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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 30512. Отображено 100.
02-02-2012 дата публикации

Nitroimidazooxazines and their uses in anti-tubercular therapy

Номер: US20120028973A1
Принадлежит: Global Alliance for TB Drug Development

The present invention relates to novel nitroimidazooxazines, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

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02-02-2012 дата публикации

Synthesis of enone intermediate

Номер: US20120029199A1
Принадлежит: Harvard College

The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously susceptible to tetracycline antibiotics. The recent development of a modular synthesis of tetracycline analogs through a chiral enone intermediate has allowed for the efficient synthesis of novel tetracycline analogs never prepared before. The present invention provides a more efficient route for preparing the enone intermediate.

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01-03-2012 дата публикации

Nitrogen-Containing Fused Heterocyclic Compounds and Their use as Beta Amyloid Production Inhibitors

Номер: US20120053171A1
Принадлежит: Eisai R&D Management Co Ltd

A compound represented by the formula [I]: or a pharmacologically acceptable salt or ester thereof, wherein Ring A represents a five-membered aromatic heterocyclic group or the like fused with a non-aromatic ring group, which may be substituted, Ring B represents a phenyl group or the like which may be substituted, X1 represents a single bond or the like, R1 and R2 each represent a C1-6 alkyl group or the like, m represents an integer of 0 to 3, and n represents an integer of 0 to 2, is effective as a therapeutic agent for a disease caused by Aβ.

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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

Method for refining of high purity of tacrolimus

Номер: US20120065393A1
Принадлежит: Chongkundang Bio Corp

The present invention relates to a process of preparing a highly pure tacrolimus, which comprising a pre-purification process carried out by means of crystallization, and particularly to a process of preparing a highly pure tacrolimus, which comprises a pre-purification process comprising the steps of (a) extracting mycelia cake collected by filtering a tacrolimus-containing oily compound with an organic solvent, (b) concentrating the extract under reduced pressure and (c) crystallizing the concentrate. In addition, a highly pure tacrolimus can be obtained by dissolving the pre-purified crystals in an organic solvent, passing through the solution in an adsorption resin and concentrating the eluate under reduced pressure, followed by crystallization. According to a process of the present invention, Tacrolimus as pure as appropriate for a pharmaceutical purpose can be prepared by a simple process and at a relatively low cost.

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29-03-2012 дата публикации

Hepatitis C Virus Inhibitors

Номер: US20120076755A1
Принадлежит: Enanta Pharmaceuticals Inc

The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, esters, or prodrugs thereof: Q-G-A-L-B-W  (I), which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

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12-04-2012 дата публикации

Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same

Номер: US20120088746A1
Принадлежит: PFIZER INC

Compounds are disclosed that have a formula represented by the following: Formula (I). The compounds may be prepared as pharmaceutical compositions, 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, pain, inflammation, traumatic injury, and others.

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19-04-2012 дата публикации

5-ht receptor modulating compounds

Номер: US20120094989A1
Принадлежит: SERODUS AS

The present invention relates to compounds having 5-hydroxytryptamine receptor modulating activity, in particular compounds having an acidic moiety held distant from the 5-HT pharmacophore by a rigid linker group, to compositions containing such compounds and methods of treatment using them. Such compounds have an increased affinity for the 5-HT receptor and a reduced hERG effect. Certain compounds of the invention further exhibit an angiotensin II receptor modulating activity. Claimed are compounds of formula (I): HT-L-A. HT is a 5-HT receptor modulating moiety containing a basic nitrogen atom; A is an acid moiety; L is a linker moiety.

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03-05-2012 дата публикации

Fused piperidine compound and pharmaceutical containing same

Номер: US20120108581A1
Принадлежит: Kowa Co Ltd

The present invention provides a low molecular weight compound having EPO production-promoting action and/or hemoglobin production-promoting action. The present invention relates to a fused piperidine compound represented by the following general formula (1): (wherein, ring A represents a C 10-14 aryl group or 5- to 10-membered heterocyclic group, X represents N—R 7 , a sulfur atom or an oxygen atom, R 1 , R 2 , R 2′ , R 3 and R 3′ independently represent a hydrogen atom, C 1-6 alkyl group or C 3-6 cycloalkyl group, and R 4 , R 5 and R 6 independently represent a hydrogen atom or halogen atom), or a salt thereof, or a solvate thereof.

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10-05-2012 дата публикации

Rifaximin

Номер: US20120116071A1
Принадлежит: Cipla Ltd

Amorphous rifaximin, methods of making it, and pharmaceutical compositions containing it. Also described are methods of converting amorphous rifaximin to crystalline rifaximin and vice versa.

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07-06-2012 дата публикации

Oxazolidinone-quinolone hybrid antibiotics

Номер: US20120142635A1

The present invention relates to compounds of the Formula (I) that are useful antimicrobial agents and effective against a variety of multi-drug resistant bacteria:

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07-06-2012 дата публикации

Heteroalkyl linked pyrimidine derivatives

Номер: US20120142680A1
Принадлежит: SBio Pte Ltd

The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to heteroalkyl linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumours and cancers as well as other conditions or disorders associated with kinases.

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21-06-2012 дата публикации

Antimicrobial heterocyclic compounds for treatment of bacterial infections

Номер: US20120157434A1
Принадлежит: CSO of MicuRx Pharmaceuticals Inc

The present invention provides heterocyclic compounds of the following formula I: or pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof useful as antibacterial agents, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.

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21-06-2012 дата публикации

Novel fused pyridine compounds as casein kinase inhibitors

Номер: US20120157440A1
Принадлежит: PFIZER INC

Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, A, R 4 , n, and R 7 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

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21-06-2012 дата публикации

Anhydrate Forms Of A Pyridine Derivative

Номер: US20120157450A1

The invention relates to the compound of formula (I) in a crystalline anhydrate form, pharmaceutical formulations containing them, their use in therapy and processes for preparing the same.

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28-06-2012 дата публикации

Quinoline derivatives as pi3 kinase inhibitors

Номер: US20120165321A1
Принадлежит: GlaxoSmithKline LLC

Invented is a method of inhibiting the activity/function of PI3 kinases using quinoline derivatives. Also invented is a method of treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries by the administration of quinoline derivatives.

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19-07-2012 дата публикации

Modulators of cell cycle checkpoints and their use in combination with checkpoint kinase inhibitors

Номер: US20120184505A1
Принадлежит: Individual

In its many embodiments, the present invention provides a novel class of pyrimidine analogs as targeted mechanism-based modulators of cell cycle checkpoints. Cancers and/or malignancies can be treated by administration of a cell cycle checkpoint modulator of the invention. Also discussed are suitable combinations of the cell cycle checkpoint modulator with a checkpoint kinase inhibitor to produce synergistic apoptosis in cancer cells. The invention also includes methods of treating cancers by administering the combination of the cell cycle checkpoint modulator and the checkpoint kinase inhibitor, pharmaceutical compositions comprising the cell cycle checkpoint modulator as well as combinations and pharmaceutical kits. An example cell cycle checkpoint modulator is shown below: formula (I).

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19-07-2012 дата публикации

[1,4]-benzodiazepines as vasopressin v2 receptor antagonists

Номер: US20120184537A1
Принадлежит: Shire Movetis NV

The invention relates to a novel class of [1,4]-benzodiazepine derivatives, processes for their preparation, intermediates usable in these processes, and pharmaceutical compositions containing the compounds. Other aspects of the invention are directed to the use of said [1,4]-benzodiazepine derivatives in therapy based on the capability of said compounds to interfere with the binding of the peptide hormone, vasopressin, to its receptors. In particular as vasopressin V2 receptor antagonists and therefore useful for treating involving increased vascular resistance, cardiac insufficiency, and water retention.

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19-07-2012 дата публикации

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

Номер: US20120184732A1
Принадлежит: Nippon Soda Co Ltd

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

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02-08-2012 дата публикации

Oxygen linked pyrimidine derivatives

Номер: US20120196855A1
Принадлежит: SBio Pte Ltd

The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to oxygen linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumours and cancers as well as other disorders or conditions related to or associated with kinases.

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16-08-2012 дата публикации

Chemokine receptor antagonists and use thereof

Номер: US20120207765A1
Принадлежит: Ono Pharmaceutical Co Ltd

A compound represented by general formula (I): a salt thereof, a solvate thereof, or a prodrug thereof wherein all symbols are as defined in the specification has an antagonistic activity against CXCR4 and is therefore useful as a preventive and/or therapeutic agent for CXCR4-mediated diseases, for example, inflammatory and immune diseases (for example, rheumatoid arthritis, arthritis, systemic erythematosus, retinopathy, macular degeneration, pulmonary fibrosis, transplanted organ rejection, etc.), allergic diseases, infections (for example, human immunodeficiency virus infection, acquired immunodeficiency syndrome, etc.), psychoneurotic diseases, cerebral diseases, cardiac/vascular disease (for example, arteriosclerosis, myocardial infarction, stenocardia, cerebral infarction, chronic arterial occlusive disease, etc.), metabolic diseases, and cancerous diseases (for example, cancer, cancer metastasis, etc.), a preventive and/or therapeutic agent for cancerous diseases or infections, or an agent for regeneration therapy.

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30-08-2012 дата публикации

Naphthoxazine benzoxazine-based monomer, polymer thereof, electrode for fuel cell including the polymer, electrolyte membrane for fuel cell including the polymer, and fuel cell using the electrode

Номер: US20120219876A1
Принадлежит: SAMSUNG ELECTRONICS CO LTD

A naphthoxazine benzoxazine-based monomer is represented by Formula 1 below: In Formula 1, R 2 and R 3 or R 3 and R 4 are linked to each other to form a group represented by Formula 2 below, and R 5 and R 6 or R 6 and R 7 are linked to each other to form a group represented by Formula 2 below, In Formula 2, * represents the bonding position of R 2 and R 3 , R 3 and R 4 , R 5 and R 6 , or R 6 and R 7 of Formula 1. A polymer is formed by polymerizing the naphthoxazine benzoxazine-based monomer, an electrode for a fuel cell includes the polymer, an electrolyte membrane for a fuel cell includes the polymer, and a fuel cell uses the electrode.

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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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13-09-2012 дата публикации

Organic compound and photovoltaic device comprising the same

Номер: US20120227802A1
Принадлежит: Cryscade Solar Ltd

The present invention provides a organic compound of the general structural formula 1 and photovoltaic device and photovoltaic layer comprising thereof Said organic compound forms rod-like supramolecules and absorbs electromagnetic radiation in at least one predetermined spectral subrange within a wavelength range from 400 to 3000 nm with excitation of electron-hole pairs. The polycyclic core Cor 1 , the bridging group B, and the polycyclic core Cor 2 form a molecular system selected from the list comprising donor-bridge-acceptor-bridge-donor and acceptor-bridge-donor-bridge-acceptor in which a dissociation of excited electron-hole pairs is carried out. A solution of the organic compound or its salt forms a solid photovoltaic layer on a substrate.

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13-09-2012 дата публикации

Methods of Treating or Preventing Autoimmune Diseases With 2,4-Pyrimidinediamine Compounds

Номер: US20120230984A1
Принадлежит: Rigel Pharmaceuticals Inc

The present invention provides methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds, as well as methods of treating, preventing or ameliorating symptoms associated with such diseases. Specific examples of autoimmune diseases that can be treated or prevented with the compounds include rheumatoid arthritis and/or its associated symptoms, systemic lups erythematosis and/or its associated symptoms and multiple sclerosis and/or its associated symptoms.

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13-09-2012 дата публикации

Use of Rapamycin and Rapamycin Derivatives for the Treatment of Bone Loss

Номер: US20120232011A1
Принадлежит: Individual

The present invention relates to a new use of rapamycin and rapamycin derivatives.

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27-09-2012 дата публикации

Mglur4 allosteric potentiators, compositions, and methods of treating neurological dysfunction

Номер: US20120245153A1
Принадлежит: VANDERBILT UNIVERSITY

Compounds useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4) and use thereof.

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04-10-2012 дата публикации

Bicyclic pyridines and analogs as sirtuin modulators

Номер: US20120252780A1

Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

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04-10-2012 дата публикации

Heterocyclic GTP Cyclohydrolase 1 Inhibitors For the Treatment of Pain

Номер: US20120252791A1
Автор: Julian Blagg
Принадлежит: Individual

The present invention relates to the field of small molecule heterocyclic inhibitors of GTP cyclohydrolase (GCH-I), or a tautomer, prodrug, or pharmaceutically acceptable salt thereof. The invention also features pharmaceutical compositions of the compounds and the medical use of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, or neuropathic pain).

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18-10-2012 дата публикации

Composition and method for controlling arthropod pests

Номер: US20120264750A1
Автор: Junko Otsuki
Принадлежит: Sumitomo Chemical Co Ltd

The present invention provides: an arthropod pests control composition comprising, as active ingredients, a condensed heterocyclic compound and a diamide compound; a method for controlling arthropod pests which comprises applying effective amounts of a condensed heterocyclic compound and a diamide compound to the arthropod pests or a locus where the arthropod pests inhabit; and so on.

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08-11-2012 дата публикации

Imidazopyridazinecarbonitriles useful as kinase inhibitors

Номер: US20120283241A1
Принадлежит: Bristol Myers Squibb Co

The invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The Formula (I) imidazopyridazines inhibit protein kinase activity thereby making them useful as anticancer agents.

