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Небесная энциклопедия

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

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Мониторинг СМИ

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

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 42737. Отображено 100.
05-01-2012 дата публикации

Modulators of cytokine mediated signalling pathways and integrin alphavbeta3 receptor antagonists for combination therapy

Номер: US20120003229A1
Принадлежит: Individual

The invention relates to the use of modulators of cytokine mediated signalling pathways in combination with integrin αvβ3 receptor antagonists for the treatment or prevention of diseases, particularly to the use of a pharmaceutical composition, comprising a modulator of cytokine mediated signalling pathways and an integrin αvβ3 receptor antagonist, for the treatment or prevention of inflammatory or autoimmune disorders, particularly for the treatment or prevention of rheumatoid arthritis and to the pharmaceutical composition itself.

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05-01-2012 дата публикации

NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-CoA DESATURASE

Номер: US20120004213A1
Принадлежит: Forest Laboratories Holdings Ltd

The present invention relates to piperazine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.

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05-01-2012 дата публикации

Modulators of atp-binding cassette transporters

Номер: US20120004216A1
Принадлежит: Vertex Pharmaceuticals Inc

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including CF Transmembrane Regulator (“CFTR”), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

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19-01-2012 дата публикации

Process for producing 2-hydroxymethylmorpholine salt

Номер: US20120016120A1
Принадлежит: Daiso Co Ltd

The invention relates to a production method of a 2-hydroxymethylmorpholine salt, which includes crystallization from a solution containing 2-hydroxymethylmorpholine of formula (1) 1,4-oxazepane compound of formula (2) and an acid.

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26-01-2012 дата публикации

Thiazole and oxazole-substituted arylamides as p2x3 and p2x2/3 antagonists

Номер: US20120022067A1
Принадлежит: Individual

Compounds of the formula I: or a pharmaceutically acceptable salt thereof, wherein, R 1 is a group of formula A or formula B, and X, R 2 , R 3 , R 4 , R 5 , R 6 , R a and R b are as defined herein. Also provided are methods of using the compounds for treating diseases mediated by a P2X 3 and/or a P2X 2/3 receptor antagonist and methods of making the subject compounds.

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26-01-2012 дата публикации

Derivatives of n-(arylamino)sulfonamides as inhibitors of mek

Номер: US20120022076A1
Принадлежит: Individual

This invention concerns N-(2-arylamino)aryl sulfonamides, which are inhibitors of MEK and are useful in treatment of cancer and other hyperproliferative diseases.

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02-02-2012 дата публикации

Animal ectoparasite-controlling agent

Номер: US20120029038A1
Автор: Kaori Ikari
Принадлежит: Sumitomo Chemical Co Ltd

The present invention provides an animal ectoparasite-controlling agent containing as an active ingredient a hydrazide compound represented by the formula (1) wherein R 3 represents a fluorine atom, a chlorine atom, a bromine atom, a methyl group, an ethyl group or a hydrogen atom, R 5 and R 6 are the same or different each other and each represents a methyl group or a hydrogen atom, R 4 represents a C1-C6 haloalkyl group, which shows excellent controlling effects on animal ectoparasites.

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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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23-02-2012 дата публикации

Developers and method of coloring lithographic printing members

Номер: US20120045720A1
Принадлежит: Individual

A color contrast image in imaged lithographic printing precursors can be obtained by contacting the imaged precursor with a coloration solution containing a colorless form of a photochromic compound. Residual amounts of this compound attached to the oleophilic surface of the imaged precursor can be changed to its colored form when exposed to UV light. The coloration solution can be an alkaline or acidic developer or an alkaline or acidic solution used separately after development. The coloration solution can also be a gum solution.

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23-02-2012 дата публикации

Diacylethylenediamine compound

Номер: US20120046292A1
Принадлежит: Astellas Pharma Inc

[Problem] A compound which is useful as an anti-obesity agent is provided. [Means for Solution] The present inventors have investigated a compound having a DGAT1 inhibitory action, which is promising as an active ingredient of a pharmaceutical composition for treating obesity, type II diabetes mellitus, fatty liver, and diseases associated with these diseases, and as a result, they have found that the diacylethylenediamine compound of the present invention has an excellent DGAT1 inhibitory action, thereby completing the present invention. That is, the diacylethylenediamine compound of the present invention has a DGAT1 inhibitory action, and can be therefore used as an agent for preventing and/or treating obesity, type II diabetes mellitus, fatty liver, and diseases associated with these diseases.

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01-03-2012 дата публикации

5-aryl isoxazolines for controlling invertebrate pests

Номер: US20120053051A9
Принадлежит: EI Du Pont de Nemours and Co

Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, wherein A 1 , A 2 and A 3 are independently selected from the group consisting of CR 3 and N; B 1 B 2 and B 3 are independently selected from the group consisting of CR 2 and N; Q is a phenyl ring or a 5- or 6-membered saturated or unsaturated heterocyclic ring, each ring optionally substituted with one or more substituents independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, —CN, —NO 2 , —N(R 4 )R 5 , —C(W)N(R4)R 5 , —C(O)OR 5 and R 8 ; or —S(O) 2 N(R 21 )R 22 , —S(O) p R 25 or —S(O)(═NR 28 )R 29 ; and R 1 , R 2 , R 3 , R 4 , R 5 , R 8 , R 21 , R 22 , R 25 , R 28 , R 29 ; p and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition' of the invention.

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01-03-2012 дата публикации

Monomer, Polymerization Method, and Polymer

Номер: US20120053315A1

A monomer of formula (III): wherein X is a polymerisable group Ar, Ar 1 and Ar 2 each independently represent an optionally substituted aryl or heteroaryl group; R 1 represents H or a substituent; and Z represents a direct bond or a divalent linking atom or group, wherein Ar 1 and Ar 2 are linked by a single bond or a divalent linking group selected from CR 1 R 2 , SiR 1 R 2 , PR 1 , NR 1 , O and S wherein R 1 and R 2 are independently selected from hydrogen; optionally substituted alkyl wherein one or more non-adjacent C atoms may be replaced with O, S, N, C═O and —COO—; alkoxy, aryl, arylalkyl, heteroaryl and heteroarylalkyl. Ar 1 and Ar 2 are preferably linked by an oxygen atom, and Ar 1 and/or Ar 2 may be fused to their respective adjacent Ar groups. Ar 1 and its adjacent Ar group and/or Ar 2 and its adjacent Ar group are optionally fused to form a fluorene unit.

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22-03-2012 дата публикации

Estrogen receptor modulators and uses thereof

Номер: US20120071535A1
Принадлежит: Aragon Pharmaceuticals Inc

Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

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05-04-2012 дата публикации

Photoelectric conversion element, production method thereof, photosensor, imaging device and their driving method

Номер: US20120080585A1
Принадлежит: Fujifilm Corp

To provide a photoelectric conversion element capable of functioning as a photoelectric conversion element when a compound having a specific structure is applied to the photoelectric conversion element, causing the element to exhibit a low dark current, and reducing the range of increase in the dark current even when the element is heat-treated, and an imaging device equipped with such a photoelectric conversion element. A photoelectric conversion element having a photoelectric conversion film which is sandwiched between a transparent electrically conductive film and an electrically conductive film and contains a photoelectric conversion layer and an electron blocking layer, wherein the electron blocking layer contains a compound having, as a substituent, a substituted amino group containing three or more ring structures.

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12-04-2012 дата публикации

Five-membered heterocycles useful as serine protease inhibitors

Номер: US20120088758A1
Принадлежит: Bristol Myers Squibb Co

The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R 3 , R 4 , R 6 , R 11 , X 1 , X 2 , and X 3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

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03-05-2012 дата публикации

Nitrogen-containing aromatic heterocyclyl compound

Номер: US20120108639A1
Принадлежит: Daiichi Sankyo Co Ltd

The present invention provides a compound having excellent regulating action on blood lipid level that is represented by the following general formula (I) or a pharmacologically acceptable salt thereof, wherein, in one embodiment, A represents a 5-membered nitrogen-containing aromatic heterocyclyl group; R 1 represents COOH; each R 2 represents an alkyl; each R 3 represents an optionally substituted phenyl, an optionally substituted phenylalkyl; m represents 0, 1, 2, or 3; n represents 0 or 1; each of R 4 , R 5 , R 6 , and R 7 represents H, an alkyl; and B represents an optionally substituted naphthyl, an optionally substituted aromatic heterocyclyl, or a group represented by the following formula (II) wherein each of B 1 and B 2 represents an optionally substituted phenyl or an optionally substituted aromatic heterocyclyl.

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10-05-2012 дата публикации

Compound inhibiting in vivo phosphorus transport and medicine containing the same

Номер: US20120115851A1
Принадлежит: Kyowa Hakko Kirin Co Ltd

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

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10-05-2012 дата публикации

N,n'-diarylurea compounds and n,n'-diarylthiourea compounds as inhibitors of translation initiation

Номер: US20120115915A1
Принадлежит: Harvard College

Compositions and methods for inhibiting translation initiation are provided. Compositions, methods and kits for treating (1) cellular proliferative disorders, (2) non-proliferative, degenerative disorders, (3) viral infections, and/or (4) disorders associated with viral infections, using N,N′-diarylureas and/or N,N′-diarylthiourea compounds are described.

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17-05-2012 дата публикации

Phenoxy substituted phenylamidine derivatives and their use as fungicides

Номер: US20120122678A1
Принадлежит: Bayer CropScience AG

The present invention relates to 3-substituted phenylamidines of the general formula (I), to a process for their preparation, to the use of the amidines according to the invention for controlling unwanted microorganisms and also to a composition for this purpose, comprising the phenoxyamidines according to the invention. Furthermore, the invention relates to a method for controlling unwanted microorganisms by applying the compounds according to the invention to the microorganisms and/or their habitat.

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17-05-2012 дата публикации

Compounds, Compositions and Methods for Modulating Uric Acid Levels

Номер: US20120122780A1
Принадлежит: Ardea Biociences Inc

Described herein are compounds useful in the reduction of blood uric acid levels, formulations containing them and methods of making and using them. In some embodiments, the compounds described herein are used in the treatment or prevention of disorders related to aberrant levels of uric acid.

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17-05-2012 дата публикации

Polyunsaturated fatty acids for the treatment of diseases related to cardiovascular, metabolic and inflammatory disease areas

Номер: US20120122940A1
Принадлежит: Individual

The present disclosure relates to lipid compounds of the general formula (I): R1-O—C(R2)(R3)-X  (I) wherein R 1 is a C 10 -C 22 alkyl group, a C 10 -C 22 alkenyl group having 1-6 double bonds, or a C 10 -C 22 alkynyl group having 1-6 triple bonds; R 2 and R 3 are the same or different and may be chosen from different substituents; and X is a carboxylic acid or a derivative thereof, such as a carboxylic ester, a carboxylic anhydride, a phospholipid, triglyceride, or a carboxamide; or a pharmaceutically acceptable salt, solvate, solvate of such salt or a prodrug thereof. The present disclosure also relates to pharmaceutical compositions and lipid compositions comprising at least one compound according to the present disclosure, and to such compounds for use as medicaments or for use in therapy, in particular for the treatment of diseases related to the cardiovascular, metabolic, and inflammatory disease area.

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17-05-2012 дата публикации

No-Carrier-Added Nucleophilic [F-18] Fluorination of Aromatic Compounds

Номер: US20120123120A1
Принадлежит: UNIVERSITY OF CALIFORNIA

Phenyliodonium ylide derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are shown for use as precursors in aromatic nucleophilic substitution reactions. The iodonium ylide group is substituted by nucleophiles such as halide ions to provide the corresponding haloaryl derivatives. No-carrier-added [F-18]fluoride ion exclusively substitutes the iodonium ylide moiety in these derivatives and provides high specific activity F-18 labeled fluoro derivatives. Protected L-dopa-6-iodonium ylide derivative have been synthesized as a precursors for the preparation of no-carrier-added 6-[F-18]fluoro-L-dopa. The iodonium ylide group in this L-dopa.derivative is nucleophilically substituted by no-carrier-added [F-18]fluoride ion to provide a [F-18]fluoro intermediates which upon acid hydrolysis yielded 6-[F-18]fluoro-L-dopa.

