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Небесная энциклопедия

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

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Мониторинг СМИ

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

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 26557. Отображено 100.
12-01-2012 дата публикации

Tetrazine monomers and copolymers for use in organic electronic devices

Номер: US20120007026A1
Принадлежит: NATIONAL RESEARCH COUNCIL OF CANADA

Copolymers of formula (I): where each A is S, Se or C═C; each x is an integer from 1 to 4; each R1 is independently H, F, CN or a C 1 -C 20 linear or branched aliphatic group; Ar is one or more substituted or unsubstituted aromatic units; and, n is an integer 5 or greater, can be formed into films or membranes that are useful as active layers in organic electronic device, such as PV solar cells, providing high power conversion efficiencies and good thermal stability. Such copolymers may be synthesized from monomers of formula (II): by Stille or Suzuki coupling reactions. Such monomers may be synthesized by a variation of the Pinner synthesis.

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12-01-2012 дата публикации

Anthranilic diamide derivatives having cyclic side-chains

Номер: US20120010249A1
Принадлежит: Bayer CropScience AG

The present invention relates to novel anthranilic diamide derivatives of the general formula (I) in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , A, Q and n have the meanings given in the description, to their use as insecticides and acaricides for controlling animal pests, also in combination with other agents for activity boosting, and a plurality of processes for their preparation.

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26-01-2012 дата публикации

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

Номер: US20120020283A1
Принадлежит: Qualcomm Inc

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

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26-01-2012 дата публикации

Triazole derivatives for treatment of alzheimer's disease

Номер: US20120022044A1
Принадлежит: Individual

According to the invention there is provided a compound of formula I or a pharmaceutically acceptable salt or hydrate thereof; wherein the variables are as defined herein. The compounds selectively attenuate the production of Aβ42 and hence are useful in treatment of Alzheimer's disease and related conditions.

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09-02-2012 дата публикации

Charge transport compositions and electronic devices made with such compositions

Номер: US20120032158A1
Принадлежит: EI Du Pont de Nemours and Co

The present invention is directed to a photoactive device comprising an anode, a cathode, and a photoactive layer, which device further comprises an electron transport and/or anti-quenching layer which minimizes both electron transfer quenching and energy transfer quenching of the photoactive layer.

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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

3-substituted propanamine compounds

Номер: US20120046312A1
Принадлежит: SK Biopharmaceuticals Co Ltd

Racemic or enantiomerically enriched 3-substituted propanamine compounds represented by the following structural formula (I): or a pharmaceutically acceptable salt thereof are disclosed. Pharmaceutical compositions containing the subject compounds are also disclosed. The subject compounds are useful for the treatment of diseases of the central nervous system, such as depression, anxiety and pain disorders.

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01-03-2012 дата публикации

Azafluorene derivative and organic light-emitting device using the derivative

Номер: US20120049176A1
Принадлежит: Canon Inc

A novel azafluorene derivative and an organic light-emitting device having the derivative are provided. The organic light-emitting device includes a pair of electrodes composed of an anode and a cathode one of which is a transparent or semi-transparent electrode, and an organic compound layer interposed between the pair of electrodes. The organic compound layer contains the azafluorene derivative represented by the following general formula (I):

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08-03-2012 дата публикации

Carbazole and carboline kinase inhibitors

Номер: US20120058988A1
Принадлежит: Bristol Myers Squibb Co

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

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15-03-2012 дата публикации

Pyridinylcarboxylic Acid Derivatives as Fungicides

Номер: US20120065197A1
Принадлежит: Bayer CropScience AG

Pyridinylcarboxylic acid derivatives of the formula (I) in which the symbols A, X, Y 1 , Y 2 , Y 3 , L 1 , L 2 , R G , and R 1 are each as defined in the description, and also salts, metal complexes and N-oxides of the compounds of the formula (I), and the use thereof for controlling phytopathogenic harmful fungi and processes for preparing compounds of the formula (I).

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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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19-04-2012 дата публикации

Novel Heterocyclic Compounds as Pesticides

Номер: US20120094837A1
Принадлежит: Bayer CropScience AG

The present invention relates to novel heterocyclic compounds, to processes for preparation thereof and to the use thereof for controlling animal pests, which include arthropods and especially insects.

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03-05-2012 дата публикации

Novel microbiocides

Номер: US20120108645A1
Принадлежит: SYNGENTA CROP PROTECTION LLC

Compounds of formula (I) in which the substituents are as defined in claim 1, are suitable for use as microbiocides.

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31-05-2012 дата публикации

Method for preparing 5-chloro-n-(methyl)thiophen-2-carboxamide derivative and intermediate used therein

Номер: US20120136149A1

Disclosed are: a method for preparing a 5-chloro-N-({(5S)-2-oxo-3-[4-(5,6-dihydro-4H-[1,2,4]triazin- 1 -yl)phenyl]-1,3-oxazolidin-5-yl}-methyl)thiophene-2-carboxamide derivative, which is a inhibitor of blood coagulation factor Xa, in a high purity and yield; and a novel intermedicate used therein.

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07-06-2012 дата публикации

Light-emitting device material and light-emitting device

Номер: US20120138907A1
Принадлежит: TORAY INDUSTRIES INC

Embodiments provide a light emitting device material characterized by containing an anthracene compound represented by the following general formula. where R 19 to R 37 are a hydrogen atom, alkyl group, cycloalkyl group, heterocyclic group or the like; n is 1 or 2; and A is a heteroarylene group or arylene group. Any one of the R 19 to R 27 and any one of the R 28 to R 37 are used for linking with A. The present teachings allow a light emitting device having high luminous efficiency and excellent durability.

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05-07-2012 дата публикации

Second-order nonlinear optical compound and nonlinear optical element comprising the same

Номер: US20120172599A1
Принадлежит: Individual

Problem to Be Solved: to provide a chromophore having a far superior nonlinear optical activity to conventional chromophores and to provide a nonlinear optical element comprising said chromophore. Solution: a chromophore comprising a donor structure D, a π-conjugated bridge structure B, and an acceptor structure A, the donor structure D comprising an aryl group substituted with a substituted oxy group; and a nonlinear optical element comprising said chromophore.

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09-08-2012 дата публикации

Processes relating to the alkylation of pyrazoles

Номер: US20120203009A1
Принадлежит: SYNGENTA CROP PROTECTION LLC

The present invention relates to processes for the preparation of a compound of formula (I) comprising reacting a compound of formula (IV) with a compound of formula III or (IIIA) in the presence of an acid; wherein R 1 is C 1 -C 4 haloalkyl; R 2 is optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl; R 3 is methyl or ethyl; R 4 is hydrogen, optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl; and n is 0 or 1.

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01-11-2012 дата публикации

Aromatic heterocyclic derivative and organic electroluminescence device using the same

Номер: US20120273766A1
Принадлежит: Idemitsu Kosan Co Ltd

An aromatic heterocyclic derivative represented by the following formula (1), a material for an organic electroluminescence device and an organic electroluminescence device including these:

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22-11-2012 дата публикации

Fredericamycin derivatives

Номер: US20120295856A1
Автор: Ulrich Abel, Werner Simon
Принадлежит: ZENTOPHARM GmbH

The invention relates to novel fredericamycin derivatives, to drugs containing said derivatives or the salts thereof, and to the use of the fredericamycin derivatives for treating diseases, especially cancer diseases.

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24-01-2013 дата публикации

Catalysts based on heterocyclic-8-anilinoquinoline ligands

Номер: US20130023635A1
Принадлежит: EQUISTAR CHEMICALS LP

A catalyst system useful for polymerizing olefins is disclosed. The catalyst system comprises an activator and a Group 4 metal complex. The complex incorporates a dianionic, tridentate heterocyclic-8-anilinoquinoline ligand. In one aspect, a supported catalyst system is prepared by first combining a boron compound having Lewis acidity with excess alumoxane to produce an activator mixture, followed by combining the activator mixture with a support and the dianionic, tridentate Group 4 metal complex. The Group 4 metal complexes are easy to synthesize, support, and activate, and they enable facile production of high-molecular-weight polyolefins.

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21-02-2013 дата публикации

Aromatic monomers deriving from glycerol units, process for their preparation and use thereof for the preparation of water-soluble conjugated polymers

Номер: US20130046072A1
Принадлежит: Eni Spa

Monomers having formula (I) and process for their synthesis which comprises the etherification reaction of a halogen-derivative (Z═Cl, Br, I) having formula (III) with the hydroxyl group of the glycerol derivative (IV), according to the following scheme:(Formula III, IV & I) (III) (IV) (I)

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28-02-2013 дата публикации

Compound for electroluminescent device and organic electroluminescent devices using the same

Номер: US20130048956A1
Принадлежит: E Ray Optoelectronics Technology Co Ltd

The present invention provides a compound of formula (I) for an organic electroluminescent device: wherein X 1 , X 2 , X 3 , Y, Ar 1 , Ar 2 , Ar 3 , Ar 4 , Ar 5 , Ar 6 , and Ar 7 are as defined in the description.

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07-03-2013 дата публикации

Maleimide-based compound, and tautomer or stereoisomer thereof, dye for photoelectric conversion, and semiconductor electrode, photoelectric conversion element and photoelectrochemical cell using the same

Номер: US20130056690A1
Принадлежит: NEC Corp

It is an object to provide a maleimide-based compound having excellent photoelectric conversion characteristics, and a tautomer or a stereoisomer thereof, a dye for photoelectric conversion, a semiconductor electrode, a photoelectric conversion element, and a photoelectrochemical cell. In order to accomplish the above-described objects, a dye for photoelectric conversion including at least one compound represented by the following general formula (1) is provided. (In the formula (1), R 1 represents a direct bond, or a substituted or unsubstituted alkylene group. X represents an acidic group. D represents an organic group containing an electron-donating substituent. Z represents a linking group that has at least one hydrocarbon group selected from aromatic rings or heterocyclic rings).

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14-03-2013 дата публикации

SUBSTITUTED N-HETEROARYL BIPYRROLIDINE CARBOXAMIDES, PREPARATION AND THERAPEUTIC USE THEREOF

Номер: US20130065923A1
Принадлежит: SANOFI

The present disclosure relates to a series of substituted N-heteroaryl bipyrrolidine carboxamides of formula (I). 2. The compound according to claim 1 , whereinm and p are 1;X is CO;{'sub': 1', '3, 'Ris CH;'}{'sub': 2', '3, 'Ris CH; and'}{'sub': 3', '1', '4', '3, 'Ris unsubstituted or substituted naphthyl, phenyl, benzyl, thiophenyl, isoxazolyl, cyclopropyl, cyclohexyl, tetrahydropyranyl or piperidinyl, wherein the substituents are selected from the group consisting of halogen, (C-C)alkyl and CHCO; and'}{'sub': '4', 'Ris H,'}or a salt thereof or an enantiomer or a diastereomer thereof.3. The compound according to claim 1 , whereinm and p are 1;{'sub': '2', 'X is SO;'}{'sub': 1', '3, 'Ris CH;'}{'sub': 2', '3, 'Ris CH; and'}{'sub': 3', '1', '4', '3, 'Ris unsubstituted or substituted phenyl, cyclopropyl or cyclohexyl, wherein the substituents are selected from the group consisting of halogen, (C-C)alkyl and CHCO; and'}{'sub': '4', 'Ris H;'}or a salt thereof or an enantiomer or a diastereomer thereof.4. The compound of selected from the group consisting of:tetrahydro-pyran-4-carboxylic acid [2-methyl-6-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-yl]-amide;tetrahydro-pyran-4-carboxylic acid [5-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-2-yl]-amide;naphthalene-1-carboxylic acid [2-methyl-6-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-yl]-amide;N-[2-methyl-6-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-yl]-2-phenyl-acetamide;cyclohexanesulfonic acid [2-methyl-6-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-yl]-amide;3,4-difluoro-N-[2-methyl-6-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-yl]-benzenesulfonamide;N-[2-methyl-6-((2S,3′S)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-yl]-benzamide;1-acetyl-piperidine-4-carboxylic acid [2-methyl-6-((2S,3′R)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-yl]-amide;5-fluoro-2-methyl-N-[2-methyl-6-((2S,3′R)-2-methyl-[1,3′]bipyrrolidinyl-1′-yl)-pyridin-3-yl]- ...

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21-03-2013 дата публикации

ORGANIC NANOFIBER STRUCTURE BASED ON SELF-ASSEMBLED ORGANOGEL, ORGANIC NANOFIBER TRANSISTOR USING THE SAME, AND METHOD OF MANUFACTURING THE ORGANIC NANOFIBER TRANSISTOR

Номер: US20130069040A1
Принадлежит:

An organic nanofiber including a gelled organic semiconductor compound. Also disclosed is an organic semiconductor transistor and a method of manufacturing an organic semiconductor transistor. 1. An organic semiconductor transistor comprising:a substrate;a gate electrode;a source electrode and a drain electrode, each of which are insulated from the gate electrode;an organic semiconductor layer, which is insulated from the gate electrode and electrically connected to the source and drain electrodes; andan insulating layer, which insulates the gate electrode from the source and drain electrodes and the organic semiconductor layer,wherein an organic nanofiber comprising a gelated organic semiconductor compound is disposed on the organic semiconductor layer.2. The organic semiconductor transistor of claim 1 , formed by self-assembly of the gelated organic semiconductor compound in an organic solvent.3. The organic semiconductor transistor of claim 1 , wherein the organic semiconductor layer is formed using bottom contact geometry and the channel layer is formed on the source and drain electrodes claim 1 , or wherein the organic semiconductor layer is formed using top contact geometry and the source and drain electrodes are formed on the channel layer.6. The organic semiconductor transistor of claim 5 , wherein the organic solvent comprises dimethyl sulfoxide. This application is a divisional of U.S. application Ser. No. 12/499,310, filed on Jul. 8, 2009, which claims priority to Korean Patent Application No. 10-2008-0066471, filed on Jul. 9, 2008, and all the benefits accruing therefrom under 35 U.S.C. §119, the contents of which in their entirety are incorporated herein by reference.The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Office upon request and payment of the necessary fee.BACKGROUND1. FieldOne or more embodiments relate to an ...

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21-03-2013 дата публикации

PROLYL HYDROXYLASE INHIBITORS

Номер: US20130072487A1
Принадлежит: GlaxoSmithKline LLC

The invention described herein relates to certain pyrimidinetrione N-substituted glycine derivatives of formula (I) 2. The method according to wherein:X is O;Y is O;{'sup': 1', '4, 'sub': 1-', '10', '2-', '10', '2-', '10', '3', '8', '3', '8', '1-', '10', '5', '8', '5', '8', '1-', '10', '3', '8', '3', '8', '1-', '10', '1-', '10', '1-', '10, 'Rand Rare each independently selected from the group consisting of hydrogen, CCalkyl, CCalkenyl, CCalkynyl, C-Ccycloalkyl, C-Ccycloalkyl-CCalkyl, C-Ccycloalkenyl, C-Ccycloalkenyl-CCalkyl, C-Cheterocycloalkyl, C-Cheterocycloalkyl-CCalkyl, aryl, aryl-CCalkyl, heteroaryl and heteroaryl-CCalkyl;'}{'sup': 2', '7', '8', '9, 'Ris —NRRor —OR;'}{'sup': '3', 'sub': 1-', '4, 'claim-text': [{'sup': 7', '8, 'sub': 1-', '10', '2-', '10', '2-', '10', '3', '8', '3', '8, 'where Rand Rare each independently selected from the group consisting of hydrogen, CCalkyl, CCalkenyl, CCalkynyl, C-Ccycloalkyl, C-Cheterocycloalkyl, aryl and heteroaryl, and'}, {'sup': '9', 'sub': 1-', '10', '3', '6, 'Ris H or a cation, or CCalkyl which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of C-Ccycloalkyl, heterocycloalkyl, aryl and heteroaryl,'}, {'sup': 1', '2', '3', '4', '7', '8', '9', '10', '5', '6', '10', '10', '10', '10', '10', '5', '6', '5', '6', '5', '10', '5', '10', '5', '6', '5', '5', '6', '5', '6', '5', '10', '5', '6', '10, 'sub': 1', '6', '1', '6', '2', '2', '2', '2', '10', '2', '10', '3', '6', '3', '6', '1', '6', '1', '6', '1-', '10', '2-', '10', '2-', '10', '1', '4', '3', '6', '3', '6', '2', '1', '4', '3', '8', '3', '8', '6', '14', '1-', '10', '1-', '10, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'where any carbon or heteroatom of R, R, R, R, R, R, Ris unsubstituted or is substituted with one or more substituents independently selected from C-Calkyl, C-Chaloalkyl, halogen, —OR, —NRR, oxo, cyano, nitro, —C(O)R, —C(O)OR, —SR, —S(O)R, —S(O)R, —NRR, —CONRR, —N(R)C(O)R, —N(R)C(O)OR, —OC(O) ...