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15-11-2012 дата публикации

Novel compounds with high therapeutic index

Номер: US20120289471A1
Автор: V. Ravi Chandran
Принадлежит: Signature R&D Holdings LLC

The present invention is directed to novel therapeutic compounds comprised of an amino acid bonded to a medicament or drug having a hydroxy, amino, carboxy or acylating derivative thereon. These high therapeutic index derivatives have the same utility as the drug from which they are made, and they have enhanced pharmacological and pharmaceutical properties. In fact, the novel drug derivatives of the present invention enhance at least one therapeutic quality, as defined herein. The present invention is also directed to pharmaceutical compositions containing same.

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15-11-2012 дата публикации

Fused pyridine derivatives

Номер: US20120289497A1
Принадлежит: Xuanzhu Pharma Co Ltd

Fused pyridine derivatives shown as the general formula (I), and their pharmaceutically acceptable salts, stereoisomers or solvates thereof are disclosed, which belong to the technical field of medicines. The R 1 , R 2 , R 3 , Q, X and Y substituents in formula (I) are defined as in the description. Also disclosed are the preparation methods, pharmaceutical compositions comprising the compounds and uses of the compounds in the manufacture of the medicine for the treatment and/or prevention of noninsulin-dependent diabetes, hyperglycemia, hyperlipidemia and insulin resistance.

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29-11-2012 дата публикации

Substituted aminothiazolone indazoles as estrogen related receptor-alpha modulators

Номер: US20120302544A1
Принадлежит: Individual

The present invention relates to compounds of Formula (I), methods for preparing these compounds, compositions, intermediates and derivatives thereof and for treating a condition including but not limited to ankylosing spondylitis, artherosclerosis, arthritis (such as rheumatoid arthritis, infectious arthritis, childhood arthritis, psoriatic arthritis, reactive arthritis), bone-related diseases (including those related to bone formation), breast cancer (including those unresponsive to anti-estrogen therapy), cardiovascular disorders, cartilage-related disease (such as cartilage injury/loss, cartilage degeneration, and those related to cartilage formation), chondrodysplasia, chondrosarcoma, chronic back injury, chronic bronchitis, chronic inflammatory airway disease, chronic obstructive pulmonary disease, diabetes, disorders of energy homeostasis, gout, pseudogout, lipid disorders, metabolic syndrome, multiple myeloma, obesity, osteoarthritis, osteogenesis imperfecta, osteolytic bone metastasis, osteomalacia, osteoporosis, Paget's disease, periodontal disease, polymyalgia rheumatica, Reiter's syndrome, repetitive stress injury, hyperglycemia, elevated blood glucose level, and insulin resistance.

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29-11-2012 дата публикации

Novel antibiotics

Номер: US20120302613A1
Принадлежит: NOVOBIOTIC PHARMACEUTICALS LLC

The invention relates generally to novel antibiotics and their analogs, to processes for the preparation of these novel antibiotics, to pharmaceutical compositions comprising the novel antibiotics; and to methods of using the novel antibiotics to treat or inhibit various disorders.

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13-12-2012 дата публикации

Bicyclic ring system substituted sulfonamide functionalised phenols as medicaments

Номер: US20120316159A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

This invention relates to bicyclic ring system substituted sulfonamide functionalized phenols of general formula 1, their use as inhibitors of CXCR2 activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin, or eyes, diseases of the peripheral or central nervous system or cancers, as well as pharmaceutical compositions which contain these compounds.

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13-12-2012 дата публикации

Forms of rifaximin and uses thereof

Номер: US20120316334A1
Принадлежит: Salix Pharmaceuticals Ltd

The present invention relates to Rifaximin polymorphic forms, to their use in medicinal preparations and to therapeutic methods using them.

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27-12-2012 дата публикации

Inhibitors of hepatitis c virus ns5b polymerase

Номер: US20120328569A1
Принадлежит: Individual

Disclosed are compounds of formula (I) that are used as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

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24-01-2013 дата публикации

Carboxylic acid derivatives having an oxazolo[5,4-b]pyridine ring

Номер: US20130023557A1
Принадлежит: SANOFI SA

The invention therefore relates to compounds of the formula I in which X, Y, R 1 , R 2 and R 3 have the given meanings. The compounds of the formula I are suitable, for example, for wound healing.

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24-01-2013 дата публикации

CARBOXYLIC ACID DERIVATIVES HAVING AN OXAZOLO[4,5-c]PYRIDINE RING

Номер: US20130023558A1
Принадлежит: SANOFI SA

Carboxylic acid derivatives having an oxazolo[4,5-c]pyridine ring The invention therefore relates to compounds of the formula I in which X, Y, R 1 , R 2 and R 3 have the given meanings. The compounds of the formula I are suitable, for example, for wound healing.

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07-02-2013 дата публикации

Biaryl compounds and methods of use thereof

Номер: US20130035326A1
Принадлежит: Ambit Bioscience Corp

Provided herein are compounds for treatment of KIT, CSF-1R and/or FLT3 kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.

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21-02-2013 дата публикации

Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same

Номер: US20130045973A1
Принадлежит: Evotec OAI AG

Compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, 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, pain, inflammation, traumatic injury, and others.

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21-03-2013 дата публикации

Soluble mtor complexes and modulators thereof

Номер: US20130072485A1

The present invention relates to small molecule modulators of mTORC1 and mTORC2, syntheses thereof, and intermediates thereto. Such small molecule modulators are useful in the treatment of proliferative diseases (e.g., benign neoplasms, cancers, inflammatory diseases, autoimmune diseases, diabetic retinopathy) and metabolic diseases. Novel small molecules are provided that inhibit one or more of mTORC1, mTORC2, and PI3K-related proteins. Novel methods of providing soluble mTORC1 and mTORC2 complexes are discussed, as well as methods of using the soluble complexes in a high-throughput manner to screen for inhibitory compounds.

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21-03-2013 дата публикации

HETEROCYCLIC CARBOXYLIC ACID DERIVATIVES HAVING A 2,5-SUBSTITUTED OXAZOLOPYRIMIDINE RING

Номер: US20130072502A1
Принадлежит: SANOFI

Heterocyclic carboxylic acid derivatives comprising a 2,5-substituted oxazolopyrimidine ring as Edg-1 receptor agonists 2. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein A is chosen from O and S.3. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein X is chosen from (C-C)-alkanediyl claim 1 , (C-C)-alkenediyl and (C-C)-alkanediyl-oxy.4. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein Y is a 4-membered to 7-membered claim 1 , saturated claim 1 , monocyclic or bicyclic heterocycle which claim 1 , in addition to the ring nitrogen atom depicted in formula I claim 1 , comprises 0 or 1 ring heteroatoms chosen from N claim 1 , O and S claim 1 , wherein an additional ring nitrogen atom can carry a hydrogen atom or a (C-C)-alkyl substituent and a ring sulfur atom can carry one or two oxo groups claim 1 , and wherein the heterocycle is optionally substituted on one or more ring carbon atoms by identical or different (C-C)-alkyl substituents.5. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein Ris chosen from ...

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21-03-2013 дата публикации

Spirooxazine radical derivatives and reversible isomerization reaction

Номер: US20130072678A1
Автор: Atsumasa Sawada
Принадлежит: NEC Corp

The present invention can provide new spirooxazine radical derivatives of the following general formula (1) which have chromic property enabling the distinction between the radical species and the cation species on the basis of absorption wavelength:

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28-03-2013 дата публикации

NITROIMIDAZOLE DERIVATIVES

Номер: US20130078185A1
Принадлежит: GE HEALTHCARE LIMITED

The present invention provides novel compounds useful in the treatment and diagnosis of mycobacterial infections. Compounds of the present invention have enhanced biological properties as compared to the related known compounds. The present invention also provides a precursor compound useful in the synthesis of certain compounds of the invention, and a method to obtain these compounds using said precursor compound. Methods of treatment and diagnosis in which the compounds of the invention fmd use are also provided. 2. The compound as defined in wherein Ris methyl.3. The compound as defined in wherein X is —O—.4. (canceled)5. The compound as defined in wherein said radioactive halogen is a gamma-emitting radioactive halogen selected from I claim 1 , I and Br.6. (canceled)7. The compound as defined in wherein said radioactive halogen is a positron-emitting radioactive halogen selected from F claim 1 , F claim 1 , Br claim 1 , Br and I.810.-. (canceled)1519.-. (canceled)20. A pharmaceutical composition comprising the compound as defined in together with a biocompatible carrier in a form suitable for mammalian administration.21. An in vivo imaging method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) administration of the compound as defined in ;'}(b) allowing said compound to bind to the cell wall of any mycobacteria present in said subject;(c) detecting by an in vivo imaging procedure signals emitted by said radioactive halogen;(d) generating an image representative of the location and/or amount of said signals; and,(e) determining the distribution of mycobacteria in said subject wherein said distribution is directly correlated with said signals.22. (canceled)23Mycobacterium tuberculosis.. The in vivo imaging method as defined in wherein said mycobacterium is24Mycobacterium tuberculosis.. The in vivo imaging method as defined in which is carried out repeatedly during the course of a treatment regimen for said subject claim 23 , said regimen ...

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28-03-2013 дата публикации

HETEROCYCLIC COMPOUND AND p27Kip1 DEGRADATION INHIBITOR

Номер: US20130079306A1
Принадлежит: Individual

A novel heterocyclic compound or a salt thereof useful for selectively inhibiting the degradation of p27 Kip1 is provided. The compound or the salt thereof is represented by the following formula (1): wherein A represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic group, the group A may have a substituent; the ring B represents a 5- to 8-membered monocyclic heterocyclic ring or a condensed ring containing the monocyclic heterocyclic ring, the ring B may have a substituent; the ring C represents an aromatic ring, the ring C may have a substituent; L represents a linker comprising a main chain having 3 to 5 atoms selected from the group consisting of a carbon atom, a nitrogen atom, an oxygen atom and a sulfur atom, wherein at least one atom in the main chain is a hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, the linker L may have a substituent; and n is 0 or 1.

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28-03-2013 дата публикации

Amine Substituted Methanesulfonamide Derivatives as Vanilloid Receptor Ligands

Номер: US20130079320A1
Принадлежит: GRUENENTHAL GmbH

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

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28-03-2013 дата публикации

BENZOXAZEPIN PI3K INHIBITOR COMPOUNDS AND METHODS OF USE

Номер: US20130079331A1
Принадлежит: Genentech, Inc.

Benzoxazepin compounds of Formula I, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, wherein: Zis CRor N; Zis CRor N; Zis CRor N; Zis CRor N; and B is a pyrazolyl, imidazolyl, or triazolyl ring fused to the benzoxepin ring, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. 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. 2. The process of wherein the palladium catalyst is Pd(dppf)Cl2.3. The process of wherein the aqueous basic reagent is lithium hydroxide.5. The pharmaceutical composition of formed into a tablet. This application is a continuation of U.S. Ser. No. 13/477,587, filed 22 May 2012, which is a divisional of U.S. Ser. No. 12/890,812, filed 27 Sep. 2010, now U.S. Pat. No. 8,242,104, issued 14 Aug. 2012, and claims the benefit under 35 USC §119(e) of U.S. Provisional Application Ser. No. 61/246,381 filed on 28 Sep. 2009 and U.S. Provisional Application Ser. No. 61/330,685 filed on 3 May 2010, all of which are incorporated by reference in entirety.The invention relates generally to compounds with anti-cancer activity and more specifically to compounds which inhibit PI3 kinase activity. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.Phosphatidylinositol (hereinafter abbreviated as “PI”) is one of a number of phospholipids found in cell membranes. In recent years it has become clear that PI plays an important role in intracellular signal transduction. Cell signaling via 3′-phosphorylated phosphoinositides has been implicated in a variety of cellular processes, e.g., malignant transformation, growth ...

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28-03-2013 дата публикации

CARBOXYLIC ACID DERIVATIVES HAVING A 2,5,7-SUBSTITUTED OXAZOLOPYRIMIDINE RING

Номер: US20130079357A1
Принадлежит: SANOFI

The invention relates to oxazolopyrimidine compounds of formula (I), where A, R, R, R, Rand X are defined as stated in the claims. The compounds of formula I are suitable, for example, for wound healing. 2. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein A is chosen from O and S.3. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein X is chosen from (C-C)-alkanediyl claim 1 , (C-C)-alkenediyl and (C-C)-alkanediyl-oxy.4. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein{'sup': '1', 'sub': 1', '6', '3', '7', 't', '2t', 't', '2t, 'Ris chosen from (C-C)-alkyl, (C-C)-cycloalkyl-CH- and Het-CH—, wherein t is chosen from 0, 1 and 2.'}5. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein{'sup': 2', '22, 'Ris chosen from phenylene and pyridinediyl, wherein the phenylene and the pyridinediyl are optionally substituted on one or more ring carbon atoms by identical or different substituents R.'}6. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in ...

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28-03-2013 дата публикации

CARBOXYLIC ACID DERIVATIVES HAVING A 2,5-SUBSTITUTED OXAZOLOPYRIMIDINE RING

Номер: US20130079358A1
Принадлежит: SANOFI

The present invention relates to oxazolopyrimidine compounds of the formula I, 2. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein A is chosen from O and S.3. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein X is chosen from (C-C)-alkanediyl claim 1 , (C-C)-alkenediyl and (C-C)-alkanediyl-oxy.4. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein Ris chosen from phenylene and pyridinediyl claim 1 , wherein the phenylene and the pyridinediyl are optionally substituted on one or more ring carbon atoms by identical or different substituents R.5. A compound of the formula I claim 1 , in any of its stereoisomeric forms claim 1 , or a mixture of stereoisomeric forms in any ratio claim 1 , or a physiologically acceptable salt thereof claim 1 , or a physiologically acceptable solvate of any of them claim 1 , as claimed in claim 1 , wherein{'sup': 3', '3', '31, 'sub': 1', '6', '3', '7', 'z', '2u', 'v', '2v', '1', '4, 'Ris chosen from (C-C)-alkyl, (C-C)-cycloalkyl-CHH— and Het-CH—, wherein u and v are chosen from 1 and 2, or Ris a residue of a saturated or unsaturated, 3-membered to 10-membered, monocyclic or bicyclic ring which comprises 0, 1 or 2 identical or different ring heteroatoms chosen from N, O and S, wherein one or two of the ring nitrogen ...