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24-05-2012 дата публикации

Materials for organic electroluminescent devices

Номер: US20120126179A1
Принадлежит: Merck Patent GmBH

The present invention relates to 4,4′-substituted spirobifluorenes which are suitable, owing to excellent properties, as functional materials in organic electroluminescent devices. In addition, the present invention relates to a process for the preparation of 4,4′-substituted spirobifluorenes and to the use of these compounds in organic electroluminescent devices.

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24-05-2012 дата публикации

Synthetic macrocyclic compounds and methods for treating cancer

Номер: US20120128657A1

Disclosed herein are macrocyclic compounds that are effective to inhibit cell migration. In one embodiment, the compounds have the structure: or any pharmaceutically acceptable salt or solvate thereof, wherein: m is 0 or 1; R 1 , R 2 and R 3 independently are H, aralkyl, acyl, lower alkyl or silyl; X is —C(O)N(R 4 )— or —C(S)N(R 4 )—; —C(O)—; —C(S)—; Y is —OC(O)—; —OC(O)N(R 5 )—; —N(R 5 )C(O)—; or —OC(O)O—; G comprises a saturated or unsaturated aliphatic chain having from 2 to about 10 atoms in the chain, the chain optionally including 1, 2, or 3 heteroatoms; the chain optionally being substituted with 1, 2 or 3 substituents independently selected from lower alkyl, —OR 6 , epoxy, aziridinyl, cyclopropyl, —NR 7 R 8 and halo; R 4 , R 5 , R 6 , R 7 and R 8 independently are selected from H, lower alkyl and acyl. Also disclosed are methods for making and using compounds as well as pharmaceutical compositions including one or more of the disclosed macrocycles.

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24-05-2012 дата публикации

Piperazinyl derivatives useful as modulators of the neuropeptide y2 receptor

Номер: US20120129870A1
Принадлежит: Janssen Pharmaceutica NV

The present invention is directed to piperidinyl and piperazinyl derivatives of formula (II) useful as inhibitors of the NPY Y2 receptor, pharmaceutical compositions comprising said compounds, processes for the preparation of said compounds and the use of said compounds for the treatment and/or prevention of disorders, diseases and conditions mediated by the NPY Y2 receptor.

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31-05-2012 дата публикации

Substituted Esters as Cannabinoid-1 Receptor Modulators

Номер: US20120135975A1
Принадлежит: Merck and Co Inc

Novel compounds of the structural formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present invention are useful as centrally acting drugs in the treatment of psychosis, memory deficits, cognitive disorders, Alzheimer's disease, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and Guillain-Barre syndrome and the inflammatory sequelae of viral encephalitis, cerebral vascular accidents, and head trauma, anxiety disorders, stress, epilepsy, Parkinson's disease, movement disorders, and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, the treatment of obesity or eating disorders, as well as the treatment of asthma, constipation, chronic intestinal pseudo-obstruction, cirrhosis of the liver, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and the promotion of wakefulness.

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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

Compounds as bradykinin b1 antagonists

Номер: US20120142695A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

Compounds of the formula I wherein n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and X are defined as described in the specification, which are bradykinin B1 antagonists, and their use as medicaments.

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07-06-2012 дата публикации

Microbiocidal heterocycles

Номер: US20120142700A1
Принадлежит: SYNGENTA CROP PROTECTION LLC

The present invention relates to heterocyclic compounds of formula (I) which have microbiocidal activity, in particular fungicidal activity, as well as methods of using the compounds of formula (I) to control microbes.

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07-06-2012 дата публикации

Synthesis of ttx intermediates

Номер: US20120142911A1

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

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14-06-2012 дата публикации

Inhibition of p38 kinase activity using substituted heterocyclic ureas

Номер: US20120149706A1
Принадлежит: Individual

This invention relates to the use of a group of aryl ureas in treating cytokine mediated diseases, other than cancer and proteolytic enzyme mediated diseases, other than cancer, and pharmaceutical compositions for use in such therapy.

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21-06-2012 дата публикации

Nuclear receptor binding agents

Номер: US20120157539A1
Принадлежит: GTx Inc

The present invention relates to a novel class of selective estrogen receptor modulators (SERMs). The SERM compounds are applicable for use in the prevention and/or treatment of a variety of diseases and conditions including prevention and treatment of cancers such as prostate and breast cancer, osteoporosis, hormone-related diseases, hot flashes or vasomotor symptoms, neurological disorders, cardiovascular disease and obesity.

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05-07-2012 дата публикации

Zinc cluster

Номер: US20120172601A1
Принадлежит: Takasago International Corp

Disclosed is a novel zinc cluster compound represented by general formula (1): Zn 4 O (OCOR) 6 (RCOOH) n , wherein R represents an alkyl group which has 1 to 4 carbon atoms and may be substituted with a halogen atom, and n represents 0.1 to 1, and also disclosed are a method for producing the compound and a reaction using the compound.

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12-07-2012 дата публикации

Pyrimidine derivatives and analogs, preparation method and use thereof

Номер: US20120178915A1
Автор: Lifeng Xu
Принадлежит: Individual

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

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19-07-2012 дата публикации

Novel compounds

Номер: US20120184553A1
Принадлежит: Glaxo Group Ltd

The present invention relates to novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by LRRK2 kinase activity, particularly Parkinson's disease and Alzheimer's disease.

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19-07-2012 дата публикации

Reduction of fused bicyclic impurities in triiodinated x-ray contrast media

Номер: US20120184773A1
Принадлежит: Mallinckrodt LLC

The present disclosure generally relates to an improved process for alkylating a triiodo-substituted arylamide to form a compound suitable for use as an X-ray contrast agent. More particularly, the present disclosure is directed to such a process that limits the formation of fused bicyclic impurities, such as Impurity G, in the alkylation reaction mixture.

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09-08-2012 дата публикации

Therapeutic isoxazole compounds

Номер: US20120202786A1
Принадлежит: Dart Neuroscience Cayman Ltd

The invention provides a compound of formula I: wherein A 1 , A 2 , A 3 , R 1 , X, Y, and B have any of the values described herein, as well as salts of such compounds, compositions comprising such compounds, and therapeutic methods that comprise the administration of such compounds. The compounds are inhibitors of monoamine oxidase B (MAO-B) enzyme function and are useful for improving cognitive function and for treating psychiatric disorders in animals.

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16-08-2012 дата публикации

Heterocyclic Benzoxazole Compositions as Inhibitors of Hepatitis C Virus

Номер: US20120208856A1
Автор: Dawn N. Ward, Paul Smith

This invention relates to benzoxazole compounds, compositions and devices for delivering them, processes for manufacturing them, and methods of using them in the treatment of Hepatitis C Virus.

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23-08-2012 дата публикации

New compounds, pharmaceutical compositions and uses thereof

Номер: US20120214785A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The invention relates to new compounds of the formula I to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

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30-08-2012 дата публикации

2-phenylethylamino derivatives as calcium and/or sodium channel modulators

Номер: US20120220592A1
Принадлежит: Newron Pharmaceuticals SpA

2-Phenylethylamino substituted carboxamide derivatives and their use as sodium and/or calcium channel modulators useful in preventing, alleviating and curing a wide range of pathologies are presented.

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06-09-2012 дата публикации

Compositions and methods useful for treating diseases

Номер: US20120225851A1
Принадлежит: Eutropics Pharmaceuticals Inc

The present invention relates to a chemotherapeutic cancer treatment in which compounds of Formula Ia′, Ib′, Ic′, or II′ (referred to as a group as BH3Is) are administered to a mammal for the treatment of B-cell Lymphoma or other hematopoietic cancers, including diseases associated with MCL-1. In another aspect, the invention provides a method for treating particular types of hematopoietic cancers, such as B-cell lymphoma, using a combination of one or more compounds selected from the group consisting of compounds or Formula Ia, Ib, Ic, or II in combination with other therapies, for example, a class of therapeutics known as 26S proteosome inhibitors, such as, for example, Bortezomib. In another aspect the present invention relates to autoimmune treatment with pharmaceutical compositions comprising one or more compounds of Formula Ia′, Ib′, Ic′, or II′. In another aspect, this invention relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have unique in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease.

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06-09-2012 дата публикации

Compounds, compositions and methods for the treatment of amyloid diseases and synucleinopathies such as alzheimer's disease, type 2 diabetes and parkinson's disease

Номер: US20120225890A1
Принадлежит: ProteoTech Inc

Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.

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20-09-2012 дата публикации

Iodine radiolabelling method

Номер: US20120237444A1
Автор: Michelle Avory
Принадлежит: Individual

The present invention provides a novel method of labelling biological targeting molecules (BTMs) of interest with radioiodine. Also provided are novel radioiodinated BTMs prepared using the method, as well as radiopharmaceutical compositions comprising such radioiodinated BTMs. The invention also provides radioiodinated intermediates useful in the method, as well as in vivo imaging methods using the radioiodinated BTMs.

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20-09-2012 дата публикации

Sphingosine kinase type 1 inhibitors, and processes for using same

Номер: US20120237448A9

Provided are novel compositions and analogs which are useful in a number of applications, indications and diseases, as well as for monitoring pharmakinetics and patient management. These compounds and analogs are applicable to treating tumors of the central nervous system, e.g., glioblastoma (GBM).

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11-10-2012 дата публикации

4-amino-1,3-thiazine or oxazine derivative

Номер: US20120258961A1
Принадлежит: Shionogi and Co Ltd

The present invention provide a medicament for treating the diseases induced by production, secretion or deposition of amyloid-β proteins, for example, a compound of the following formula (I) wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, ring A, Y and the dotted line are defined in the specification, its pharmaceutically acceptable salt or a solvate thereof.

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18-10-2012 дата публикации

Efficient process to induce enantioselectivity in procarbonyl compounds

Номер: US20120264933A1
Принадлежит: Laurus Labs Pvt Ltd

The present invention provides an efficient method to induce the enantioselectivity in procarbonyl compounds using chiral organometallic complexes. The present invention also provides a method for producing chiral organometallic complexes using a chiral additive, achiral additive, a base and a metal salt.

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25-10-2012 дата публикации

Novel Polymorphs of Efavirenz

Номер: US20120271047A1
Принадлежит: Hetero Drugs Ltd

The present invention relates to novel amorphous and crystalline forms of efavirenz, processes for their preparation and pharmaceutical compositions containing them. In accordance with the present invention efavirenz crude is dissolved in acetone at 25° C.-30° C., the solution is slowly added to water for 30 minutes at 0° C.-5° C., stirred for 1 hour at the same temperature, the separated solid is filtered, washed with water and dried at 55° C.-60° C. for 5 hours to give amorphous efavirenz.

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25-10-2012 дата публикации

Aryl compounds as ppar ligands and their use

Номер: US20120271055A1

The present invention relates to a compound as a peroxisome proliferator activated receptor (PPAR) activator and a hydrate, a solvate, a stereoisomer and a pharmaceutically acceptable salt thereof, and a pharmaceutical composition, a cosmetic composition, a muscle strengthening agent, a memory improving agent, a therapeutic agent for dementia and Parkinson's disease, a functional food and a feed composition containing the same.

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01-11-2012 дата публикации

Amino acid conjugates of quetiapine, process for making and using the same

Номер: US20120276168A1
Принадлежит: Individual

The presently described technology provides a novel class of prodrugs of quetiapine that can be synthesized bu chemically conjugating amino acids to quetiapine. The present technology also provides methods of treating patients, pharmaceutical compositions and methods of synthesizing conjugates of the present technology.

