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Небесная энциклопедия

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

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Мониторинг СМИ

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

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 9463. Отображено 100.
26-01-2012 дата публикации

Process for the purification of eslicarbazepine acetate

Номер: US20120022047A1
Автор: Joseph Prabahar Koilpillai, Nagesh Devidasrao Limbekar, Pravin Bhalchandra Kulkarni, Sachin Bapurao Sawant
Принадлежит: Glenmark Generics LTD

The present invention relates to the purification and particle size of eslicarbazepine acetate. The present invention also relates to the physical characteristics of solid state eslicarbazepine acetate, and pharmaceutical compositions containing the same.

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Номер записи: 1
01-03-2012 дата публикации

Azafluorene derivative and organic light-emitting device using the derivative

Номер: US20120049176A1
Автор: Akihiro Senoo, Hiroki Ohrui, Masanori Muratsubaki, Tetsuya Kosuge
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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Номер записи: 2
07-06-2012 дата публикации

Manufacture of 4-((1r,3s)-6-chloro-3-phenyl-indan-1-yl)-1,2,2-trimethyl-piperazine and 1-((1r,3s)-6-chloro-3-phenyl-indan-1-yl)-3,3-dimethyl-piperazine

Номер: US20120142923A1
Автор: Allan Carsten Dahl, Svend Treppendahl
Принадлежит: H Lundbeck AS

The present invention relates to a process for the manufacture of 4-((1R,3S)-6-Chloro-3-phenyl-indan-1-yl)-1,2,2-trimethyl-piperazine or a pharmaceutically acceptable salt thereof and a process for the manufacture of 1-((1R,3S)-6-Chloro-3-phenyl-indan-1-yl)-3,3-dimethyl-piperazine or a pharmaceutically acceptable salt thereof.

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Номер записи: 3
26-07-2012 дата публикации

Ionic liquids

Номер: US20120190844A1
Автор: Keith Whiston, Kenneth Richard Seddon, Stewart Forsyth
Принадлежит: Invista North America LLC

The invention relates to an ionic liquid composition and a method for preparing the ionic liquid. The ionic liquid comprises a cation containing the Formula I, as herein disclosed, and wherein: n is 2, R 1 is selected from the group consisting of: H, C 1 -C 12 alkyl, aryl or together with R 2 may form a heterocyclic ring, and R 2 is selected from the group consisting of: H, C 1 -C 12 alkyl, aryl or together with R 1 may form a heterocyclic ring, and R 3 is selected from the group consisting of hydrogen and C 1 -C 12 alkyl, and wherein R 1 and R 2 are not simultaneously selected from hydrogen.

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Номер записи: 4
27-12-2012 дата публикации

Method of manufacturing epsilon-caprolactam

Номер: US20120330006A1
Автор: Hideto Nagami
Принадлежит: Sumitomo Chemical Co Ltd

An epsilon-caprolactam manufacturing method capable of manufacturing in good yield, high-quality epsilon-caprolactam containing less impurity has an epsilon-caprolactam purification step A of obtaining purified epsilon-caprolactam from raw epsilon-caprolactam by applying a drop crystallization method, a first-stage epsilon-caprolactam recovery step B of obtaining first recovered epsilon-caprolactam and a first recovered mother liquor by applying an evaporative crystallization method to a crystallization mother liquor obtained in the epsilon-caprolactam purification step A, and a second-stage epsilon-caprolactam recovery step C of obtaining second recovered purified epsilon-caprolactam by applying a melt crystallization method to the first recovered mother liquor, first recovered epsilon-caprolactam being recovered as a raw material for the epsilon-caprolactam purification step A and second recovered purified epsilon-caprolactam being recovered as a raw material for the epsilon-caprolactam purification step A and/or the first-stage epsilon-caprolactam recovery step B.

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Номер записи: 5
03-01-2013 дата публикации

Novel compound and process for producing amide compound therewith

Номер: US20130005961A1
Автор: Hideo Shimomura, Junichi Kugimoto, Kazunori Kurosawa, Mitsuru Kishishita, Ryouta Yasumatsu, Tsunemi Sugimoto
Принадлежит: UBE Industries Ltd

The present invention provides novel cyclododecanone-O-azacyclotridecen-2-yloxime and cyclododecanone-O-azacyclotridecen-2-yloxime hydrochloride. The invention also provides a process for producing an amide compound wherein cyclododecanone-O-azacyclotridecen-2-yloxime, hydrogen chloride and/or Lewis acid or cyclododecanone-O-azacyclotridecen-2-yloxime hydrochloride are used as a rearrangement catalyst and/or a reaction starting material in a reaction step.