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28-03-2013 дата публикации

Benzisoxazoles and Azabenzisoxazoles as MGLUR4 Allosteric Potentiators, Compositions, and Methods of Treating Neurological Dysfunction

Номер: US20130079366A1
Принадлежит: VANDERBILT UNIVERSITY

Benzisoxazole and azabenzisoxazole compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds, for example, in treating neurological and psychiatric disorders or other disease state associated with glutamate dysfunction. 2. The method of claim 1 , wherein the mammal is a human.3. The method of claim 1 , wherein the dysfunction is Parkinson's disease.4. The method of claim 1 , wherein the dysfunction is schizophrenia claim 1 , psychosis claim 1 , “schizophrenia-spectrum” disorder claim 1 , depression claim 1 , bipolar disorder claim 1 , cognitive disorder claim 1 , delirium claim 1 , amnestic disorder claim 1 , anxiety disorder claim 1 , attention disorder claim 1 , obesity claim 1 , eating disorder claim 1 , or NMDA receptor-related disorder.5. The method of claim 1 , wherein the dysfunction is Parkinson's disease; anxiety; motor effects after alcohol consumption; neurogenic fate commitment and neuronal survival; epilepsy; or certain cancers claim 1 , for example claim 1 , medulloblastoma claim 1 , inflammation (for example claim 1 , multiple sclerosis) and metabolic disorders (for example claim 1 , diabetes) and taste enhancing associated with glutamatergic dysfunction and diseases in which mGluR4 receptor is involved.6. The method of claim 1 , wherein the mammal has been diagnosed with the dysfunction prior to the administering step.7. The method of claim 1 , further comprising the step of identifying a mammal having a need for treatment of the dysfunction.8. The method of claim 1 , wherein the endogenous ligand for mGluR4 potentiation is glutamate claim 1 , L-SOP claim 1 , or a neurotransmitter.925-. (canceled)28. The compound of claim 26 , wherein one X is CRwith Rbeing H claim 26 , and the other X is N.29. The compound of claim 26 , wherein Y is O ...

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28-03-2013 дата публикации

CYCLIC CARBODIIMIDE COMPOUND

Номер: US20130079510A1
Автор: Shoji Shinichiro
Принадлежит: TEIJIN LIMITED

Disclosed is a cyclic carbodiimide compound useful as an end-capping agent for polymer compounds. The cyclic carbodiimide compound is represented by the following formula (i): 2. The compound according to claim 1 , wherein Arto Arare each independently an o-phenylene group or 1 claim 1 ,2-naphthalene-diyl group substituted with a substituent other than a Calkyl group and a phenyl group.9. An end-capping agent for polymer compounds claim 1 , comprising the cyclic carbodiimide compound represented by formula (i) of as an active ingredient.10. An acidic group scavenger claim 1 , comprising the cyclic carbodiimide compound represented by formula (i) of as an active ingredient. The present invention relates to a carbodiimide compound. More specifically, the invention relates to a cyclic carbodiimide compound.Polyesters, polyamides, polyimides, polycarbonates, polyurethanes, and the like have excellent mechanical physical properties and thus have been used for a wide variety of applications. These polymers have a hydrolyzable ester bond, amide bond, imide bond, carbonate bond, or urethane bond in the molecule. Accordingly, when they are used in a more severe environment, a problem with reliability may occur, against which urgent countermeasures have been demanded.The catalytic hydrolysis of a hydrolyzable bond such as an ester bond is promoted by the presence of a polar group such as a carboxyl group in the molecule. Therefore, a method for suppressing such a disadvantage by applying a carboxyl-group-capping agent to reduce the carboxyl group concentration has been proposed (Patent Document 1 and Patent Document 2).As a capping agent for carboxyl groups and like acidic groups, a mono- or polycarbodiimide compound has been used considering the stability and reactivity of the capping agent, the color tone of the resulting product, and the like, and this has been effective to a certain degree. However, mono- and polycarbodiimide compounds are both linear carbodiimide ...

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28-03-2013 дата публикации

BICYCLIC METHYLENE AZIRIDINES AND REACTIONS THEREOF

Номер: US20130079511A1
Принадлежит: WISCONSIN ALUMNI RESEARCH FOUNDATION

The oxidative functionalization of olefins is a common method for the formation of vicinal carbon-heteroatom bonds. However, oxidative methods to transform allenes into synthetic motifs containing three contiguous carbon-heteroatom bonds are much less developed. The use of bicyclic methylene aziridines (MAs), prepared via intramolecular allene aziridination, as scaffolds for functionalization of all three allene carbons, among other reactions, is described herein. 1. A method comprising forming a bicyclic methylene aziridine by an intramolecular allene aziridination reaction;{'sub': '2', 'wherein an allene group is tethered to an —NHgroup, and the amino group is separated from the proximal allene carbon by 3, 4, 5, or 6 atoms linearly;'}the method comprising combining the allene, an effective rhodium catalyst, a solvent, and an oxidant, to provide a reaction mixture, thereby initiating an intramolecular allene aziridination reaction, to provide a bicyclic methylene aziridine.2. The method of wherein the rhodium catalyst is Rh(esp)where esp is α claim 1 ,α claim 1 ,α′ claim 1 ,α′-tetramethyl-1 claim 1 ,3-benzenedipropionate claim 1 , or Rh(TPA)where TPA is triphenylacetate.3. The method of wherein the oxidant is a hypervalent iodide oxidant or a one-electron cerium or lead oxidant.4. The method of wherein the oxidant is PhIO claim 3 , PhI(OAc) claim 3 , PhI(OPiv) claim 3 , Ce(SO) claim 3 , or Pb(OAc).5. The method of wherein the reaction mixture further comprises a drying agent claim 4 , an acid neutralizing agent claim 4 , or a combination thereof.6. The method wherein the aziridine nitrogen of the bicyclic methylene aziridine is substituted by an electron-withdrawing group.7. The method of wherein the allene is mono-substituted claim 1 , di-substituted claim 1 , tri-substituted claim 1 , or tetra-substituted.9. The method of further comprising contacting the bicyclic methylene aziridine with a nucleophile to provide a nucleophile-addition product.10. The method of ...

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04-04-2013 дата публикации

6-(4-Hydroxy-phenyl)-3-alkyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors

Номер: US20130085128A1
Принадлежит: SANOFI

The present invention relates to pyrazolo[3,4-b]pyridine compounds of the formula I, 10. A pharmaceutical composition comprising the compound of .11. A method of treating a disease associated with diabetes or a diabetic complication claim 1 , comprising administering to a human in need thereof a therapeutically effective amount of the compound of .12. A method of preventing or treating a neuropathy claim 1 , a retinopathy claim 1 , an ischemia claim 1 , inflammation claim 1 , a central nervous system disorder claim 1 , a cardiovascular disease claim 1 , a dermatological disease claim 1 , an autoimmune disease claim 1 , or cancer claim 1 , the method comprising administering to a human in need thereof a therapeutically effective amount of the compound of .13. A method of treating a disease associated with the PKC receptor claim 1 , the method comprising administering to a human in need thereof a therapeutically effective amount of the compound of .14. A method of treating a disease associated with diabetes or a diabetic complication claim 9 , comprising administering to a human in need thereof a therapeutically effective amount of the pharmaceutical composition of .15. A method of preventing or treating a neuropathy claim 9 , a retinopathy claim 9 , an ischemia claim 9 , inflammation claim 9 , a central nervous system disorder claim 9 , a cardiovascular disease claim 9 , a dermatological disease claim 9 , an autoimmune disease claim 9 , or cancer claim 9 , the method comprising administering to a human in need thereof a therapeutically effective amount of the pharmaceutical composition of .16. A method of treating a disease associated with the PKC receptor claim 9 , the method comprising administering to a human in need thereof a therapeutically effective amount of the pharmaceutical composition of . Protein kinase C (PKC) comprises a family of several related isoenzymes that function as serine/threonine kinases. PKC plays an important role in intercellular and ...

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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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04-04-2013 дата публикации

PROCESS FOR PRODUCING AN INTERMEDIATE FOR A CYCLIC CARBODIIMIDE COMPOUND

Номер: US20130085273A1
Автор: Shoji Shinichiro
Принадлежит: TEIJIN LIMITED

A process for producing an intermediate for a cyclic carbodiimide compound. 2. The production process according to claim 1 , wherein the metal catalyst is at least one selected from the group consisting of palladium claim 1 , ruthenium claim 1 , platinum claim 1 , rhodium claim 1 , nickel claim 1 , copper claim 1 , metal oxides thereof claim 1 , metal hydroxides thereof and metal-supported catalysts obtained by precipitating any one of them on a carrier selected from activated carbon claim 1 , alumina claim 1 , titania and silica.31. The production process according to claim 1 , wherein the basic compound is triethylamine.5. The production process according to claim 4 , wherein methyl ethyl ketone is used as a reaction solvent. The present invention relates to a process for producing an amine compound or a thiourea compound which is useful as an intermediate for a cyclic carbodiimide compound.Since the hydrolysis of a compound having an ester bond such as a polyester is promoted by a polar group such as a carboxyl group, it is proposed to reduce the concentration of the carboxyl group by using a sealing agent for a carboxyl group (Paten Document 1, Patent Document 2). A carbodiimide compound is used as the sealing agent for a carboxyl group.However, since this carbodiimide compound is a linear compound, a volatile isocyanate compound is by-produced during use and generates a bad odor, thereby deteriorating work environment.Then, the inventors of the present invention found as the sealing agent a cyclic carbodiimide compound which does not by-produce an isocyanate compound when it reacts with a carboxyl group and filed an international application (Patent Document 3). However, industrial processes for producing this useful cyclic carbodiimide compound and an intermediate therefor have not been established.It is an object of the present invention to improve the reaction yield of an amine compound represented by the following formula (B) when it is synthesized by ...

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04-04-2013 дата публикации

PROCESS FOR THE PRODUCTION OF A CARBODIIMIDE

Номер: US20130085274A1
Принадлежит:

A process for the production of a carbodiimide, comprising the steps of: 2. The production process according to claim 1 , wherein the step (1) is carried out in the presence of a hydrogen sulfide capture agent.3. The production process according to claim 1 , wherein the step (1) is carried out in a sealed condition.4. The production process according to claim 1 , wherein the catalyst used in the step (1) is a compound having basicity with a pKa of its conjugate acid of 5 or more.5. The production process according to claim 4 , wherein the compound having basicity with a pKa of its conjugate acid of 5 or more is a substituted tertiary amine claim 4 , a substituted imine claim 4 , a substituted amide or a substituted heterocyclic ring.7. The production process according to claim 1 , wherein the hypochlorite used in the step (2) is sodium hypochlorite.8. The production process according to claim 1 , wherein the basic compound in the step (2) is sodium hydroxide claim 1 , potassium hydroxide or a mixture thereof.9. The production process according to claim 1 , wherein the purification of the step (3) is recrystallization or extraction.12. The production process according to claim 10 , wherein the phase transfer catalyst is at least one compound selected from the group consisting of tetraethylammonium salts claim 10 , tetrabutylammonium salts claim 10 , trioctylmethylammonium salts claim 10 , benzyldimethyloctadecylammonium salts claim 10 , benzyltriethylammonium salts claim 10 , benzyltrimethylammonium salts and benzyltributylammonium salts.13. The production process according to claim 10 , wherein the aqueous solution of an alkali metal hydroxide is a sodium hydroxide aqueous solution or a potassium hydroxide aqueous solution. The present invention relates to a process for the production of a carbodiimide and, more specifically, to a process for the production of a specific carbodiimide.It is proposed that the concentration of carboxyl groups should be reduced by using ...

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11-04-2013 дата публикации

AZABENZOXAZINE DERIVATIVES AS CRAC MODULATORS

Номер: US20130090334A1
Принадлежит: Hoffmann-La Roche Inc

Compounds of the formula (I): 2. The compound according to claim 1 , wherein Ris phenyl mono- or bi-substituted independently with F or Cl.3. The compound according to claim 1 , wherein Ris difluoro-phenyl.4. The compound according to claim 1 , wherein Ris chloro-fluoro-phenyl.5. The compound according to claim 1 , wherein Ris phenyl claim 1 , unsubstituted or mono- or bi-substituted independently with lower alkyl claim 1 , halogen claim 1 , halo-lower alkyl claim 1 , alkoxy claim 1 , unsubstituted five-membered heteroaryl ring or five-membered heteroaryl ring substituted with lower alkyl.6. The compound according to claim 1 , wherein Ris phenyl substituted with methyl and oxazole.7. The compound according to claim 1 , wherein Ris pyridine claim 1 , unsubstituted or mono- or bi-substituted independently with lower alkyl claim 1 , halogen claim 1 , halo-lower alkyl claim 1 , alkoxy claim 1 , SOCHCH claim 1 , unsubstituted five-membered heteroaryl ring claim 1 , five-membered heteroaryl ring substituted with lower alkyl claim 1 , unsubstituted six-membered heteroaryl ring or six-membered heteroaryl ring substituted with an amino moiety.8. The compound according to claim 1 , wherein Ris pyridine claim 1 , unsubstituted or mono- or bi-substituted independently with —CH claim 1 , —OCH claim 1 , —SOCHCH claim 1 , chlorine claim 1 , oxazole claim 1 , methyl-pyrimidine-amine claim 1 , methyl-thiazole or methyl-tetrazole.9. The compound according to claim 1 , wherein Ris a five-membered heteroaryl ring claim 1 , unsubstituted or mono- or bi-substituted independently with lower alkyl claim 1 , halogen claim 1 , halo-lower alkyl claim 1 , alkoxy claim 1 , unsubstituted five-membered heteroaryl ring claim 1 , five-membered heteroaryl ring substituted with lower alkyl claim 1 , unsubstituted six-membered heteroaryl ring or six-membered heteroaryl ring substituted with lower alkyl.10. The compound according to claim 1 , wherein Ris pyrazole or thiazole claim 1 , mono- or bi- ...