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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

Compounds for the treatment of proliferative disorders

Номер: US20120289483A1
Принадлежит: Synta Phamaceuticals Corp

The invention relates to compounds of structural formula (I): or a pharmaceutically acceptable salt, solvate, clathrate, and prodrug thereof, wherein R a , R b , and R 2 are defined herein. These compounds inhibit tubulin polymerization and/or target vasculature and are useful for treating proliferative disorders, such as cancer.

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13-12-2012 дата публикации

Isoxazoline derivatives as insecticides

Номер: US20120316124A1
Принадлежит: SYNGENTA CROP PROTECTION LLC

The present invention relates to compounds formula (I), wherein P is P1, P2, heterocyclyl or heterocyclyl substituted by one to five Z; and wherein A 1 , A 2 , A 3 , A 4 , G 1 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 17 , R 18 , R 19 and R 20 are as defined in claim 1 ; or a salt or N-oxide thereof. Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (I), to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising the compounds of formula (I) and to methods of using the compounds of formula (I) to control insect, acarine, nematode and mollusc pests.

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13-12-2012 дата публикации

Substituted benzamide derivatives

Номер: US20120316165A1
Принадлежит: Hoffmann La Roche Inc

The present invention relates to compounds of formula wherein R 1 , R 2 , R 3 , X, Z, Ar, and n are as described in the claims, Ar is phenyl or heteroaryl, selected from the group consisting of 1H-indazole-3yl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, pyrimidine-5-yl, 1H-pyrazole-3-yl, 1H-pyrazole-4-yl and 1H-pyrazole-5-yl; or to a pharmaceutically suitable acid addition salt thereof, which may be used for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder (ADHD), stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, hypertension, substance abuse, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.

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27-12-2012 дата публикации

Novel modulators of sphingosine phosphate receptors

Номер: US20120329838A1
Принадлежит: Scripps Research Institute

Compounds that activate a sphingosine-1-phosphate receptor of the subtype 1 are provided. Certain compounds selectively activate the receptor subtype 1 in relation to the sphinogosine-1-phosphate receptor subtype 3. Uses and methods of inventive compounds for treatment of malconditions wherein activation, agonism, inhibition or antagonism of the S1P1 is medically indicated are provided.

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27-12-2012 дата публикации

Triarylamine Compound, Light-Emitting Element, Light-Emitting Device, Electronic Device, and Lighting Device

Номер: US20120330025A1
Принадлежит: Semiconductor Energy Laboratory Co Ltd

A novel triarylamine compound having a bipolar property is provided. The triarylamine compound can be used for a hole-injection layer, a hole-transport layer, a light-emitting layer, or an electron-transport layer in a light-emitting element. The triarylamine compound can also be used as a host material with a light-emitting material which emits relatively short-wavelength light, in a structure where the host material and the guest material constitute a light-emitting layer. The triarylamine compound of the present invention is a fluorescent compound and therefore can also be used as a light-emitting substance of a light-emitting layer. A light-emitting element having high emission efficiency is provided. A light-emitting device, an electronic device, or a lighting device having low power consumption is provided.

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10-01-2013 дата публикации

Fluorine-free fused ring heteroaromatic photoacid generators and resist compositions containing the same

Номер: US20130011788A1
Принадлежит: International Business Machines Corp

The present invention relates to a fluorine-free photoacid generator (PAG) and a photoresist composition containing the same. The PAG is characterized by the presence of an onium cationic component and a fluorine-free fused ring heteroaromatic sulfonate anionic component containing one or more electron withdrawing substituents. The onium cationic component of the PAG is preferably a sulfonium or an iodonium cation. The photoresist composition further contains an acid sensitive imaging polymer. The photoresist composition is especially useful for forming material patterns on a semiconductor substrate using 193 nm (ArF) lithography.

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10-01-2013 дата публикации

Fluorine-free fused ring heteroaromatic photoacid generators and resist compositions containing the same

Номер: US20130011793A1
Принадлежит: International Business Machines Corp

The present invention relates to a fluorine-free photoacid generator (PAG) and a photoresist composition containing the same. The PAG is characterized by the presence of an onium cationic component and a fluorine-free fused ring heteroaromatic sulfonate anionic component containing one or more electron withdrawing substituents. The onium cationic component of the PAG is preferably a sulfonium or an iodonium cation. The photoresist composition further contains an acid sensitive imaging polymer. The photoresist composition is especially useful for forming material patterns on a semiconductor substrate using 193 nm (ArF) lithography.

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10-01-2013 дата публикации

Aminoalkyloxazole and aminoalkylthiazolecarboxylic acid amides as regeneration-promoting substances for sensory organs and post-mitotic tissue

Номер: US20130012514A1
Принадлежит: EMC microcollections GmbH

Aminoalkyloxazole and aminoalkylthiazolecarboxylic acid amides of formulae (1) and (2) where X represents O or S, Y represents C or N, where the two atoms must be different from one another, R2 represents hydrogen or acyl and R1 and R3, which may be identical or different, represent a substituent selected from the group consisting of branched or straight-chain, substituted or unsubstituted alkyl groups, alkylcycloalkyl groups, alkylaryl groups, cycloalkyl groups, cycloalkylaryl groups, aryl groups and arylcycloalkyl groups which optionally contain heteroatoms, a pharmaceutically acceptable salt, a stereoisomer, a stereoisomer mixture, a tautomer or a prodrug compound, preferably a prodrug ester and a prodrug peptide, thereof.

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31-01-2013 дата публикации

Phenylacetic acid compound

Номер: US20130028887A1
Принадлежит: Ono Pharmaceutical Co Ltd

A compound represented by formula (I), wherein R 1 represents a hydrogen atom, etc., R 2 and R 3 each independently represents a hydrogen atom, optionally oxidized C1-4 alkyl group or optionally protected hydroxyl group, or R 2 and R 3 taken together represent optionally oxidized C2-5 alkylene group, R 4 represents an optionally oxidized C1-6 alkyl group, etc., R 5 represents an optionally oxidized C1-6 alkyl group, etc., R 6 represents an optionally oxidized C1-6 alkyl group, etc., m represents 0 or an integer from 1 to 3, n represents 0 or an integer from 1 to 4, and i represents 0 or an integer from 1 to 7.

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14-02-2013 дата публикации

Therapeutic agent and preventative agent for alzheimer's disease

Номер: US20130041158A1
Принадлежит: TORAY INDUSTRIES INC

A therapeutic agent or prophylactic agent for Alzheimer's disease has an effect to inhibit or delay the progress of Alzheimer's disease and exhibits a long-lasting therapeutic effect on Alzheimer's disease even when used for a long period of time. The therapeutic agent or prophylactic agent for Alzheimer's disease includes as an effective ingredient a cyclohexane derivative exemplified by the formula below, or a pharmaceutically acceptable salt thereof or a prodrug thereof.

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21-02-2013 дата публикации

Pharmaceutical composition for inhibiting apoptosis of neuron or neurodegeneration

Номер: US20130046001A1
Принадлежит: SK Biopharmaceuticals Co Ltd

Provided is a pharmaceutical composition for inhibiting apoptosis of neurons or neurodegeneration. The pharmaceutical composition effectively prevents or treats diseases related to apoptosis of neurons or neurodegeneration.

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28-02-2013 дата публикации

Cyclopentanecarboxamide derivatives, medicaments containing such compounds and their use

Номер: US20130053412A1
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The invention relates to cyclopentanecarboxamide derivatives of formula 1, to their use as Fatty Acid Synthase inhibitors, to methods for their therapeutic use and to pharmaceutical compositions containing them, wherein R 1 , R 2 , R 3 , LO, W, AR 1 , n are as defined in claim 1 .

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14-03-2013 дата публикации

2,5-disubstituted arylsulfonamide ccr3 antagonists

Номер: US20130065889A1
Принадлежит: Axikin Pharmaceuticals Inc

Provided herein are 2,5-disubstituted arylsulfonamide CCR3 antagonists, e.g., compounds of Formula I, and pharmaceutical compositions thereof: Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a CCR3-mediated disorder, disease, or condition.

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21-03-2013 дата публикации

Process for Producing Aliskiren

Номер: US20130071899A1
Принадлежит: Chemo Iberica SA

A new route of synthesis of the compound Aliskiren of formula (I), used in the treatment of hypertension, is described.

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21-03-2013 дата публикации

LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS

Номер: US20130072449A1
Принадлежит: INTERMUNE, INC.

Compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or diagnose diseases, disorders, or conditions associated with one or more of the lysophosphatidic acid receptors are provided. 5. The compound or pharmaceutically acceptable salt of claim 2 , wherein m=1 claim 2 , and wherein Ris hydrogen and Ris selected from the group consisting of optionally substituted phenyl claim 2 , imidazole claim 2 , pyridine claim 2 , thiazole claim 2 , and oxazole.6. The compound or pharmaceutically acceptable salt thereof of claim 2 , wherein m=1 claim 2 , and wherein Rand Rare joined together with the atom to which they are attached to form an optionally substituted azetidine claim 2 , an optionally substituted oxetane claim 2 , an optionally substituted beta-lactam claim 2 , an optionally substituted tetrahydropyran claim 2 , an optionally substituted cyclopropyl claim 2 , an optionally substituted cyclobutyl claim 2 , an optionally substituted cyclopentyl claim 2 , or an optionally substituted cyclohexyl.711.-. (canceled)13. (canceled)15. (canceled)18. (canceled)20. (canceled)21. (canceled)22. (canceled)24. The compound or salt thereof of claim 1 , selected from compounds of Table 1 claim 1 , and pharmaceutically acceptable salts thereof.25. The compound or salt thereof of claim 1 , selected from compounds of Table 2 claim 1 , and pharmaceutically acceptable salts thereof.26. The compound or salt thereof of claim 1 , selected from compounds of Table 3 claim 1 , and pharmaceutically acceptable salts thereof.28. The compound or pharmaceutically acceptable salt thereof of claim 27 , wherein Rand Rare joined together with the atom to which they are attached to form an optionally substituted azetidine claim 27 , an optionally substituted oxetane claim 27 , an optionally substituted beta-lactam claim 27 , an optionally substituted tetrahydropyran claim 27 , an optionally ...

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21-03-2013 дата публикации

ARALKYL DIAMINE DERIVATIVES AND USES THEREOF AS ANTIDEPRESSANTS

Номер: US20130072488A1

Aralkyl diamine derivative of the following formula, pharmaceutically acceptable salts or uses thereof as antidepressants. The derivatives have triplex inhibiting activities of the reuptake of 5-HT, dopamine and noradrenalin, which can be administered to the patients in need of such treatment in the form of compositions orally or injectedly et al. 2. The compound according to claim 1 , wherein the substituted amino group is an amino group substituted with C-Calkyl or C-Chaloalkyl.3. The compound according to claim 1 , wherein the substituted phenyl or the substituted benzyl has 1-4 substituents on the benzene ring claim 1 , with R claim 1 , Rand Rrepresenting the substituents.4. The compound according to claim 1 , wherein the salt is a pharmaceutically acceptable inorganic or organic salt.5. The compound according to claim 4 , wherein the hydrate contains 0.5-3 molecules of crystal water.6. The compound according to claim 1 , wherein the compound is selected from the group consisting of:VI-1 N,N-diethyl-3-(3,4-dichlorophenyl)-3-(pyrrolidin-1-yl)-propylamine,VI-2 N,N-dimethyl-3-(3,4-dichlorophenyl)-3-(pyrrolidin-1-yl)-propylamine,VI-3 N,N-dimethyl-3-(3,4-dichlorophenyl)-3-(piperazin-1-yl)-propylamine,VI-4 N,N-dimethyl-3-(3,4-dichlorophenyl)-3-morpholinyl-propylamine,VI-5 N-methyl-N-benzyl-3-(3,4-dichlorophenyl)-3-morpholinyl-propylamine,VI-6 4-(3-(3,4-dichlorophenyl)-3-(pyrrolidin-1-yl)propylmorpholine,VI-7 N,N-dimethyl-3-(3,4-dichlorophenyl)-3-piperidyl-propylamine,VI-8 N,N-dimethyl-3-(4-chlorophenyl)-3-morpholinyl-propylamine,VI-9 4-(3-(4-chlorophenyl)-3-(pyrrolidin-1-yl)propylmorpholine,VI-10 N,N-dimethyl-3-(4-methylphenyl)-3-morpholinyl-propylamine,VI-11 4-(3-(4-methylpiperazin-1-yl)-1-(4-methylphenyl)propylmorpholine,VI-12 4-(3-(4-methylphenyl)-3-(morpholinyl)propylpyrrole,VI-13 N,N-dimethyl-3-(benzothiophen-3-yl)-3-(pyrrolidin-1-yl)-propylamine,VI-14 N-methyl-N-benzyl-3-(benzothiophen-3-yl)-3-(pyrrolidin-1-yl)-propylamine,VI-15 N-methyl-3-(benzothiophen-3-yl)-3 ...