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21-03-2013 дата публикации

INHIBITORS OF JUN N-TERMINAL KINASE

Номер: US20130072494A1
Принадлежит:

The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula: 3. The compound of claim 1 , wherein ring A is chosen from thiophene claim 1 , thiazole claim 1 , and pyrazole claim 1 , wherein the thiophene claim 1 , the thiazole claim 1 , or the pyrazole is optionally substituted with 1 or 2 substituents chosen from C-C-alkyl claim 1 , C-C-alkenyl claim 1 , C-C-alkynyl claim 1 , C-C-haloalkyl claim 1 , 2- to 4-membered heteroalkyl claim 1 , C-C-cycloalkyl claim 1 , 3- to 6-membered heterocycloalkyl claim 1 , CN claim 1 , and halogen.6. The compound of claim 1 , wherein W is methylene (—CH—).7. The compound of claim 1 , wherein Ris H.8. The compound of claim 1 , wherein Cy is chosen from phenyl claim 1 , naphthyl claim 1 , quinoline claim 1 , isoquinoline claim 1 , quinoxaline claim 1 , quinazoline claim 1 , 3 claim 1 ,4-dihydroquinolin-2-one claim 1 , and 3 claim 1 ,4-dihydro-1 claim 1 ,6-naphthyridin-2-one claim 1 , each optionally substituted with 1-6 substituents independently chosen from C-C-alkyl claim 1 , C-C-alkenyl claim 1 , C-C-alkynyl claim 1 , C-C-haloalkyl claim 1 , 2- to 6-membered heteroalkyl claim 1 , C-C-cycloalkyl claim 1 , 3- to 8-membered heterocycloalkyl claim 1 , aryl claim 1 , 5- or 6-membered heteroaryl claim 1 , CN claim 1 , halogen claim 1 , OR claim 1 , SR claim 1 , NRR claim 1 , C(O)R claim 1 , C(O)NRR claim 1 , OC(O)NRR claim 1 , C(O)OR claim 1 , NRC(O)R claim 1 , NRC(O)OR claim 1 , NRC(O)NRR claim 1 , NRC(S)NRR claim 1 , NRS(O)R claim 1 , S(O)NRR claim 1 , S(O)Rand S(O)R claim 1 ,wherein{'sup': 52', '53', '55', '52', '53, 'sub': 1', '6', '3', '8, 'R, Rand Rare independently chosen from H, acyl, C-C-alkyl, 2- to 6-membered heteroalkyl, aryl, 5- or 6-membered heteroaryl, C-Ccycloalkyl and 3- to 8-membered heterocycloalkyl, wherein Rand R, together with the nitrogen atom to which they are bound are optionally joined to form a 5- to 7-membered heterocyclic ring; and'}{'sup ...

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21-03-2013 дата публикации

BICYCLIC COMPOUNDS AS alpha4 beta2 NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS

Номер: US20130072518A1
Принадлежит: Suven Life Science Limited

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

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21-03-2013 дата публикации

Compositions And Methods Of Synthesis Of Pyridinolypiperidine 5-HT1F Agonists

Номер: US20130072524A1
Принадлежит:

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

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21-03-2013 дата публикации

COMPOUNDS WITH BOTH ANALGESIC AND ANTI-HYPERALGESIC EFFICACY

Номер: US20130072533A1
Принадлежит:

The present invention relates to molecules of formula (I), deriving from lipoic acid and camosine, their preparation and use as analgesics. 2. Compounds of formula (I) according to for use as a medicament.3. Compounds according to for use as analgesics.4. Compounds of formula (I) according to for the treatment of neuropathic pain.5. Compositions comprising at least one compound of formula (I) according to and at least one other pharmaceutically acceptable ingredient.6. Process for the preparation of compounds of formula (I) according to starting from lipoic acid and carnosine.8. Compounds of formula (II) as defined in . The present invention relates to the field of organic compounds containing heterocycles having pharmacological efficacy as analgesics.The World Health Organisation (W.H.O.) defines neuropathic pain as: “An unpleasant sensation and a negative-affective emotional experience, associated with actual or potential tissue damage, or described in terms of such damage”. The International Association for the Study of Pain (1ASP) defines it as: “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described as such”.Neuropathic pain is a significant problem in neurology in that it occurs frequently and is often disabling due to its irritating and chronic character.Examples thereof are: post-herpetic pain, phantom limb pain which can arise after an amputation, pain present in peripheral neuropathy such as with diabetes or AIDS, so-called complex regional pain syndrome or reflex sympathetic dystrophy pain, and pain from lesions of the central nervous system. These latter can be sequelae of stroke, trauma, tumours or due to systemic diseases. In most cases, the pain often present in multiple sclerosis is of such origin. In recent years, interest has focussed on neuropathic pain induced by chemotherapy drugs (vincristine, paclitaxel, oxaliplatin, bortezomib, etc.)The characteristics of this pain vary from patient to ...

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28-03-2013 дата публикации

N-[(HET)ARYLALKYL)] PYRAZOLE(THIO)CARBOXAMIDES AND THEIR HETEROSUBSTITUTED ANALOGUES

Номер: US20130079302A1
Принадлежит:

The present invention relates to fungicidal N-[(het)arylalkyl)]pyrazolecarboxamide or thiocarboxamide and their heterosubstituted analogues, their process of preparation and intermediate compounds for their preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions. 2. A compound according to wherein Xand Xindependently represent a chlorine or a fluorine atom.3. A compound according to wherein Y represents methyl.4. A compound according to wherein T represents O.5. A compound according wherein B represents a substituted or non-substituted phenyl ring; a substituted or non-substituted naphthyl ring; a substituted or non-substituted pyridyl ring; a substituted or non-substituted thienyl ring; or a substituted or non-substituted benzothienyl ring; preferably a substituted or non-substituted phenyl ring or a substituted or non-substituted 2-pyridyl ring.6. A compound according to wherein X independently represents a halogen atom; substituted or non-substituted C-C-alkyl; C-C-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; substituted or non-substituted tri(C-C-alkyl)silyl; substituted or non-substituted C-C-alkoxy or C-C-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different; substituted or non-substituted C-C-alkylsulfanyl or C-C-halogenoalkylsulfanyl comprising up to 9 halogen atoms that can be the same or different; or wherein two consecutive substituents X together with the phenyl ring form a substituted or non-substituted cyclopentyl or cyclohexyl ring.7. A compound according to wherein X independently represents fluorine claim 1 , chlorine claim 1 , bromine claim 1 , iodine claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , isobutyl claim 1 , secbutyl claim 1 , terbutyl claim 1 , cyclopropyl claim 1 , cyclopentyl claim 1 , ...

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28-03-2013 дата публикации

N-PHENYL IMIDAZOLE CARBOXAMIDE INHIBITORS OF 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE-1

Номер: US20130079326A1
Принадлежит:

The present invention provide Imidazole Carboxamide Compounds of Formula (I): wherein D, T, R, R, R, and Rare as defined herein, and pharmaceutically acceptable salts of such Imidazole Carboxamide Compounds. The Imidazole Carboxamide Compounds are useful in the treatment of cancer and other aberrant conditions that result from overstimulation of the PDK-1 signaling pathway. 2. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.5. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein T is selected from the group consisting ofH, and Br; and{'sup': A', 'A', 'A', '9', '11, 'sub': 1', '3', '1', '3', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '2, 'R, wherein Ris selected from the group consisting of cyclopropyl, phenyl, pyrazolyl, thienyl, pyridinyl, pyrimidinyl, pyridazinyl, indolyl, piperidinyl, piperazinyl, and dihydropyranyl, wherein Ris unsubstituted or substituted by one to three moieties selected from the group consisting of C-Calkyl, C-Calkoxy, halo, trifluoromethyl, hydroxy, amino, C-Calkylamino, C-Cdialkylamino, C-Chydroxyalkyl, cyano, —C(O)—(C-Calkyl), —C(O)—O—(C-Calkyl), sulfonamido, —N(H)—C(O)—(C-Calkyl), benzylamino, —Y—R, and —C(O)N(R).'}8. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein R claim 1 , R claim 1 , and Rare independently selected from the group consisting of H claim 1 , halo claim 1 , and pyrazolyl.12. A compound selected from one of the following compounds:N-[5-amino-2-(3(R)-amino-1-piperidinyl)phenyl]-1H-imidazole-2-carboxamide;1-[4-amino-2-[(1H-imidazol-2-ylcarbonyl)amino]phenyl]-4-(methylamino)-4-piperidinecarboxamide;N-[5-amino-2-[4-(aminomethyl)-1-piperidinyl]phenyl]-1H-imidazole-2-carboxamide;N-[2-(3(R)-amino-1-piperidinyl)-3-fluorophenyl]-4-[1-(phenylmethyl)-1H-pyrazol-4-yl]-1H-imidazole-2-carboxamide;N-[2-(3(R)-amino-1-piperidinyl)-3-fluorophenyl]-4-[1-(2-thienylmethyl)-1H-pyrazol-4-yl]-1H-imidazole-2-carboxamide;N-[2-[2-( ...

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28-03-2013 дата публикации

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

Номер: US20130079361A1
Принадлежит:

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

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28-03-2013 дата публикации

N-Thio-anthranilamid compounds and their use as pesticides

Номер: US20130079513A1
Принадлежит: BASF SE

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

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04-04-2013 дата публикации

HETEROCYCLIC COMPOUND, LIGHT-EMITTING ELEMENT, LIGHT-EMITTING DEVICE, ELECTRONIC DEVICE, AND LIGHTING DEVICE

Номер: US20130082591A1

To provide a novel heterocyclic compound that can be used as a host material in which a light-emitting substance of a light-emitting layer is dispersed. A heterocyclic compound comprising a dibenzo[f,h]quinoxaline ring and two hole-transport skeletons, where the dibenzo[f,h]quinoxaline ring and the two hole-transport skeletons are bonded to an aromatic hydrocarbon group. A heterocyclic compound represented by the following general formula (G1) is provided. 1. A heterocyclic compound comprising:a dibenzo[f,h]quinoxaline ring;a first hole-transport skeleton;a second hole-transport skeletons; andan aromatic hydrocarbon group,wherein the dibenzo[f,h]quinoxaline ring, the first hole-transport skeleton and the second hole-transport skeleton are bonded to the aromatic hydrocarbon group.2. The heterocyclic compound according to claim 1 ,wherein the aromatic hydrocarbon group is bonded to a 2-position of the dibenzo[f,h]quinoxaline ring.3. The heterocyclic compound according to claim 1 ,wherein the first hole-transport skeleton includes a first π-electron rich heteroaromatic ring, andwherein the second hole-transport skeleton includes a second π-electron rich heteroaromatic ring.4. The heterocyclic compound according to claim 3 ,wherein the first π-electron rich heteroaromatic ring and the second π-electron rich heteroaromatic ring are each independently selected from any one of a carbazole ring, a dibenzofuran ring, and a dibenzothiophene ring.6. The heterocyclic compound according to claim 5 ,wherein the aromatic hydrocarbon group has a substituent.7. The heterocyclic compound according to claim 5 ,wherein the aromatic hydrocarbon group has substituents, andwherein the substituents are bonded to each other to form a ring.9. The heterocyclic compound according to claim 8 ,wherein the aromatic hydrocarbon group has a substituent.10. The heterocyclic compound according to claim 8 ,wherein the aromatic hydrocarbon group has substituents, andwherein the substituents are bonded ...

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04-04-2013 дата публикации

PYRAZOLE COMPOUNDS

Номер: US20130085126A1
Принадлежит: National Health Research Institutes

Compounds of formula (I): 3. The compound of claim 2 , wherein Ris aryl substituted with halo.4. The compound of claim 3 , wherein Ris 2 claim 3 ,4-dichlorophenyl.5. The compound of claim 2 , wherein each of Rand R claim 2 , independently claim 2 , is H or piperidinyl.6. The compound of claim 2 , wherein each of Rand R claim 2 , independently claim 2 , is H or S(O)NRR claim 2 , in which each of Rand R claim 2 , independently claim 2 , is H claim 2 , C-Calkyl claim 2 , C-Ccycloalkyl claim 2 , C-Cheterocycloalkyl claim 2 , aryl claim 2 , or heteroaryl; or R claim 2 , together with Rand the nitrogen atom to which they are attached claim 2 , is C-Cheterocycloalkyl claim 2 , C-Cheterocycloalkenyl claim 2 , or heteroaryl.7. The compound of claim 6 , wherein each of Rand R claim 6 , independently claim 6 , is H or S(O)NRR claim 6 , in which R claim 6 , together with Rand the nitrogen atom to which they are attached claim 6 , is C-Cheterocycloalkyl claim 6 , C-Cheterocycloalkenyl claim 6 , or heteroaryl.8. The compound of claim 2 , wherein Ris C-Calkyl claim 2 , C-Ccycloalkyl claim 2 , or aryl.11. The compound of claim 10 , wherein Ris aryl substituted with halo.12. The compound of claim 11 , wherein Ris 2 claim 11 ,4-dichlorophenyl.13. The compound of claim 10 , wherein each of Rand R claim 10 , independently claim 10 , is H or piperidinyl.14. The compound of claim 10 , wherein each of Rand R claim 10 , independently claim 10 , is H or S(O)NRR claim 10 , in which each of Rand R claim 10 , independently claim 10 , is H claim 10 , C-Calkyl claim 10 , C-Ccycloalkyl claim 10 , C-Cheterocycloalkyl claim 10 , aryl claim 10 , or heteroaryl; or R claim 10 , together with Rand the nitrogen atom to which they are attached claim 10 , is C-Cheterocycloalkyl claim 10 , C-Cheterocycloalkenyl claim 10 , or heteroaryl.15. The compound of claim 14 , wherein each of Rand R claim 14 , independently claim 14 , is H or S(O)NRR claim 14 , in which R claim 14 , together with Rand the nitrogen ...

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04-04-2013 дата публикации

PYRAZOLE COMPOUND AND PHARMACEUTICAL USE THEREOF

Номер: US20130085132A1
Принадлежит: JAPAN TOBACCO INC.

The present invention provides a pyrazole compound of the following general Formula [Ib] having SGLT1 inhibitory activity, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the same, and its pharmaceutical use: 5. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the ring Cy is Caryl.6. The compound or a pharmaceutically acceptable salt thereof according to claim 5 , wherein the ring Cy is phenyl.7. The compound or a pharmaceutically acceptable salt thereof according to wherein Ris(1) a halogen atom,{'sub': '1-6', '(2) a Calkyl group,'}{'sub': '1-6', '(3) a Calkoxy group,'}{'sub': '1-6', '(4) a halo Calkyl group,'}{'sub': 1-6', '1-6, '(5) a Calkoxy Calkyl group,'}{'sub': 1-6', '1-6, '(6) a halo Calkoxy Calkyl group or'}{'sub': '1-6', '(7) a halo Calkoxy group,'}{'sup': '1a', 'provided that when n1 is 2, 3, or 4, each Ris the same or different.'}8. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris a Caryl group and{'sub': '6-10', 'wherein the Caryl group is optionally substituted by 1 to 4 substituents selected from the group consisting of(a) a halogen atom,{'sub': '1-6', '(b) a Calkyl group,'}{'sub': '1-6', '(c) a Calkoxy group and'}{'sub': '1-6', '(d) a carboxy Calkoxy group.'}9. The compound or a pharmaceutically acceptable salt thereof according to claim 8 , wherein Ris a phenyl group andwherein the phenyl group is optionally substituted by 1 to 4 substituents selected from the group consisting of:(a) a halogen atom,{'sub': '1-6', '(b) a Calkyl group,'}{'sub': '1-6', '(c) a Calkoxy group and'}{'sub': '1-6', '(d) a carboxy Calkoxy group.'}11. A pharmaceutical composition which comprises a compound or a pharmaceutically acceptable salt thereof according to and a pharmaceutically acceptable carrier.12. A SGLT1 inhibitor which comprises a compound or a pharmaceutically acceptable salt thereof according to .1314.-. (canceled)15. A method for ...

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04-04-2013 дата публикации

5H-CYCLOPENTA[D]PYRIMIDINES AS AKT PROTEIN KINASE INHIBITORS

Номер: US20130085135A1
Принадлежит:

Compounds of Formula I are useful for inhibiting AKT protein kinases. Methods of using compounds of Formula I and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed. 13. The method of claim 1 , wherein X is a direct bond from L to Y claim 1 , Y is CH and Z is O.14. The method of claim 1 , wherein X is C(═O)NH claim 1 , Y is CH and Z is absent.15. The method of claim 1 , wherein X is a direct bond from L to Y claim 1 , Y is CH and Z is absent.16. The method of claim 1 , wherein X is NH claim 1 , Y is CH and Z is absent.17. The method of claim 1 , wherein X is C═O claim 1 , Y is N claim 1 , Z is absent and b is 1 or 2.18. The method of claim 1 , wherein X is C═O claim 1 , Y is CH and Z is absent.19. The method of claim 1 , wherein Ris hydrogen.20. The method of claim 1 , wherein Ris methyl.21. The method of claim 1 , wherein Ris hydrogen.22. The method of claim 1 , wherein Ris methyl.23. The method of claim 1 , wherein Ris hydrogen.24. The method of claim 1 , wherein Ris C-Calkyl.25. The method of claim 1 , wherein Ris selected from methyl claim 1 , isopropyl and tert-butyl.26. The method of claim 1 , wherein Ris hydrogen.27. The method of claim 1 , wherein Ris methyl.29. The method of claim 28 , wherein c is 1.31. The method of claim 1 , wherein G is selected from the group consisting of 4-chlorophenyl claim 1 , 4-bromophenyl claim 1 , 4-trifluoromethylphenyl and 2 claim 1 ,4-dichlorophenyl.32. The method of wherein:(5R,7R)-4-(4-((S)-(4-chlorophenyl)(2-(dimethylamino)ethoxy)methyl)piperidin-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;(5R,7R)-4-(4-((R)-(4-chlorophenyl)(2-(dimethylamino)ethoxy)methyl)piperidin-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol;N—((S)-1-amino-3-(2,4-dichlorophenyl)propan-2-yl)-5-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)thiophene-2- ...