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11-04-2013 дата публикации

POLYMORPHIC FORMS OF RIFAXIMIN

Номер: US20130090348A1
Принадлежит: APOTEX PHARMACHEM INC.

Provided for in the instant application are two additional polymorphic forms of rifaximin; namely substantially pure APO-I and APO-II. Also provided are processes for preparing substantially pure APO-I and APO-II. Rifaximin is a non-aminoglycoside antibiotic that has previously been found to be useful for the treatment of traveller's diarrhea caused by bacteria, as well as in the treatment of irritable bowel syndrome, diverticular disease, hepatic encephalopathy, pyogenic skin infections and as an antibacterial prophylactic prior to colon surgery. 1. Substantially pure polymorphic form APO-I of Rifaximin.2. The polymorphic form APO-I of Rifaximin of having a PXRD diffractogram comprising peaks claim 1 , in terms of degrees 2-theta claim 1 , at approximately 6.32 claim 1 , 6.70 claim 1 , 8.36 claim 1 , 9.57 claim 1 , 12.67 and 18.733. The polymorphic form APO-I of Rifaximin of having a PXRD diffractogram comprising peaks claim 1 , in terms of degrees 2-theta claim 1 , at approximately 6.32 claim 1 , 6.52 claim 1 , 6.54 claim 1 , 6.70 claim 1 , 8.36 claim 1 , 8.38 claim 1 , 9.57 claim 1 , 12.67 claim 1 , 12.68 claim 1 , 18.73 and 24.94.4. (canceled)5. The polymorphic form APO-I of Rifaximin of having a PXRD diffractogram as depicted in .6. The polymorphic form APO-I of Rifaximin of having a 1% KBr FTIR spectrum comprising peaks claim 1 , in terms of cm claim 1 , at approximately 3427.9 claim 1 , 2968.1 claim 1 , 2934.1 claim 1 , 1714.2 1647.7 claim 1 , 1587.3 claim 1 , 1507.1 claim 1 , 1373.7 claim 1 , 1338.1 claim 1 , 1226.4 claim 1 , 1157.0 claim 1 , and 1124.1.78.-. (canceled)9. The polymorphic form APO-I of Rifaximin of having a FTIR spectrum as depicted in .10. A pharmaceutical formulation comprising the polymorphic form APO-I of Rifaximin of and a pharmaceutically acceptable excipient.11. A process for preparation of a substantially pure polymorphic form APO-I of Rifaximin comprising:dissolving Rifaximin in a first organic solvent thereby forming a Rifaximin ...

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18-04-2013 дата публикации

Compounds for the Treatment of Hepatitis C

Номер: US20130095066A1
Принадлежит:

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

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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

AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS

Номер: US20130096102A1
Принадлежит: Genentech, Inc.

Compounds of the formula I: 126-. (canceled)28. The compound of claim 27 , wherein X is —NH—.29. The compound of claim 27 , wherein X is —O—.30. The compound of claim 27 , wherein Ris Calkyl.32. The compound of claim 28 , wherein Ris: methyl; ethyl; orcyclopropyl.33. The compound of claim 32 , wherein Ris trifluoromethyl.34. The compound of claim 27 , wherein Ris: halo; or Calkoxy;35. The compound of claim 27 , wherein Ris: halo; Calkyl; or Calkoxy.36. The compound of claim 33 , wherein Ris: methoxy; chloro; or fluoro.37. The compound of claim 34 , wherein Ris: fluoro; chloro; methyl; or methoxy.38. The compound of claim 36 , wherein m is 1.39. A composition comprising:(a) a pharmaceutically acceptable carrier; and{'claim-ref': {'@idref': 'CLM-00027', 'claim 27'}, '(b) a compound of .'}40. A method for treating Parkinson's disease claim 27 , said method comprising administering to a subject in need thereof an effective amount of a compound of . This invention pertains to compounds that modulate the function of LRRK2 and are useful for treatment of LRRK2-mediated diseases and conditions such as Parkinson's disease.Neurodegenerative diseases such as Parkinson's disease, Lewy body dementia and Huntington's disease affect millions of individuals. Parkinson's disease is a chronic, progressive motor system disorder that afflicts approximately one out of every 1000 people, with hereditary Parkinson's disease accounting for 5-10% of all of patients. Parkinson's disease is caused by progressive loss of mid-brain dopamine neurons, leaving patients with impaired ability to direct and control their movements. The primary Parkinson's disease symptoms are trembling, rigidity, slowness of movement, and impaired balance. Many Parkinson's disease patients also experience other symptoms such as emotional changes, memory loss, speech problems, and sleeping disorders.The gene encoding the leucine-rich repeat kinase 2 protein (LRRK2) has been identified in association with hereditary ...

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18-04-2013 дата публикации

Pyridone derivative having integrase inhibitory activity

Номер: US20130096109A1
Принадлежит: Shionogi and Co Ltd

An object of the present invention is to provide a novel integrase inhibitor. The present invention relates to a novel compound having an antiviral effect, more specifically, a pyridone derivative having HIV integrase inhibitory activity, and a medicament containing the same, in particular, an anti-HIV agent. The compound of the present invention has integrase inhibitory activity and/or cell proliferation inhibitory activity against viruses, in particular, HIV and drug-resistant strains thereof. Thus, the compound is useful in preventing or treating various diseases, viral infections (for example, AIDS), and the like in which integrase participates.

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18-04-2013 дата публикации

PROCESSES AND INTERMEDIATES

Номер: US20130096277A1
Автор: Tanoury Gerald J.
Принадлежит: VERTEX PHARMACEUTICALS INCORPORATED

A process for preparing enantioselectively a compound of formula I-1a or I-1b: 2. The process of claim 1 , wherein ring A is Ccycloaliphatic.32. The process of - claims 1 , wherein ring A is cyclopropyl.42. The process of - claims 1 , wherein ring A is cyclopentyl.52. The process of - claims 1 , wherein ring A is 1 claims 1 ,1-dimethylcyclopropyl.9. The process of claim 1 , wherein ring B is a 5-membered heterocyclic ring.11. The process of claim 1 , wherein ring B is substituted with an aryl ring optionally substituted with 0 to 4 groups claim 1 , each independently selected from alkyl claim 1 , halo claim 1 , alkoxy claim 1 , and hydroxyl.12. The process of claim 11 , wherein the aryl ring is phenyl.1514. The process of - claims 1 , wherein Ris H.1614. The process of - claims 1 , wherein Ris Caliphatic.1714. The process of - claims 1 , wherein Ris tert-butyl.2120. The process of - claims 18 , wherein Ris Caliphatic.2220. The process of - claims 18 , wherein Ris a cycloaliphatic.2320. The process of - claims 18 , wherein Ris Caliphatic.2420. The process of - claims 18 , wherein Ris Calkyl.2520. The process of - claims 18 , wherein Ris selected from methyl claims 18 , ethyl claims 18 , n-propyl claims 18 , iso-propyl claims 18 , iso-butyl claims 18 , n-butyl claims 18 , n-pentyl claims 18 , and iso-pentyl.2620. The process of - claims 1 , wherein Ris iso-butyl.2726. The process of - claims 1 , wherein Ris tert-butyl carbamate (Boc).2827. The process of - claims 1 , wherein the carboxylation step includes treating a compound of formula II with carbon dioxide and a lithium base in the presence of an aprotic solvent.29. The process of claim 28 , wherein the aprotic solvent is toluene claim 28 , ethyl acetate claim 28 , benzene claim 28 , and methyl tert-butyl ether.30. The process of claim 28 , wherein the aprotic solvent is methyl tert-butyl ether.31. The process of claim 28 , wherein the lithium base is sec-butyl lithium.3231. The process of - claims 1 , wherein the ...

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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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09-05-2013 дата публикации

HETEROARYL PYRIDONE AND AZA-PYRIDONE COMPOUNDS

Номер: US20130116235A1
Принадлежит: Genentech, Inc.

Heteroaryl pyridone and aza-pyridone compounds of Formula I are provided, where one or two of X, X, and Xare N, and including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 2. The compound of wherein Xis N.3. The compound of wherein Xis N.4. The compound of wherein Xis N.5. The compound of wherein Xand Xare N claim 1 , Xand Xare N claim 1 , or Xand Xare N.6. The compound of wherein Ris optionally substituted C-Cheteroaryl selected from pyrazolyl claim 1 , pyridinyl claim 1 , pyrimidinyl claim 1 , 5-methyl-4 claim 1 ,5 claim 1 ,6 claim 1 ,7-tetrahydropyrazolo[1 claim 1 ,5-a]pyrazin-2-yl claim 1 , 5-acetyl-4 claim 1 ,5 claim 1 ,6 claim 1 ,7-tetrahydropyrazolo[1 claim 1 ,5-a]pyrazin-2-yl claim 1 , 6 claim 1 ,7-dihydro-4H-pyrazolo[5 claim 1 ,1-c][1 claim 1 ,4]oxazin-2-yl claim 1 , and 1-methyl-5-(5-(4-methylpiperazin-1-yl)pyridin-2-yl.7. The compound of wherein Ris —(C-Cheteroaryl)-(C-Cheterocyclyl) where heteroaryl is optionally substituted pyridinyl and heterocyclyl is optionally substituted piperazinyl.8. The compound of wherein Ris phenyl claim 1 , optionally substituted with one or more groups selected from F claim 1 , Cl claim 1 , —CH claim 1 , —S(O)CH claim 1 , cyclopropyl claim 1 , azetidinyl claim 1 , oxetanyl claim 1 , and morpholino.11. The compound of wherein Ris CH.12. The compound of wherein Yis CH and Yis N.13. The compound of wherein Yis N and Yis CH.14. The compound of wherein Yand Yare each CH.15. The compound of wherein Yand Yare each CH claim 1 , and Ris CH.16. The compound of selected from Table 1.17. The compound of selected from Table 218. A pharmaceutical composition comprised of a compound of and a pharmaceutically ...

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09-05-2013 дата публикации

ALKYLATED PIPERAZINE COMPOUNDS

Номер: US20130116245A1
Принадлежит: Genentech, Inc.

Alkylated piperazine compounds of Formula I are provided, including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed. 2. The compound of wherein X is CR claim 1 , and Ris H3. The compound of wherein X is N.4. The compound of wherein Ris —CHOH.5. The compound of wherein Ris F.6. The compound of wherein Rand Rare H.7. The compound of wherein Ris CH.8. The compound of selected from Table 1.9. The compound of selected from Table 2.10. A pharmaceutical composition comprised of a compound of and a pharmaceutically acceptable carrier claim 1 , glidant claim 1 , diluent claim 1 , or excipient.11. The pharmaceutical composition according to claim 10 , further comprising a therapeutic agent.12. A process for making a pharmaceutical composition which comprises combining a compound of with a pharmaceutically acceptable carrier.13. A method of treating a disease or disorder which comprises administering a therapeutically effective amount of the pharmaceutical composition of to a patient with a disease or disorder selected from immune disorders claim 10 , cancer claim 10 , cardiovascular disease claim 10 , viral infection claim 10 , inflammation claim 10 , metabolism/endocrine function disorders and neurological disorders claim 10 , and mediated by Bruton's tyrosine kinase.14. The method of wherein the disease or disorder is an immune disorder.15. The method of wherein the immune disorder is rheumatoid arthritis.16. The method of wherein the disease or disorder is systemic and local inflammation claim 13 , arthritis claim 13 , inflammation related to immune suppression claim 13 , organ transplant rejection claim 13 , allergies claim 13 , ulcerative colitis ...

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09-05-2013 дата публикации

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

Номер: US20130116246A1
Принадлежит: Genentech, Inc.