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21-03-2013 дата публикации

Polycyclic compounds as lysophosphatidic acid receptor antagonists

Номер: US20130072490A1
Принадлежит: Amira Pharmaceuticals Inc

Described herein are compounds that are antagonists of lysophosphatidic receptor(s). Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such antagonists, alone and in combination with other compounds, for treating LPA-dependent or LPA-mediated conditions or diseases.

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28-03-2013 дата публикации

Reversed biaryl spiroaminooxazoline analogues as alpha2c adrenergic receptor modulators

Номер: US20130079271A1
Принадлежит: Individual

In its many embodiments, the present invention provides a novel class of biaryl spiroaminooxazoline analogues as modulators of α2C adrenergic receptor agonists, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more conditions associated with the α2C adrenergic receptors using such compounds or pharmaceutical compositions.

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28-03-2013 дата публикации

TRPV1 VANILLOID RECEPTOR ANTAGONISTS WITH A BICYCLIC PORTION

Номер: US20130079339A1
Принадлежит: PHARMESTE S.R.L.

The invention discloses compounds of formula I 3. Compounds according to wherein R1 and R2 are independently pyrrolidin-1-yl claim 2 , piperidin-1-yl claim 2 , morpholin-4-yl claim 2 , or 2-(dimethylamino)ethoxy.4. A compound according to selected from the group consisting of:1-(4-(trifluoromethyl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(2-fluoro-4-(trifluoromethyl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(2-chloro-4-(trifluoromethyl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(2-(dimethylamino)-4-(trifluoromethyl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-(trifluoromethyl)-2-(pyrrolidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-(trifluoromethyl)-2-morpholinobenzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-(trifluoromethyl)-2-(1H-1,2,4-triazol-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-fluorobenzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-chlorobenzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-chloro-2-(dimethylamino)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-chloro-2-(pyrrolidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-chloro-2-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-(dimethylamino)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-(pyrrolidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-methylbenzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(2-(dimethylamino)-4-methylbenzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(4-methyl-2-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea,1-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)-3-((pyridin-4-yl) ...

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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

TRICYCLIC COMPOUND AND PHARMACEUTICAL USE THEREOF

Номер: US20130079374A1
Принадлежит: Takeda Pharmaceutical Company Limited

The present invention provides a compound represented by the formula 123-. (canceled)26. The compound of claim 24 , wherein Ris Calkyl optionally having substituent(s) claim 24 , Ccycloalkyl optionally having substituent(s) or Calkenyl optionally having substituent(s).27. The compound of claim 24 , wherein Ris a hydrogen atom or Calkyl optionally having substituent(s).28. The compound of claim 24 , wherein Ris a hydrogen atom or Calkyl optionally having substituent(s).29. The compound of claim 24 , wherein Ris a hydrogen atom claim 24 , a hydrocarbon group optionally having substituent(s) or a heterocyclic group optionally having substituent(s).30. The compound of claim 24 , wherein Ris a hydrogen atom claim 24 , Calkyl optionally having substituent(s) claim 24 , Calkenyl optionally having substituent(s) or amino optionally having substituent(s).31. The compound of claim 24 , wherein Rand Rare the same or different and each is a hydrogen atom claim 24 , a halogen atom claim 24 , hydroxy optionally having a substituent or Calkyl optionally having substituent(s).32. The compound of claim 24 , wherein Ris Calkyl optionally having substituent(s) claim 24 , Ccycloalkyl optionally having substituent(s) or Calkenyl optionally having substituent(s);{'sup': '2', 'Ris a hydrogen atom, a hydrocarbon group optionally having substituent(s) or a heterocyclic group optionally having substituent(s);'}{'sup': '3', 'sub': 1-6', '2-6, 'Ris a hydrogen atom, Calkyl optionally having substituent(s), Calkenyl optionally having substituent(s) or amino optionally having substituent(s);'}{'sup': 4a', '4b, 'sub': '1-6', 'Rand Rare the same or different and each is a hydrogen atom, a halogen atom, hydroxy optionally having a substituent or Calkyl optionally having substituent(s);'}{'sup': '5', 'sub': '1-6', 'Ris a hydrogen atom or Calkyl optionally having substituent(s); and'}{'sup': '6', 'sub': '1-6', 'Ris a hydrogen atom or Calkyl optionally having substituent(s).'}33. The compound of claim ...

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04-04-2013 дата публикации

Hepatitis C Virus Inhibitors

Номер: US20130085147A1
Принадлежит: BRISTOL-MYERS SQUIBB COMPANY

The present disclosure is generally directed to antiviral compounds, and more specifically directed to compounds which can inhibit the function of the NS5A protein encoded by Hepatitis C virus (HCV), compositions comprising such compounds, and methods for inhibiting the function of the NS5A protein. 13. A compound , or a stereoisomer or a pharmaceutically acceptable salt thereof , selected from the group consisting of:(4,5-bis(4-(((2S)-2-(((benzyloxy)carbonyl)amino)propanoyl)amino)phenyl)-1,3-oxazol-2-yl)acetic acid;ethyl (4,5-bis(4-(((2S)-2-(((benzyloxy)carbonyl)amino)propanoyl)amino)phenyl)-1,3-oxazol-2-yl)acetate;dibenzyl((2-methyl-1,3-oxazole-4,5-diyl)bis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))biscarbamate;dibenzyl (1H-imidazole-4,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))biscarbamate;(2S,2′S)—N,N′-(1H-imidazole-4,5-diyldi-4,1-phenylene)bis(2-((phenylacetyl)amino)propanamide);dibenzyl((5-oxo-1,5-dihydro-4H-1,2,4-triazole-3,4-diyl)bis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))biscarbamate;dibenzyl (4H-1,2,4-triazole-3,4-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))biscarbamate;dibenzyl (1H-1,2,3-triazole-4,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))biscarbamate;(2S,2′S)—N,N′-(1H-pyrazole-3,5-diyldi-4,1-phenylene)bis(2-(((2S)-2-hydroxy-2-phenylacetyl)amino)propanamide);(2S,2′S)—N,N′-(1H-pyrazole-3,5-diyldi-4,1-phenylene)bis(2-(((2R)-2-hydroxy-2-phenylacetyl)amino)propanamide);(2S,2′S)—N,N′-(1H-pyrazole-3,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))bis(2-hydroxy-2-phenylpropanamide);(2R,2′R)—N,N′-(1H-pyrazole-3,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))bis(2-hydroxy-2-phenylpropanamide);N,N′-(1H-pyrazole-3,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))bis(3-chloro-1-naphthamide);N,N′-(1H-pyrazole-3,5-diylbis(4,1-phenyleneimino((2S)-1-oxo-1,2-propanediyl)))bis(3-chloro-1-isoquinolinecarboxamide);(2S,2′S)—N,N′-(1,3-oxazole-2,5-diyldi-4,1-phenylene)bis(2-(((2S)-2-hydroxy ...

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04-04-2013 дата публикации

CARBOXYLATION CATALYSTS

Номер: US20130085276A1
Принадлежит:

The use of a complex of the form Z—M—OR in the carboxylation of a substrate is described. The group Z is a two-electron donor ligand, M is a metal and OR is selected from the group consisting of OH, alkoxy and aryloxy. The substrate may be carboxylated at a C—H or N—H bond. The metal M may be copper, silver or gold. The two-electron donor ligand may be a phosphine, a carbene or a phosphite ligand. Also described are methods of manufacture of the complexes and methods for preparing isotopically labelled caboxylic acids and carboxylic acid derivatives. 134-. (canceled)25. A method of carboxylation of a substrate , the method comprising;{'sub': '2', 'contacting a complex of the form Z—M—OR ,wherein the group Z is a two-electron donor ligand, M is a metal, and OR is selected from the group consisting of OH, alkoxy and aryloxy; with a substrate and a source of CO.'}26. The method according to claim 25 , wherein the metal M is selected from the group consisting of copper claim 25 , silver and gold.27. The method according to claim 25 , wherein the carboxylation is carried out in the presence of a base.28. The method according to claim 27 , wherein the base is an alkali metal hydroxide or alkoxide.29. The method according to claim 25 , wherein the two-electron donor ligand Z is selected from the group consisting of phosphines claim 25 , carbenes claim 25 , or phosphites.30. The method according to claim 29 , wherein the two-electron donor ligand Z is a nitrogen containing heterocyclic carbene ligand.33. The method according to claim 26 , wherein the complex is selected from the group consisting of: [M(OH)(IMes)] claim 26 , [M(OH)(SIMes)] claim 26 , [M(OH)(IPr)] claim 26 , [M(OH)(ItBu)] claim 26 , and [M(OH)(SIPr)] claim 26 , where M is Au claim 26 , Ag or Cu.34. The method according to claim 25 , wherein the substrate is carboxylated at a C—H or N—H bond.35. The method according to claim 25 , wherein the substrate is a substituted or unsubstituted aromatic compound.36. The ...

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11-04-2013 дата публикации

Compounds Having Activating Effect on Subtypes of Peroxisome Proliferator-Activated Receptors and its Preparation Method and Uses

Номер: US20130089613A1
Принадлежит: ZHEJIANG HISUN PHARMACEUTICAL CO., LTD.

Phenyl propanoic acid compounds having activating effect on peroxisome proliferator-activated receptors (PPARα,δ,γ) and a preparation method and uses thereof are provided in the present invention. The compounds can be used for treating or preventing diseases associated with peroxisome proliferator-activated receptors (PPARα,δ,γ). 2. The compound according to claim 1 , wherein X is S claim 1 , O claim 1 , or NR claim 1 , Y is O.3. The compound according to claim 1 , wherein Ris independently H or C-Calkyl.4. The compound according to claim 3 , wherein Ris methyl or H.5. The compound according to claim 4 , wherein Gis selected from C-Calkyl.6. The compound according to claim 5 , wherein Gand Gare each independently selected from H claim 5 , C-Calkyl claim 5 , C-Calkoxy claim 5 , trifluoromethyl claim 5 , F claim 5 , Cl claim 5 , Br claim 5 , nitro claim 5 , NRR claim 5 , C-Calkylthio claim 5 , amido claim 5 , cyano claim 5 , carboxyl and tetrazolyl.7. The compound according to claim 6 , wherein Gis ethyl; G claim 6 , Gare F claim 6 , CFor methyl.9. A pharmaceutical composition claim 1 , comprising the compound according to or pharmaceutical acceptable salts thereof.10. The pharmaceutical composition according to claim 9 , with a dosage form selected from tablets claim 9 , film-coated tablets claim 9 , sugar coated tablets claim 9 , enteric coated tablets claim 9 , dispersible tablets claim 9 , capsules claim 9 , granules claim 9 , oral solutions and oral suspensions.11. Use of a compound according to in the manufacture of a medicament for treating or preventing diseases associated with α subtype claim 1 , δ subtype claim 1 , and γ subtype of peroxisome proliferator-activated receptors.12. The use according to claim 11 , wherein the diseases associated with α subtype claim 11 , δ subtype claim 11 , and γ subtype of peroxisome proliferator-activated receptors are selected from hyperglycaemia claim 11 , insulin resistance claim 11 , hyperlipidemia and obesity.13. Use of ...