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11-04-2013 дата публикации

COMPOUND FOR ORGANIC PHOTOELECTRIC DEVICE AND ORGANIC PHOTOELECTRIC DEVICE INCLUDING THE SAME

Номер: US20130087776A1
Принадлежит:

A compound for an organic photoelectric device, the compound being represented by the following Chemical Formula 1: 2. The compound as claimed in claim 1 , wherein the Arand Arare each independently selected from the group of a substituted or unsubstituted phenyl group claim 1 , a substituted or unsubstituted naphthalenyl group claim 1 , a substituted or unsubstituted fluorenyl group claim 1 , a substituted or unsubstituted biphenyl group claim 1 , a substituted or unsubstituted dibenzofuranyl group claim 1 , a substituted or unsubstituted dibenzothiophenyl group claim 1 , a substituted or unsubstituted anthracenyl group claim 1 , a substituted or unsubstituted phenanthryl group claim 1 , a substituted or unsubstituted naphthacenyl group claim 1 , a substituted or unsubstituted pyrenyl group claim 1 , a substituted or unsubstituted biphenylyl group claim 1 , a substituted or unsubstituted p-terphenyl group claim 1 , a substituted or unsubstituted m-terphenyl group claim 1 , a substituted or unsubstituted chrysenyl group claim 1 , a substituted or unsubstituted triphenylenyl group claim 1 , a substituted or unsubstituted perylenyl group claim 1 , a substituted or unsubstituted indenyl group claim 1 , a substituted or unsubstituted furanyl group claim 1 , a substituted or unsubstituted thiophenyl group claim 1 , a substituted or unsubstituted pyrrolyl group claim 1 , a substituted or unsubstituted pyrazolyl group claim 1 , a substituted or unsubstituted imidazolyl group claim 1 , a substituted or unsubstituted triazolyl group claim 1 , a substituted or unsubstituted oxazolyl group claim 1 , a substituted or unsubstituted thiazolyl group claim 1 , a substituted or unsubstituted oxadiazolyl group claim 1 , a substituted or unsubstituted thiadiazolyl group claim 1 , a substituted or unsubstituted pyridyl group claim 1 , a substituted or unsubstituted pyrimidinyl group claim 1 , a substituted or unsubstituted pyrazinyl group claim 1 , a substituted or unsubstituted ...

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18-04-2013 дата публикации

MATERIAL FOR ORGANIC ELECTROLUMINESCENCE ELEMENT, AND ORGANIC ELECTROLUMINESCENCE ELEMENT USING SAME

Номер: US20130092905A1
Принадлежит: IDEMITSU KOSAN CO., LTD.

Provided is a material for an organic electroluminescence device, which further has a bulky carbazolyl group at each of the 3-position and 6-position of its central carbazole skeleton, and which has a dibenzofuran skeleton or a dibenzothiophene skeleton at the N atom of the central carbazole skeleton through a linking group as required. Also provided is an organic electroluminescence device, including one or more organic thin film layers including a light emitting layer between a cathode and an anode, in which at least one layer of the organic thin film layers contains the material for an organic electroluminescence device. 2. The material of claim 1 , wherein the X is an oxygen atom.3. An organic electroluminescence device claim 1 , comprising:one or more organic thin film layers,wherein the one or more organic thin film layers comprise a light emitting layer between a cathode and an anode, and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a layer of the one or more organic thin film layers comprises the material for an organic electroluminescence device of .'}4. The organic electroluminescence device of claim 3 , wherein the light emitting layer comprises the material for an organic electroluminescence device as a host material.5. The organic electroluminescence device of claim 3 ,wherein the light emitting layer comprises a host material and a phosphorescent material, andthe host material comprises the material for an organic electroluminescence device.6. The organic electroluminescence device of claim 5 , wherein the phosphorescent light emitting material comprises a compound comprising iridium (Ir) claim 5 , osmium (Os) claim 5 , or platinum (Pt).7. The organic electroluminescence device of claim 6 , wherein the compound comprises an orthometallated metal complex.8. The organic electroluminescence device of claim 3 , further comprising a reductive dopant at an interfacial region between the cathode and the one or more organic thin film layers.9. The organic ...

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18-04-2013 дата публикации

COMPOUNDS FOR THE TREATMENT OF CLOSTRIDIUM DIFFICILE-ASSOCIATED DISEASE

Номер: US20130095057A1
Принадлежит:

Disclosed are compounds of formula (I): 2. The compound of wherein Ris: (a) a pyridyl group; or (b) a thiazole group.3. The compound of wherein Ris an optionally substituted aromatic 8-10 membered fused bicyclic ring system in which one or more of the carbon atoms may be replaced by N claim 1 , O claim 1 , S claim 1 , SO or SOand the optional substitution being with one or more substituents selected from halo claim 1 , CN claim 1 , NO claim 1 , R claim 1 , OR claim 1 , N(R) claim 1 , COR claim 1 , COR claim 1 , C(═O)SR claim 1 , SR claim 1 , S(═O)R claim 1 , SOR claim 1 , NRC(═O)R claim 1 , NRCOR claim 1 , OC(═O)NRR claim 1 , NRSOR claim 1 , C(═NR)NRR claim 1 , C(═S)NRR claim 1 , NRC(═NR)NRR claim 1 , NRC(═S)NRR claim 1 , NRC(═O)NRR claim 1 , CONRRand SONRR.4. The compound of wherein R is an optionally substituted aromatic 9-membered bicyclic ring system in which one or more of the carbon atoms may be replaced by N claim 3 , O claim 3 , S claim 3 , SO or SOand the optional substitution being with one or more substituents selected from halo claim 3 , CN claim 3 , NO claim 3 , R claim 3 , OR claim 3 , N(R) claim 3 , COR claim 3 , COR claim 3 , C(═O)SR claim 3 , SR claim 3 , S(═O)R claim 3 , SOR claim 3 , NRC(═O)R claim 3 , NRCOR claim 3 , OC(═O)NRR claim 3 , NRSOR claim 3 , C(═NR)NRR claim 3 , C(═S)NRR claim 3 , NRC(═NR)NRR claim 3 , NRC(═S)NRR claim 3 , NRC(═O)NRR claim 3 , CONRRand SONRR.5. The compound of wherein Ris an optionally substituted aromatic fused 5- and 6-membered bicyclic ring system.6. The compound of wherein Ris: (a) a thienopyridyl group; or (b) a benzothiophene group; or (c) a benzofuran group; or (d) a pyridyl imidazole group; or (e) a benzodioxol group; or (f) an indole group.7. The compound of wherein Ris an optionally substituted aromatic fused 6- and 6-membered bicyclic ring system.8. The compound of wherein Ris: (a) a isoquinolone group; or (b) a quinoxaline group; or (c) an isoquinoline group; or (d) a quinoline group; or (e) a naphthyridine ...

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18-04-2013 дата публикации

NOVEL HETEROCYCLIC COMPOUNDS AS ERK INHBITORS

Номер: US20130096084A1
Принадлежит:

The present invention provides a compound of the Formula I: (Formular I should be inserted here) or a pharmaceutically acceptable salt, solvate or ester thereof, wherein R, R1, R2 and R3 are as defined herein. The compounds are ERK inhibitors. Also disclosed are pharmaceutical compositions comprising the above compounds and methods of treating cancer using the same. 2. The compound of claim 1 , wherein R is H.4. The compound of wherein Ris selected from the group consisting of: phenyl claim 1 , pyridyl claim 1 , methylpyridyl claim 1 , methylindazolyl claim 1 , methylbenzothiazolyl claim 1 , pyridazinyl claim 1 , dihydropyran claim 1 , dioxidodihydrothiopyran claim 1 , dioxidotetrahydrothiopyran claim 1 , imidazolyl claim 1 , teterahydropyran claim 1 , benzofuranyl claim 1 , indazolyl claim 1 , pyridazinyl claim 1 , indazolyl claim 1 , imidazopyridly claim 1 , benzooxazolyl claim 1 , benzothiadiazolyl claim 1 , benzooxadiazolyl claim 1 , benzothiazolyl claim 1 , pyridine-one claim 1 , triazolopyridinyl claim 1 , dihydrobenzoimidazolyl claim 1 , benzohydrofuranyl; and wherein said Ris optionally substituted with 1 or more substitutents independently selected from the group consisting of: ═O claim 1 , —OH claim 1 , alkyl claim 1 , cycloalkyl claim 1 , haloalkyl claim 1 , alkoxy claim 1 , halo claim 1 , —NH—C(═O)-alkyl claim 1 , —S(═O)—N(alkyl)—C(═O)-alkyl claim 1 , cyano claim 1 , —S(═O)-alkyl claim 1 , —NH claim 1 , and —OC(═O)alkyl.5. The compound of claim 1 , wherein said Ris alkyl claim 1 , which is unsubstituted or substituted with at least one aryl.7. The compound of claim 6 , wherein:(a) n is 1; or(b) n is 1 and m is 0, 1 or 2; or{'sup': 3', '3', '3, 'sub': 3', '3, '(c) n is 1, m is 1 or 2, and Ris selected from the group consisting of halo, haloalkyl, —OSi(alkyl), hydroxyl, alkyl, cycloalkyl, alkoxy, aryl, —C(═O)OH, —C(═O)—O-alkyl, —C(═O)N(alkyl), —C(═O)NH-alkyl; or wherein two Rgroups together with the carbon atom to which both Rgroups are attached form —C(═O ...

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18-04-2013 дата публикации

COMPOUNDS AND METHODS FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTIONS

Номер: US20130096106A1

Compounds represented by formula: 3. A compound according to claim 1 , wherein Z is 6-7 membered heterocycle or 6-7 membered cycloalkyl.4. A compound according to claim 1 , wherein Z is cyclohexyl claim 1 , piperidinyl claim 1 , N—(Calkyl)-piperidinyl claim 1 , hexahydrothiopyranyl claim 1 , azepanyl claim 1 , methylazepanyl claim 1 , N—(Calkyl)-piperidinylmethyl claim 1 , tetrahydropyranyl claim 1 , piperidinylmethyl claim 1 , pyridinyl claim 1 , pyridinylmethyl claim 1 , tetrahydrothiopyranyl claim 1 , dioxolanylmethyl or dioxanylmethyl which in each case is unsubstituted or substituted by one or more substituent chosen from halogen claim 1 , nitro claim 1 , nitroso claim 1 , SORf claim 1 , SORf claim 1 , PORcRd claim 1 , CONRgRh claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Caralkyl claim 1 , Caryl claim 1 , Calkyloxy claim 1 , Calkenyloxy claim 1 , Calkynyloxy claim 1 , Caryloxy claim 1 , C(O)Calkyl claim 1 , C(O)Calkenyl claim 1 , C(O)Calkynyl claim 1 , C(O)Caryl claim 1 , C(O)Caralkyl claim 1 , C(O)NHRf claim 1 , Cheterocycle claim 1 , hydroxyl claim 1 , NRgRh claim 1 , C(O)ORf claim 1 , cyano claim 1 , azido claim 1 , amidino or guanido;{'sub': 1-6', '2-6', '2-6', '6-10', '3-10', '3-10', '6-10, 'wherein Rf, Rc, Rd, Rg and Rh in each case is H, Calkyl, Calkenyl, Calkynyl, Caryl, Cheterocycle, Cheteroaralkyl or Caralkyl;'}or Rc and Rd are taken together with the oxygens to form a 5 to 10 membered heterocycle;or Rg and Rh are taken together with the nitrogen to form a 3 to 10 membered heterocycle.5. A compound according to claim 1 , wherein Z is cyclohexyl unsubstituted or substituted by one or more substituent chosen from halogen claim 1 , SORf claim 1 , CONRgRh claim 1 , Calkyl claim 1 , Caralkyl claim 1 , Caryl claim 1 , Calkyloxy claim 1 , C(O)Calkyl claim 1 , Cheterocycle claim 1 , hydroxyl claim 1 , NRgRh claim 1 , C(O)Orf or cyano;{'sub': '1-6', 'wherein Rf, Rg and Rh in each case is H or Calkyl.'}6. A compound according to claim 1 , ...

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18-04-2013 дата публикации

PYRAZOLE COMPOUNDS USEFUL AS PROTEIN KINASE INHIBITORS

Номер: US20130096128A1
Принадлежит:

This invention describes novel pyrazole compounds of formula III: 126-. (canceled)28. The compound of claim 27 , wherein Q is S.29. The compound of claim 27 , wherein Q is NH.3029. The compound of any one of - claims 27 , wherein Zis CH and Zis N.3129. The compound of any one of - claims 27 , wherein Z and Zare N.32. The compound of claim 31 , wherein Ris phenyl claim 31 , pyridyl claim 31 , indazolyl claim 31 , benzothiazolyl claim 31 , or thiophene.33. The compound of claim 32 , wherein R1 is phenyl.34. The compound of claim 31 , wherein R1 is thiophene or phenyl.36135. A composition comprising a compound according to any of claims or claim 31 , and a pharmaceutically acceptable carrier. This application is a continuation application of U.S. patent application Ser. No. 12/109,598, filed Apr. 25, 2008, which is a continuation application of U.S. patent application Ser. No. 10/775,699, filed Feb. 10, 2004, now U.S. Pat. No. 7,427,681, which is a divisional application of U.S. patent application Ser. No. 10/034,019, filed Dec. 20, 2001, now U.S. Pat. No. 6,727,251, which claims the benefit, under 35 U.S.C. §119 of U.S. Provisional Patent Application 60/257,887 filed Dec. 21, 2000 and U.S. Provisional Patent Application 60/286,949 filed Apr. 27, 2001, the contents of which are incorporated herein by reference.The present invention is in the field of medicinal chemistry and relates to compounds that are protein kinase inhibitors, compositions containing such compounds and methods of use. More particularly, this invention relates to compounds that are inhibitors of Aurora-2 protein kinase. The invention also relates to methods of treating diseases associated with protein kinases, especially diseases associated with Aurora-2, such as cancer.The search for new therapeutic agents has been greatly aided in recent years by better understanding of the structure of enzymes and other biomolecules associated with target diseases. One important class of enzymes that has been the ...

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18-04-2013 дата публикации

ACTIVATORS OF CLASS I HISTONE DEACETLYASES (HDACS) AND USES THEREOF

Номер: US20130096129A1
Принадлежит:

The present invention provides compounds of Formulae (A), (B), (C), and (D), pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof, pharmaceutical compositions thereof, and kits thereof. The present invention further provides methods of using the compounds to treat or prevent neurological disorders. In one aspect, the methods include administering to a subject in need of treatment for a neurological disorder a therapeutically effective amount of DAC-001, DAC-002, DAC-003, DAC-009, or DAC-012, or a compound of Formula (A), (B), (C), or (D). 35.-. (canceled)6. The compound of claim 1 , wherein{'sup': A1', 'A3, 'Xand Xare oxygen;'}{'sup': 'A2', 'Xis sulfur; and'}{'sup': A1', 'A2, 'Rand Rare hydrogen.'}7. The compound of claim 1 , wherein Ar is optionally substituted aryl.11. The compound of claim 1 , wherein Ar is optionally substituted heteroaryl.15. The compound of claim 14 , wherein{'sup': A1', 'A3, 'Xand Xare oxygen;'}{'sup': 'A2', 'Xis sulfur; and'}{'sup': A1', 'A2, 'Rand Rare hydrogen.'}1934-. (canceled)3146-. (canceled)4857-. (canceled)58. A pharmaceutical composition comprising a compound of any claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and optionally a pharmaceutically acceptable excipient.59. (canceled)60. A method for treating or preventing a neurological disorder in a subject claim 1 , the method comprising administering to a subject in need of treatment for a neurological disorder a therapeutically effective amount of an HDAC (histone deacetylase) activator of to treat the neurological disorder.61. The method in claim 60 , wherein the HDAC activator is a class I HDAC activator.62. The method in claim 61 , wherein the class I HDAC activator is an HDAC1 (histone deacetylase 1) activator.64. The method of claim 60 , wherein the neurological disorder is Alzheimer's disease claim 60 , Parkinson's disease claim 60 , Huntington's ...