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

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16-05-2013 дата публикации

Herbicidal Isoxazolo[5,4-B]pyridines

Номер: US20130123105A1
Принадлежит: BASF SE

The invention relates to isoxazolo[5,4-b]pyridine compounds of formula I, 116-. (canceled)18. The method as claimed in claim 17 , wherein in formula I{'sup': '1', 'sub': 1', '6', '1', '6, 'Ris hydrogen, halogen, C-C-alkyl, or C-C-haloalkyl.'}19. The method as claimed in claim 17 , wherein in formula I{'sup': '2', 'sub': 1', '6', '1', '6', '1', '6', '3', '6', '3', '6', '2', '6', '2', '6, 'Ris hydrogen, C-C-alkyl, C-C-haloalkyl, C-C-hydroxyalkyl, C-C-cycloalkyl, C-C-halocycloalkyl, C-C-alkenyl, or C-C-alkynyl.'}20. The method as claimed in claim 17 , wherein in formula I{'sup': '1', 'Ris hydrogen;'}{'sup': '2', 'sub': 1', '6', '1', '6', '1', '6', '3', '6', '3', '6', '2', '6', '2', '6, 'Ris hydrogen, C-C-alkyl, C-C-haloalkyl, C-C-hydroxyalkyl, C-C-cycloalkyl, C-C-halocycloalkyl, C-C-alkenyl, or C-C-alkynyl;'}{'sup': 3', '3, 'sub': 1', '6', '1', '6', '3', '6', '1', '6', '3', '6', '1', '6', '3', '6', '3', '6', '1', '4', '3', '6', '1', '6', '1', '6', '1', '4', '1', '4', '1', '4', '1', '4', '3', '6', '2', '6', '2', '6', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'Ris C-C-alkyl, C-C-haloalkyl, C-C-cycloalkyl-C-C-alkyl, C-C-halocycloalkyl-C-C-alkyl, C-C-cycloalkyl, C-C-halocycloalkyl, C-C-alkyl-C-C-cycloalkyl, C-C-alkoxy, C-C-haloalkoxy, or phenyl; wherein the phenyl moieties of Rcan be unsubstituted or substituted with one or more radicals selected from the group consisting of halogen, hydroxy, nitro, cyano, C-C-alkyl, C-C-haloalkyl, C-C-alkoxy-C-C-alkyl, C-C-cycloalkyl, C-C-alkenyl, C-C-alkynyl, C-C-alkoxy, C-C-haloalkoxy, C-C-alkoxycarbonyl, C-C-alkylsulfinyl, C-C-alkylsulfonyl, amino, C-C-alkylamino, N,N-di-(C-C)-alkylamino, heterocyclyl, or phenyl;'}{'sup': 4', '5, 'X is ORor SR.'}21. The method as claimed in claim 17 , wherein in formula I{'sup': '4', 'X is OR;'}{'sup': '4', 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2', '6', '2', '6', '2', '6, 'Ris hydrogen, C-C-alkyl, C-C-haloalkyl, C-C-cyanoalkyl, C-C- ...

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16-05-2013 дата публикации

TETRACYCLINE DERIVATIVES WITH REDUCED ANTIBIOTIC ACTIVITY AND NEUROPROTECTIVE BENEFITS

Номер: US20130123217A1
Принадлежит: NEUMEDICS

The present disclosure is directed to compositions and methods which utilize the tetracycline scaffold, preferably the scaffold of tetracycline or minocycline, and which significantly lack antibiotic activity. The compounds have neuroprotective attributes without interfering with the drugs capacity to pass through the blood brain barrier. These compounds have neuroprotective activity because of their inhibition of neuronal cell cycle progression. The compounds are characterized in part by a fifth ring joining positions 9 and 10. 2. The compound of claim 1 , where Ris NH(CH)OH.3. The compound of claim 2 , where the compound is an up epimer at R.4. The compound of claim 1 , where Ris disubstituted.5. The compound of claim 4 , where one Rsubstitution is N(CH)and the other substitution is an alkyl.6. The compound of claim 1 , where Ris a substitutent that reduces antibiotic potency.7. The compound of claim 1 , where R″ at Ris benzyl or phenyl.8. The compound of claim 1 , where Rand Rtaken together form a 2 to 5 membered ring of the formula O—Y—HN— claim 1 , and where Y is CH or CO.9. The compound of claim 1 , where Rcontains nitrogen.10. The compound of claim 1 , where Ris a capped phenolic O.11. A method of ameliorating a neurodegenerative disease claim 1 , comprising the step of administering to a subject in need thereof a composition comprising a therapeutically effective amount of a compound of .12. The method of claim 11 , wherein the composition inhibits neuronal cell cycle progression before entry of a neuronal cell into a synthesis (S) phase.13. The therapeutic method of claim 11 , wherein the composition inhibits neuronal cell cycle progression at or prior to the early growth (G 1) phase.14. The method of claim 11 , further comprising the administration of a secondary agent selected from the group consisting of acetylsalicylic acid claim 11 , any salicylate which inhibits early phase cell cycle progression claim 11 , sirolimus claim 11 , any sirolimus ...

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16-05-2013 дата публикации

NOVEL BENZOXAZINE OXAZOLIDINONE COMPOUNDS, PREPARATION METHODS AND USES THEREOF

Номер: US20130123249A1
Принадлежит:

Novel benzoxazine oxazolidinone compounds, preparation methods and uses thereof are disclosed, which belong to the field of pharmacy. More specifically, novel benzoxazine oxazolidinone compounds represented by the following general formula (I), preparation methods and uses thereof in preparing medicament for treating infectious diseases, especially infectious diseases caused by multi-drug resistant bacteria, are disclosed. 112-. (canceled)14. Benzoxazine oxazolidinone compounds represented by the general formula (I) claim 13 , optical isomers or pharmaceutically acceptable salts thereof according to claim 13 , wherein said five membered or six membered aromatic or non-aromatic heterocyclic group comprises 1 to 2 N atoms;{'sub': 2', '2', '3', '2', '3', '3', '3', '3', '4', '3', '3', '4', '1', '3, 'Said five membered or six membered aromatic or non-aromatic heterocyclic group may optionally be substituted by the following functional groups: F, Cl, Br, —OH, —NO, —CHO, —CN, —NH, —CF, —C≡CH, —C≡CCHOH, —COOH, —OR, —NHCOR, —COR; —CONRR, and —COOR, wherein each of Rand Rcan independently be C-Calkyl;'}{'sub': 1', '6', '3', '6', '1', '6', '3', '6', '2, 'or said five membered or six membered aromatic or non-aromatic heterocyclic group may optionally be substituted by C-Cstraight chain or branched chain alkyl group, or C-Ccycloalkyl group, and said C-Cstraight chain or branched chain alkyl group or C-Ccycloalkyl group may optionally be substituted by —OH, —CN, or —NH;'}{'sub': 1', '3, 'or said five membered or six membered aromatic or non-aromatic heterocyclic group may optionally be substituted by five membered or six membered aromatic or non-aromatic heterocyclic group, which contains at least one heteroatom selected from N and O and is either unsubstituted or substituted by C-Calkyl or oxygen.'}15. Benzoxazine oxazolidinone compounds represented by the general formula (I) claim 13 , optical isomers or pharmaceutically acceptable salts thereof according to claim 13 , wherein ...

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16-05-2013 дата публикации

SPIRO (PIPERIDINE-4,2'-PYRROLIDINE)-1-(3,5-TRIFLUOROMETHYLPHENYL) METHYLCARBOXAMIDES AS NK1 TACHIKYNIN RECEPTOR ANTAGONISTS

Номер: US20130123250A1
Принадлежит: GLAXO WELLCOME MANUFACTURING PTE LTD

Compounds of formula (I) or pharmaceutically acceptable salts thereof 2. The method according to claim 1 , wherein the compound of formula (I) is selected from:{'sup': 8', '8, '(5R,7R)—N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-7-(4-fluoro-2-methylphenyl)-N-methyl-1,8-diazaspiro[4.5]decane-2,8-dicarboxamide (diastereoisomer 1);'}{'sup': 8', '8, '(5R,7R)—N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-7-(4-fluoro-2-methylphenyl)-N-methyl-1,8-diazaspiro[4.5]decane-2,8-dicarboxamide (diastereoisomer 2);'}{'sup': 8', '8, '(2R,5S,7R)—N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-7-(4-fluoro-2-methylphenyl)-N-methyl-1,8-diazaspiro[4.5]decane-2,8-dicarboxamide;'}{'sup': 8', '8, '(2R,5S,7R)—N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-7-(4-fluoro-2-methylphenyl)-N-methyl-1,8-diazaspiro[4.5]decane-2,8-dicarboxamide;'}{'sup': 8', '8, '(2S,5S,7R)—N-{[3,5-bis(trifluoromethyl)phenyl]methyl}-7-(4-fluoro-2-methylphenyl)-N-methyl-1,8-diazaspiro[4.5]decane-2,8-dicarboxamide;'}{'sup': 8', '8, '(2S,5S,7R)—N-{[3,5-bis(trifluoromethyl)phenyl]methyl}-7-(4-fluoro-2-methylphenyl)-N-methyl-1,8-diazaspiro[4.5]decane-2,8-dicarboxamide;'}{'sup': 8', '8, '(2S,5S,7R)—N-{(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-7-(4-fluoro-2-methylphenyl)-N-methyl-1,8-diazaspiro[4.5]decane-2,8-dicarboxamide;'}{'sup': 8', '8, '(2S,5S,7R)—N-{(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-7-(4-fluoro-2-methylphenyl)-N-methyl-1,8-diazaspiro[4.5]decane-2,8-dicarboxamide;'}sodium(5S,7R)-8-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-7-(4-fluoro-2-methylphenyl)-1,8-diazaspiro[4.5]decane-3-carboxylate;lithium(4S,5R,7R)-8-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-7-(4-fluoro-2-methylphenyl)-1,8-diazaspiro[4.5]decane-4-carboxylate;(5S,7R)—N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-7-(4-fluoro-2-methylphenyl)-N-methyl-1,8-diazaspiro[4.5]decane-8-carboxamide;(2R,5S,7R)—N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-7-(4-fluoro-2-methylphenyl)- ...

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23-05-2013 дата публикации

SUBSTITUTED ISOQUINOLINES AND THEIR USE AS TUBULIN POLYMERIZATION INHIBITORS

Номер: US20130131018A1
Принадлежит: Exonhit S.A.

The present invention relates generally to substituted isoquinolines and their use as tubulin polymerization inhibitors. In particular, the invention relates to substituted isoquinolines which possess useful therapeutic activity, use of these compounds in methods of therapy and the manufacture of medicaments as well as compositions containing these compounds. 117.-. (canceled)19. The compound according to wherein:{'sup': '+', 'sub': 1', '6, 'X represents N or N—Z, wherein Z is selected in the group consisting of a (C-C)alkyl, an aryl and an acyl;'}{'sub': 1', '1', '5, 'claim-text': wherein Ra represents a NRa′Ra″ or ORa′″ group;', {'sub': 1', '5, 'wherein Ra′ and Ra″, independently from each other, are selected from the group consisting of H and (C-C)alkyl;'}, {'sub': 1', '5, 'wherein Ra′″ represents H or (C-C)alkyl;'}], 'Rrepresents H, CN, a CORa or a (C-C)alkyl;'}{'sub': 3', '2', '1', '5, 'claim-text': wherein Rb represents a NRb′Rb″ or ORb′″ group;', {'sub': 1', '5, 'wherein Rb′ and Rb′, independently from each other, are selected from the group consisting of H and (C-C)alkyl;'}, {'sub': 1', '5, 'wherein Rb′″ represents H or (C-C)alkyl;'}], 'Rrepresents H, CN, OH, a CORb, NHor a (C-C)alkyl;'}{'sub': 7', '1', '5', '1', '5', '1', '5', '1', '5', '1', '5, 'Rrepresents a (C-C)alkyl, a (C-C)alkoxy, a (C-C)alkylthio, a (C-C)alkylamino, a (C-C)dialkylamino;'}{'sub': 8', '1', '6', '2, 'claim-text': [{'sub': 1', '6', '2', '6', '2, 'wherein R and R′, independently from each other, are selected from the group consisting of H, a (C-C)alkyl, a (C-C)alkenyl, an acyl, an aryl, a heterocyclyl, amino acid, a Y—SOgroup, a P(O)(OG)(OG′) group,'}, {'sub': 1', '6', '2', '1', '6', '1', '6', '1', '6, 'wherein Y is selected in the group consisting of a hydrogen atom, (C-C)alkyl, NH, (C-C)alkylamino, di(C-C)alkylamino and (C-C)alkoxycarbonylamino;'}, {'sub': 1', '6, 'wherein G and G′, independently from each other, are selected in the group consisting of H, (C-C)alkyl and aryl;'}], ' ...

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23-05-2013 дата публикации

5,7-SUBSTITUTED-IMIDAZO[1,2-C]PYRIMIDINES AS INHIBITORS OF JAK KINASES

Номер: US20130131039A1
Принадлежит: ARRAY BIOPHARMA INC.

Compounds of Formula I: (Formula should be inserted here) and stereoisomers and pharmaceutically acceptable salts and solvates thereof in which R, R, R, R, R, R, R, Xand Xhave the meanings given in the specification, are inhibitors of one or more JAK kinases and are useful in the treatment of autoimmune diseases, inflammatory diseases, rejection of transplanted organs, tissues and cells, as well as hematologic disorders and malignancies and their co-morbidities. 2. (canceled)2. A compound according to claim 1 , wherein Ris hetAror hetAr.3. A compound according to claim 1 , wherein Ris hetAr.4. A compound according to claim 1 , wherein hetAris pyrazolyl claim 1 , thiazolyl claim 1 , oxazolyl claim 1 , thiadiazolyl claim 1 , imidazolyl claim 1 , pyrrolyl or thiophenyl optionally substituted with one or more substituents independently selected from (1-6C)alkyl claim 1 , fluoro(1-6C)alkyl claim 1 , difluoro(1-6C)alkyl claim 1 , trifluoro(1-6C)alkyl claim 1 , (1-4C alkoxy)(1-6C)alkyl claim 1 , trimethylsilyl(1-4C alkoxy)(1-6C)alkyl claim 1 , (3-6C)cycloalkyl claim 1 , a 4-6 membered oxacyclic ring claim 1 , hetCyc(1-2C)alkyl and hetAr(1-2C)alkyl.5. A compound according to claim 1 , wherein hetAris pyrazol-4-yl claim 1 , thiazol-5-yl claim 1 , imidazol-1-yl or 1 claim 1 ,3 claim 1 ,4-thiadiazol-2-yl optionally substituted with one or more substituents independently selected from methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , isobutyl claim 1 , 2 claim 1 ,2 claim 1 ,2-trifluoroethyl claim 1 , (2-isopropoxy)ethyl claim 1 , trimethylsilylethoxymethyl claim 1 , cyclobutyl claim 1 , oxetanyl claim 1 , 4-tetrahydro-2H-pyranyl claim 1 , (4-methylpiperazinyl)ethyl and pyrid-3-ylmethyl.6. A compound according to claim 1 , wherein hetAris pyrazol-4-yl optionally substituted with a substituent selected from methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , isobutyl claim 1 , 2 claim 1 ,2 claim 1 ,2-trifluoroethyl claim 1 , (2-isopropoxy)ethyl claim 1 , ...