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11-04-2013 дата публикации

Compounds Useful as Inhibitors of ATR Kinase

Номер: US20130089624A1
Принадлежит: VERTEX PHARMACEUTICALS INCORPORATED

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. 2. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.3. A method for treating cancer in a patient comprising administering a compound of or a pharmaceutically acceptable derivative thereof.4. The method of claim 3 , further comprising administering to said patient an additional therapeutic agent selected from a DNA-damaging agent; wherein said additional therapeutic agent is appropriate for the disease being treated; and said additional therapeutic agent is administered together with said compound as a single dosage form or separately from said compound as part of a multiple dosage form.56-. (canceled)76. The method of claim claim 3 , wherein said DNA-damaging agent is selected from ionizing radiation claim 3 , a platinating agent claim 3 , a Topo I inhibitor claim 3 , a Topo II inhibitor claim 3 , an antimetabolite claim 3 , an alkylating agent claim 3 , or an alkyl sulphonates.816-. (canceled)176. The method of claim claim 3 , wherein the DNA-damaging agent is selected from one or more of the following: Cisplatin claim 3 , Carboplatin claim 3 , gemcitabine claim 3 , Etoposide claim 3 , Temozolomide claim 3 , or ionizing radiation.18. (canceled)19. The method of claim 3 , wherein said cancer is selected from a cancer of the ...

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11-04-2013 дата публикации

Benzoxazole Derivatives Having Inhibitory Activity Against Interleukin-6, Preparation Method Thereof, and Pharmaceutical Composition Containing the Same

Номер: US20130090480A1
Принадлежит:

The present invention relates to benzoxazole derivatives represented by the Formula 1, which has an inhibitory activity against interleukin-6 (IL-6), a method for preparation thereof, and a pharmaceutical composition containing the same. The compound represented by the Formula 1 according to the present invention has a superior inhibitory activity against interleukin-6, and therefore, can be practically applied for prevention and treatment of diseases caused by abnormal interleukin-6 activity. 3. The compound according to characterized in that said Ris phenyl substituted with two identical or different substitutents each independently selected from the group consisting of halogen claim 1 , nitro claim 1 , Chaloalkyl claim 1 , and Calkoxy.4. The compound according to characterized in that said Ris phenyl substituted with halogen and nitro claim 3 , phenyl substituted with halogen and Chaloalkyl claim 3 , phenyl substituted with two halogens claim 3 , or phenyl substituted with two Calkoxy.5. The compound according to characterized in that said Ris phenyl substituted with three Calkoxy.7. The compound according to characterized in that said Ris trifluoromethyl.8. The compound according to characterized in that the compound is selected from the group consisting of:N-(2-(4-ethylphenyl)benzo[d]oxazole-2,5-diamine,N-(2-(4-ethylphenylamino)benzo[d]oxazol-5-yl)-2-phenylacetamide,N-(2-(4-ethylphenylamino)benzo[d]oxazol-5-yl)benzamide,4-chloro-N-(2-(4-ethylphenylamino)benzo[d]oxazol-5-yl)benzamide,2-chloro-N-(2-(4-ethylphenylamino)benzo[d]oxazol-5-yl)-4-nitrobenzamide,2-chloro-N-(2-(4-ethylphenylamino)benzo[d]oxazol-5-yl)-5-nitrobenzamide,3,4-dichlorobenzamide-N-(2-(4-ethylphenylamino)benzo[d]oxazol-5-yl)benzamide,3-(chloromethyl)-N-(2-(4-ethylphenylamino)benzo[d]oxazol-5-yl)benzamide,4-ethyl-N-(2-(4-ethylphenylamino)benzo[d]oxazol-5-yl)benzamide,N-(2-(4-ethylphenylamino)benzo[d]oxazol-5-yl)-3-fluoro-5-(trifluoromethyl)benzamide,2-ethoxy-N-(2-(4-ethylphenylamino)benzo[d] ...

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18-04-2013 дата публикации

ArylSulfonamide Based Matrix Metalloprotease Inhibitors

Номер: US20130096105A1
Принадлежит: NOVARTIS AG

The present invention provides a compound of formula (I): 2. The compound of claim 1 , wherein Ris selected from (C-C) aryl claim 1 , (5-14) membered heteroaryl claim 1 , and (4-14) membered heterocycloalkyl claim 1 , each of which is optionally substituted by one to three substituents selected from the group consisting of HC(O)— claim 1 , (5-9) membered heteroaryl claim 1 , and (4-9) membered heterocycloalkyl claim 1 , (C-C) alkyl claim 1 , (C-C) cycloakyl claim 1 , R—O— claim 1 , R—C(O)— claim 1 , R—SO— claim 1 , (R)NH—C(O)— claim 1 , and (R)(R)N— claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare independently (C-C) alkyl or (C-C) aryl claim 1 , each of which is further optionally substituted by one to two substituents selected from the group consisting of (C-C) alkyl claim 1 , halo claim 1 , hydroxy claim 1 , (C-C) alkoxy claim 1 , (C-C) aryl claim 1 , (C-C) dialkylamino claim 1 , and (4-9) membered heterocycloalkyl; Rand Rare independently hydrogen claim 1 , or (C-C) alkyl; X is selected from hydrogen claim 1 , amine claim 1 , cyano claim 1 , halogen claim 1 , nitro claim 1 , alkyl-S— claim 1 , alkyl-SO— claim 1 , alkyl-SO— claim 1 , HN—SO— claim 1 , R—C(O)— claim 1 , alkyl claim 1 , and R—O claim 1 , wherein Rand Rare defined above; ora pharmaceutically acceptable salt thereof, or an optical isomer thereof; or a mixture of optical isomers.4. The compound of claim 3 , wherein R′ claim 3 , is selected from (C-C) alkyl claim 3 , (C-C) cycloalkyl claim 3 , (C-C) alkoxy claim 3 , HC(O)— claim 3 , (5-9) membered heteroaryl claim 3 , and (4-9) membered heterocycloalkyl claim 3 , or (C-C) aryl claim 3 , said (C-C) aryl claim 3 , (5-9) membered heteroaryl claim 3 , and (4-9) membered heterocycloalkyl are optionally substituted by one or two substituents selected from hydroxy claim 3 , halo claim 3 , (C-C) alkyl claim 3 , carboxyl claim 3 , (C-C) alkoxycarbonyl claim 3 , and HC(O)—;{'sub': 2', '3, 'Rand Rare hydrogen;'}{'sub': 1', '7, 'X is ...

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18-04-2013 дата публикации

SUBSTITUTED AMINOPROPIONIC DERIVATIVES AS NEPRILYSIN INHIBITORS

Номер: US20130096127A1
Принадлежит: NOVARTIS AG

The present invention provides a compound of formula I′; 3. The compound of wherein:{'sup': '1', 'sub': '1-7', 'Ris H or Calkyl;'}{'sup': 2', 'a', 'b', 'a', 'b, 'sub': 1-7', '3-7', '1-7', '1-7', '6-20', '1-7, 'Rfor each occurrence, is independently Calkyl, halo, Ccycloalkyl, hydroxy, Calkoxy, haloCalkyl, —NRR, Caryl, heteroaryl or heterocyclyl; wherein Rand Rfor each occurrence are independently H or Calkyl;'}{'sup': 3', '1', '1, 'Ris A-C(O)X;'}{'sup': '5', 'Ris H; and'}{'sup': 1', 'a', 'b, 'sub': '1-7', 'X and Xare independently OH, —O—Calkyl or NRR;'}{'sup': '1', 'Bis —C(O)NH— or —NHC(O)—;'}{'sup': '1', 'sub': 1-7', '3-7', '1-7', '3-7, 'Ais a linear or branched Calkylene; which is optionally substituted with one or more substituents independently selected from the group consisting of halo, Ccycloalkyl, Calkoxy, hydroxy and O-acetate; in which two geminal alkyl can optionally combine to form a Ccycloalkyl; or'}and wherein each heteroaryl is a monocyclic or bicyclic aromatic ring comprising 5-10 ring atoms selected from carbon atoms and 1 to 5 heteroatoms, and', 'each heterocyclyl is a monocyclic saturated or partially saturated but non-aromatic moiety comprising 4-7 ring atoms selected from carbon atoms and 1-5 heteroatoms, wherein each heteroatom of a heteroaryl or a heterocyclyl is independently selected from O, N and S, or a pharmaceutically acceptable salt thereof., 'n is 0, 1, 2, 3, 4 or 5;'}6. The compound of wherein Ais an optionally substituted linear or branched Calkylene claim 1 , or a pharmaceutically acceptable salt thereof.7. The compounds of wherein Ais CHCH claim 1 , or a pharmaceutically acceptable salt thereof.810-. (canceled)11. The compound of wherein Ris H claim 1 , Ris independently halo claim 1 , Calkoxy claim 1 , hydroxy claim 1 , Calkyl or halo-Calkyl claim 1 , n is 0 claim 1 , 1 or 2 and X and Xare independently OH or —O—Calkyl claim 1 , or a pharmaceutically acceptable salt thereof.12. The compounds of wherein n is 1 or 2; Ris meta-chloro ...

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18-04-2013 дата публикации

Substituted carbamoylmethylamino acetic acid derivatives as novel NEP inhibitors

Номер: US20130096168A1
Принадлежит: NOVARTIS AG

The present invention provides a compound of formula I; 119-. (canceled)22. The compound according to wherein s is 0; or a pharmaceutically acceptable salt thereof.23. The compounds according to wherein{'sup': '2', 'Xis Cl, or a pharmaceutically acceptable salt thereof.'}24. The compound according to selected from:(S)-2-[(S)-2-(3′-chloro-biphenyl-4-yl)-1-(1H-tetrazol-5-ylcarbamoyl)-ethylamino]-propionic acid ethyl ester;(S)-2-[(S)-2-(3′-chloro-biphenyl-4-yl)-1-(1H-tetrazol-5-ylcarbamoyl)-ethylamino]-propionic acid; and(S)-2-[(S)-2-(3′-Chloro-biphenyl-4-yl)-1-(3-hydroxy-isoxazol-5-ylcarbamoyl)-ethylamino]-propionic acid; or a pharmaceutically acceptable salt thereof.25. A pharmaceutical composition comprising a compound according to or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers.26. A pharmaceutical composition comprising a compound according to or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers.27. A combination comprising: a compound according to claim 20 , or a pharmaceutically acceptable salt thereof and one or more therapeutically active agents selected from HMG-Co-A reductase inhibitor claim 20 , an anigiotensin receptor blocker claim 20 , angiotensin converting enzyme Inhibitor claim 20 , a calcium channel blocker claim 20 , an endothelin antagonist claim 20 , a renin inhibitor claim 20 , a diuretic claim 20 , an ApoA-I mimic claim 20 , an anti-diabetic agent claim 20 , an obesity-reducing agent claim 20 , an aldosterone receptor blocker claim 20 , an endothelin receptor blocker claim 20 , an aldosterone synthase inhibitors claim 20 , a CETP inhibitor and a phophodiesterase type 5 (PDE5) inhibitor.28. A combination comprising: a compound according to or a pharmaceutically acceptable salt thereof and one or more therapeutically active agents selected from HMG-Co-A reductase inhibitor claim 24 , an anigiotensin receptor blocker claim 24 , angiotensin converting ...