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18-04-2013 дата публикации

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

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

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

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18-04-2013 дата публикации

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

Номер: US20130096311A1
Принадлежит:

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

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25-04-2013 дата публикации

MATERIALS FOR ORGANIC ELECTROLUMINESCENT DEVICES

Номер: US20130099171A1
Принадлежит: Merck Patent GmBH

The present invention relates to compounds of the formula (1) which are suitable for use in electronic devices, in particular organic electroluminescent devices, and to electronic devices which comprise these compounds. 115-. (canceled)19. The compound according to claim 16 , wherein L is a single bond claim 16 , a divalent straight-chain alkylene or alkylidene group having 1 to 10 C atoms claim 16 , or a branched or cyclic alkylene or alkylidene group having 3 to 10 C atoms claim 16 , which is optionally substituted by in each case one or more radicals R claim 16 , where one or more CHgroups claim 16 , is optionally replaced by Si(R) claim 16 , C═O claim 16 , P(═O)R claim 16 , S═O claim 16 , SO claim 16 , —O— claim 16 , —S— or —CONR— and where one or more H atoms is optionally replaced by D or F claim 16 , or a divalent aromatic or heteroaromatic ring system having 5 to 24 aromatic ring atoms claim 16 , which may also be substituted by one or more radicals R claim 16 , or Si(R) claim 16 , C(═O) claim 16 , S(═O) claim 16 , SO claim 16 , P(═O)R claim 16 , O or S.20. The compound according to claim 16 , wherein L is a single bond claim 16 , a divalent straight-chain alkylene or alkylidene group having 1 to 5 C atoms claim 16 , or a branched or cyclic alkylene or alkylidene group having 3 to 6 C atoms claim 16 , which is optionally substituted by in each case one or more radicals R claim 16 , where one or more CHgroups claim 16 , which are not bonded directly to N and are not adjacent claim 16 , is optionally replaced by Si(R) claim 16 , C═O claim 16 , P(═O)R claim 16 , S═O claim 16 , SO claim 16 , —O— claim 16 , —S— or —CONR— and where one or more H atoms is optionally replaced by D or F claim 16 , or a divalent aromatic or heteroaromatic ring system having 5 to 24 aromatic ring atoms claim 16 , which may also be substituted by one or more radicals R claim 16 , or Si(R) claim 16 , C(═O) claim 16 , S(═O) claim 16 , SO claim 16 , P(═O)R claim 16 , O or S.22. The ...

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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

COMPOUNDS AND METHODS FOR TREATING INFLAMMATORY AND FIBROTIC DISORDERS

Номер: US20130102597A1
Принадлежит: INTERMUNE, INC.

Disclosed are compounds and methods for treating inflammatory and fibrotic disorders, including methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of the p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the p38 MAPK by the compound. Also disclosed are derivatives and analogs of pirfenidone, useful for modulating a stress activated protein kinase (SAPK) system. 3. The method of claim 2 , wherein{'sup': '1', 'Ris selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, cyano, sulfonamido, halo, alkenylenearyl, and heteroaryl;'}{'sup': 2', '2', '1, 'sub': 3', '2', '2', '2', '2', '2, 'Ris selected from the group consisting of aryl; unsubstituted heteroaryl; heteroaryl substituted with one or more substituents selected from halo, unsubstituted alkyl, alkenyl, OCF, NO, CN, NC, OH, alkoxy, haloalkoxy, amino, COH, and COalkyl; haloalkylcarbonyl; cycloalkyl; hydroxylalkyl; sulfonamide; unsubstituted cycloheteroalkyl and cycloheteroalkyl substituted with one to three substituents independently selected from alkyleneOH, C(O)NH, NH, aryl, haloalkyl, halo, and OH; or Rand Rtogether form an optionally substituted 5-membered nitrogen-containing heterocyclic ring;'}{'sup': '4', 'Ris selected from the group consisting of hydrogen, haloalkyl, alkoxy, alkenyl, and alkenylenearyl; and'}{'sup': '5', 'Xis hydrogen.'}4. The method of claim 1 , wherein one of X claim 1 , X claim 1 , and Xis not hydrogen.5. The method of claim 4 , wherein Ris selected from the group consisting of aryl; unsubstituted heteroaryl; heteroaryl substituted with one or more substituents selected from halo claim 4 , unsubstituted alkyl claim 4 , alkenyl claim 4 , OCF claim 4 , NO claim 4 , CN claim 4 , NC claim 4 , OH claim 4 , alkoxy claim 4 , haloalkoxy claim 4 , amino claim 4 , COH ...

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25-04-2013 дата публикации

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

Номер: US20130102785A1
Принадлежит: GEORGIA TECH RESEARCH CORPORATION

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

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25-04-2013 дата публикации

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

Номер: US20130102786A1
Принадлежит:

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

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02-05-2013 дата публикации

METHODS OF TREATING HIV INFECTION: INHIBITION OF DNA DEPENDENT PROTEIN KINASE

Номер: US20130109687A1
Автор: Cooper Arik, Nabel Gary J.
Принадлежит:

Methods of treating HIV-1 infection/AIDS in a patient infected with an HIV-1 virus comprising providing a DNA-PK inhibitor to the patient are provided herein. In one embodiment the DNA-PK inhibitor is compound of the Formula I 1. A method of treating HIV-1 infection in a patient infected with an HIV-1 virus comprising providing a therapeutically effective amount of a DNA-PK inhibitor to the patient.5. The method of claim 2 , wherein Ais N claim 2 , Ais O claim 2 , and Ais O.6. The method of claim 2 , wherein Ris hydrogen claim 2 , halogen claim 2 , C-Calkyl claim 2 , or C-Calkoxy.7. The method of wherein Ais CR claim 2 , Ais CR claim 2 , and Ais CR.8. The method of claim 7 , wherein Rand Rare independently chosen from hydrogen claim 7 , halogen claim 7 , C-Calkyl claim 7 , and C-Calkoxy.9. The method of claim 5 , wherein Rand Rare joined to form an optionally substituted phenyl ring.10. The method of claim 9 , wherein Rand Rare joined to form a phenyl ring that is unsubstituted or substituted with 1 claim 9 , 2 claim 9 , or 3 substituents independently chosen from hydrogen claim 9 , halogen claim 9 , hydroxyl claim 9 , cyano claim 9 , amino claim 9 , thiol claim 9 , C-Calkyl claim 9 , C-Calkoxy claim 9 , mono- or di-C-Calkylamino claim 9 , C-Chaloalkyl claim 9 , and C-Chaloalkoxy.11. The method of claim 9 , wherein Rand Rare joined to form an unsubstituted phenyl ring.13. The method of claim 12 , wherein Xis S.15. The method of claim 1 , wherein the DNA-PK inhibitor is provided together with instructions for treating an HIV-1 infection.16. A method of inhibiting CD4 cell death in a patient infected with HIV-1 comprisingPerforming a count of CD4 cells in the patient's blood; andAdministering an effective amount of a DNA-PK inhibitor to the patient. This application claims priority from U.S. Provisional Patent application No. 61/329,775, filed Apr. 30, 2010, which is hereby incorporated by reference in its entirety.This invention was made in part with government ...

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02-05-2013 дата публикации

POLYCYCLIC HETEROARYL SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS

Номер: US20130109695A1
Принадлежит: Rigel Pharmaceuticals, Inc.

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

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09-05-2013 дата публикации

Compounds Useful as Inhibitors of ATR Kinase

Номер: US20130115313A1
Принадлежит: Vertex Pharmaceuticals Inc

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. The compounds of this invention have formula I: wherein the variables are as defined herein.

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09-05-2013 дата публикации

IRE-1alpha INHIBITORS

Номер: US20130116247A1
Принадлежит: MANNKIND CORPORATION

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

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09-05-2013 дата публикации

Substituted indole derivatives

Номер: US20130116283A1
Принадлежит: Grünenthal GmbH

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

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09-05-2013 дата публикации

LIPOIC ACID AND NITROXIDE DERIVATIVES AND USES THEREOF

Номер: US20130116284A1
Автор: Salzman Andrew Lurie
Принадлежит: RADIKAL THERAPEUTICS INC.

Provided are bifunctional compounds comprising a poly(ADP-ribose) polymerase (PARP) inhibitor moiety and a reactive oxygen species (ROS) scavenger moiety, more particularly, a lipoic acid or cyclic nitroxide derivative, covalently attached either directly or via a linker, as well as pharmaceutical compositions comprising them. The compounds and pharmaceutical compositions are useful for prevention, treatment, or management of diseases, disorders and conditions associated with elevated PARP activity or expression. 3. The compound of claim 2 , wherein said PARP inhibitor moiety is the radical of the formula A claim 2 , wherein Y and Z are each H; the radical of the formula A claim 2 , wherein Z is H; or the radical of the formula A claim 2 , wherein Y and Z are each H.5. The compound of claim 1 , wherein said PARP inhibitor is selected from the group consisting of benzamide derivatives claim 1 , benzimidazole derivatives claim 1 , phthalizinone derivatives claim 1 , isoindolinone derivatives claim 1 , phenanthridinone derivatives claim 1 , and indenoisoquinolinone derivatives.7. The compound of claim 1 , wherein X represents:{'sub': 1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'one divalent moiety selected from the group consisting of —O—, —S—, CO—, —NH—, —NHCONH—, —(C-C)alkylene-, —N—(C-C)alkylene-, —(C-C)alkylene-O—CO—(C-C)alkylene-, —(C-C)alkylene-O—CO—, —(C-C)alkylene-NH—CO—(C-C)alkylene-, —(C-C)alkylene-NH—CO—, —O—(C-C)alkylene-, —O—CO—(C-C)alkylene-, and —O—C(O)—;'}{'sub': a', 'b', 'a', '6', '14', '4', '12', '2', '2', '1', '4', '1', '4', '1', '4', 'b', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'two divalent moieties linked to each other —X—X—, wherein Xis selected from the group consisting of pyrrolidine-diyl, piperidine-diyl, (C-C)arylene-diyl, (C-C)cycloalkane-diyl, and 4-12-membered heterocyclic-diyl, optionally substituted with one or more ...

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09-05-2013 дата публикации

NOVEL NICOTINAMIDE DERIVATIVE OR SALT THEREOF

Номер: US20130116430A1
Принадлежит: FUJIFILM Corporation

An object of the present invention is to provide to a compound and a pharmaceutical composition, which have excellent Syk-inhibitory activity. The present invention provides a nicotinamide derivative represented by the following formula (I) (wherein Rrepresents a halogen atom; Rrepresents a Calkyl group, a Calkenyl group, a Calkynyl group, a Ccycloalkyl group, an aryl group, an ar-Calkyl group or a heterocyclic group, each optionally having at least one substituent; Rrepresents an aryl group or a heterocyclic group each optionally having at least one substituent; and Rand Reach independently represent a hydrogen atom; and Rand Rmay form a cyclic amino group optionally having at least one substituent together with the nitrogen atom to which they bind) or a salt thereof, and a pharmaceutical composition for use in the treatment of a Syk-related disease which comprises the nicotinamide derivative or a salt thereof. 2. The nicotinamide derivative or a salt thereof according to claim 1 , wherein the substituent optionally possessed by the Calkyl group claim 1 , Calkenyl group claim 1 , Calkynyl group claim 1 , Ccycloalkyl group claim 1 , aryl group claim 1 , ar-Calkyl group or heterocyclic group claim 1 , represented by R claim 1 , is selected from the following substituent group α claim 1 , wherein{'sub': 1-1', '1-6', '2-6', '2-6', '3-8', '1-6', '1-6', '1-6', '2-6', '2-6', '3-8', '1-6', '1-6', '2-6', '2-6', '1-12', '2-12', '2-12', '3-8', '1-6', '1-6, 'sup': 1', '2', '6', '7', '6', '7', '6', '7', '1', '2', '7', '7', '29', '29, 'the substituent group αconsists of a halogen atom; a cyano group; a nitro group; an oxo group; an optionally protected carboxyl group; an optionally protected hydroxyl group; an optionally protected amino group; a Calkyl group optionally having at least one substituent; a Calkenyl group optionally having at least one substituent; a Calkynyl group optionally having at least one substituent; a Ccycloalkyl group optionally having at least one ...

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09-05-2013 дата публикации

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

Номер: US20130116439A1
Принадлежит: YUHAN CORPORATION

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

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09-05-2013 дата публикации

PROCESS OF PREPARING A THROMBIN SPECIFIC INHIBITOR

Номер: US20130116440A1
Принадлежит: ESTEVE QUÁMICA, S.A.

A process of preparation of a compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein Rand Rrepresent H; or either Rrepresents ethyl and Rrepresents n-hexyloxycarbonyl that applies to industrial scale, novel intermediates useful for the preparation thereof, and processes of preparing said intermediates. 2. The process according to claim 1 , wherein an ammonia solution in an organic solvent is used.4. The process according to claim 3 , wherein the starting compound is the compound of formula (IV-HCl).5. The process according to claim 4 , wherein the starting compound is the crystalline compound of formula (IV-HCl).6. The process according to claim 4 , wherein the cosolvent is toluene.7. The process according to claim 4 , wherein the reaction is carried out in a temperature range between 30-35° C.9. The process according to claim 8 , wherein the compound of formula (IV-HCl) is isolated as a solid.10. A compound of formula (II-HCl) as defined in claim 1 , which is in a crystalline form essentially free from other crystalline forms claim 1 , that shows an X-Ray powder diffraction pattern comprising 2θ angle values at 6.8 claim 1 , 7.8 claim 1 , 9.2 claim 1 , 11.7 claim 1 , 12.3 claim 1 , 15.6 claim 1 , 18.4 and 23.5 measured in an X-ray diffractometer with Cu Kα radiation (1.5418 Å).11. A compound of formula (II-HCl) as defined in claim 1 , which is in a crystalline form that shows an X-Ray powder diffraction pattern comprising 2θ angle values at 6.8 claim 1 , 7.1 claim 1 , 7.8 claim 1 , 9.2 claim 1 , 11.7 claim 1 , 12.3 claim 1 , 15.6 claim 1 , 18.4 and 23.5 measured in an X-ray diffractometer with Cu Kα radiation (1.5418 Å).12. A compound of formula (II-HCl) as defined in claim 1 , which is in a crystalline form essentially free from other crystalline forms claim 1 , that shows an X-Ray powder diffraction pattern comprising 2θ angle values at 6.7 claim 1 , 9.4 claim 1 , 14.1 claim 1 , 17.6 claim 1 , 18.0 claim 1 , 19.8 claim 1 , 21.9 claim 1 , ...

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09-05-2013 дата публикации

PROCESS FOR CABAZITAXEL, AND INTERMEDIATES THEREOF

Номер: US20130116444A1
Принадлежит: ScinoPharm Taiwan, Ltd.

The present invention relates to processes for making cabazitaxel, cabazitaxel analogues and intermediates thereof. The invention provides novel compounds useful in the synthesis of cabazitaxel. 1. A process for preparing 7 ,10-di-O-alkyl taxane derivatives , wherein 1 ,3-dithiolane derivatives or 1 ,3-dithiane derivatives are used as synthetic intermediates.4. A process according to claim 3 , wherein step a) is conducted in the presence of a weak base selected from the group consisting of pyridine; a tertiary amine; 1 claim 3 ,8-diazabicyclo[5.4.0]undec-7-ene; 1 claim 3 ,5-diazabicyclo[4.3.0]non-5-ene; a saturated heterocyclic base; a pyridine derivative; or an aromatic heterocyclic base.5. A process according to claim 3 , wherein the converting to the compound of formula (I) comprises hydrodesulfurization with a hydrodesulfurization agent claim 3 , wherein the hydrodesulfurization agent is selected from the group consisting of Raney Nickel claim 3 , [NiCl]6HO in the presence of NaBH claim 3 , and a transition metal.7. A process according to claim 6 , wherein the strong base is selected from the group consisting of an alkali metal hydride claim 6 , an alkali metal alkoxide claim 6 , silver oxide claim 6 , a mixture of an alkali metal amide and an alkali metal tert-butoxide claim 6 , and a mixture of an alkyllithium and an alkali metal tert-butoxide.8. A process according to claim 6 , wherein the step a) is carried out at not more than 0° C.9. A process according to claim 6 , wherein the converting to the compound of formula (I) comprises hydrodesulfurization with a hydrodesulfurization agent claim 6 , wherein the hydrodesulfurization agent is selected from the group consisting of Raney Nickel claim 6 , [NiCl]6HO in the presence of NaBH claim 6 , and a transition metal.10. A process according to claim 3 , wherein the compound of formula (I) is further converted into cabazitaxel claim 3 , with the proviso that each of Rand Ris a methyl group.12. A process according ...