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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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23-05-2013 дата публикации

SPIROXAZOLIDINONE COMPOUNDS

Номер: US20130131042A1
Принадлежит: Merck Sharp & Dohme Corp.

Substituted spirocyclic amines of structural formula (I) are selective antagonists of the somatostatin subtype receptor 5 (SSTR5) and are useful for the treatment, control or prevention of disorders responsive to antagonism of SSTR5, such as Type 2 diabetes, insulin resistance, lipid disorders, obesity, atherosclerosis, Metabolic Syndrome, depression, and anxiety. 2. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein at each occurrence of Ra claim 1 , Ra is hydrogen.3. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris phenyl.4. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris pyridine.5. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris substituted with OH claim 1 , —C-Calkyl claim 1 , —COOH claim 1 , COO—C-Calkyl claim 1 , —O—C-Calkyl —C-Ccycloalkyl claim 1 , —CON(C-Calkyl)NH(C-Calkyl) or heterocycle claim 1 , wherein the —C-Calkyl claim 1 , —C-Ccycloalkyl or —OC-Calkyl is unsubstituted or substituted with 1-4 substituents selected from the group consisting of halogen and —COOH.6. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris imidazole claim 1 , naphthalene claim 1 , phenyl claim 1 , pyridine claim 1 , benzimidazole claim 1 , indole claim 1 , oxazole claim 1 , thiazole claim 1 , benzofuran claim 1 , benzocyclopentane claim 1 , benzotetrahydropyran or pyrazole.7. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris phenyl.8. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris pyridine.9. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris imidazole.10. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris substituted with two substituents independently selected from α.11. A compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris substituted with three substituents ...

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23-05-2013 дата публикации

FUROPYRIDINYL-SUBSTITUTED 1,4-DIHYDROPYRIDINE DERIVATIVES AND METHODS OF USE THEREOF

Номер: US20130131055A1
Принадлежит: Bayer Intellectual Property GmbH

This invention relates to novel 4-(furo[3,2-c]pyridin-2-yl)-1,4-dihydropyridine derivatives having protein tyrosine kinase inhibitory activity, to a process for the manufacture thereof and to the use thereof for the treatment of c-Met-mediated diseases or c-Met-mediated conditions, particularly cancer and other proliferative disorders. 5. (canceled)6. (canceled)7. (canceled)8. A pharmaceutical composition comprising a compound as defined in claim 1 , or a pharmaceutically acceptable salt claim 1 , hydrate and/or solvate thereof claim 1 , and a pharmaceutically acceptable excipient.9. The pharmaceutical composition of further comprising one or more additional therapeutic agents.10. The pharmaceutical composition of claim 9 , wherein the additional therapeutic agent is an anti-tumor agent.11. (canceled)12. A method of treating or preventing a cell proliferative disorder in a mammal claim 1 , comprising administering to a mammal in need thereof a therapeutically effective amount of a compound as defined in .13. The method of claim 12 , wherein the cell proliferative disorder is cancer.14. The method of claim 13 , wherein the cancer is a cancer of the breast claim 13 , respiratory tract claim 13 , brain claim 13 , reproductive organs claim 13 , digestive tract claim 13 , urinary tract claim 13 , eye claim 13 , liver claim 13 , skin claim 13 , head or neck claim 13 , thyroid claim 13 , parathyroid claim 13 , or a distant metastasis of a solid tumor.15. The method of claim 13 , wherein the compound is administered in conjunction with surgery or radiation therapy.16. A method of treating or preventing a cell proliferative disorder in a mammal claim 8 , comprising administering to a mammal in need thereof a therapeutically effective amount of a pharmaceutical composition as defined in .17. The method of claim 16 , wherein the cell proliferative disorder is cancer.18. The method of claim 17 , wherein the cancer is a cancer of the breast claim 17 , respiratory tract claim 17 ...

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23-05-2013 дата публикации

Quinuclidine Compounds as Alpha-7 Nicotinic Acetylcholine Receptor Ligands

Номер: US20130131064A1
Принадлежит: BRISTOL-MYERS SQUIBB COMPANY

The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic α7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders. 2. A compound of claim 1 , or a stereoisomer thereof claim 1 , wherein Ris N-(halopyrrolo[1 claim 1 ,2-f][1 claim 1 ,2 claim 1 ,4]triazin-4-yl); or a pharmaceutically acceptable salt thereof.3. A compound of claim 1 , or a stereoisomer thereof claim 1 , wherein Ris N-(7-halopyrrolo[1 claim 1 ,2-f][1 claim 1 ,2 claim 1 ,4]triazin-4-yl); or a pharmaceutically acceptable salt thereof.5. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.7. A method for the treatment of schizophrenia claim 1 , Alzheimer's Disease claim 1 , cognitive disorders claim 1 , rheumatoid arthritis claim 1 , osteoarthritis claim 1 , ulcerative colitis claim 1 , Crohn's Disease claim 1 , or diabetes comprising administering a therapeutically affective amount of a compound of to a patient.8. The method of directed to schizophrenia.10. The method of directed to Alzheimer's disease. This Continuation application claims the benefit of U.S. Ser. No. 13/270,121 filed Oct. 10, 2011 which in turn is a Continuation application which claims the benefit of U.S. Ser. No. 12/607,354 filed Oct. 28, 2009, now U.S. Pat. No. 8,309,577 which in turn is a Continuation-in-Part application which claims the benefit of U.S. Ser. No. 12/423,299 filed Apr. 14, 2009, now U.S. Pat. No. 7,863,291 which in turn claims the benefit of U.S. Provisional Application U.S. Ser. No. 61/047,211 filed Apr. 23, 2008, now expired.The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the ...

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23-05-2013 дата публикации

Harmful organism control agent

Номер: US20130131091A1
Принадлежит: Meiji Seika Pharma Co Ltd

The present invention provides a composition for use as a harmful organism control agent comprising as an active ingredient one or more of compounds represented by formula (I) or salts thereof and an agriculturally or zootechnically acceptable carrier. wherein Het represents pyridyl; X represents an oxygen atom; R 1 , R 2 , R 3 , R 7 , R 10a , R 10b , R 11 , and R 12 represent a hydrogen atom; R 4 , R 5 , and R 6 represent a hydrogen atom, hydroxyl, optionally substituted C 1-18 alkylcarbonyloxy, optionally substituted C 1-18 alkylsulfonyloxy, optionally substituted arylcarbonyloxy, C 1-6 alkyloxy-C 1-6 alkyloxy, C 1-6 alkyloxy-C 1-6 alkyloxy-C 1-6 alkyloxy; R 8 represents a hydrogen atom; and R 13a , R 13b , and R 13c represent methyl.

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30-05-2013 дата публикации

HETEROARYL (ALKYL) DITHIOCARBAMATE COMPOUNDS, PREPARATION METHODS AND USES THEREOF

Номер: US20130136794A1
Принадлежит: PEKING UNIVERSITY

Heteroaryl(alkyl)dithiocarbamate compounds represented by general formula (I) or their pharmaceutically acceptable salts, their preparing methods, and their uses for preparing antitumor medicines are disclosed, wherein each said substituent is defined as in the description. The compounds are new tyrosine kinase inhibitors useful as an anti-tumor agents, preferably useful in the preparation of medicines for treating breast cancer, liver cancer, non-small cell lung cancer, gastric cancer, colon cancer, leukaemia or nasal cancer. 2. The compound according to claim 1 , wherein the group A is substituted or unsubstituted heterocyclic group claim 1 , is the heterocyclic group being selected from pyridyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , furyl claim 1 , oxazolyl claim 1 , pyrazolyl claim 1 , thiazolyl or oxadiazolyl; preferably the group A is substituted or unsubstituted pyridyl claim 1 , or pyridyl fused with benzene or morpholine ring claim 1 , the fused benzene or morpholine ring being unsubstituted or substituted with methyl.3. The compounds according to claim 2 , wherein the Calkyl is methyl claim 2 , the Calkoxy is methoxy claim 2 , the Calkoxycarbonyl is methoxycarbonyl claim 2 , and/or the Calkylamido is pentylamido .4. The compound according to claim 3 , wherein the Rgroup is cyano.5. The compound according to claim 1 , wherein the compound is:3-(furan-2-ylmethyl)-4-hydroxy-1,3-thiazinane-2-thione (compound 1);2-(methoxycarbonyl)ethyl(furan-2-ylmethyl)dithiocarbamate (compound 2);2-cyanoethyl(furan-2-ylmethyl)dithiocarbamate (compound 3);3-(furan-2-ylmethyl)-4-hydroxy-4,5-dimethyl-3,4-dihydro-2H-1,3-thiazine-2-thione (compound 4);2-sulfamoylethyl(furan-2-ylmethyl)dithiocarbamate (compound 5);2-boronoethyl(furan-2-ylmethyl)dithiocarbamate (compound 6);2-(methylsulfinyl)ethyl(furan-2-ylmethyl)dithiocarbamate (compound 7);2-(benzylsulfinyl)ethyl(furan-2-ylmethyl)dithiocarbamate (compound 8);4-hydroxy-3-(pyridin-3-ylmethyl)-1,3-thiazinane-2-thione ( ...

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30-05-2013 дата публикации

Heterocyclic compound and use thereof

Номер: US20130137675A1
Принадлежит: Takeda Pharmaceutical Co Ltd

The present invention aims to provide a compound having a PDE inhibitory action and useful as a medicament for the prophylaxis or treatment of schizophrenia and the like. A compound represented by the formula (1 x ): wherein each symbol is as described in the DESCRIPTION, or the formula (1): W 1 —W 2   (1) wherein each symbol is as described in the DESCRIPTION, or a salt thereof.

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30-05-2013 дата публикации

2,5,7-substituted oxazolopyrimidine derivatives

Номер: US20130137685A1
Принадлежит: SANOFI SA

The invention relates to oxazolopyrimidine compounds of formula (I), where A, R 1 , R 2 and R 3 are defined as stated in the claims. The compounds of formula (I) are suitable, for example, for wound healing.

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06-06-2013 дата публикации

COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY

Номер: US20130142807A1
Принадлежит: Rigel Pharmaceuticals, Inc.

The invention encompasses compounds having formula I-V and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK3, may be therapeutically useful. 3. A method of inhibiting an activity of a JAK kinase claim 1 , comprising contacting the JAK kinase with an amount of a compound of effective to inhibit an activity of the JAK kinase.4. A method of inhibiting an activity of a JAK kinase claim 1 , comprising contacting in vitro a JAK3 kinase with an amount of a compound of effective to inhibit an activity of the JAK kinase.5. A method of treating a T-cell mediated autoimmune disease claim 1 , comprising administering to a patient suffering from such an autoimmune disease an amount of a compound of effective to treat the autoimmune disease.6. The method of in which the compound is administered in combination with claim 5 , or adjunctively to claim 5 , a compound that inhibits Syk kinase with an ICin the range of at least 10 μM.7. A method of treating or preventing allograft transplant rejection in a transplant recipient claim 1 , comprising administering to the transplant recipient an amount of a compound of effective to treat or prevent the rejection.8. The method of in which the rejection is acute rejection.9. The method of in which the rejection is chronic rejection.10. The method of in which the rejection is mediated by HVGR or GVHR.11. The method of in which the allograft transplant is selected from a kidney claim 7 , a heart claim 7 , a liver and a lung.12. The method of in which the compound is administered in combination with claim 7 , or adjunctively to claim 7 , another immunosuppressant.13. The method of in which the immunosuppressant is selected from cyclosporine claim 12 , tacrolimus claim 12 , sirolimus claim 12 , an inhibitor of IMPDH claim 12 , mycophenolate claim 12 , mycophanolate mofetil claim 12 , an anti-T-cell antibody and OKT3.14. A method ...

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06-06-2013 дата публикации

(6,7-DIHYDRO-2-NITRO-5H-IMIDAZOL[2,1-B][1,3]OXAZIN-6YL) AMIDE COMPOUNDS, PREPARATION METHODS AND USES THEREOF

Номер: US20130143864A1
Принадлежит:

(6,7-Dihydro-2-nitro-5H-imidazo[2,1-b][1,3]oxazin-6-yl)amide compounds of formula (I), and their pharmaceutically acceptable salts, preparation methods and pharmaceutical compositions thereof are disclosed, wherein m and R are defined as in the description. The uses of the compounds in preparing medicaments for treating infectious diseases caused by , especially infectious diseases caused by multi-drug resistance are also disclosed. 2. The compound of claim 1 , wherein claim 1 , Rrepresents substituted or unsubstituted benzyl; Rrepresents substituted or unsubstituted phenyl.3. The compound of claim 1 , wherein claim 1 , said Ris selected from: p-trifluoromethoxybenzyl claim 1 , p-methylbenzyl claim 1 , 4-(isopropoxy)benzyl or 4-(difluoromethoxy)benzyl.4. The compound of claim 1 , wherein claim 1 , said Ris selected from: p-trifluoromethoxyphenyl claim 1 , 2-fluoro-4-(trifluoromethoxy)phenyl claim 1 , 3-fluoro-4-(trifluoromethoxy)phenyl claim 1 , 3-fluoro-4-(trifluoromethoxy)phenyl claim 1 , 3-fluoro-4-(trifluoromethyl)phenyl claim 1 , 3 claim 1 ,5-difluoro-4-(trifluoromethoxy)phenyl claim 1 , 4-(2 claim 1 ,2 claim 1 ,2-trifluoroethoxy)phenyl claim 1 , 4-(difluoromethoxy)phenyl claim 1 , 4-(2-methoxyethoxy)phenyl claim 1 , 4-(2-ethoxyethoxy)phenyl claim 1 , 4-(2-(2 claim 1 ,2 claim 1 ,2-trifluoroethoxy)ethoxy)phenyl claim 1 , 4-isopropoxyphenyl claim 1 , 4-isobutoxyphenyl or 4-(2-(cyclopropoxy)ethoxy)phenyl.5. A pharmaceutical composition comprising pharmaceutically acceptable excipients or carriers and the compound according to claim 1 , or optical isomers claim 1 , crystal forms and pharmaceutically acceptable salts claim 1 , hydrates or solvates thereof as the active ingredient.6. The pharmaceutical composition of claim 5 , wherein claim 5 , said composition is in oral dosage form.7Mycobacterium tuberculosi.. The use of a compound according to claim 1 , or optical isomers claim 1 , crystal forms and pharmaceutically acceptable salts claim 1 , hydrates or solvates ...