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25-04-2013 дата публикации

FLUORINATED RESORUFIN COMPOUNDS AND THEIR APPLICATION

Номер: US20130102014A1
Принадлежит: LIFE TECHNOLOGIES CORPORATION

The invention provides novel fluorinated resorufin compounds that are of use in a variety of assay formats. Also provided are methods of using the compounds and kits that include a compound of the invention and instructions detailing the use of the compound in one or more assay formats. 2. The compound according to claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , and Ris fluorine.3. The compound according to claim 1 , wherein A is OR claim 1 , E is OR claim 1 , E is OR claim 1 , and Ris hydrogen.46.-. (canceled)7. The compound according to claim 1 , wherein Rand Rare fluorine.8. The compound according to claim 1 , wherein Rand Rare each fluorine.9. The compound according to claim 1 , wherein R claim 1 , R claim 1 , Rand Rare each fluorine.10. The compound according to claim 1 , wherein Rand Rare each fluorine and R claim 1 , R claim 1 , Rand Rare hydrogen claim 1 , substituted alkyl claim 1 , unsubstituted alkyl claim 1 , substituted alkoxy claim 1 , unsubstituted alkoxy claim 1 , substituted alkylthio claim 1 , unsubstituted alkylthio claim 1 , substituted aryl claim 1 , unsubstituted aryl claim 1 , substituted heteroaryl claim 1 , or unsubstituted heteroaryl.11. The compound according to claim 1 , wherein Rand Rare each fluorine and R claim 1 , R claim 1 , Rand Rare each hydrogen.12. The compound according to claim 1 , wherein Rand Rare each fluorine and R claim 1 , R claim 1 , Rand Rare hydrogen claim 1 , substituted alkyl claim 1 , unsubstituted alkyl claim 1 , substituted alkoxy claim 1 , unsubstituted alkoxy claim 1 , substituted alkylthio claim 1 , unsubstituted alkylthio claim 1 , substituted aryl claim 1 , unsubstituted aryl claim 1 , substituted heteroaryl claim 1 , or unsubstituted heteroaryl.13. The compound according to claim 1 , wherein Rand Rare each fluorine and R claim 1 , R claim 1 , Rand Rare each hydrogen.1417-. (canceled)18. The compound according to claim 1 , wherein Ris hydrogen claim 1 , substituted alkyl or unsubstituted ...

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25-04-2013 дата публикации

Process for Producing Imine Compounds for Combating Invertebrate Pests

Номер: US20130102462A1
Принадлежит: BASF SE

The present invention relates to a process for producing aromatic carbonyl compounds of formula I and aromatic imine compounds of formula III 145-. (canceled)48. The process as claimed in claim 46 , where Z is Br claim 46 , I or —OSO—R.49. The process as claimed in claim 48 , where Z is Br claim 48 , I or —OSO—R claim 48 , where Ris selected from the group consisting of CH claim 48 , CFand 4-methylphenyl claim 48 , and is preferably Br.50. The process as claimed in claim 46 , where carbon monoxide and hydrogen are used in a molar ratio of from 20:1 to 1:10.51. The process as claimed in claim 50 , where carbon monoxide and hydrogen are used in a molar ratio of from 2:1 to 1:2 and are preferably used in the form of synthesis gas.52. The process as claimed in claim 46 , where the catalyst is a group VIII metal complex.53. The process as claimed in claim 52 , where the metal is selected from the group consisting of Pd claim 52 , Pt claim 52 , Ni claim 52 , Rh claim 52 , Ir and Ru and is preferably Pd.54. The process as claimed in claim 46 , where the catalyst contains a monodentate and/or bidentate ligand.55. The process as claimed in claim 46 , where the catalyst contains a phosphorus-containing ligand.56. The process as claimed in claim 55 , where the phosphorus-containing ligand is a monodentate ligand selected from the group consisting of phosphorus compounds of formula PRRR claim 55 , where{'sup': a', 'b', 'c', 'd', 'e, 'sub': 3', '12', '3', '12', '3', '10', '3', '10', '5', '18', '5', '18, 'claim-text': or', {'sup': a', 'b', 'e, 'sub': 3', '10, 'Rand Rtogether with the phosphorus atom to which they are bound form a 5-, 6-, 7- or 8-membered heterocyclic ring which may be additionally fused to one, two or three C-C-cycloalkyl, heterocyclyl, aryl or hetaryl groups, where the heterocyclic ring and, if present, the fused-on groups may each independently carry one, two, three or four substituents R;'}, {'sup': d', '1', '2', '1', '2', '3+', '−, 'sub': 3', '10', '3', '10', ...

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25-04-2013 дата публикации

OXAZOLE TYROSINE KINASE INHIBITORS

Номер: US20130102592A1
Принадлежит: SAREUM LIMITED

The invention provides a compound which is an amide of the formula (1), or a salt, solvate, N-oxide or tautomer thereof; wherein: a is 0 or 1; b is 0 or 1: provided that the sum of a and b is 0 or 1; T is O or NH Aris a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S, and being optionally substituted en by one or more substituents R; ArJs a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S and being optionally substituted by one or more substituents R; and Rand Rare as defined in the claims. The compounds are inhibitors of kinases and in particular FLT3, FLT4 and Aurora kinases. 176-. (canceled)85. A compound according to wherein Aris selected from substituted monocyclic 5- and 6-membered aryl and heteroaryl rings containing up to 2 heteroatoms selected from O claim 77 , N and S claim 77 , each of the aryl and heteroaryl rings being optionally substituted by one or more substituents R.86. A compound according to wherein Aris selected from optionally substituted phenyl claim 85 , thiophene claim 85 , furan claim 85 , pyridine and pyrazole rings.87. A compound according to wherein Aris phenyl optionally substituted by one or more substituent groups R.88. A compound according to wherein the aryl or heteroaryl group Aris substituted by 0 claim 77 , 1 or 2 substituents R.89. A compound according to wherein Ris selected from halogen; cyano; or a group R—R;{'sup': aa', 'cc', 'cc', 'cc', 'cc', 'cc', 'cc', 'cc, 'sub': 2', '2', '2, 'Ris a bond, O, CO, OC(O), C(O)O, NRC(O), C(O)NR, NR, OC(O)O, NRC(O)O, OC(O)NR, NRC(O)NR, S, SO, SO, SONR″ or NR″SOwherein'}{'sup': 'bb', 'claim-text': hydrogen; or', {'sup': '3a', 'a 3 to 8-membered non-aromatic carbocyclic or heterocyclic ring containing up to 2 heteroatoms selected from O, N and S and being optionally substituted by one or more substituents R; or'}, {'sup': '3a', 'a 5- or 6-membered ...

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25-04-2013 дата публикации

PHENOXY ACETIC ACIDS AS PPAR DELTA ACTIVATORS

Номер: US20130102610A1
Принадлежит: HIGH POINT PHARMACEUTICALS, LLC

Novel compounds of the general formula (I), the use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds are activators of PPARδ and should be useful for treating conditions mediated by the same. 1. A compound selected from the group consisting of:(Z)-[2-Methyl-4-[3-(4-methylphenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-phenoxy]acetic acid;(E)-[2-Methyl-4-[3-[4-[3-(pyrazol-1-yl)prop-1-ynyl]phenyl]-3-(4-trifluoromethylphenyl)allyloxy]phenoxy]acetic acid;(E)-[2-Methyl-4-[3-[4-[3-(morpholin-4-yl)propynyl]phenyl]-3-(4-trifluoromethylphenyl) allyloxy]-phenoxy]acetic acid;(E)-[2-Methyl-4-[3(4-methylphenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-phenoxy]acetic acid; and(Z)-[2-Methyl-4-[3-[4-[3-(morpholin-4-yl)propynyl]phenyl]-3-(4-trifluoromethylphenyl) allyloxy]-phenoxy]acetic acid;or a pharmaceutically acceptable salt thereof.2. The compound of claim 1 , wherein the compound is (Z)-[2-Methyl-4-[3(4-methylphenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof.3. A compound selected from the group consisting of: (E)-[2-Methyl-4-[3-[4-[3-(pyrazol-1-yl)prop-1-ynyl]phenyl]-3-(4-trifluoromethylphenyl)-allyloxy]phenoxy]acetic acid or a pharmaceutically acceptable salt thereof.4. The compound of claim 3 , wherein the compound is (E)-[2-Methyl-4-[3-[4-[3-(morpholin-4-yl)propynyl]phenyl]-3-(4-trifluoromethylphenyl)allyloxy]-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof.5. A compound selected from the group consisting of: (E)-[2-Methyl-4-[3-(4-methylphenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof.6. The compound of claim 1 , wherein the compound is (Z)-[2-Methyl-4-[3-[4-[3-(morpholin-4-yl)propynyl]phenyl]-3-(4-trifluoromethylphenyl)allyloxy]-phenoxy]acetic ...

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25-04-2013 дата публикации

METHOD OF TREATING DIABETES, METABOLIC SYNDROME AND OBESITY USING PHENYLACETAMIDE DERIVATIVE

Номер: US20130102617A1
Принадлежит: Astellas Pharma Inc.

Phenylacetamide compounds of the formula 1. (canceled)2. The method of claim 18 , wherein n is 0.3. The method of claim 2 , wherein Ris methyl claim 2 , trifluoromethyl claim 2 , or cyclopropyl.4. The method of claim 3 , wherein Ris cyclopropyl.6. The method of claim 5 , wherein Ring A is pyrazolyl claim 5 , thiazolyl claim 5 , thiadiazolyl claim 5 , pyridyl or pyrazinyl claim 5 , each of which may be substituted with up to five moieties independently selected from the group consisting of halogen claim 5 , cyano claim 5 , lower alkyl which may be substituted with —OR claim 5 , —OR claim 5 , —O-lower alkylene —OR claim 5 , and —C(O)R.7. The method of claim 6 , wherein [Chem. 21] is a single bond.8. The method of claim 6 , wherein [Chem. 22] is a double bond.9. The method of claim 18 , wherein the compound is selected from the group consisting of:(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methylpyrazin-2-yl)-3-[(1S)-3-oxocyclopentyl]acrylamide,(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(1-methyl-1H-pyrazol-3-yl)-3-[(1S)-3-oxocyclopentyl]acrylamide,(2E)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-fluoro-1,3-thiazol-2-yl)-3-[(1S)-3-oxocyclopentyl]acrylamide,(2R)—N-(4-acetyl-1,3-thiazol-2-yl)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methylpyridin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methylpyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-[5-(hydroxymethyl)pyrazin-2-yl]-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)—N-(5-chloropyrazin-2-yl)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-N-(5-methoxypyrazin-2-yl)-3-[(1R)-3-oxocyclopentyl]propanamide,(2R)-2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(1R)-3-hydroxycyclopentyl]-N-(5 ...

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25-04-2013 дата публикации

Substituted Tetracycline Compounds

Номер: US20130102779A1
Автор: Abato Paul
Принадлежит: PARATEK PHARMACEUTICALS, INC.

The present invention pertains to tetracycline compounds of formula (VIIa): 2. The tetracycline compound of claim 1 , wherein Ris oxazolyl.3. The tetracycline compound of claim 2 , wherein oxazolyl is substituted with methyl or isopropyl.4. The tetracycline compound of claim 1 , wherein Ris oxadiazolyl.5. The tetracycline compound of claim 4 , wherein oxadiazolyl is substituted with alkyl.6. The tetracycline compound of claim 1 , wherein Ris isoxazolyl.7. The tetracycline compound of claim 1 , wherein Ris pyrazolyl.8. The tetracycline compound of claim 7 , wherein Ris methylpyrazolyl.9. The tetracycline compound of claim 1 , wherein Ris —CONRR claim 1 , in which Ris hydrogen and Ris hydroxyl claim 1 , hydroyxalkyl claim 1 , alkoxy claim 1 , phenyl claim 1 , or alkyl.10. The tetracycline compound of claim 1 , wherein Ris wherein Ris —CONRR claim 1 , in which Ris alkyl and Ris alkyl or hydroxyl.11. The tetracycline compound of claim 1 , wherein Ris dialkylamino.12. The tetracycline compound of claim 11 , wherein Ris dimethylamino.13. The tetracycline compound of claim 1 , wherein each of R claim 1 , R claim 1 , R claim 1 , and R is hydrogen.14. The tetracycline compound of claim 13 , wherein Ris dialkylamino.15. The tetracycline compound of claim 14 , wherein Ris dimethylamino.19. A pharmaceutical composition comprising a tetracycline compound of and a pharmaceutically acceptable carrier.20. A method for treating a tetracycline responsive state in a subject claim 1 , comprising administering to said subject an effective amount of a tetracycline compound of claim 1 , such that said subject is treated. This application is a divisional application of U.S. Ser. No. 11/963,540, filed on Dec. 21, 2007 and issued as U.S. Pat. No. 8,318,706 on Nov. 27, 2012, which claims priority to U.S. Provisional Patent Application No. 60/876,313, filed on Dec. 21, 2006 and U.S. Provisional Patent Application No. 60/943,003, filed Jun. 8, 2007. The contents of the foregoing applications ...