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Номер записи: 6
28-03-2013 дата публикации

DIHYDROETHIDINE ANALOGUES AND USES THEREOF

Номер: US20130079522A1
Автор: Chu Wenhua, Dugan Laura, Mach Robert H., Mintun Mark
Принадлежит: WASHINGTON UNIVERSITY

Tracers for imaging distribution of reactive oxygen species (ROS) are disclosed. The tracers include radiolabeled dihydroethidine (DHE) analogues. Further disclosed are uses of the compounds, including methods of imaging tissue distribution of ROS in vivo by positron emission tomography (PET). Methods of synthesizing the compounds are also disclosed. 2. A radiolabeled compound or salt thereof in accordance with claim 1 , wherein the radioisotope is a positron-emitting radioisotope.3. A radiolabeled compound or salt thereof in accordance with claim 1 , wherein Ris H.4. A radiolabeled compound or salt thereof in accordance with claim 1 , wherein the compound or salt thereof comprises an CH.5. A radiolabeled compound or salt thereof in accordance with claim 1 , wherein Ris (CH)—CHand q is 0.6. A radiolabeled compound or salt thereof in accordance with claim 5 , wherein Ris CH.8. A radiolabeled compound or salt thereof in accordance with claim 1 , wherein Ris O—R claim 1 , Ris CH.9. A radiolabeled compound or salt thereof in accordance with claim 8 , wherein Ris O—R claim 8 , wherein Ris CH.11. A radiolabeled compound or salt thereof in accordance with claim 10 , wherein n is 1.12. A radiolabeled compound or salt thereof in accordance with claim 10 , wherein m is 2.13. A radiolabeled compound or salt thereof in accordance with claim 10 , wherein n is 1 and m is 2.15. A radiolabeled compound or salt thereof in accordance with claim 13 , wherein p is 2. The disclosed subject matter was developed in part with Government support under grant RC1AG036045 from the National Institutes of Health. The Government has certain rights in the invention.This application claims priority to U.S. Provisional Application Ser. No. 61/287,115 filed on Dec. 16, 2009, which is incorporated herein by reference in its entirety.The present teachings relate to the field of free radicals in biology and medicine.Free radicals play key roles in the pathogenesis of a large number of diseases and ...

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Номер записи: 7
04-04-2013 дата публикации

Process for Preparing Caprolactam and Polyamides Therefrom

Номер: US20130085255A1
Автор: Bui Vu, Coudray Laetitia, Frost John W., Schweitzer Dirk
Принадлежит: AMYRIS, INC.

Provided herein are processes for preparing caprolactam from a starting material such as one or more of the cis,cis-, cis,trans- and trans,trans-double-bond isomers of muconamide, muconic acid ester, or muconic acid. The starting material, intermediates, and caprolactam prepared therefrom can contain carbon atoms derived from biomass containing detectable C content determined according to ASTM D6866 and optionally containing a C content up to 0.0000000001% (one part per trillion). Caprolactam so prepared can be used to make various polyamides. 2. The process of claim 1 , wherein the reacting step comprises reactions via Route 1:{'sub': 2', '3, 'converting Q,Q-MA to caprolactam 1 in an aprotic polar solvent, using Hand NHgases at a total initial pressure from about 250 to about 2050 psi, at a temperature from about 200 to about 300° C., and in the presence of at least one catalyst.'}3. The process of claim 2 , wherein the aprotic polar solvent is 1 claim 2 ,4-dioxane claim 2 , diglyme or DMSO.4. The process of claim 2 , wherein the aprotic polar solvent is mixed with water or an alcohol.5. The process of claim 4 , wherein the alcohol is MeOH.6. The process of claim 2 , wherein the at least one catalyst comprises one or more of Pd claim 2 , Pt claim 2 , Rh and Ru.7. The process of claim 6 , wherein the at least one catalyst comprises Ru and Pt or Ru and Pd.8. The process of claim 2 , wherein the at least one catalyst is present at from about 0.3 to about 1 mol %.9. The process of claim 2 , wherein the converting step takes about 0.5 to about 3 hours.10. The process of claim 1 , wherein the reacting step comprises reactions via Route 2:{'sup': α', 'β, '(1) converting one or both of the cis,cis-MA and cis,trans-MA to one or both of Δ-muconolactone and Δ-muconolactone; and'}{'sup': α', 'β, 'sub': 2', '3, '(2) reacting one or both of Δ-muconolactone and Δ-muconolactone to form caprolactam 1, using Hand NHgases, and in the presence of at least one catalyst.'}11. The ...