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16-05-2013 дата публикации

Novel nicotine derivatives

Номер: US20130123106A1
Автор: Gandhi Paresh T.
Принадлежит:

Described are novel nicotine derivatives represented by general formulas (I) and (III), and salts thereof, and herbicide & pharmaceutical compositions containing the same as the active ingredient. The compound and salts thereof can control annual or perennial weed growing on the land where various crops such as rice plant, wheat, cotton and corn grow for a wide period ranging from the pre-emergence to growth in a remarkably small dose. The compounds and salts thereof can be useful as an anti-microbial and anti-fungal agents and also for the treatment of blood pressure, skeletal muscle, attention deficit disorder, mental disorders, schizophrenia, Alzheimer disease, Parkinson's disease and depression. Also described is the preparation of the nicotine derivatives having formula (I) and (III). 2. The compound as claimed in claim 1 , which is selected from the group consisting of:3-(5-(5-acetylthiophen-2-yl)nicotinoyl)-1-methylpyrrolidin-2-one;3-(5-(4-fluorophenyl)nicotinoyl)-1-methylpyrrolidin-2-one;3-(5-(1-methyl-2-oxopyrrolidine-3-carbonyl)pyridin-3-yl)benzaldehyde;1-methyl-3-(5-m-tolylnicotinoyl)pyrrolidin-2-one;3-(5-(4-chlorophenyl)nicotinoyl)-1-methylpyrrolidin-2-one;4-(5-(1-methyl-2-oxopyrrolidine-3-carbonyl)pyridin-3-yl)benzaldehyde;3-(5-(3-methoxyphenyl)nicotinoyl)-1-methylpyrrolidin-2-one;3-(5-(4-methoxyphenyl)nicotinoyl)-1-methylpyrrolidin-2-one;1-methyl-3-(5-p-tolylnicotinoyl)pyrrolidin-2-one;1-methyl-3-(5-phenylnicotinoyl)pyrrolidin-2-one;3-(5-(3-fluorophenyl)nicotinoyl)-1-methylpyrrolidin-2-one;1-methyl-3-(5-(3-nitrophenyl)nicotinoyl)pyrrolidin-2-one;3-(5-(2-methoxyphenyl)nicotinoyl)-1-methylpyrrolidin-2-one;1-methyl-3-(5-o-tolylnicotinoyl)pyrrolidin-2-one;3-(5-(3,5-dichlorophenyl)nicotinoyl)-1-methylpyrrolidin-2-one;1-methyl-3-(5-(naphthalen-1-yl)nicotinoyl)pyrrolidin-2-one;3-(5-(3-acetylphenyl)nicotinoyl)-1-methylpyrrolidin-2-one;3-(5-cyclopropylnicotinoyl)-1-methylpyrrolidin-2-one;1-methyl-3-(5-(naphthalen-2-yl)nicotinoyl)pyrrolidin-2-one;4-(5-(1-methyl- ...

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16-05-2013 дата публикации

2,5-DIOXOIMIDAZOLIDIN-1-YL-3-PHENYLUREA DERIVATIVES AS FORMYL PEPTIDE RECEPTOR LIKE-1 (FPRL-1) RECEPTOR MODULATORS

Номер: US20130123215A1
Принадлежит: ALLERGAN, INC.

The present invention relates to novel 2,5-dioxoimidazolidin-1-yl-3-phenylurea derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor like-1 (FPRL-1) receptor. 2. A compound according to claim 1 , wherein:{'sup': '1', 'sub': '1-8', 'Ris halogen, hydrogen or optionally substituted Calkyl;'}{'sup': 2', '15', '9, 'sub': 1-8', '3, 'Ris halogen, optionally substituted Calkyl, CF, SR, ORor CN;'}{'sup': '3', 'sub': 1-8', '3-8', '3-8, 'Ris hydrogen, optionally substituted Calkyl, optionally substituted Ccycloalkyl or optionally substituted Ccycloalkenyl;'}{'sup': '4', 'sub': 1-8', '3-8', '3-8', '6-10, 'Ris optionally substituted Calkyl, optionally substituted Ccycloalkyl, optionally substituted Ccycloalkenyl, optionally substituted Caryl or optionally substituted heterocycle;'}{'sup': '5', 'sub': 1-8', '3-8', '3-8', '6-10, 'Ris optionally substituted Calkyl, optionally substituted Ccycloalkyl, optionally substituted Ccycloalkenyl, optionally substituted Caryl or optionally substituted heterocycle;'}{'sup': '6', 'sub': '1-8', 'Ris halogen, hydrogen or optionally substituted Calkyl;'}{'sup': '7', 'sub': '1-8', 'Ris halogen, hydrogen or optionally substituted Calkyl;'}{'sup': '8', 'sub': '1-8', 'Ris halogen, hydrogen or optionally substituted Calkyl;'}{'sup': '9', 'sub': 1-8', '1-8, 'Ris hydrogen, C(O)(Calkyl) or optionally substituted Calkyl; and'}{'sup': '15', 'sub': 1-8', '1-8, 'Ris hydrogen, optionally substituted Calkyl or O(Calkyl).'}7. A compound according to claim 1 , wherein:{'sup': '1', 'sub': '1-8', 'Ris halogen, hydrogen or optionally substituted Calkyl;'}{'sup': 2', '15', '9, 'sub': 1-8', '3, 'Ris halogen, optionally substituted Calkyl, SR, CF, ORor CN;'}{'sup': '3', 'sub': 1-8', '3-8', '3-8, 'Ris hydrogen, optionally substituted Calkyl, optionally substituted Ccycloalkyl or optionally substituted Ccycloalkenyl;'}{'sup': '4', 'sub': '1-8', 'Ris ...

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16-05-2013 дата публикации

2-Thiopyrimidinones

Номер: US20130123230A1
Принадлежит:

Myeloperoxidase inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, cardiovascular conditions. 111.-. (canceled)12. The compound 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3 ,4-dihydropyrimidin-1(2H)-yl)acetamide or a pharmaceutically acceptable salt thereof.13. (canceled)15. A method of treating cardiovascular conditions comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of or a prodrug thereof or a pharmaceutically acceptable salt of said compound or of said prodrug.16. A method as recited in wherein the cardiovascular condition is heart failure claim 15 , congestive heart failure claim 15 , peripheral arterial disease claim 15 , pulmonary hypertension or vasculitis.17. A method as recited in wherein the mammal has unstable angina or has experienced myocardial infarction.18. A pharmaceutical composition which comprises a therapeutically effective amount of a compound of or a prodrug thereof or a pharmaceutically acceptable salt of said compound or of said prodrug and a pharmaceutically acceptable carrier claim 12 , vehicle or diluent.19. A pharmaceutical combination composition comprising: a therapeutically effective amount of a composition comprising:{'claim-ref': {'@idref': 'CLM-00012', 'claim 12'}, 'a first compound, said first compound being a compound of , a prodrug thereof, or a pharmaceutically acceptable salt of said compound or of said prodrug;'}a second compound, said second compound being an angiotensin converting enzyme inhibitor, a HMG-CoA reductase inhibitor, a non-steroidal anti-inflammatory agent, a Factor Xa inhibitor or warfarin; anda pharmaceutical carrier, vehicle or diluents.2029.-. (canceled) This nonprovisional application claims priority from U.S. Provisional Application No. 61/558,605, filed on Nov. 11, 2011.This invention relates to compounds that are myeloperoxidase inhibitors, pharmaceutical compositions ...

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16-05-2013 дата публикации

AZETIDINYL DIAMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS

Номер: US20130123233A1
Принадлежит: Janssen Pharmaceutica NV

Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: 117.-. (canceled)19. A pharmaceutical composition comprising a compound of and at least one of a pharmaceutically acceptable carrier claim 18 , a pharmaceutically acceptable excipient and a pharmaceutically acceptable diluent.20. A pharmaceutical composition of claim 19 , wherein the composition is a solid oral dosage form.21. A pharmaceutical composition of claim 19 , wherein the composition is a syrup claim 19 , an elixir or a suspension. This application claims priority to U.S. provisional patent application Nos. 61/171,658 and 61/171,649, each filed Apr. 22, 2009, which are hereby incorporated by reference in their entirety.The research and development of the invention described below was not federally sponsored.has been used for the treatment of pain for many years. Δ-tetrahydrocannabinol is a major active ingredient from and an agonist of cannabinoid receptors (Pertwee, 2008, 153, 199-215). Two cannabinoid G protein-coupled receptors have been cloned, cannabinoid receptor type 1 (CBMatsuda et al., Nature, 1990, 346, 561-4) and cannabinoid receptor type 2 (CBMunro et al., 1993, 365, 61-5). CBis expressed centrally in brain areas, such as the hypothalamus and nucleus accumbens as well as peripherally in the liver, gastrointestinal tract, pancreas, adipose tissue, and skeletal muscle (Di Marzo et al., 2007, 18, 129-140). CBis predominantly expressed in immune cells, such as monocytes (Pacher et al., 2008, 294, H1133-H1134), and under certain conditions, also in the brain (Benito et al., 2008, 153, 277-285) and in skeletal (Cavuoto et al., 2007, 364, 105-110) and cardiac (Hajrasouliha et al., 2008, 579, 246-252) muscle. An abundance of pharmacological, anatomical and electrophysiological data, using synthetic agonists, indicate that increased cannabinoid signaling through CB/ ...

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16-05-2013 дата публикации

Aryl- or Heteroaryl-Substituted Benzene Compounds

Номер: US20130123234A1
Принадлежит:

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

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16-05-2013 дата публикации

COMPOUNDS AND METHODS FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTIONS

Номер: US20130123242A1

The present invention provides novel compounds represented by formula I: 197.-. (canceled)101. A compound according to claim 98 , wherein Z is H.102. A compound according to claim 98 , wherein Ris Calkyl claim 98 , Caryl claim 98 , or Cheterocycle claim 98 , which in each case is substituted or unsubstituted.103. A compound according to claim 98 , wherein Ris H claim 98 , Calkyl claim 98 , Caralkyl claim 98 , Cheterocycle claim 98 , or Cheteroaralkyl claim 98 , which in each case is substituted or unsubstituted.104. A compound according to claim 98 , wherein{'sub': 3', '3', '3', '12', '3', 'c', 'd', '13', '14', '1-6', '2-6', '2-6', '6-12', '6-12', '1-6', '2-6', '2-6', '6-12', '1-6', '2-6', '2-6', '6-12', '6-12', '3-10', '13', '14', '12, 'Ris H, or Ris methyl, ethyl, isopropyl, cyclopropyl, cyclohexyl, allyl, piperidinyl, piperazinyl, pyrrolidinyl, azetidinyl, aziridinyl, pyridinyl, piperidinylmethyl, dioxanyl, azepanyl or benzyl, which in each case is unsubstituted or substituted by one or more substituents chosen from halogen, nitro, nitroso, SOR, PORR, CONRR, Calkyl, Calkenyl, Calkynyl, Caralkyl, Caryl, Calkyloxy, Calkenyloxy, Calkynyloxy, Caryloxy, C(O)Calkyl, C(O)Calkenyl, C(O)Calkynyl, C(O)Caryl, C(O)Caralkyl, Cheterocycle, hydroxyl, NRR, C(O)OR, cyano, azido, amidino, and guanido; and'}{'sub': 12', 'c', 'd', '13', '14', '1-12', '2-12', '2-12', '6-14', '3-12', '3-18', '6-18, 'R, R, R, Rand Rare each independently H, Calkyl, Calkenyl, Calkynyl, Caryl, Cheterocycle, Cheteroaralkyl, or Caralkyl,'}{'sub': c', 'd, 'or Rand R, taken together with the oxygens, form a 5 to 10 membered heterocycle,'}{'sub': 13', '14, 'or Rand R, taken together with the nitrogen, form a 3 to 10 membered heterocycle.'}105. A compound according to claim 104 , wherein Ris isopropyl or cyclohexyl claim 104 , which in each case is substituted or unsubstituted.106. A compound according to claim 98 , wherein Ris Calkyl claim 98 , Caryl claim 98 , or Cheterocycle claim 98 , which in each case is ...

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16-05-2013 дата публикации

SUBSTITUTED 3-(5-MEMBERED UNSATURATED HETEROCYCLYL-1, 3-DIHYDRO-INDOL-2-ONES AND DERIVATIVES THEREOF AS KINASE INHIBITORS

Номер: US20130123259A1
Принадлежит: ALLERGAN, INC.

The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction in order to regulate, modulate and/or inhibit abnormal cell proliferation. 2. The compound of wherein A is a carbocyclic aryl group.3. The compound of wherein A is a heterocyclic aryl group.4. The compound of wherein Ris a carbocyclic aryl group.5. The compound of wherein Ris a heterocyclic aryl group.6. The compound of wherein N(R) is selected from the group consisting of pyrrolidine claim 1 , 3-fluoropyrrolidine claim 1 , piperidine claim 1 , 4-fluoropiperidine claim 1 , N-methylpiperazine claim 1 , morpholine claim 1 , 2 claim 1 ,6-dimethylmorpholine claim 1 , thiomorpholine wherein said heterocyclic ring may be substituted with one or more of R.7. A method for treating diseases related to unregulated tyrosine kinase signal transduction claim 1 , the method comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of .8. The method of wherein said disease is selected from the group consisting of cancer claim 7 , blood vessel proliferative disorders claim 7 , fibrotic disorders claim 7 , mesangial cell proliferative disorders and metabolic diseases.9. The method of wherein the blood vessel proliferative disorder is selected from the group consisting of diabetic retinopathy claim 8 , age-related macular degeneration claim 8 , retinopathy of prematurity claim 8 , arthritis and restenosis.10. The method of wherein the fibrotic disorder is selected from the group consisting of hepatic cirrhosis and atherosclerosis.11. The method of wherein the mesangial cell proliferative disorder is selected from the group consisting of glomerulonephritis claim 7 , diabetic nephropathy claim 7 , malignant nephrosclerosis claim 7 , thrombotic microangiopathy syndromes claim 7 , transplant rejection and glomerulopathies.12. The method of wherein the metabolic disorder is selected from the group consisting of psoriasis ...

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16-05-2013 дата публикации

PYRAZINE DERIVATIVES

Номер: US20130123275A1
Принадлежит: AstraZeneca AB

The invention concerns pyrazine derivatives of the Formula I 19-. (canceled)1112-. (canceled)1415-. (canceled)17. (canceled)18. A method according to claim 16 , wherein the cancer is multiple myeloma.19. A method according to claim 16 , or claim 16 , wherein the compound of formula I is 3-amino-6-(4-{3-[(3-methoxypropyl)amino]propyl}phenyl)-N-pyridin-3-ylpyrazine-2-carboxamide claim 16 , or a pharmaceutically acceptable salt thereof.20. A method of claim 19 , wherein the compound of formula I is a pharmaceutically acceptable salt of 3-amino-6-(4-{3-[(3-methoxypropyl)amino]propyl}phenyl)-N-pyridin-3-ylpyrazine-2-carboxamide.21. A method of claim 20 , wherein the pharmaceutically acceptable salt is a tri-hydrochloride claim 20 , a mono-besylate or a mono-tosylate salt. This application is a continuation of U.S. application Ser. No. 13/008,154 (filed Jan. 18, 2011), which claims the benefit under 35 U.S.C. §119(e) of U.S. Application No. 61/296,196 (filed Jan. 19, 2010).The invention concerns certain novel pyrazine derivatives, or pharmaceutically-acceptable salts thereof, which possess bone formation activity and are accordingly useful in methods of treatment of the human or animal body. The invention also concerns processes for the manufacture of said pyrazine derivatives, pharmaceutical compositions containing said pyrazine derivatives and use of said pyrazine derivatives in therapeutic methods, for example in the manufacture of medicaments for use in the prevention or treatment of bone-related disorders or conditions in a warm-blooded animal such as man.The present invention especially relates to pyrazine derivatives that are inhibitors of Glycogen synthase kinase 3 (GSK3).GSK3 is a serine/threonine protein kinase composed of two isoforms (α and β), which are encoded by distinct genes but are highly homologous within the catalytic domain. GSK3 is highly expressed in the central and peripheral nervous system. GSK3 is a multi-functional kinase that regulates a number ...

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16-05-2013 дата публикации

COMPOUNDS AND METHODS FOR TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS

Номер: US20130123299A1

Small molecule compounds are provided for treating lupus as are methods of treating lupus using these compounds. 2. The compound of claim 1 , wherein Ris isoquinoline claim 1 , partially or fully hydrated claim 1 , and optionally substituted with R′ claim 1 , OR′ claim 1 , SR′ claim 1 , (CH)NHR′ or (CH)N(R′) claim 1 , wherein n′=0-6 claim 1 , and R′ is independently H claim 1 , or branched or unbranched Calkyl or heteroalkyl.3. The compound of claim 2 , wherein in R claim 2 , isoquinoline is fully hydrated.4. The compound of claim 1 , wherein in R claim 1 , isoquinoline is substituted with (CH)NHR′ or CHNHR′.5. The compound of claim 1 , wherein R′ is branched or unbranched Calkyl.6. The compound of claim 1 , wherein R′ is branched Calkyl.8. The compound of claim 1 , wherein Ris R″ or OR″.9. The compound of claim 1 , wherein Ris OH.10. The compound of claim 1 , wherein Ris (CH)R.11. The compound of claim 1 , wherein Ris benzyl.12. The compound of claim 1 , wherein Ris H.13. The compound of claim 1 , wherein Ris (CH)N(R).14. The compound of claim 1 , wherein Ris (CH)NH.15. The compound of claim 1 , wherein m=1.16. The compound of claim 1 , wherein Ris quinoline claim 1 , partially or fully hydrated claim 1 , and optionally substituted with R claim 1 , OR claim 1 , SR claim 1 , (CH)NHRor (CH)N(R) claim 1 , wherein n=0-6 claim 1 , and Ris independently H claim 1 , or branched or unbranched Calkyl or heteroalkyl.17. The compound of claim 1 , wherein in R claim 1 , quinoline is partially hydrated.18. The compound of claim 1 , wherein in R claim 1 , the partially hydrated quinoline is 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydroquinoline.19. The compound of claim 1 , wherein in R claim 1 , quinoline is substituted with Ror OR.20. The compound of claim 1 , wherein in R claim 1 , quinoline is substituted with OH.23. The compound of claim 1 , wherein the compound is tagged with a radioisotope or a toxin.24. The compound of claim 1 , wherein the compound is coupled to an ...