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25-04-2013 дата публикации

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

Номер: US20130102780A1
Принадлежит: Rhodes Technologies

The present disclosure provides processes for the N-dealkylation of tertiary amines and the use of transition metal catalysts to prepare tertiary N-allyl amine derivatives and secondary amine derivatives thereof. The tertiary amines can be alkaloids and, more particularly, the tertiary amines can be opioids. In specific embodiments, the present disclosure provides methods for use in processes for the synthesis of naloxone and naltrexone from oripavine. 3. The method of claim 1 , wherein the transition metal catalyst comprises a transition metal selected from the group consisting of Pd[0] claim 1 , Pd[II] claim 1 , Ni[0] claim 1 , Ni[II] claim 1 , Mo[0] claim 1 , Ru[II] claim 1 , Rh[I] claim 1 , and combinations of two or more thereof.4. The method of claim 3 , wherein the transition metal catalyst is selected from the group consisting of Pd(PPh) claim 3 , Pd(PhP(CH)PPh) claim 3 , Ni(PPh) claim 3 , Ni(PhP(CH)PPh) claim 3 , ((pentamethylcyclopentadienyl)RuCl) claim 3 , [Pd(DBA)]/PPh claim 3 , [Pd(OAc)]/PPh claim 3 , [Ni(COD)]/PPh claim 3 , NiCl/PPh claim 3 , Ni[P(OEt)] claim 3 , [Mo(CO)-DPPE] claim 3 , RhH(PPh)-P(n-Bu) claim 3 , and combinations of two or more thereof.6. The method of claim 5 , wherein the solvent is selected from the group consisting of ether solvents claim 5 , acetonitrile claim 5 , benzene claim 5 , N claim 5 ,N-dimethylformamide claim 5 , dimethyl sulfoxide claim 5 , N claim 5 ,N-dimethylpropionamide claim 5 , 1 claim 5 ,3-dimethyl-3 claim 5 ,4 claim 5 ,5 claim 5 ,6-tetrahydro-2(1H)-pyrimidinone claim 5 , 1 claim 5 ,3-dimethyl-2-imidazolidinone claim 5 , 1 claim 5 ,2-dimethoxyethane claim 5 , N claim 5 ,N-dimethylacetamide claim 5 , N-methylpyrrolidinone claim 5 , ethyl acetate claim 5 , ethyl formate claim 5 , ethyl-methyl ketone claim 5 , iso-butylmethylketone claim 5 , formamide claim 5 , hexamethylphosphoramide claim 5 , methyl acetate claim 5 , N-methylacetamide claim 5 , N-methylformamide claim 5 , nitrobenzene claim 5 , nitromethane claim 5 ...

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02-05-2013 дата публикации

C7-Fluoro Substituted Tetracycline Compounds

Номер: US20130109657A1
Принадлежит: Tetraphase Pharmaceuticals Inc

The present invention is directed to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

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02-05-2013 дата публикации

ACTIVATORS OF HUMAN PYRUVATE KINASE

Номер: US20130109672A1

Disclosed are pyruvate kinase M2 activators which are compounds of Formula (I), including those of Formula (II), wherein A, A, L, R, Rto R, Xto X, k, n, and m are as defined herein, that are useful in treating a number of diseases that are treatable by the activation of PKM2, for example, cancer. A-NR-L-A(I). 2. (canceled)3. The compound or salt of claim 1 , wherein the phenyl ring of the bicyclic ring of R′ is fused with an aryl claim 1 , a heteroaryl claim 1 , a cyclyl claim 1 , or a heterocyclyl claim 1 , each of which is optionally substituted with one or more substituents selected from the group consisting of aryl claim 1 , heteroaryl claim 1 , cyclyl claim 1 , alkyl claim 1 , alkoxyl claim 1 , halogen claim 1 , NH claim 1 , NH—(C-C)alkyl claim 1 , N—(C-C)alkyl-(C-C)alkyl claim 1 , (C-C)alkyl-OC— claim 1 , and heterocyclyl claim 1 , each of which other than halogen and NHis further optionally substituted with one or more substituents selected from the group consisting of NH claim 1 , OH claim 1 , NH—(C-C)alkyl and N—(C-C)alkyl-(C-C)alkyl.4. The compound or salt of claim 1 , wherein the cyclyl or heterocyclyl of R′ or R″ is a five-membered claim 1 , six-membered claim 1 , or seven-membered ring.5. The compound or salt of claim 1 , wherein the heterocyclyl contains one or two heteroatoms.6. The compound or salt of claim 1 , wherein R is methyl or H.8. The compound or salt of claim 7 , wherein one Ris at the ortho position relative to the carbon attached to the NR-L moiety.9. The compound or salt of claim 7 , wherein one Ris H claim 7 , F claim 7 , Cl claim 7 , Br claim 7 , methyl claim 7 , N(Me) claim 7 , NHMe claim 7 , 1-piperidinyl claim 7 , 2-(dimethylamino)ethyl)(methyl)amino claim 7 , pyrrolidin-1-yl claim 7 , 3-(dimethylamino)pyrrolidin-1-yl claim 7 , 2-hydroxy-2-methylpropylamino claim 7 , isopropylamino claim 7 , diethylamino claim 7 , 1-hydroxypropan-2-ylamino claim 7 , 2-hydroxyethylamino claim 7 , or phenyl.10. The compound or salt of claim 1 , wherein ...

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02-05-2013 дата публикации

5,6-DIHYDRO-2H-[1,4]OXAZIN-3-YL-AMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE)

Номер: US20130109683A1
Принадлежит: Janssen Pharmaceutica NV

The present invention relates to novel 5,6-dihydro-2H-[1,4]oxazin-3-ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease and dementia associated with beta-amyloid. 2. The compound according to wherein R claim 1 , Rand Rare hydrogen claim 1 , Ris fluoro and L is —N(R)CO— wherein Ris hydrogen.3. The compound according to wherein R claim 2 , Rand Rare hydrogen claim 2 , Ris fluoro claim 2 , L is —N(R)CO— wherein Ris hydrogen claim 2 , and Ris methyl claim 2 , ethyl or cyclopropyl.4. The compound according to wherein R claim 2 , Rand Rare hydrogen claim 2 , Ris fluoro claim 2 , L is —N(R)CO— wherein Ris hydrogen claim 2 , and Ris methyl claim 2 , ethyl or cyclopropyl claim 2 , X claim 2 , Xand Xare CH claim 2 , and Xis CH claim 2 , CF or N.5. The compound according to wherein R claim 2 , Rand Rare hydrogen claim 2 , Ris fluoro claim 2 , L is —N(R)CO— wherein Ris hydrogen claim 2 , and Ris methyl claim 2 , ethyl or cyclopropyl claim 2 , and Ar is pyridyl claim 2 , or pyrazyl claim 2 , each optionally substituted with one or two substituents selected from halo claim 2 , cyano claim 2 , methoxy claim 2 , trifluoroethoxy and difluoromethyl.6. The compound according to wherein R claim 1 , Rand Rare hydrogen claim 1 , Ris trifluoromethyl and L is —N(R)CO— wherein Ris hydrogen.7. The compound according to wherein R claim 6 , Rand Rare hydrogen claim 6 , Ris trifluoromethyl claim 6 , L is —N(R)CO— wherein Ris hydrogen ...

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02-05-2013 дата публикации

GRP94 INHIBITORS

Номер: US20130109684A1
Принадлежит: University of Kansas

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

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02-05-2013 дата публикации

Small Molecule Inhibitors of Functions of the HIV-1 Matrix Protein

Номер: US20130109698A1
Автор: Simon Cocklin
Принадлежит: Simon Cocklin

The present invention includes a method of inhibiting, suppressing or preventing retroviral infection in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising one or more of the compounds of the invention.

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02-05-2013 дата публикации

SPIRO COMPOUNDS AND PHARMACEUTICAL USE THEREOF

Номер: US20130109710A1
Принадлежит: JAPAN TOBACCO INC.

The spiro compound represented by the following general formula [Ia], its pharmaceutically acceptable salt or a solvate thereof 3. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 , wherein the number of the double bond in ring A of the spiro-ring AB is 0 or 1.4. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 , wherein the number of the double bond in ring B of the spiro-ring AB is 0 or 1.5. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 , wherein n3 is 1 or 2.6. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed claim 1 , wherein the spiro-ring AB may be substituted by 1 to 3 same or different substituent(s).7. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 ,{'sup': '1', 'wherein Ris'}(1) a hydrogen atom,{'sub': 1', '6, '(2) a C-Calkyl group,'}{'sub': 2', '6, '(3) a C-Calkenyl group,'}{'sub': 2', '6, '(4) a C-Calkynyl group,'}{'sub': 1', '6, '(5) a C-Calkoxy group,'}{'sub': 1', '6', '1', '6, '(6) a C-Calkoxy(C-C)alkyl group,'}{'sup': 11', '12', '11', '12, 'sub': 1', '6, '(7) —CONRRin which Rand Rare the same or different and each represents a hydrogen atom or a C-Calkyl group, or'}{'sub': 1', '6, '(8) a five-membered heteroaryl group which has at least one heteroatom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and which may be substituted by a C-Calkyl group.'}8. The spiro compound claim 1 , the pharmaceutically acceptable salt thereof or the solvate thereof as claimed in claim 1 ,{'sup': '1', 'wherein Ris'}(1) a hydrogen atom,{'sub': 2', '6, '(2) a C-Calkenyl group,'}{'sub': 2', '6, '(3) a C-Calkynyl group,'}{'sub': 1', '6, '(4) a C-Calkoxy group or'}{'sub': 1', '6, '(5) a five- ...

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02-05-2013 дата публикации

PREPARATION METHOD OF 5-[[2(R)-[1(R)-[3,5-BIS(TRIFLUOROMETHYL) PHENYL]ETHOXY]-3(S)-4-FLUOROPHENYL-4-MORPHOLINYL]METHYL]-1,2-DIHYDRO-3H-1,2,4-TRIAZOLE-3-ONE

Номер: US20130109853A1
Принадлежит:

Disclosed is a synthesis method of a compound of formula 1,5-[[2(R)-[1(R)-[3,5-bis(trifluoromethyl)phenyl]ethoxyl]-3(S)-4-fluorophenyl-4-morpholinyl]methyl]-1,2-dihydro-3H-1,2,4-triazole-3-one (i.e. aprepitant), which comprises cyclizing a compound of formula 4 in a solvent, wherein R is C-Calkyl. The intermediate for preparing aprepitant is also disclosed. The present method is especially suitable for industrial production of aprepitant. 2. The method according to claim 1 , wherein R is selected from methyl claim 1 , ethyl and t-butyl.3. The method according to claim 1 , wherein the alcohol is C-Cfatty alcohol claim 1 , preferably selected from methanol claim 1 , ethanol claim 1 , propanol claim 1 , n-butanol claim 1 , t-butanol and propanediol; the ester is an organic acid ester claim 1 , preferably selected from ethyl acetate claim 1 , methyl acetate claim 1 , ethyl formate and t-butyl acetate; and the ether is selected from tetrahydrofuran claim 1 , dioxane and 3-methyl tetrahydrofuran.4. The method according to claim 1 , wherein the solvent is alcohol claim 1 , water or alcohol-water mixed solvent.5. The method according to claim 1 , wherein the solvent is ethanol-water mixed solvent.6. The method according to claim 5 , wherein the volume ratio of the ethanol-water mixed solvent is 1:0.1 to 1:100.7. The method according to claim 1 , wherein the solvent is the ether-water mixed solvent claim 1 , preferably a tetrahydrofuran-water mixed solvent with a volume ratio of 1:0.1 to 1:100.8. The method according to claim 1 , wherein the cyclization reaction is performed under the action of an inorganic base.9. The method according to claim 1 , wherein the temperature of the cyclization reaction is 60 to 100° C.11. The method according to claim 8 , wherein the inorganic base is selected from KHCO claim 8 , KCO claim 8 , NaCO claim 8 , NaHCO claim 8 , KOH claim 8 , NaOH and CsCO.12. The method according to claim 8 , wherein the inorganic base is KOH or NaOH.13. The method ...

