention provides a compound of formula (II): 2. (canceled)3. A compound of claim 1 , wherein Ais CH and Ais CH.4. A compound of claim 1 , wherein Ais CH and Ais N.5. (canceled)6. A compound of claim 1 , wherein Ais NH.7. A compound of claim 1 , wherein Ais O.810-. (canceled)11. A compound of claim 1 , wherein Ris cyclohexyl substituted with —NRR claim 1 ,{'sub': 12', '18', '1-6', '1-6', '3-6', '3-6', '22', '12', '22', '0-2', '12', '22', '2', '13', '14', '22', '12', '22', '19', '22', '19', '22', '13', '14', '22', '15', '2', '12', '22', '23', '24', '22', '15', '19', '22', '15', '2', '22', '15', '12', '22', '15', '13', '14, 'wherein Rand Rare each, independently, selected from the group consisting of hydrogen, hydroxyl, Calkyl, Chaloalkyl, Cbranched alkyl, Ccycloalkyl, —R—OR, —R—S(O)R, —R—S(O)NRR, —R—C(O)OR, —R—C(O)R, —R—OC(O)R, —R—C(O)NRR, —R—NRS(O)R, —R—NRR, —R—NRC(O)R, —R—NRC(O)OCHPh, —R—NRC(O)OR, —R—NRC(O)NRR, cyclo alkyl, heterocycloalkyl and heteroaryl;'}{'sub': 17', '18', '20', '21, 'or Rand Ralong with the nitrogen atom to which they are attached can be taken together to form a four to six or seven membered heterocyclic ring that can contain an additional O, N or S as a ring member, wherein the carbon atoms of said ring are optionally substituted with R, and the nitrogen atoms of said ring are optionally substituted with R.'}12. (canceled)1415-. (canceled)17. The compound of claim 16 , wherein Z is CN.1823-. (canceled)26. (canceled)27. The compound of claim 25 , wherein Ais NH.28. The compound of claim 25 , wherein Ais O.2934-. (canceled)36. The compound of claim 1 , which is selected from:1-(((5′-chloro-2′-((trans-4-(((R)-1-methoxypropan-2-yl)amino)cyclohexyl)amino)-[2,4′-bipyridin]-6-yl)amino)methyl)cyclopropanecarbonitrile4-(((2′-(azetidin-3-ylamino)-5′-chloro-[2,4′-bipyridin]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile4-(((5′-chloro-2′-(piperidin-4-ylamino)-[2,4′-bipyridin]-6-yl)amino)methyl)tetrahydro-2H-pyran-4-carbonitrile5′-chloro ...

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14-11-2013 дата публикации

NOVEL TRIAZINE COMPOUNDS

Номер: US20130303516A1
Принадлежит:

The present invention relates to novel triazine compounds of formula (1), methods of their preparation, pharmaceutical compositions containing these compounds and the use of these compounds to treat proliferative disorders such as tumors and cancers and also other conditions and disorders related to or associated with dysregulation of PI3 Kinases, PI3 Kinase pathway, mTOR and/or the mTOR pathway. 10. A novel triazine compound having Formula (I) claimed in claim 1 , their isomer claim 1 , salt and solvate thereof wherein said compound is selected from group comprising:(1) 4-8-{[4-1-(2-11-amino-1,3-thiazol-5-yl)-6-5-{3-oxa-8-azabicyclo[3.2.1]octan-8-yl}-1,3,5-triazin-2-yl]oxy}-N,N-dimethylbenzamide(2) 4-9-{[4-1-(2-17-amino-1,3-thiazol-5-yl)-6-5-(1,4-oxazepan-4-yl)-1,3,5-triazin-2-yl]oxy}-N,N-dimethylbenzamide(3) 4-9-{[4-1-(2-22-amino-1,3-thiazol-5-yl)-6-5-(3-25-methylmorpholin-4-yl)-1,3,5-triazin-2-yl]oxy}-N,N-dimethylbenzamide(4) 4-{[4-1-(2-27-amino-1,3-thiazol-5-yl)-6-5-(morpholin-4-yl)-1,3,5-triazin-2-yl]oxy}-N,N-dimethylbenzamide(5) 5-(4-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-6-morpholino-1,3,5-triazin-2-yl)pyrimidin-2-amine(6) 2-26-(4-20-{[4-3-(2-15-aminopyrimidin-5-yl)-6-5-(morpholin-4-yl)-1,3,5-triazin-2-yl]oxy}phenyl)-N,N-dimethylacetamide(7) N-(4-(2-aminothiazol-5-yl)-6-morpholino-1,3,5-triazin-2-yl)thiazol-2-amine(8) 4-14-{[4-1-(2-17-aminopyrimidin-5-yl)-6-5-(morpholin-4-yl)-1,3,5-triazin-2-yl]oxy}-N,N-dimethylpiperidine-1-carboxamide(9) 4-14-{[4-1-(5-17-aminopyrazin-2-yl)-6-5-(morpholin-4-yl)-1,3,5-triazin-2-yl]oxy}-N,N-dimethylbenzamide(10) 6-20-{[4-1-(6-11-aminopyridin-3-yl)-6-5-(morpholin-4-yl)-1,3,5-triazin-2-yl]oxy}-1,2,3,4-tetrahydroquinolin-2-one(11) 4-14-{[4-1-(2-27-aminopyrimidin-5-yl)-6-5-(morpholin-4-yl)-1,3,5-triazin-2-yl]oxy}-N,N-dimethylbenzamide(12) 4-9-{[4-1-(6-12-aminopyridin-3-yl)-6-5-[3-oxa-8-azabicyclo[3.2.1]octan-8-yl]-1,3,5-triazin-2-yl]oxy}-N,N-dimethylbenzamide(13) 2-26-(3-20-{[4-1-(6-11-aminopyridin-3-yl)-6-5-(morpholin-4-yl)-1 ...

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14-11-2013 дата публикации

QUINOXALINES AND AZA-QUINOXALINES AS CRTH2 RECEPTOR MODULATORS

Номер: US20130303517A1
Принадлежит:

The invention provides certain quinoxalines and aza-quinoxalines of the Formula (I), and their pharmaceutically acceptable salts, wherein J, J, R, R, R, R, R, R, R, R, X, Y, b, n, and q are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions associated with uncontrolled or inappropriate stimulation of CRTHfunction. 3. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris substituted at the 4 or 5 position of the illustrated bicyclic ring of Formula (I).5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of:{'sup': 6a', '6b, '(i) —C(O)—N(R)(R), and'}{'sub': '2', 'sup': 6a', '6b, '(ii) —S(O)—N(R)(R).'}6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein{'sup': '6a', 'claim-text': {'sup': 6b', 'AH', 'HC, 'Ris -Q-Ror -Q-R; or'}, '(i) Ris H and'}{'sup': 6a', '6b', '6H, '(ii) Rand Rtogether with the N atom to which they are attached form R.'}7. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris —C(O)—N(R)(R).8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein{'sup': '6a', 'Ris H and'}{'sup': 6b', 'AH', 'HC, 'Ris -Q-Ror -Q-R.'}9. The compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein Rand Rtogether with the N atom to which they are attached form R.14. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein the compound is selected from the group consisting of:(14) 5-(3-phenyl-7-{[4-(trifluoromethyl)benzyl]carbamoyl}pyrido[2,3-b]pyrazin-2-yl)pentanoic acid;(14D) 5-{7-[4-chlorobenzyl)carbamoyl]-3-phenylpyrido[2,3-b]pyrazin-2-yl}pentanoic acid;(14G) 5-{3-phenyl-7-[(4-phenylpiperazin-1-yl)carbonyl]pyrido[2,3-b]pyrazin-2-yl}pentanoic acid;(15A) 5-(3-phenyl-7-{[(1R)-1- ...

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21-11-2013 дата публикации

SUBSTITUTED SPIROCYCLIC PIPERIDINE DERIVATIVES AS HISTAMINE-3 (H3) RECEPTOR LIGANDS

Номер: US20130310389A1
Принадлежит: CEPHALON, INC.