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16-05-2013 дата публикации

PYRIDINE NON-CLASSICAL CANNABINOID COMPOUNDS AND RELATED METHODS OF USE

Номер: US20130123304A1

Disclosed are compounds of the formula I: 2. A method according to whereinX is selected from cycloheptyl and cyclohexyl optionally substituted with one to three groups independently selected from halo, carbonyl, hydroxyl, alkyl and alkoxy;Y is selected from carbonyl, dimethylmethylene and hydroxymethylene; andZ is selected from alkyl, cycloalkyl, substituted cycloalkyl, phenyl, substituted phenyl, thiophenyl and substituted thiophenyl.3. A method according to wherein X is selected from cycloheptyl and cyclohexyl optionally substituted with carbonyl or hydroxyl.4. A method according to wherein Y is dimethylmethylene.5. A method according to wherein Z is alkyl claim 2 , phenyl or cycloalkyl.6. A method according to wherein the compound is selected froma) 3-(3-Hydroxycyclohexyl)-6-(2-methyloctan-2-yl)pyridine-2,4-diol;b) 3-(2,4-Dihydroxy-6-(2-methyloctan-2-yl)pyridin-3-yl)cyclohexanone;c) 4-(4,6-Dihydroxy-2-(2-phenylpropan-2-yl)pyridin-5-yl)-6,6-dimethylbicyclo[3.1.1]heptan-2-one;d) 4-Allyl-3-(4,6-dihydroxy-2-(2-phenylpropan-2-yl)pyridin-5-yl)cyclohexanone;e) 6-(2-Cyclohexylpropan-2-yl)-3-(5-hydroxy-2-(3-hydroxypropyl)cyclohexyl)pyridine-2,4-diol; andf) 3-(5-Hydroxy-2-(3-hydroxypropyl)cyclohexyl)-6-(2-(thiophen-2-yl)propan-2-yl)pyridine-2,4-diol. This application is a continuation of and claims priority benefit from application Ser. No. 12/579,282 filed Oct. 13, 2009, which is a continuation in-part of and claims priority benefit from application Ser. No. 12/468,776 filed May 19, 2009 which claims priority benefit from application Ser. No. 61/128,088 filed May 19, 2008, and from prior provisional application Ser. No. 61/105,143 filed Oct. 14, 2008, incorporated herein by reference in its entirety.The classical cannabinoid, delta-9-tetrahydrocannabinol (Δ-THC), is the major active constituent extracted from . The effects of cannabinoids are due to an interaction with specific high-affinity receptors. Presently, two cannabinoid receptors have been characterized: CB-1, a ...

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16-05-2013 дата публикации

POLYMORPHIC FORMS OF LAPATINIB DITOSYLATE AND PROCESSES FOR THEIR PREPARATION

Номер: US20130123497A1
Принадлежит: APOTEX PHARMACHEM INC.

There is provided a crystalline form of Lapatinib, termed APO-I, and methods for making APO-I. There is also provided a crystalline solvate form of Lapatinib, termed APO-II, and methods for making APO-II. 1. APO-I polymorphic form of Lapatinib ditosylate.2. The APO-I polymorphic form of Lapatinib ditosylate of having a powder X-ray diffraction pattern comprising peaks claim 1 , in terms of degrees 2-theta claim 1 , at approximately 4.6 claim 1 , 18.8 claim 1 , 19.5 claim 1 , 21.3 claim 1 , 22.0 and 23.0.3. The APO-I polymorphic form of Lapatinib ditosylate of wherein the powder X-ray diffraction pattern further comprising peaks claim 2 , in terms of degrees 2-theta claim 2 , at approximately 8.3 claim 2 , 9.3 claim 2 , 11.8 claim 2 , 13.8 claim 2 , 14.9 claim 2 , 16.8 claim 2 , 17.3 claim 2 , 25.2 and 26.2.4. The APO-I polymorphic form of Lapatinib ditosylate of having a DSC thermogram comprising two endothermic peaks with peak onset temperatures of approximately 169.5° C. and 247.9° C. and peak maximums of approximately 179.5° C. and 250.5° C.5. The APO-I polymorphic form of Lapatinib ditosylate of having a PXRD diffractogram substantially similar to a PXRD diffractogram as depicted in .6. The APO-I polymorphic form of Lapatinib ditosylate of having a DSC thermogram substantially similar to a DSC thermogram as depicted in .7. APO-II polymorphic form of Lapatinib ditosylate.8. The APO-II polymorphic form of Lapatinib ditosylate of having a powder X-ray diffraction pattern comprising peaks claim 7 , in terms of degrees 2-theta claim 7 , at approximately 4.4 claim 7 , 8.3 claim 7 , 13.1 claim 7 , 19.3 claim 7 , 20.9 and 21.4.9. The APO-II polymorphic form of Lapatinib ditosylate of wherein the powder X-ray diffraction pattern further comprising peaks claim 8 , in terms of degrees 2-theta claim 8 , at approximately 9.6 claim 8 , 10.5 claim 8 , 14.0 claim 8 , 15.0 16.9 claim 8 , 18.2 claim 8 , 25.3 claim 8 , and 26.6.10. The APO-II polymorphic form of Lapatinib ...

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16-05-2013 дата публикации

PHARMACOLOGICALLY ACTIVE COMPOUNDS CONTAINING SULFUR

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

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

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16-05-2013 дата публикации

BICYCLO-SUBSTITUTED PYRAZOLON AZO DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF

Номер: US20130123507A1
Принадлежит:

The bicyclo-substituted pyrazolon-azo derivatives of formula (I) or pharmaceutical acceptable salts, hydrates or solvates thereof, methods for their preparation, pharmaceutical compositions containing the same and their use as a therapeutic agent, especially as thrombopoietin (TPO) mimetics and their use as agonists of thrombopoietin receptor are disclosed. The definition of substituents in formula (I) are the same as defined in the description. 113-. (canceled)15. The compound according to claim 14 , wherein R claim 14 , R claim 14 , and Rare hydrogen.16. The compound according to claim 14 , wherein R claim 14 , R claim 14 , R claim 14 , and Rare each independently hydrogen claim 14 , methyl claim 14 , and ethyl. This disclosure relates to novel bicyclo-substituted pyrazolon-azo derivatives represented by formula (I), methods for their preparation, pharmaceutical compositions containing the same, and their use as a therapeutic agent, particularly as thrombopoietin (TPO) mimetics and their use as agonists of the thrombopoietin receptor.Thrombopoietin (TPO), also called megakaryocyte growth and development factor (MGDF), thrombocytopoiesis stimulating factor (TSF), c-myeloproliferative leukemia ligand (c-Mpl), mpl ligand, or megapoietin, is a glycoprotein that has been shown to be involved in the production of platelets. See Wendling, F., et. al., Biotherapy 10(4): 269-77 (1998); Kuter D. I. et al., The Oncologist, 1: 98-106 (1996); Metcalf, Nature 369: 519-520 (1994).Under certain circumstances, the activity of TPO results from the binding of TPO with the TPO receptor (also called MPL). The TPO receptor has been cloned and its amino acid sequence has been described. See Vigon et al., Proc. Nat. Acad. Sci., 89: 5640-5644 (1992).TPO is a 332-amino acid glycosylated polypeptide that plays a key role in the regulation of megakaryocytopoiesis, and in the process in which platelets are produced by bone marrow megakaryocytes. See Kuter et al., Proc. Natl. Acad. Sci. USA 91 ...

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23-05-2013 дата публикации

INHIBITION AND DISPERSION OF BACTERIAL BIOFILMS WITH IMIDAZOLE-TRIAZOLE DERIVATIVES

Номер: US20130129795A1
Принадлежит:

Disclosure is provided for imidazole-triazole derivative compounds that prevent, remove and/or inhibit the formation of biofilms, compositions comprising these compounds, devices comprising these compounds, and methods of using the same. 122.-. (canceled)24. The method of claim 23 , wherein said method comprises the step of clearing a preformed biofilm from said substrate by administering an effective amount of the compound to said substrate claim 23 , wherein said effective amount will reduce the amount of said biofilm on said substrate.26. The method of claim 25 , wherein said chronic bacterial infection is selected from the group consisting of urinary tract infection claim 25 , gastritis claim 25 , respiratory infection claim 25 , cystitis claim 25 , pyelonephritis claim 25 , osteomyelitis claim 25 , bacteremia claim 25 , skin infection claim 25 , rosacea claim 25 , acne claim 25 , chronic wound infection claim 25 , infectious kidney stones claim 25 , bacterial endocarditis claim 25 , and sinus infection.27. The method of claim 25 , wherein said compound is administered in combination with an antibiotic.29. The medical device of claim 28 , wherein said medical device substrate is selected from the group consisting of stents claim 28 , fasteners claim 28 , ports claim 28 , catheters claim 28 , scaffolds and grafts.30. The medical device of claim 28 , wherein said compound is covalently coupled to said substrate.31. The method of claim 23 , wherein said compound is a compound of Formula (II)(a).32. The method of claim 31 , wherein n=1 to 6.33. The method of claim 32 , wherein m=1 to 3.34. The method of claim 33 , wherein Ris aryl.36. The method of claim 23 , wherein said compound is a compound of Formula (IV)(a) or a compound of Formula (V)(a).37. The method of claim 36 , wherein n=1 to 6.38. The method of claim 37 , wherein m=1 to 3.39. The method of claim 38 , wherein Ris H.40. The method of claim 38 , wherein p=0 and Ris aryl claim 38 , substituted aryl or ...

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23-05-2013 дата публикации

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

Номер: US20130131015A1
Принадлежит:

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

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23-05-2013 дата публикации

Novel Estrogen Receptor Ligands

Номер: US20130131061A1
Принадлежит: KARO BIO AB

The invention provides a compound of formula (I) or a pharmaceutically acceptable ester, amide, carbamate, solvate or salt thereof, including a salt of such an ester, amide or carbamate, and a solvate of such an ester, amide, carbamate or salt. The invention also provides also provides the use of such compounds in the treatment or prophylaxis of a condition associated with a disease or disorder associated with estrogen receptor activity, wherein R, R, R, Rand Rare as defined in the specification. 125.-. (canceled)27. A method as claimed in claim 26 , in which each Ris independently selected from the group consisting of hydrogen claim 26 , Calkyl claim 26 , Calkenyl claim 26 , Calkynyl claim 26 , Ccycloalkyl claim 26 , phenyl and benzyl.28. A method as claimed in claim 27 , in which each Rindependently represents hydrogen or Calkyl.29. A method as claimed in claim 26 , in which each Ris independently selected from the group consisting of hydrogen and Calkyl.30. A method as claimed in claim 26 , in which is selected from the group consisting of OR claim 26 , N(R) claim 26 , —C(O)Calkyl claim 26 , Calkyl claim 26 , Calkenyl claim 26 , Calkynyl claim 26 , haloCalkyl claim 26 , dihaloCalkyl claim 26 , trihaloCalkyl claim 26 , haloCalkenyl claim 26 , dihaloCalkenyl claim 26 , trihaloCalkenyl claim 26 , phenyl claim 26 , and 5-6 membered heterocyclyl claim 26 , wherein said phenyl or heterocyclyl group can either be unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of OR claim 26 , halogen claim 26 , cyano claim 26 , —C(O)Calkyl claim 26 , Calkyl claim 26 , Calkenyl claim 26 , Calkynyl claim 26 , haloCalkyl claim 26 , dihaloCalkyl and trihaloCalkyl.31. A method as claimed in claim 30 , in which Ris selected from the group consisting of OR claim 30 , N(R) claim 30 , —C(O)Calkyl claim 30 , Calkyl claim 30 , Calkenyl claim 30 , Calkynyl claim 30 , phenyl claim 30 , and 5-6 membered heterocyclyl claim 30 , wherein said phenyl or ...

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23-05-2013 дата публикации

PYRIDAZINONES AND FURAN-CONTAINING COMPOUNDS

Номер: US20130131062A1
Принадлежит:

The present invention is directed to pyridazinone compounds of formula (I) and furan compounds of formula (II), pharmaceutical compositions of compounds of formula (I) and (II), kits containing these compounds, methods of syntheses, and a method of treatment of a proliferative disease in a subject by administration of a therapeutically effective amount of a compound of formulae (I) or (II). Both classes of compounds were identified through screening of a collection of small molecule libraries. 2. The compound according to claim 1 , wherein 4 claim 1 ,5-dichloro-2-m-tolyl-2H-pyridazin-3-one is specifically excluded.3. The compound according to claim 1 , wherein Rand Rare the same claim 1 , Ris hydrogen claim 1 , halo claim 1 , optionally substituted acyl claim 1 , optionally substituted heterocyclic claim 1 , optionally substituted aryl claim 1 , optionally substituted heteroaryl claim 1 , or optionally substituted hydroxy.4. The compound according to claim 3 , wherein Rand Rare both hydrogen.5. The compound according to claim 3 , wherein Rand Rare both chloro claim 3 , bromo claim 3 , iodo claim 3 , or fluoro.6. The compound according to claim 3 , wherein Rand Rare both optionally substituted hydroxy.7. The compound according to claim 3 , wherein Rand Rare both optionally substituted thio.8. The compound according to claim 3 , wherein Rand Rare both optionally substituted amino.9. The compound according to claim 3 , wherein Rand Rare both optionally substituted aliphatic.10. The compound according to claim 3 , wherein Rand Rare both optionally substituted heterocyclic.11. The compound according to claim 3 , wherein Rand Rare both cyano.12. The compound according to claim 1 , wherein Rand Rare the different claim 1 , Ris hydrogen claim 1 , halo claim 1 , optionally substituted acyl claim 1 , optionally substituted heterocyclic claim 1 , optionally substituted aryl claim 1 , optionally substituted heteroaryl claim 1 , or optionally substituted hydroxy.13. The compound ...

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23-05-2013 дата публикации

SALTS OF LAPATINIB

Номер: US20130131090A1
Принадлежит:

The present invention provides novel dioxalate salt of lapatinib, process for its preparation and pharmaceutical compositions comprising it. The present invention also provides novel monobesylate salt of lapatinib, process for its preparation and pharmaceutical compositions comprising it. The present invention further provides a process for the preparation of monohydrate form of lapatinib ditosylate. The present invention further provides a process for the preparation of anhydrous form of lapatinib ditosylate. 1. A dioxalate salt of lapatinib or monobesylate salt of lapatinib.2. A process for the preparation of lapatinib dioxalate , comprising:a. suspending lapatinib in an ether solvent to form a suspension;b. heating the suspension to an elevated temperature to form a solution;c. adding oxalic acid to the solution obtained in step (b); andd. isolating lapatinib dioxalate from the solution of step (c).3. The process according to claim 2 , wherein the ether solvent used in the process is selected from the group consisting of tetrahydrofuran claim 2 , 1 claim 2 ,4-dioxane claim 2 , tert-butyl methyl ether claim 2 , diethyl ether claim 2 , and mixtures thereof.4. The process according to claim 3 , wherein the ether solvent is tetrahydrofuran.5. The process according to claim 2 , wherein heating in step (b) is above 25° C.6. The process according to claim 5 , wherein heating is at 60 to 70° C.7. (canceled)8. A process for the preparation of lapatinib monobesylate claim 5 , comprising:a. dissolving lapatinib in a nitrile solvent to form a solution;b. heating the solution to an elevated temperature;c. adding benzenesulfonic acid to the solution obtained in step (b); andd. isolating lapatinib monobesylate from the solution from the solution of step (c).9. The process according to claim 8 , wherein the nitrile solvent used in the process is selected from the group consisting of acetonitrile claim 8 , propionitrile claim 8 , butyronitrile claim 8 , benzonitrile claim 8 , and ...

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23-05-2013 дата публикации

Novel Dihydropyrimidin-2(1H)-One Compounds As Neurokinin-3 Receptor Antagonists

Номер: US20130131093A1
Автор: Qiu Jian, Sun Xicheng
Принадлежит: N30 PHARMACEUTICALS, INC.