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09-05-2013 дата публикации

BIARYL AMIDE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF

Номер: US20130116227A1
Принадлежит: DAINIPPON SUMITOMO PHARMA CO., LTD.

Disclosed is a novel biaryl amide derivative represented by formula (1) and having an affinity for the aldosterone receptor; also disclosed is a pharmaceutically acceptable salt thereof. (In the formula, A is any of the groups represented by formula (a); L is —CONH—, etc.; Ris a substitutable aminosulfonyl group, etc.; Ris a hydrogen atom, etc.; Ris a hydrogen atom, etc.; Ris a hydrogen atom, a halogen atom, hydroxy group, a substitutable amino group, a substitutable Calkoxy group, a substitutable 4- to 7-membered cyclic amino group, etc.; R, Rand Rare each independently hydrogen atoms, etc.; Ris a halogen atom, a cyano group, etc.; Rand Rare each independently a hydrogen atom, etc.; and m is an integer such as 0.) 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A is a group of formula (a).3. The compound of either claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is —NHCO—.4. The compound of either claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is —CONH—.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris [{'sub': '1-6', 'claim-text': [{'sub': '1-6', '(i) amino (in which the amino may be optionally substituted with the same or different 1 to 2 Calkyl),'}, {'sub': '1-6', '(ii) Calkoxy, or'}, '(iii) 4- to 7-membered cyclic amino),, '(a) Calkyl (in which the group may be optionally substituted with'}, {'sub': '1-6', '(b) Calkylcarbonyl,'}, '(c) aminocarbonyl, and', {'sub': '2', '(d) —C(═NH)—NH),'}], '1: aminosulfonyl group (in which the amino may be optionally substituted with the same or different 1 to 2 groups selected from the group consisting of'}{'sub': '1-6', '2: Calkylsulfonyl group, or'}{'sub': '1-6', '3: Calkylsulfonylamino group, or a pharmaceutically acceptable salt thereof.'}6. The compound of claim 5 , wherein Ris aminosulfonyl group claim 5 , or a pharmaceutically acceptable salt thereof.7. The compound of claim ...

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09-05-2013 дата публикации

MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS

Номер: US20130116238A1
Принадлежит: VERTEX PHARMACEUTICALS INCORPORATED

Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention. 2. The compound of of formula I claim 1 , wherein two R taken together form —OCFO— claim 1 , Ris H claim 1 , and Ris F.3. The compound of of formula I claim 1 , wherein two R taken together form —OCFO— claim 1 , Ris H claim 1 , Ris F claim 1 , and Ris CH.4. The compound of of formula I claim 1 , wherein two R taken together form —OCFO— claim 1 , Ris H claim 1 , Ris F claim 1 , Ris CH claim 1 , and X is COH.5. The compound of of formula I claim 1 , wherein two R taken together form —OCFO— claim 1 , Ris H claim 1 , Ris F claim 1 , Ris CH claim 1 , X is COH claim 1 , and Y is OH.6. The compound of of formula II claim 1 , wherein two R taken together form —OCFO— claim 1 , Ris H claim 1 , and Ris F.7. The compound of of formula II claim 1 , wherein two R taken together form —OCFO— claim 1 , Ris H claim 1 , Ris F claim 1 , and Ris CH.9. The compound of claim 8 , wherein Ris F.13. A pharmaceutical composition comprising{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(i) a compound according to ; and'}(ii) a pharmaceutically acceptable carrier.14. The composition of claim 13 , further comprising an additional agent selected from a mucolytic agent claim 13 , bronchodialator claim 13 , an anti-biotic claim 13 , an anti-infective agent claim 13 , an anti-inflammatory agent claim 13 , CFTR corrector claim 13 , CFTR potentiator claim 13 , or a nutritional agent.15. A method of increasing the number of functional ABC transporters in a membrane of a cell claim 1 , comprising the step of contacting the cell with a compound of .16. The method of claim 15 , wherein the ABC transporter is CFTR.17. A ...

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09-05-2013 дата публикации

Selective Androgen Receptor Modulators

Номер: US20130116288A1
Автор: Chris P. Miller
Принадлежит: Radius Health Inc

This invention provides compounds of formulas I, Ia, Ib, Ic, Id, Ie, If or Ig or salts thereof, pharmaceutical compositions comprising a compound of formulas I, Ia, Ib, Ic, Id, If or Ig and a pharmaceutically acceptable excipient, methods of modulating the androgen receptor, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type 2 diabetes related disorders or diseases, anemia, depression, and renal disease) and processes for making compounds of formulas I, Ia, Ib, Ic, Id, Ie, If or Ig and intermediates useful in the preparation of same.

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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

DIAMINE DERIVATIVES AS INHIBITORS OF LEUKOTRIENE A4 HYDROLASE

Номер: US20130123243A1
Принадлежит:

This invention is directed to compounds of formula (I): 3. A compound according to wherein{'sup': 1a', '13', '10', '13', '10, 'Ris hydrogen, —R—C(O)OR, —R—C(O)R, alkyl, halo, haloalkyl, cyano, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, optionally substituted heterocyclyl, or optionally substituted heterocyclylalkyl; and'}{'sup': 1b', '1c', '1d', '1e, 'R, R, Rand Rare each independently hydrogen or halo.'}4. A compound according to wherein{'sup': 1a', '13', '10', '13', '10, 'Ris hydrogen, —R—C(O)OR, —R—C(O)R, alkyl, halo, haloalkyl, optionally substituted phenyl, furanyl, thienyl, thiazolyl, or optionally substituted oxazolyl; and'}{'sup': 1b', '1c', '1d', '1e, 'R, R, Rand Rare each hydrogen.'}6. A compound according to wherein R an optionally substituted heteroaryl.7. A compound according to wherein R is furanyl claim 6 , oxazoyl claim 6 , pyrazolyl claim 6 , pyridinyl claim 6 , triazolyl claim 6 , thiazolyl claim 6 , or benzothiazolyl claim 6 , each of which is optionally substituted.8. A compound according to wherein:{'sup': 2', '7', '5a', '5b', '5c, 'Rand R, together with the nitrogens to which they are attached and one of R, Rand R, form an optionally substituted 6- to 10-membered bridged N-heterocyclyl.'}10. A compound according to wherein:{'sup': 3', '12', '12', '12, 'Ris a direct bond, —O—, —R—O—, —O—R—, —O—R—O—, or an optionally substituted straight or branched alkylene chain;'}{'sup': 4', '12a, 'Ris a direct bond, —O—R— or an optionally substituted straight or branched alkylene chain;'}{'sup': 8', '13', '10', '13', '10', '13', '10', '11, 'Ris aralkyl optionally substituted with one or more substituents selected from the group consisting of —R—OR, —R—C(═O)ORand —R—C(═O)N(R)R;'}{'sup': 9', '10, 'each Ris independently alkyl, halo or —O—R;'}{'sup': '12', 'Ris an optionally substituted straight ...

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16-05-2013 дата публикации

BENZOXAZINE DERIVATIVES AND USES THEREOF

Номер: US20130123251A1
Принадлежит: Roche Palo Alto LLC

The present invention provides a compound of the formula: 169-. (canceled)71. The compound according to claim 70 , wherein Zis N.74. The compound according to claim 73 , wherein n and p are 2.75. The compound according to claim 74 , wherein Y is —SO—.76. The compound according to claim 75 , wherein Rand Rare hydrogen.77. The compound according to claim 76 , wherein each Ris independently halo or alkyl.78. The compound according to claim 77 , wherein each Ris independently chloro or methyl.79. The compound according to claim 78 , wherein m is 1.80. The compound according to claim 79 , wherein Ris aryl.81. The compound according to claim 80 , wherein Ris optionally substituted phenyl or optionally substituted naphthyl.82. The compound according to claim 81 , wherein Ris phenyl claim 81 , 2-fluorophenyl claim 81 , 2-chlorophenyl claim 81 , 3 claim 81 ,4-dichlorophenyl claim 81 , 4-chlorophenyl claim 81 , 3-chlorophenyl claim 81 , 4-methoxyphenyl claim 81 , 3 claim 81 ,5-dichlorophenyl claim 81 , 2 claim 81 ,6-dichlorophenyl claim 81 , 2 claim 81 ,4-dichlorophenyl claim 81 , 3-methanesulfonylaminophenyl claim 81 , 2-methanesulfonylphenyl claim 81 , 2-carbamoylphenyl claim 81 , 3-methanesulfonylphenyl claim 81 , 4-methanesulfonylphenyl claim 81 , 3-fluorophenyl claim 81 , naphthyl claim 81 , 2 claim 81 ,4-difluorophenyl claim 81 , 2-cyanophenyl claim 81 , 2-chloro-4-fluorophenyl claim 81 , 2-methyl-5-fluorophenyl claim 81 , or 5-chloronaphthyl.83. The compound according to claim 81 , wherein Ris phenyl or halide substituted phenyl.84. The compound according to claim 83 , wherein Ris phenyl claim 83 , 2-chlorophenyl or 2-fluorophenyl.87. A method for treating a CNS disease state in a subject claim 70 , said method comprising administering to said subject a therapeutically effective amount of a compound of . This application is entitled to the benefit of U.S. Provisional Application No. 60/378,003, filed on May 13, 2002, the disclosure of which is incorporated herein by ...

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23-05-2013 дата публикации

Mediator For Test Sensor

Номер: US20130126350A1
Принадлежит: Bayer HealthCare LLC

A method of forming a 3-phenylimino-3H-phenothiazine or a 3-phenylimino-3H-phenoxazine mediator includes providing a first reactant including phenothiazine or phenoxazine, providing a first solvent, providing a second reactant and providing a second solvent. The first reactant, first solvent, second reactant and second solvent are combined to form a reactants solution. Sodium persulfate is added to the reactants solution to couple the first and second reactants resulting in a reaction solution including the 3-phenylimino-3H-phenothiazine or the 3-phenylimino-3H-phenoxazine mediator. 125-. (canceled)26. A 3-phenylimino-3H-phenothiazine mediator or 3-phenylimino-3H-phenoxazine mediator wherein the background current is less than 200 nA after being exposed to a temperature of 50° C. for a duration of two weeks.27. The mediator of wherein the mediator is a 3-phenylimino-3H-phenothiazine mediator.28. The mediator of wherein the mediator is a 3-phenylimino-3H-phenoxazine mediator.29. The mediator of wherein the 3-phenylimino-3H-phenothiazine mediator or 3-phenylimino-3H-phenoxazine mediator is in the form of a salt.30. The mediator of wherein the -phenylimino-3H-phenothiazine mediator or 3-phenylimino-3H-phenoxazine mediator is in the form of a acid.31. A test sensor including a base claim 26 , the base including an enzyme adapted to react with an analyte claim 26 , and a mediator claim 26 , the mediator having a background current being less than 200 nA after being exposed to a temperature of 50° C. for a duration of two weeks.32. The test sensor of further including a neutralizing agent.33. The test sensor of wherein the neutralizing agent is sodium hydroxide.34. The test sensor of wherein the neutralizing agent is sodium bicarbonate.35. The test sensor of further including a buffer.36. The test sensor of wherein the buffer is sodium phosphate.37. The test sensor of wherein the test sensor is an electrochemical test sensor.38. The test sensor of wherein the test sensor ...

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