The present invention is directed to methods of treating disorders mediated by Histamine Hreceptors by administering novel substituted spirocyclic piperidine derivatives according to Formula (I). 2. A method according to wherein the disorder is narcolepsy or sleep/wake disorders.3. A method according to wherein the disorder is attention deficit hyperactivity disorder.4. A method according to wherein the disorder is cognition disorder.5. A method according to wherein Ris C-Ccycloalkyl.6. A method according to wherein W is —CH— or —CH—CH—.8. A method according to wherein Rand R claim 1 , together with the carbon atoms to which they are attached claim 1 , form a fused cyclopropyl or cyclobutyl ring.9. A method according to wherein Rand R claim 1 , together with the carbon atoms to which they are attached claim 1 , form a fused phenyl claim 1 , thienyl claim 1 , pyrrolyl claim 1 , oxazolyl claim 1 , pyridinyl claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , or cyclohexyl ring.10. A method according to wherein k is 1.11. A method according to wherein m is 1.12. A method according to wherein the sum of m and k is 2.13. A method according to wherein Y═Yis —C(X)═CH—.14. A method according to wherein X is R.15. A method according to wherein X is —OR.16. A method according to wherein Ris H.17. A method according to wherein Ris C-Calkyl optionally substituted by 1-3 R.18. A method according to wherein Ris C-Calkyl.19. A method according to wherein n is 0.20. A method according to wherein n is 1.21. A method according to wherein z is 0. This application is a continuation application of U.S. Ser. No. 12/846,108, filed Jul. 29, 2010, which is a continuation of International Application No. PCT/US2009/032195, filed Jan. 28, 2009, which claims priority to U.S. Provisional Application Ser. No. 61/062,909, filed Jan. 30, 2008. The disclosures of the aforementioned applications are incorporated herein by reference in their entireties for all purposes.The ...

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28-11-2013 дата публикации

INHIBITORS OF BETA-SECRETASE

Номер: US20130317014A1
Принадлежит:

The present invention is directed to a compound represented by the following structural formula: 156-. (canceled)58. The method of claim 57 , wherein the disorder is selected from the group consisting of Alzheimer's disease claim 57 , cognitive impairment claim 57 , Down's Syndrome claim 57 , HCHWA-D claim 57 , cognitive decline claim 57 , senile dementia claim 57 , cerebral amyloid angiopathy claim 57 , degenerative dementia claim 57 , other neurodegenerative disorders claim 57 , and glaucoma.5963-. (canceled)66. The method of claim 65 , wherein X is —O— and Ris —H claim 65 , —Br claim 65 , —F claim 65 , (C-C)alkyl claim 65 , (C-C)cycloalkyl claim 65 , aryl claim 65 , heteroaryl claim 65 , phenoxy claim 65 , or benzyloxy claim 65 , each optionally substituted with 1 to 3 substituents independently selected from the group consisting of —F claim 65 , —Cl claim 65 , —Br claim 65 , —CN claim 65 , —OR claim 65 , —NRR claim 65 , —S(O)R claim 65 , —NRS(═O)R claim 65 , —C(═O)OR claim 65 , —C(═O)NRR claim 65 , —NRC(═O)R claim 65 , —C(═S)NRR claim 65 , —C(═O)R claim 65 , (C-C)alkyl claim 65 , (C-C)cycloalkyl claim 65 , (C-C)alkenyl claim 65 , halo(C-C)alkyl claim 65 , (C-C)alkylsulfonylaminoalkyl claim 65 , hydroxy(C-C)alkyl claim 65 , cyano(C-C)alkyl claim 65 , (C-C)alkylcarbonylamino(C-C)alkyl claim 65 , (C-C)alkoxy claim 65 , halo(C-C)alkoxy claim 65 , (C-C)alkoxy(C-C)alkyl and a heteroaryl group.68. The method of claim 67 , wherein ring A is tetrahydrofuran claim 67 , tetrahydropyran claim 67 , cyclopentane claim 67 , cyclohexane claim 67 , cycloheptane claim 67 , oxepane claim 67 , 1 claim 67 ,3-dioxane claim 67 , piperidine claim 67 , 6 claim 67 ,7 claim 67 ,8 claim 67 ,9-tetrahydro-5H-benzo[7]annulene claim 67 , 2 claim 67 ,3-dihydro-1H-indene claim 67 , tetrahydronaphthalene claim 67 , decahydronaphthalene claim 67 , 5 claim 67 ,6 claim 67 ,7 claim 67 ,8-tetrahydroquinoline claim 67 , 5 claim 67 ,6 claim 67 ,7 claim 67 ,8-tetrahydroisoquinoline claim 67 , 2- ...