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06-06-2013 дата публикации

ISOXAZOLO-QUINAZOLINES AS MODULATORS OF PROTEIN KINASE ACTIVITY

Номер: US20130143896A1
Принадлежит: NERVIANO MEDICAL SCIENCES S.R.L.

The present invention relates to substituted isoxazolo-quinazolines which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular human MPS1 and PERK. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such these compounds or the pharmaceutical compositions containing them. 2. A compound of formula (I) as defined in wherein:X is O, S or NH;R1 is an optionally substituted heterocyclyl or aryl, and{'sub': 1', '6', '3', '7, 'R2 is —NR′R″ or OR′ wherein R′ and R″ are, each independently, hydrogen or an optionally substituted group selected from straight or branched C-Calkyl, C-Ccycloalkyl, cycloalkyl-alkyl, heterocyclyl, eterocyclylalkyl, aryl and arylalkyl.'}3. A compound of formula (I) as defined in wherein:R1 is an optionally substituted aryl.4. A compound of formula (I) as defined in wherein:{'sub': 1', '6, 'R2 is —NR′R″, wherein R′ and R″ are independently hydrogen or an optionally substituted group selected from C-Calkyl, cycloalkyl, aryl and heterocyclyl.'}5. A compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in which is selected from the group consisting of:N-(2,6-diethylphenyl)-8-{[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydroisoxazolo[4,3-h]quinazoline-3-carboxamide,8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydroisoxazolo[4,3-h]quinazoline-3-carboxamide,N-(2,6-diethylphenyl)-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydroisoxazolo[4,3-h]quinazoline-3-carboxamide,N-(2,6-diethylphenyl)-8-({4-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methoxyphenyl}amino)-4,5-dihydroisoxazolo[4,3-h]quinazoline-3-carboxamide,N-(2,6-diethylphenyl)-8-{[2-methoxy-4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]amino}-4,5-dihydroisoxazolo[4,3-h]quinazoline-3-carboxamide,8-{[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino ...

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13-06-2013 дата публикации

2,4-Pyrimidinediamine Compounds and Prodrugs and Their Uses

Номер: US20130150329A1
Принадлежит: Rigel Pharmaceuticals, Inc.

The present disclosure provides biologically active 2,4-pyrimidinediamine compounds of formulae (I)-(III): 5. A method according to claim 1 , comprising administering to the subject a pharmaceutically effective amount of a pharmaceutically acceptable salt of a compound of any of formulae (I)-(III).6. A method according to claim 1 , comprising administering to the subject a pharmaceutically effective amount of a mono- or di-sodium salt claim 1 , a mono- or di-potassium salt claim 1 , a mono- or di-lithium salt claim 1 , a calcium salt claim 1 , a magnesium salt claim 1 , or an ammonium salt of a compound of any of formulae (I)-(III).7. A method according to claim 1 , comprising administering to the subject a pharmaceutically effective amount of a mono- or di-trifluoroacetic acid salt claim 1 , a p-toluenesulfonic acid salt claim 1 , a hydrochloride salt claim 1 , a benzenesulfonic acid salt claim 1 , or an ethanesulfonic acid salt of a compound of any of formulae (I)-(III)8. A method according to claim 1 , comprising administering to the subject a pharmaceutically effective amount of a pharmaceutical composition comprising a compound of any of formulae (I)-(III) or a pharmaceutically acceptable salt thereof claim 1 , and an acceptable carrier claim 1 , excipient and/or diluent.9. The method according to in which the disease is rheumatoid arthritis.10. The method according to in which the amount of the compound or salt administered is effective to achieve a serum concentration of the corresponding drug that is at or above the ICof Syk inhibition of the drug claim 9 , as measured in an in vitro assay.12. The method according to in which the autoimmune disease is selected from autoimmune diseases that are frequently designated as single organ or single cell-type autoimmune disorders and autoimmune disease that are frequently designated as involving systemic autoimmune disorder.13. The method according to in which the autoimmune disease is selected from Hashimoto's ...

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13-06-2013 дата публикации

Bicyclic Aryl and Heteroaryl Sodium Channel Inhibitors

Номер: US20130150339A1
Принадлежит: Amgen Inc.

The present invention provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav 1.7. 2. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein one of X claim 1 , Xand Xis N and the other two of X claim 1 , Xand Xis CR.3. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein two of X claim 1 , Xand Xare N and the other one of X claim 1 , Xand Xis CR.4. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein one of X claim 1 , Xand Xis N and the other two of X claim 1 , Xand Xis CH.5. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein two of X claim 1 , Xand Xare N and the other one of X claim 1 , Xand Xis CH.6. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein X claim 1 , Xand Xare CH.7. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis N claim 1 , Xis CH and Xis CR.8. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis N claim 1 , Xis CH and Xis N.9. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis CH claim 1 , Xis CH and Xis N.10. A compound in accordance with claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis CH claim 1 , Xis N and Xis CH.11. A compound in accordance with any one of claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein Ris a 6 membered aryl claims 1 , heteroaryl or heterocycloalkyl group claims 1 , where the heteroaryl or heterocycloalkyl group can have from 1 to 3 heteroatoms independently selected from O claims 1 , N or S claims 1 , and the aryl claims 1 , heteroaryl or heterocycloalkyl ...

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13-06-2013 дата публикации

6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors

Номер: US20130150340A1
Принадлежит: SANOFI

The present invention relates to 1H-pyrazolo[3,4-b]pyridine compounds of the formula I, 8. The compound of selected from the group consisting of:6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (2,2,6,6-tetramethyl-piperidin-4-yl)-amide;6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid piperidin-4-ylamide;(3-Amino-piperidin-1-yl)-[6-(4-hydroxy-phenyl)-H-pyrazolo[3,4-b]pyridin-4-yl]-methanone;[6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-piperazin-1-yl-methanone;6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid pyrrolidin-3-ylamide;6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ((3S,4S)-4-methoxy-pyrrolidin-3-yl)-amide;[1,4]Diazepan-1-yl-[6-(4-hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanone;6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (cis-4-amino-cyclohexyl)-amide;6-(4-Hydroxy-phenyl)-1H-pyrazolo[4-b]pyridine-4-carboxylic acid (trans-4-amino-cyclohexyl)-amide;(2,2-Dimethyl-piperazin-1-yl)-[6-(4-hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanone;6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid trans-4-amino-cyclohexylmethyl)-amide;6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (cis-4-amino-cyclohexylmethyl)-amide;6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (azetidin-3-ylmethyl)-amide;6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (3-amino-cyclobutyl)-amide;[6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-(5-isopropyl-2,2-dimethyl-piperazin-1-yl)-methanone;((R)-3-Amino-pyrrolidin-1-yl)-[6-(4-hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanone;((S)-3-Amino-pyrrolidin-1-yl)-[6-(4-hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanone;6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid-(R)-(1-Aza-bicyclo[2.2.2]oct-3-yl)amide;6-(4-Hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (R)-piperidin-3-ylamide;(2,7-Diaza-spiro[3.5]non-2-yl)-[6-(4- ...

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13-06-2013 дата публикации

PYRROLOPYRIMIDINE COMPOUNDS AS INHIBITORS OF CDK4/6

Номер: US20130150342A1
Принадлежит: NOVARTIS AG

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

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13-06-2013 дата публикации

HETEROCYCLIC COMPOUND

Номер: US20130150344A1
Принадлежит:

The present invention provides a compound represented by the formula (1): 3. The compound or salt of claim 2 , wherein Ris a halogen atom or an optionally substituted Calkoxy group.5. 5-{3-[1-(3-Chlorophenyl)-1H-pyrazol-5-yl]-5-methoxy-4-oxopyridazin-1(4H)-yl}-4-fluoro-1 claim 2 ,3 claim 2 ,3-trimethyl-1 claim 2 ,3-dihydro-2H-indol-2-one or a salt thereof.6. 1-(Cyclopropylmethyl)-4-fluoro-5-[5-methoxy-4-oxo-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-1(4H)-yl]-3 claim 2 ,3-dimethyl-1 claim 2 ,3-dihydro-2H-indol-2-one or a salt thereof.7. 1-[1-(1-Cyclopropylethyl)-1H-pyrazol-4-yl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one or a salt thereof.8. 5-Methoxy-1-[2-methoxy-6-(3 claim 2 ,3 claim 2 ,4 claim 2 ,4-tetrafluoropyrrolidin-1-yl)pyridin-3-yl]-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one or a salt thereof.9. 1-[6-(3 claim 2 ,4-difluoro-1H-pyrrol-1-yl)-2-methoxypyridin-3-yl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one or a salt thereof.10. A medicament comprising the compound or salt of .11. The medicament of claim 10 , which is a phosphodiesterase 10A inhibitor.12. The medicament of claim 10 , which is for preventing or treating schizophrenia.13. A method for preventing or treating schizophrenia which comprises administering an effective amount of the compound or salt of to mammal.14. Use of the compound or salt of in the manufacture of a medicament for preventing or treating schizophrenia.15. The compound or salt of for preventing or treating schizophrenia. The present invention relates to a novel heterocyclic compound, a production method thereof and a medicament containing same and the like. More particularly, the present invention relates to a compound having an inhibitory action on phosphodiesterase 10A and effective as a prophylactic or therapeutic medicament for mental diseases such as schizophrenia and the like, and the like.Phosphodiesterase (PDE) is an enzyme that hydrolyzes cAMP and cGMP that function as intracellular second ...

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13-06-2013 дата публикации

NOVEL COMPOUNDS

Номер: US20130150347A1
Принадлежит:

This invention relates to compounds of formula I 2. The compound according to claim 1 , wherein{'sup': '1', 'sub': 1-4', '3-6', '1-3', '1-3, 'Rrepresents phenyl, Calkyl or Ccycloalkyl which latter three groups are optionally substituted with one or more substituents selected from fluoro, Calkyl and —O—Calkyl.'}12. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable adjuvant claim 1 , diluent and/or carrier.13. A method of treating schizophrenia claim 1 , schizoaffective disorder and substance induced psychotic disorder; cognitive disorders and dementias including age-associated learning and memory impairments or losses claim 1 , post stroke dementia claim 1 , deficits in concentration claim 1 , mild cognitive impairment claim 1 , the cognitive dysfunction in Alzheimers disease or the cognitive dysfunction of schizophrenia comprising administering to a patient a therapeutically effective amount of a compound according to . This invention relates to substituted imidazoles and their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment.Glutamate is the primary excitatory amino acid in the mammalian central nervous system. Neurotransmission mediated by glutamate has been demonstrated to be critical in many physiological processes, such as synaptic plasticity, long term potentiation involved in both learning and memory as well as sensory perception (Riedel et al., Behay. Brain Res. 2003, 140:1-47). Furthermore, it has been demonstrated that an imbalance of glutamate neurotransmission plays a critical role in the pathophysiology of various ...

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13-06-2013 дата публикации

2,4-PYRIMIDINEDIAMINE COMPOUNDS AND THEIR USES

Номер: US20130150349A1
Принадлежит: Rigel Pharmaceuticals, Inc.

The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades. 2. The compound of claim 1 , wherein Ris fluoro or (C1-C4)alkanyl optionally substituted with one or more of the same or different Rgroups.3. The compound of claim 2 , wherein each Ris independently —OR claim 2 , —OCF claim 2 , —NRR claim 2 , halogen claim 2 , —CF claim 2 , —CN claim 2 , —NO claim 2 , —N claim 2 , —SONRR claim 2 , —C(O)R claim 2 , —C(O)ORor —C(O)NRR.4. The compound of claim 3 , wherein Ris fluoro or —CF.5. The compound of claim 4 , wherein each m is 1.6. The compound of claim 5 , wherein Ris fluoro.7. The compound of claim 1 , wherein Ris phenyl monosubstituted with —O—(CH)—NRR.9. The method according to wherein the disease is selected from osteoarthritis claim 8 , inflammatory bowel disease claim 8 , ulcerative colitis claim 8 , Crohn's disease claim 8 , idiopathic inflammatory bowel disease claim 8 , irritable bowel syndrome claim 8 , or spastic colon.10. The method according to wherein the disease is associated with inflammation in the lungs.11. The method according to wherein the disease is human allergic asthma.12. The method according to wherein the compound is administered with a second thereapeutic.13. The method according to wherein the second therapeutic is an anti-inflammatory.14. The method according to comprising administering the compound prophylactically. This application is a continuation of U.S. patent application Ser. No. 13/288,813, filed Nov. 3, 2011, which is a continuation of U.S. patent application Ser ...