The present invention is directed to novel dihydropyrimidin-2(1H)-one compounds useful as Neurokinin-3 (NK3) receptor antagonists, pharmaceutical compositions comprising such compounds, and methods of making and using the same. 2. The method of treatment of wherein R claim 1 , Rand Rare independently selected from the group consisting of hydrogen and methyl;{'sub': 3', '1', '6, 'Ris selected from the group consisting of hydrogen, nitro, cyano, carboxyl, carbamoyl, methylsulfonamido, fluoro, chloro, bromo, methylsulfonyl, and methylsulfinyl, isoxazol-4-yl, C-Calkoxy, —C(NH)NHOH, sulfonic acid, and acetyl;'}{'sub': '4', 'Ris selected from the group consisting of hydroxy, carboxyl, and tetrazol-5-yl;'}{'sub': 5', '2', '2', '2', '1', '6', '2', '2', '3', '2', '2', '3, 'Ris selected from the group consisting of hydrogen, hydroxyl, carboxy, chloro, fluoro, cyano, —O(CH)NMe, C-Calkyl, —O(CH)OCH, —O(CH)OH, acetyl, CF, methoxy, ethoxy, isopropoxy, and n-propoxy; and'}{'sub': '6', 'Ris hydrogen.'}3. The method of treatment of wherein X is selected from the group consisting of phenyl claim 1 , substituted phenyl claim 1 , thiophen-yl claim 1 , substituted thiophen-yl claim 1 , thiazol-yl claim 1 , substituted thiazol-yl claim 1 , pyrazin-yl claim 1 , substituted pyrazin-yl claim 1 , pyridin-yl claim 1 , and substituted pyridin-yl claim 1 , cyclohexyl claim 1 , and substituted cyclohexyl.4. The method of treatment of wherein X is selected from the group consisting of phenyl claim 1 , thiophen-2-yl claim 1 , thiophen-3-yl claim 1 , thiazol-2-yl claim 1 , 2-fluorophenyl claim 1 , p-tolyl claim 1 , m-tolyl claim 1 , biphenyl-4-yl claim 1 , 4-methoxyphenyl claim 1 , 3-chlorophenyl claim 1 , 3 claim 1 ,4-dichlorophenyl claim 1 , 3-methoxyphenyl claim 1 , 3 claim 1 ,4-dimethoxyphenyl claim 1 , 4-bromophenyl claim 1 , o-tolyl claim 1 , 4-chlorophenyl claim 1 , 2-chlorophenyl claim 1 , 3-cyanophenyl claim 1 , 3 claim 1 ,4-difluorophenyl claim 1 , 4-cyanophenyl claim 1 , 3- ...

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23-05-2013 дата публикации

HCV PROTEASE INHIBITORS AND USES THEREOF

Номер: US20130131105A1
Принадлежит: CELGENE AVILOMICS RESEARCH, INC.

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same. 145-. (canceled)47. The method according to claim 46 , wherein the HCV protease claim 46 , or a mutant thereof claim 46 , activity is inhibited irreversibly.48. The method according to claim 47 , wherein the HCV protease claim 47 , or a mutant thereof claim 47 , activity is inhibited irreversibly by covalently modifying a cysteine residue conserved at an equivalent position to Cys159 of HCV protease subtype 1b.49. The method of claim 48 , wherein the HCV protease genotype or subtype is selected from the group consisting of 1a claim 48 , 1b claim 48 , 1c claim 48 , 2a claim 48 , 2b claim 48 , 2c claim 48 , 2i claim 48 , 2k claim 48 , 3a claim 48 , 3b claim 48 , 3k claim 48 , 4a claim 48 , 4d claim 48 , 4f claim 48 , 5a claim 48 , 6a claim 48 , 6b claim 48 , 6c claim 48 , 6d claim 48 , 6e claim 48 , 6f claim 48 , 6g claim 48 , 6h claim 48 , 6i claim 48 , 6j claim 48 , 6k claim 48 , 6l claim 48 , 6m claim 48 , 6n claim 48 , 6o claim 48 , 6p claim 48 , 6q claim 48 , 6t claim 48 , and 7a.50. The method of claim 49 , wherein the HCV protease genotype or subtype is 1a claim 49 , 1b claim 49 , 2a claim 49 , or 3a.51. The method according to claim 47 , wherein the HCV protease claim 47 , or a mutant thereof claim 47 , activity is inhibited irreversibly by covalently modifying Cys16.53. The method according to claim 52 , wherein the HCV protease claim 52 , or a mutant thereof claim 52 , activity is inhibited irreversibly.54. The method according to claim 53 , wherein the HCV protease claim 53 , or a mutant thereof claim 53 , activity is inhibited irreversibly by covalently modifying a cysteine residue conserved at an equivalent position to Cys159 of HCV protease subtype 1b.55. The method of claim 54 , wherein the HCV protease genotype or subtype is selected from the group consisting of 1a claim 54 , 1b claim 54 , 1c claim 54 , 2a claim 54 , 2b claim 54 , ...

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23-05-2013 дата публикации

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

Номер: US20130131112A1
Автор: ZHANG Hesheng
Принадлежит:

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

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23-05-2013 дата публикации

NOVEL ALKENE OXINDOLE DERIVATIVES

Номер: US20130131114A1
Принадлежит: Hoffmann-La Roche Inc.

The present invention provides compounds of formula (I), 2. The method according to claim 1 , wherein Ris selected from the group consisting of: hydrogen claim 1 , halogen and alkoxy.3. The method according to claim 1 , wherein Ris selected from the group consisting of: hydrogen claim 1 , fluoro and chloro.4. The method according to claim 1 , wherein Ris selected from the group consisting of: hydrogen claim 1 , halogen and alkoxy.5. The method according to claim 1 , wherein Ris hydrogen or fluoro.6. The method according to claim 1 , wherein Ris selected from the group consisting of: hydrogen claim 1 , halogen and alkoxy.7. The method according to claim 1 , wherein Ris selected from the group consisting of: hydrogen claim 1 , fluoro claim 1 , chloro and methoxy.8. The method according to claim 1 , wherein Ris selected from the group consisting of: hydrogen claim 1 , halogen and alkoxy.9. The method according to claim 1 , wherein Ris hydrogen or fluoro.10. The method according to claim 1 , wherein Ris selected from the group consisting of: alkyl claim 1 , halophenylalkyl claim 1 , phenyl claim 1 , substituted phenyl claim 1 , thiophenyl and pyridinyl claim 1 , wherein said substituted phenyl is phenyl substituted with one to three substituents independently selected from the group consisting of alkyl claim 1 , alkoxy claim 1 , halogen claim 1 , cyano claim 1 , haloalkyl claim 1 , alkylsulfanyl claim 1 , aminosulfonyl claim 1 , alkylsulfonyl claim 1 , haloalkoxy and alkylcarbonyl.11. The method according to claim 1 , wherein Ris halophenyl or cyanophenyl.12. The method according to claim 1 , wherein Ris chlorophenyl or cyanophenyl.13. The method according to claim 1 , wherein Ris selected from the group consisting of: alkyl claim 1 , hydroxyalkyl claim 1 , cycloalkyl claim 1 , phenyl and halophenyl.14. The method according to claim 1 , wherein Ris alkyl or phenyl.15. The method according to claim 1 , wherein Ris isopropyl or phenyl.16. The method according to claim 1 , ...

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23-05-2013 дата публикации

N-[(HET)ARYLETHYL)] PYRAZOLE(THIO)CARBOXAMIDES AND THEIR HETEROSUBSTITUTED ANALOGUES

Номер: US20130131119A1
Принадлежит:

The present invention relates to fungicidal N-[(het)arylethyl)] pyrazolecarboxamide or thiocarboxamide and their heterosubstituted analogues, their process of preparation and intermediate compounds for their preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions. 2. A compound according to wherein Xand Xindependently represent a chlorine or a fluorine atom.3. A compound according to wherein Y represents methyl.4. A compound according to wherein T represents O.5. A compound according to wherein B represents a substituted or non-substituted phenyl ring; a substituted or non-substituted naphthyl ring; a substituted or non-substituted pyridyl ring; a substituted or non-substituted thienyl ring; or a substituted or non-substituted benzothienyl ring; preferably a substituted or non-substituted phenyl ring or a substituted or non-substituted 2-pyridyl ring.6. A compound according to wherein X independently represents a halogen atom; substituted or non-substituted C-C-alkyl; C-C-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; substituted or non-substituted tri(C-C-alkyl)silyl; substituted or non-substituted C-C-alkoxy or C-C-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different; substituted or non-substituted C-C-alkylsulfanyl or C-C-halogenoalkylsulfanyl comprising up to 9 halogen atoms that can be the same or different; or wherein two consecutive substituents X together with the phenyl ring form a substituted or non-substituted cyclopentyl or cyclohexyl ring.7. A compound according to wherein X independently represents fluorine claim 1 , chlorine claim 1 , bromine claim 1 , iodine claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , isobutyl claim 1 , secbutyl claim 1 , terbutyl claim 1 , cyclopropyl claim 1 , cyclopentyl claim 1 ...

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23-05-2013 дата публикации

INSECTICIDAL COMPOUNDS

Номер: US20130131137A1
Принадлежит: SYNGENTA CROP PROTECTION LLC

The invention relates to compounds of formula (I) where A, A, A, A, G, R, R, Rand Rare as defined in claim 1; or a salt or JV-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. 2. A compound according to where Ais C—R claim 1 , Ais C—H claim 1 , Ais C—H or nitrogen and Ais C—H or nitrogen;3. A compound according to or where G is oxygen.4. A compound according to any one of to where Ris hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , methylcarbonyl- claim 1 , or methoxycarbonyl-.6. A compound according to any one of to where Ris chlorodifluoromethyl or trifluoromethyl.7. A compound according to any one of to where Ris phenyl or phenyl substituted by one to five R.11. A method of controlling insects claim 1 , acarines claim 1 , nematodes or molluscs which comprises applying to a pest claim 1 , to a locus of a pest claim 1 , or to a plant susceptible to attack by a pest an insecticidally claim 1 , acaricidally claim 1 , nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in any one of to .12. An insecticidal claim 1 , acaricidal claim 1 , nematicidal or molluscicidal composition comprising an insecticidally claim 1 , acaricidally claim 1 , nematicidally or molluscicidally effective amount of a compound of formula (I) as defined in any one of to .13. An insecticidal claim 12 , acaricidal claim 12 , nematicidal or molluscicidal composition according to comprising an additional compound having biological activity.14. A method of treatment of insect pests in or on animals claim 12 , comprising administering an effective amount of a compound as defined in any one of to claim 12 , or a composition comprising said compound claim 12 , to an ...

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23-05-2013 дата публикации

LIGANDS FOR ANTIBODY AND Fc-FUSION PROTEIN PURIFICATION BY AFFINITY CHROMATOGRAPHY

Номер: US20130131321A1
Принадлежит: GRAFFINITY PHARMACEUTICALS GMBH

The present invention relates to the use for affinity purification of an antibody or an fragment of an antibody, of a ligand-substituted matrix comprising a support material and at least one ligand covalently bonded to the support material, the ligand being represented by formula (I) 2. The use of wherein Aris phenylene claim 1 , preferably methoxy-substituted phenylene.3. The use of wherein the C═O and the NH group are bonded to Arin meta position to each other.4. The use of wherein the 5- or 6-membered heterocyclic aromatic ring of Aris attached to the C═O group via a carbon ring atom which is adjacent to a ring heteroatom claim 1 , preferably a nitrogen or oxygen atom.5. The use of wherein the 5- or 6-membered heterocyclic aromatic ring of Arcontains two or more nitrogen atoms or one or more nitrogen atoms and an oxygen atom.6. The use of wherein the 5- or 6-membered heterocyclic aromatic ring of Aris N-methyl-substituted pyrazole claim 5 , pyridine claim 5 , isoxazole or oxadiazole.7. The use according to wherein the support material comprises a material selected from carbohydrates or crosslinked carbohydrates claim 1 , preferably agarose claim 1 , cellulose claim 1 , dextran claim 1 , starch claim 1 , alginate and carrageenan claim 1 , Sepharose claim 1 , Sephadex; synthetic polymers claim 1 , preferably polystyrene claim 1 , styrene-divinylbenzene copolymers claim 1 , polyacrylates claim 1 , PEG-Polycacrylate copolymers polymethacrylates claim 1 , polyvinyl alcohol claim 1 , polyamides and perfluorocarbons; inorganic materials claim 1 , preferably glass claim 1 , silica and metal oxides; and composite materials.8. The use according to wherein the protein is an antibody claim 1 , preferably an IgG type antibody claim 1 , or an Fc fusion protein.9. The use of wherein the purification is attained by binding of the ligand of the ligand-substituted matrix to an Fc fragment or domain of the antibody or the fusion protein.10. The use according to wherein the Fc ...

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23-05-2013 дата публикации

Process for Preparing Pyridyl-Substituted Pyrazoles

Номер: US20130131347A1
Принадлежит: Bayer Intellectual Property GmbH

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

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23-05-2013 дата публикации

PROCESS FOR PRODUCING AMIDE COMPOUND

Номер: US20130131349A1
Принадлежит: Sumitomo Chemical Company, Limited

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

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23-05-2013 дата публикации

PREPARATION OF PROTECTED ALPHA-KETO BETA-AMINO ESTERS AND AMIDES

Номер: US20130131356A1
Принадлежит: VERTEX PHAMACEUTICALS INCORPORATED

The invention provides β-sulfonamide α-keto esters and amides in which the α-keto is protected as a 1,3-dithiolane derivative. Also provided are methods for preparing such esters and amides and for incorporating them into peptides. 2. The method of claim 1 , wherein at least 95% of the β-sulfonamide α-keto ester is a single (R claim 1 ,R) or (S claim 1 ,S) enantiomer.3. The method of claim 2 , wherein the at least 99% of the β-sulfonamide α-keto ester is a single (R claim 2 ,R) or (S claim 2 ,S) enantiomer.4. The method of claim 1 , wherein the reaction between compounds of Formula II and Formula III is carried out in a solvent selected from the group consisting of tetrahydrofuran claim 1 , 2-methyltetrahydrofuran claim 1 , ethanol claim 1 , methanol claim 1 , dioxane claim 1 , and mixtures thereof.5. The method of claim 1 , wherein the reaction between compounds of Formula II and Formula III is in the presence of a base containing lithium claim 1 , potassium claim 1 , or sodium.6. The method of claim 5 , wherein the base is lithium hexamethyldisilamide claim 5 , hexynyllithium claim 5 , lithium diisoproplyamide claim 5 , sodium hexamethyldisilamide claim 5 , lithium bis(trimethylsilyl)amide claim 5 , potassium bis(trimethylsilyl)amide claim 5 , sodium hydride claim 5 , sodium bis(trimethylsilyl)amide claim 5 , potassium hexamethyldisilamide claim 5 , potassium tert-butoxide claim 5 , potassium hydride claim 5 , or potassium tert-amyloxide.7. The method of claim 5 , wherein the base is lithium diisoproplyamide claim 5 , hexynyl lithium claim 5 , sodium bis(trimethylsilyl)amide claim 5 , or lithium bis(trimethylsilyl)amide.8. The method of claim 1 , wherein Ris optionally substituted phenyl.9. The method of claim 8 , wherein Ris methylphenyl.10. The method of claim 9 , wherein Ris p-methylphenyl.11. The method of claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , propyl claim 1 , isopropyl claim 1 , butyl claim 1 , or tert-butyl.12. The method of claim 1 , ...

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30-05-2013 дата публикации

DYES FOR ANALYSIS OF PROTEIN AGGREGATION

Номер: US20130137112A1
Принадлежит:

Provided are dyes and compositions which are useful in a number of applications, such as the detection and monitoring protein aggregation, kinetic studies of protein aggregation, neurofibrillary plaques analysis, evaluation of protein formulation stability, and analysis of molecular chaperone activity. 2. The compound of claim 1 , wherein the compound exhibits increased fluorescence in the presence of an aggregated form of a protein when compared to the fluorescence exhibited when the compound is in the presence of the unaggregated form of the protein.3. The compound of claim 2 , wherein the protein is immunoglobulin claim 2 , a DNA polymerase or a fragment thereof claim 2 , α-synuclein claim 2 , synphilin-1 claim 2 , TCRα claim 2 , P23H mutant of rhodopsin claim 2 , ΔF508 mutant of CFTR claim 2 , amyloid-Jβ claim 2 , prion protein claim 2 , Tau claim 2 , SOD1 claim 2 , Ig light chains claim 2 , ataxin-1 claim 2 , ataxin-3 claim 2 , ataxin-7 claim 2 , calcium channel claim 2 , atrophin-1 claim 2 , androgen receptor claim 2 , p62/sequestosome1 (SQSTM1) claim 2 , Pael receptor claim 2 , serum amyloid A claim 2 , transthyretin claim 2 , β2-microglobulin claim 2 , apolipoprotein A-1 claim 2 , gelsolin claim 2 , atrial natriuretic factor claim 2 , lysozyme claim 2 , insulin claim 2 , fibrinogen claim 2 , crystallin claim 2 , surfactant protein C claim 2 , lactoferrin claim 2 , βig-h3 claim 2 , PAPB2 claim 2 , corneodesmosin claim 2 , neuroserpin claim 2 , cochlin claim 2 , RET claim 2 , myelin claim 2 , protein 22/0 claim 2 , SCAD claim 2 , prolactin claim 2 , lactadherin claim 2 , p53 claim 2 , procalcitonin claim 2 , cytokeratin claim 2 , GFAP claim 2 , ATP7B claim 2 , prolyl hydroxylase PHD3 claim 2 , presenilin claim 2 , or huntingtin.5. The compound of claim 4 , wherein each of R claim 4 , R claim 4 , Rand Rare a methyl or an ethyl moiety.6. The compound of claim 1 , wherein the compound comprises S25 claim 1 , S43 claim 1 , TOL3 claim 1 , YAT2134 claim 1 , YAT2148 ...