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28-11-2013 дата публикации

CARBOXY X RHODAMINE ANALOGS

Номер: US20130317207A1
Принадлежит: PROMEGA CORPORATION

The present invention provides novel fluorescent dyes and kits containing the same, which are useful for labeling a wide variety of biomolecules, cells and microorganisms. The present invention also provides various methods of using the fluorescent dyes for research and development, forensic identification, environmental studies, diagnosis, prognosis and/or treatment of disease conditions. 24.-. (canceled)5. A compound according to wherein at least one of R claim 8 , Ror Ris H.67.-. (canceled)9. A compound according to wherein X is CH.1011.-. (canceled)12. A compound according to wherein Rand Rform a 5-7 membered carbocyclic ring.1315.-. (canceled)16. A compound according to wherein Ris H claim 8 , Cl or OMe.17. A compound according to wherein Rand Rform a 5-7 membered carbocyclic ring.18. (canceled)19. A compound according to wherein at least one of R claim 8 , R claim 8 , Rand Ris H.2024.-. (canceled)25. A compound according to wherein Ris H claim 8 , Cl or OMe.26. A compound according to wherein Ris Calkyl.27. A compound according to wherein Ris methyl or ethyl.28227. A compound according to any one of claims - wherein Ris Calkyl.29. A compound according to wherein Ris methyl or ethyl.30. A compound according to wherein Ris part of a heterocycle.31. (canceled)32. A compound according to wherein Ris part of a heterocycle.3344.-. (canceled)45. A compound according to wherein Ris H.46. A compound according to wherein Ris H.47. A compound according to wherein Ris H or halogen.48. A compound according to wherein Ris H or halogen.49. A compound according to wherein Ris H claim 8 , F claim 8 , Cl COH or SOH.50. A compound according to wherein one of Rand Ris -L-R claim 8 , -L-COH or -L-Cand the other is H claim 8 , Cl claim 8 , or F.51. A compound according to wherein L is —CO— claim 8 , —SCHCO— claim 8 , or —SO—.52. A compound according to is a self-immolative linker.54. A compound according to wherein Cis NHCHCH(OCHCH)(CH)Cl claim 8 , wherein n is 2-6.55. A compound ...

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05-12-2013 дата публикации

SUBSTITUTED HETEROCYCLIC COMPOUNDS

Номер: US20130324525A1
Принадлежит: Gilead Sciences, Inc.

The present invention relates to novel heterocyclic compounds and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula (I): 2. The compound of claim 1 , wherein R4 is optionally substituted cycloalkyl claim 1 , optionally substituted heterocyclyl claim 1 , optionally substituted aryl claim 1 , or optionally substituted heteroaryl.3. The compound of claim 1 , wherein R4 is aryl substituted with one or more groups selected from aryl claim 1 , lower alkyl claim 1 , heteroaryl claim 1 , halo claim 1 , heterocyclyl claim 1 , amino claim 1 , and carboxyl claim 1 , wherein said one or more groups are optionally substituted with alkyl claim 1 , aryl claim 1 , heteroaryl claim 1 , heterocyclyl claim 1 , halo claim 1 , or carboxyl.4. The compound of claim 1 , wherein R5 is —NR52R53 claim 1 , where R52 and R53 are each independently selected from hydrogen claim 1 , lower alkyl claim 1 , optionally substituted cycloalkyl claim 1 , optionally substituted aryl claim 1 , or optionally substituted benzyl; or where R52 and R53 taken together with the nitrogen to which they are both directly attached form a 5 or 6 membered heterocyclyl or heteroaryl moiety claim 1 , said 5 or 6 membered heterocyclyl or heteroaryl moiety optionally substituted by a group selected from halo claim 1 , alkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , alkoxy claim 1 , aryl claim 1 , and cycloalkyl and combinations thereof claim 1 , wherein said alkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , alkoxy claim 1 , aryl claim 1 , or cycloalkyl is each optionally substituted.5. The compound of claim 1 , wherein R5 and R6 taken together with the carbons to which R5 and R6 are directly attached and the carbon directly attached to both of the carbons to which R5 and R6 are directly attached form a 5 or 6 membered heterocyclyl claim 1 , heteroaryl claim 1 , cycloalkyl claim 1 , or a ...

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