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13-06-2013 дата публикации

Fused Tricyclic Inhibitors of Mammalian Target of Rapamycin

Номер: US20130150353A1
Принадлежит:

This invention relates to novel fused tricyclic compounds that are inhibitors of mammalian Target of Rapamycin (mTOR) kinase, which is also known as FRAP, RAFT, RAPT or SEP, and are useful in the treatment of cellular proliferative diseases, for example cancer and other proliferative disorders. 3. The compound of wherein Ris aryl or heteroaryl claim 2 , wherein said aryl and heteroaryl groups are optionally substituted with one to three substituents independently selected from the group consisting of R claim 2 , halo claim 2 , Calkyl and OR; or a pharmaceutically acceptable salt thereof.4. The compound of wherein Ris hydrogen claim 3 , or a pharmaceutically acceptable salt thereof.6. The compound of wherein Ris hydrogen claim 5 , halo claim 5 , Calkyl claim 5 , aryl claim 5 , heteroaryl or heterocyclyl claim 5 , wherein said alkyl claim 5 , aryl claim 5 , heteroaryl and heterocyclyl groups are optionally substituted with one to three substituents independently selected from the group consisting of halo claim 5 , hydroxyl claim 5 , cyano claim 5 , Calkyl claim 5 , Chaloalkyl claim 5 , and SOR; or a pharmaceutically acceptable salt thereof.7. The compound of wherein Ris aryl or heteroaryl claim 6 , wherein said aryl or heteroaryl groups are optionally substituted with one to three substituents independently selected from the group consisting of halo claim 6 , Calkyl claim 6 , Chaloalkyl and OR claim 6 , or a pharmaceutically acceptable salt thereof.9. A pharmaceutical composition comprising a pharmaceutically effective amount of the compound according to claim 1 , and a pharmaceutically acceptable carrier.10. A method for the treatment or prevention of proliferative disorders or cancer in a mammal comprising the step of administering the compound of . This invention relates to novel fused tricyclic compounds that are inhibitors of mammalian Target of Rapamycin (mTOR) kinase, which is also known as FRAP, RAFT, RAPT or SEP, and are useful in the treatment of cellular ...

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13-06-2013 дата публикации

NEW SELECTIVE CCR2 ANTAGONISTS

Номер: US20130150354A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to novel and selective 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 as well as pain. 2. The compound of claim 1 ,{'sub': 4', '5', '4', '5', '4', '5, 'wherein Z denotes a five-, or six-membered ring formed by a —C-C-alkylene, wherein the —C-C-alkylene is bi-valently linked to the N atom, and in which one carbon center of the —C-C-alkylene may optionally be replaced by 1 hetero atom selected from N, and O,'}{'sub': 3', '4', '1', '3', '2', '1', '3', '2', '1', '3', '2', '1', '3, 'and wherein the ring Z is further bi-valently substituted on two neighbouring ring atoms, such that an annellated ring is formed by a group selected from among —C-C-alkylene, in which one carbon center may optionally be replaced by 1 hetero atom selected from O, and N, and wherein the bivalent group is optionally substituted by one or more groups selected from —N(C-C-alkyl)-SO—C-C-alkyl, —NH—SO—C-C-alkyl, and —SO—C-C-alkyl.'}7. The compound of claim 1 , wherein Ris a group selected from among —CH claim 1 , —OCH claim 1 , and -cyclopropyl.8. The compound of claim 1 , wherein Ris selected from among —H claim 1 , —CH claim 1 , —OCH claim 1 , —CF claim 1 , and -cyclopropyl.9. The compound of claim 1 , wherein Ris selected from among —H claim 1 , —CH claim 1 , —CH claim 1 , —O—CH claim 1 , —O—CH claim 1 , —F claim 1 , —CF claim 1 , and —OCF.10. The compound of claim 1 , wherein A denotes —NH-L-Rand Lis a bond.11. The compound of claim 1 , wherein G and E are N.12. The compound of claim 1 , wherein n is 2.13. A method for the treatment of an inflammatory disease of the respiratory tract selected from chronic obstructive pulmonary disease claim 1 , asthma claim 1 , and cystic fibrosis claim 1 , comprising administering to a patient in need thereof a therapeutic amount of a compound according to or a pharmacologically acceptable salt thereof.14 ...

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13-06-2013 дата публикации

SOLID STATE FORMS OF MACROCYCLIC KINASE INHIBITORS

Номер: US20130150378A1
Принадлежит:

Provided herein are salt forms of macrocyclic protein kinase inhibitors, pharmaceutical compositions containing the same, methods of making and using these compounds and compositions to treat proliferative disease mediated by kinase activity. 1. A citiric acid salt of 14-methyl-20-oxa-5 ,7 ,14 ,27-tetraazatetracyclo-[19.3.1.12 ,6.18 ,12]heptacosa-1(25) ,2 ,4 ,6 ,8 ,10 ,12(26) ,16 ,21 ,23-decaene.2. A fumaric acid salt of 14-methyl-20-oxa-5 ,7 ,14 ,27-tetraazatetracyclo-[19.3.1.12 ,6.18 ,12]heptacosa-1(25) ,2 ,4 ,6 ,8 ,10 ,12(26) ,16 ,21 ,23-decaene.3. Crystalline citrate pattern 1 of 14-methyl-20-oxa-5 ,7 ,14 ,27-tetraazatetracyclo-[19.3.1.12 ,6.18 ,12]heptacosa-1(25) ,2 ,4 ,6 ,8 ,10 ,12(26) ,16 ,21 ,23-decaene citrate.4. Crystalline citrate pattern 2 of 14-methyl-20-oxa-5 ,7 ,14 ,27-tetraazatetracyclo-[19.3.1.12 ,6.18 ,12]heptacosa-1(25) ,2 ,4 ,6 ,8 ,10 ,12(26) ,16 ,21 ,23-decaene citrate.5. Crystalline fumarate pattern 1 of 14-methyl-20-oxa-5 ,7 ,14 ,27-tetraazatetracyclo-[19.3.1.12 ,6.18 ,12]heptacosa-1(25) ,2 ,4 ,6 ,8 ,10 ,12(26) ,16 ,21 ,23-decaene fumarate.6. Crystalline fumarate pattern 2 of 14-methyl-20-oxa-5 ,7 ,14 ,27-tetraazatetracyclo-[19.3.1.12 ,6.18 ,12]heptacosa-1(25) ,2 ,4 ,6 ,8 ,10 ,12(26) ,16 ,21 ,23-decaene fumarate.7. The composition of having a melting point of 191° C. as determined by differential scanning calorimetry.8. The composition of having a melting point of 240° C. as determined by differential scanning calorimetry.9. The composition of or characterized by a powder x-ray diffraction pattern having reflections at 2 theta=21.5°.10. The composition of or characterized by a powder x-ray diffraction pattern having reflections at 2 theta=21.5° claim 6 , and 15.0°.11. The composition of or characterized by a powder x-ray diffraction pattern having reflections at 2 theta=21.5° claim 6 , 19.8° claim 6 , and 15.0°.12. The composition of or characterized by a powder x-ray diffraction pattern as provided in .13. The composition of or characterized ...

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20-06-2013 дата публикации

TRPM8 ANTAGONISTS AND THEIR USE IN TREATMENTS

Номер: US20130157996A1
Принадлежит: Amgen Inc.

Compounds of Formula I are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: 3. The compound of or the pharmaceutically-acceptable salt thereof claim 2 , the tautomer thereof claim 2 , the pharmaceutically-acceptable salt of the tautomer claim 2 , or the mixture thereof claim 2 , wherein{'sup': '2', 'Xis selected from CH or N;'}{'sup': 1', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a', 'a, 'sub': 1-6', '1-2', '1-2', '1-6', '1-6', '1-4', '2', '2-6', '2-6', '2', '2', '2', '2', '2', '2', '2', '2-6', '2-6', '2', '2', '1-6', '1-4', '2', '2, 'Ris selected from Calk or a direct-bonded, Calk-linked, CalkO-linked, saturated, partially-saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered monocyclic or 7-, 8-, 9-, 10- or 11-membered bicyclic ring containing 0, 1, 2, 3 or 4 heteroatoms selected from N, O and S, but containing no more than one O or S atom, the Calk and ring being substituted by 0, 1, 2 or 3 substituents independently selected from halo, oxo, Calk, Chaloalk, cyano, nitro, —C(═O)R, —C(═O)OR, —C(═O)NRR, —C(═NR)NRR, —OR, —OC(═O)R, —OC(═O)NRR, —OC(═O)N(R)S(═O)R, —OCalkNRR, —OCalkOR, —SR, —S(═O)R, —S(═O)R, —S(═O)NRR, —S(═O)N(R)C(═O)R, —S(═O)N(R)C(═O)OR, —S(═O)N(R)C(═O)NRR, —NRR, —N(R)C(═O)R, —N(R)C(═O)OR, —N(R)C(═O)NRR, —N(R)C(═NR)NRR, —N(R)S(═O)R, —N(R)S(═O)NRR, —NRCalkNRRand —NRCalkOR, wherein the ring is additionally substituted by 0 or 1 ...

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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

HETEROARYL COMPOUNDS AND METHODS OF USE THEREOF

Номер: US20130158003A1
Принадлежит: SUNOVION PHARMACEUTICALS INC

Provided herein are heteroaryl compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. In one embodiment, the compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and metabolic disorders, including, but not limited to, e.g., neurological disorders, psychosis, schizophrenia, obesity, and diabetes. 2. The compound of claim 1 , wherein L is —CH—CH— claim 1 , —CH═CH— claim 1 , —O—CH— claim 1 , —NH—CH— claim 1 , —CH—NH— claim 1 , —CH—S— claim 1 , or —S—.3. The compound of claim 2 , wherein L is —CH—CH—.5. The compound of claim 4 , wherein Ais NR; and Ris (i) hydrogen; or (ii) (C-C)alkyl claim 4 , (C-C)alkenyl claim 4 , (C-C)heteroalkyl claim 4 , (C-C)cycloalkyl claim 4 , (6 to 10 membered) aryl claim 4 , (5 to 10 membered) heteroaryl claim 4 , (3 to 12 membered)heterocyclyl claim 4 , carbonyl claim 4 , or sulfonyl claim 4 , each of which is optionally substituted with one or more R; or (iii) Rand Rtogether with the atoms to which they are attached form a ring optionally substituted with one or more R.6. The compound of claim 5 , wherein Ris H or CH.8. The compound of claim 7 , wherein Ris (i) hydrogen; or (ii) alkyl claim 7 , aryl claim 7 , or heteroaryl claim 7 , each of which is optionally substituted with one or more R.9. The compound of claim 7 , wherein Ris (i) hydrogen; or (ii) alkyl claim 7 , aryl claim 7 , or heteroaryl claim 7 , each of which is optionally substituted with one or more R.10. The compound of claim 7 , wherein Ris (i) hydrogen; or (ii) alkyl claim 7 , aryl claim 7 , or heteroaryl claim 7 , each of which is optionally substituted with one or more R.11. The compound of claim 7 , wherein each occurrence of Ris independently (i) hydrogen; or (ii) alky claim 7 , aryl or heteroaryl claim 7 , each of which is optionally substituted with one or more R.14. The compound of any claim 4 , wherein Rand Rtogether with the ...

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20-06-2013 дата публикации

Azetidine Derivatives

Номер: US20130158004A1
Принадлежит:

Azetidine derivatives of which the following is exemplary 2. A compound according to whereinX is O, and{'sub': '3', 'R is H or CH.'}3. A compound according to wherein Aris selected from a group consisting of: [{'sup': '1', 'wherein the above-mentioned phenyl, pyridinyl and pyrimidinyl are each substituted with one to three groups independently selected from R, and/or'}, {'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '2, 'wherein two adjacent carbon atoms of a phenyl group may be linked to each other via a —O—CH—O—, —O—CF—O—, —O—CH—CH—O—, —O—CH—CH—CH—CH—, —O—CH—CH—CH—C(CH)—, —O—CH—CH—CH—O— or —O—CH—C(CH)—CH—O— bridge, and'}, {'sub': '3', 'wherein the above-mentioned benzoxazolyl, benzoisoxalyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl and oxazolopyrimidinyl groups are each optionally substituted with Cl, CHor phenyl.'}], 'phenyl, pyridinyl, pyrimidinyl, benzoxazolyl, benzoisoxalyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl and oxazolopyrimidinyl,'}4. A compound according to wherein Ris selected from the group consisting of:{'sub': 1-4', '2-4', '3-7', '3-7', '2', '1-4', '3-7', '3-7', '1-3', '1-4', '2', '1-4', '2, 'sup': N1', 'N2, 'claim-text': wherein each alkyl, cycloalkyl and heterocyclyl may be optionally substituted with one to three substituents independently selected from the group consisting of F and CN, and', {'sub': '3', 'wherein each phenyl and pyridinyl group may be optionally substituted with one F or —OCH.'}], 'H, F, Cl, Br, CN, OH, C-alkyl, C-alkenyl, C-cycloalkyl, C-cycloalkyl-CH—, C-alkyl-O—, C-cycloalkyl-O—, C-cycloalkyl-C-alkyl-O—, C-alkyl-S(═O), RRN—, HO—C(═O)—, C-alkyl-O—C(═O)—, phenyl, phenyl-O—, phenyl-CH—O—, pyridinyl,'}5. A compound according to wherein Aris selected from the group consisting of:{'sup': '2', 'claim-text': {'sup': '2', 'sub': 1-2', '1-2', '1-3', '2, 'wherein Ris F, Cl, C-alkyl-, C-alkyl-O—, C-alkyl-C(═O)—NH or HO—CH—C(═O)—NH—.'}, 'phenylene and ...

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