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30-05-2013 дата публикации

AZETIDINYL DIAMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS

Номер: US20130137674A1
Принадлежит: Janssen Pharmaceutica, NV

Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: 118.-. (canceled)20. A pharmaceutical composition comprising a compound of and at least one of a pharmaceutically acceptable carrier claim 19 , a pharmaceutically acceptable excipient and a pharmaceutically acceptable diluent.21. A pharmaceutical composition of claim 20 , wherein the composition is a solid oral dosage form.22. A pharmaceutical composition of claim 20 , wherein the composition is a syrup claim 20 , an elixir or a suspension. This application claims priority to U.S. provisional patent application Nos. 61/171,658 and 61/171,649, each filed Apr. 22, 2009, which are hereby incorporated by reference in their entirety.The research and development of the invention described below was not federally sponsored.has been used for the treatment of pain for many years. Δ-tetrahydrocannabinol is a major active ingredient from and an agonist of cannabinoid receptors (Pertwee, 2008, 153, 199-215). Two cannabinoid G protein-coupled receptors have been cloned, cannabinoid receptor type 1 (CBMatsuda et al., 1990, 346, 561-4) and cannabinoid receptor type 2 (CBMunro et al., 1993, 365, 61-5). CBis expressed centrally in brain areas, such as the hypothalamus and nucleus accumbens as well as peripherally in the liver, gastrointestinal tract, pancreas, adipose tissue, and skeletal muscle (Di Marzo et al., 2007, 18, 129-140). CBis predominantly expressed in immune cells, such as monocytes (Pacher et al., 2008, 294, H1133-H1134), and under certain conditions, also in the brain (Benito et al., 2008, 153, 277-285) and in skeletal (Cavuoto et al., 2007, 364, 105-110) and cardiac (Hajrasouliha et al., 2008, 579, 246-252) muscle. An abundance of pharmacological, anatomical and electrophysiological data, using synthetic agonists, indicate that increased cannabinoid signaling through CB/ ...

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30-05-2013 дата публикации

Heterocyclic compound and use thereof

Номер: US20130137675A1
Принадлежит: Takeda Pharmaceutical Co Ltd

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

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30-05-2013 дата публикации

HAEMATOPOIETIC-PROSTAGLANDIN D2 SYNTHASE INHIBITORS

Номер: US20130137684A1
Принадлежит: The University of Queensland

The present invention generally relates to compounds that inhibit haematopoietic-prostaglandin Dsynthase (H-PGDS), to compositions containing them and to their use in treating or preventing conditions and diseases associated with H-PGDS, such as allergies and inflammation. 2. The method according to claim 1 , wherein Y is CH.5. The method according to claim 1 , wherein Ris unsubstituted or substituted thienyl.6. The method according to claim 5 , wherein the thienyl is substituted with one or more of cyano claim 5 , nitro claim 5 , halo claim 5 , —Calkyl claim 5 , —C(═O)—R claim 5 , —C(═O)—O—Ror —O—C(═O)—R; wherein Ris selected H or —Calkyl.7. The method according to claim 1 , wherein Ris —C(═O)—NRR.8. The method according to claim 7 , wherein Ris —CHRR.9. The method according to claim 8 , wherein Ris —CONH claim 8 , —CONR—CHR—CONHor optionally substituted aryl.10. The method according to wherein Rand Rare independently selected from hydrogen or alkyl.11. The method according to claim 8 , wherein Ris hydrogen claim 8 , —Calkyl claim 8 , —Cperfluoroalkyl or —Calkylaryl.12. The method according to claim 7 , wherein Ris hydrogen.13. The method according to wherein Rand Rtogether form a heterocyclyl or heteroaryl ring.16. The method according to claim 1 , wherein the haematopoietic-prostaglandin Dsynthase associated disease or condition is selected from allergies claim 1 , inflammation claim 1 , pain claim 1 , bronchoconstriction claim 1 , muscle necrosis claim 1 , cancer claim 1 , arthritis claim 1 , irritable bowel diseases claim 1 , irritable bowel syndrome claim 1 , skin inflammation and irritation claim 1 , or cardiovascular diseases or conditions.19. The compound according to claim 17 , wherein L and M are both CR.20. The compound according to wherein each Ris independently selected from hydrogen cyano claim 19 , nitro claim 19 , halo claim 19 , —Calkyl claim 19 , —Calkenyl claim 19 , —Calkynyl claim 19 , —C(═O)—R claim 19 , —C(═O)—O—R claim 19 , —O—C(═O)—R claim ...

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30-05-2013 дата публикации

BENZENE, PYRIDINE, AND PYRIDAZINE DERIVATIVES

Номер: US20130137686A1
Принадлежит:

Disclosed are compounds and pharmaceutically acceptable salts of Formula I 2. A compound according to claim 1 , wherein Qis C—R.3. A compound according to claim 1 , wherein Xis N.46-. (canceled)9. A compound according to claim 8 , wherein Xis N.10. A compound according to claim 9 , wherein{'sub': 3', '4', '1', 'Z1, 'claim-text': [{'sub': '1', 'Zis —O— or —NH—;'}, {'sub': Z1', '1', '14', '22', '2, 'claim-text': {'sub': Z1', '1', '10', '1', '10', '2', '10', '2', '10', '1', '6', '2', '1', '6', '2', '2', '2', '1', '6', '2', '2', '1', '6', '2', '1', '6', '2', '10', '2', '10', '1', '10', '1', '10', '23, 'wherein Ris optionally substituted at any available position with C-Calkyl, C-Chaloalkyl, C-Calkenyl, C-Calkynyl, hydroxy, carboxy, carboxamido, oxo, halo, amino, cyano, nitro, —SH, —S—(C-C)alkyl, —SO—(C-C)alkyl, —SONH, —SONH—(C-C)alkyl, —SONH-aryl, —SO-aryl, —SO—(C-C)alkyl, —SO-aryl, C-Calkoxy, C-Calkenyloxy, C-Calkynyloxy, mono- or di-(C-C)alkylamino, —OC-Calkyl-Z, or R.'}, 'Ris a C-Calkyl group where up to five of the carbon atoms in the alkyl group are optionally replaced independently by R, carbonyl, ethenyl, ethynyl or a moiety selected from N, O, S, SO, or SO, with the proviso that two O atoms, two S atoms, or an O and S atom are not immediately adjacent each other,'}], 'Rand Rare independently hydrogen, halo, or —ZR, wherein'}11. A compound according to claim 9 , wherein{'sub': '4', 'Ris H; and'}{'sub': 3', '1', 'Z1, 'claim-text': [{'sub': '1', 'Zis —O— or —NH—;'}, {'sub': Z1', '1', '14', '22', '2, 'claim-text': {'sub': Z1', '1', '10', '1', '10', '2', '10', '2', '10', '1', '6', '2', '1', '6', '2', '2', '2', '1', '6', '2', '2', '1', '6', '2', '1', '6', '2', '10', '2', '10', '1', '10', '1', '10', '23, 'wherein Ris optionally substituted at any available position with C-Calkyl, C-Chaloalkyl, C-Calkenyl, C-Calkynyl, hydroxy, carboxy, carboxamido, oxo, halo, amino, cyano, nitro, —SH, —S—(C-C)alkyl, —SO—(C-C)alkyl, —SONH, —SONH—(C—O)alkyl, —SONH-aryl, —SO-aryl, —SO—(C-C ...

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30-05-2013 дата публикации

NOVEL COMPOUNDS

Номер: US20130137688A1
Принадлежит:

This invention relates to compounds of formula I 2. The compound according to claim 1 , wherein{'sup': '1', 'sub': 1-4', '3-6', '1-3', '1-3', '1-3, 'Rrepresents phenyl, thienyl-, pyridinyl, Calkyl, Ccycloalkyl or —O—Calkyl which latter six groups are optionally substituted with one or more substituents selected from chloro, bromo, fluoro, Calkyl and —O—Calkyl.'}4. The compound according to claim 3 , wherein{'sup': '1', 'sub': 1-4', '3-6', '1-3, 'Rrepresents phenyl, 2-pyridinyl, 2-thienyl-, Calkyl, Ccycloalkyl or O—Calkyl which latter six groups are optionally substituted with one or more substituents selected from chloro, fluoro, methyl and methoxy.'}6. The compound according to claim 5 , whereinA represents N or CH;B represents CH.12. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable adjuvant claim 1 , diluent and/or carrier.13. A method of treating schizophrenia claim 1 , schizoaffective disorder and substance induced psychotic disorder; cognitive disorders and dementias including age-associated learning and memory impairments or losses claim 1 , post stroke dementia claim 1 , deficits in concentration claim 1 , mild cognitive impairment claim 1 , the cognitive dysfunction in Alzheimers disease or the cognitive dysfunction of schizophrenia comprising administering to a patient a therapeutically effective amount of a compound according to . This invention relates to substituted pyrazoles and their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment.Glutamate is the primary excitatory amino acid in the mammalian central nervous ...

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06-06-2013 дата публикации

INHIBITORS OF CALCIUM-ACTIVATED CHLORIDE CHANNELS

Номер: US20130143765A1

Provided herein are methods for identifying compounds that are inhibitors of a calcium-activated chloride channel. Aminothiophene and aminothiazole compounds, and compositions comprising these compounds, described herein that inhibit efflux of chloride through a calcium-activated chloride channel are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased chloride and fluid secretion, for example, secretory diarrhea. 425-. (canceled)27. The composition of wherein at least one of Rand Ris not hydrogen.29112.-. (canceled)113. An isolated epithelial cell comprising (i) a calcium-activated chloride channel and (ii) a recombinant cytoplasmic indicator protein that binds halide.114. The epithelial cell of wherein the epithelial cell is an intestinal epithelial cell or a pulmonary epithelial cell.115. The epithelial cell of wherein the intestinal epithelial cell is an HT-29 cell.116. The epithelial cell of wherein the cytoplasmic indicator protein is a yellow fluorescent protein (YFP) mutant.117. The epithelial cell of claim 116 , wherein the YFP mutant is YFP-H148Q/I152L.118. The epithelial cell of wherein the calcium-activated chloride channel is TMEM16A.119. The epithelial cell of wherein TMEM16A is human TMEM16A.120. The epithelial cell of wherein the recombinant cytoplasmic indicator protein is introduced into the cell by a recombinant expression vector that is a viral vector.121. The method of wherein the viral vector is a retroviral vector.122. The method of wherein the retroviral vector is a lentiviral vector.123. A method of identifying an agent that is an inhibitor of a calcium-activated chloride channel comprising:{'claim-ref': {'@idref': 'CLM-00113', 'claim 113'}, '(a) contacting the isolated epithelial cell of and a candidate agent in a test sample to permit interaction between the candidate agent and the cell;'}{'sup': '2', '(b) adding to the test sample (i) at least one ...

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06-06-2013 дата публикации

BENZOHETEROCYCLIC ANTI-BACTERIAL AGENTS

Номер: US20130143841A1
Принадлежит: University of Notre Dame du Lac

Embodiments herein provide compounds and methods of making and using such compounds for prevention and treatment of multidrug resistant bacteria. In particular, embodiments are directed to anti-bacterial agents from benzo[d]heterocyclic scaffolds for prevention and treatment of multidrug resistant bacteria. 2. A method of treating a drug-resistant bacterial strain , comprising:{'i': 'Staphylococcus aureus', 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering a compound to an individual infected with or suspected of being infected with a methicillin-resistant strain, a vancomycin-resistant strain, or a linezolid-resistant strain, a compound of .'} This application is a continuation of U.S. patent application Ser. No. 12/995,437, filed Nov. 30, 2010, which is a continuation of International Application No. PCT/US2009/045737, filed May 29, 2009, which claims priority to U.S. Provisional Patent Application No. 61/057,282, filed May 30, 2008, the entire disclosures of which are hereby incorporated by reference in their entirety.This invention was made with government support under Grant No. R01 AI 054193 awarded by the National Institutes of Health. The United States Government has certain rights in the invention.Embodiments herein relate to anti-bacterial agents, and, more specifically, to anti-bacterial agents from benzo[d]heterocyclic scaffolds for prevention and treatment of multidrug resistant bacteria.In 2004, the IDSA (Infectious Disease Society of America) reported that each year 90,000 of the 2 million people who acquire a hospital bacterial infection will die. That is a 4.5% mortality rate arising from just being within the hospital. Multi-drug resistance bacterial strains are a major problem and one that has been increasing very rapidly every year during the last few decades. In brief, from its discovery in 1968 multi-drug resistant (MRSA) had already accounted for greater than 50% of patient isolates by 1999 in ICUs (intensive care units) within ...

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06-06-2013 дата публикации

PYRIMIDYL CYCLOPENTANES AS AKT PROTEIN KINASE INHIBITORS

Номер: US20130143865A1
Принадлежит:

The present invention provides compounds of Formula I, including tautomers, resolved enantiomers, diastereomers, solvates, metabolites, salts and pharmaceutically acceptable prodrugs thereof. 3. The method of wherein Ris H.4. The method of wherein Ris methyl.5. The method of claim 4 , wherein said methyl is optionally in the (S) configuration.6. The method of wherein Ris ethyl.7. The method of wherein Ris methyl.8. The method of claim 7 , wherein said methyl is optionally in the (R) configuration.9. The method of wherein Ris hydrogen.10. The method of wherein Ris hydrogen.11. The method of wherein Ris methyl.12. The method of wherein Ris H.13. The method of wherein Ris F.14. The method of wherein Ris OH.15. The method of wherein Ris H.16. The method of wherein Ris F.17. The method of wherein G is phenyl optionally substituted with one to four Rgroups.18. The method of claim 17 , wherein G is phenyl optionally substituted with one to four groups independently selected from F claim 17 , Cl claim 17 , Br claim 17 , I claim 17 , methyl claim 17 , ethyl claim 17 , isopropyl claim 17 , tert-butyl claim 17 , cyclopropyl claim 17 , CN claim 17 , CF claim 17 , OMe claim 17 , OEt claim 17 , OCF claim 17 , NO claim 17 , SMe and OCHPh.19. The method of claim 18 , wherein G is 4-chlorophenyl claim 18 , 4-fluorophenyl claim 18 , 4-bromophenyl claim 18 , 4-iodophenyl claim 18 , 4-trifluoromethylphenyl claim 18 , 4-trifluormethoxyphenyl claim 18 , 4-thiomethylphenyl claim 18 , 3-fluoro-4-chlorophenyl claim 18 , 2 claim 18 ,4-dichlorophenyl or 3 claim 18 ,4-dichlorophenyl.20. The method of claim 1 , wherein G is a 5-6 membered monocyclic heteroaryl optionally substituted by one or more halogens.22. The method of wherein Ris H.23. The method of wherein Ris H.24. The method of wherein Ris H.25. The method of wherein Ris H.26. The method of wherein Ris H or ethyl.27. The method of wherein Ris H or ethyl.28. The method of wherein m is 1 and n is 1.29. The method of wherein p is 0.31. ...

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06-06-2013 дата публикации

PIPERAZINE DERIVATIVES AND METHODS OF USE

Номер: US20130143893A1
Принадлежит: MERCK SERONO SA

The invention provides 2-carboxamide piperazine compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are useful for the treatment of mammalian infertility. 2. The method of claim 1 , wherein Ris H.3. The method of claim 1 , wherein Ris selected from aryl claim 1 , heteroaryl claim 1 , 3-8 membered cycloalkyl and heterocycloalkyl.4. The method of claim 1 , wherein Ris selected from C-C-alkyl claim 1 , amino claim 1 , aryl claim 1 , heteroaryl claim 1 , 3-8-membered cycloalkyl and heterocycloalkyl.5. The method of treatment of claim 1 , wherein Ris H; Ris aryl; Ris selected from C-C-alkyl claim 1 , C-C-acyl amino and C-C-alkyl acyl and Ris selected from C-C-alkyl claim 1 , amino claim 1 , aryl and heteroaryl.8. The method of wherein Ris hydrogen and Ris other than hydrogen.9. The method of wherein Ris aryl or heteroaryl.10. The method of wherein Ris an n-alkyl group.11. The method of wherein Ris an alkyl having five or more carbon atoms.12. The method of wherein Ris optionally substituted alkyl claim 1 , aryl claim 1 , or heteroaryl.13. The method of wherein Rcomprises a carbazolyl claim 1 , tetrahydro-beta-carbolinyl or benzimidazolyl moiety.14. The method of wherein the compound of formula I is selected from the following group:4-hexyl-1-(thiophene-2-sulfonyl)-piperazine-2-carboxylic acid (1-ethyl-2-pyridinyl-3-yl-1H-benzoimidazol-5-yl)-amide);4-(thiophene-2-sulfonyl)-piperazine-1,3-dicarboxylic acid 3-[(9-ethyl-9H-carbazol-3-yl)amide]-1-pentylamide;4-(thiophene-2-sulfonyl)-piperazine-1,3-dicarboxylic acid 1-ethylamide 3-[(9-ethyl-9H-carbazol-3-yl)amide];{[3-(9-ethyl-9H-carbazol-3-ylcarbamoyl)-4-(thiophene-2-sulfonyl)-piperazine-1-carbonyl]-amino}acetic acid ethyl ester;4-pentanoyl-1-(thiophene-2-sulfonyl)-piperazine-2-carboxylic acid (9-ethyl-9H-carbazol-3-yl)amide;4-hexyl-1-(thiophene-2-sulfonyl)-piperazine-2-carboxylic acid (9-ethyl-9H-carbazol-3-yl)amide;4- ...

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