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Номер записи: 8
04-04-2013 дата публикации

MATERIALS AND METHODS FOR THE PREPARATION OF ANISOTROPICALLY-ORDERED SOLIDS

Номер: US20130085280A1
Автор: Carson Travis D., Casey Sean M., Iverson Isaac K., Seo Wonewoo, Tam-Chang Suk-Wah
Принадлежит: Board of Regents of the Nevada System of Higher Education, on Behalf of the University of Nevada,

The invention provides materials and methods for making anisotropic solids which may be in the form of films, layers, shaped elements, and other shaped articles. The methods provide anisotropic solids without the need for rolling, rubbing, or stretching to impart orientational alignment of the molecules of the solid. The methods employ organic or organometallic compounds which are soluble orienting molecules. The solvent or solvent system must be sufficiently volatile to be removed without disruption of the molecular orientation. The soluble orienting molecules include those containing one or more hydrophilic and/or ionic groups and the solvent or solvent system can be a polar organic solvent or solvent system or an aqueous solvent or solvent system. The invention also provides novel compounds having quaterrylene, perylene and naphthalene ring systems carrying one or more hydrophilic and/or ionic groups. These novel compounds can exhibit useful absorption and fluorescence properties in solution and in the solid phase and can exhibit useful liquid crystalline properties. 127-. (canceled)28. A compound of formula III herein.2933-. (canceled) This invention takes priority under 35 U.S.C.119(e) from U.S. provisional application U.S. Ser. No. 60/524,272, filed Nov. 21, 2003, which is incorporated by reference herein in its entirety.This invention was funded in part by the United States government through the National Science Foundation grants NSF DMR 9876027 and NSF DMR0405532, NSF EPSCoR Infrastructure Enhancement Grant UCCSN-02-124. The United States government has certain rights in this invention.The construction of devices and materials through molecular self-assembly and self-organization processes is of considerable interest. This invention relates to methods for controlling the self-organization of organic compounds, particularly into a lyotropic (solvent- and concentration-dependent) liquid-crystalline phase, in order to prepare micro-patterned organic solids in ...

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Номер записи: 9
25-04-2013 дата публикации

INDENOQUINOLONE COMPOUND, PREPARATION METHOD AND USE THEREOF

Номер: US20130102598A1
Автор: Fu Xiaodan, Qi Yunpeng, Song Yunlong
Принадлежит: SECOND MILITARY MEDICAL UNIVERSITY, PLA

An indenoquinolone compounds of Formula (A) is disclosed, wherein the definition of each group is described in the description. These compounds may specifically inhibit topoisomerase I, and they have good activities against many kinds of human tumor cells, such as lung cancer, colon cancer, breast cancer, liver cancer and the like. They can be used in the manufacture of antitumor drugs. The method for preparing the compound of formula (A), and pharmaceutical compositions containing such compounds and the use in the manufacture of antitumor drugs are also disclosed. 3. The compound according to claim 1 , wherein claim 1 , Rmay be located at one or two positions of 2- and 3-position; and/or Rmay be located at one or two positions of 8- and 9-position.4. The compound according to claim 1 , wherein claim 1 , Ris any one of the following groups: a) a hydrogen; b) a C1-8 straight-chain or branched alkyloxy; c) a halogen; and/or{'sub': '2', 'Ris any one of the following groups: a) a hydrogen; b) a C1-8 straight-chain or branched alkyloxy; c) a halogen; and/or'}{'sub': 3', '2', '4', '4', '5', '6', '5', '6, 'Ris —(CH)mR, wherein m is 1-4, and Rmay be a saturated or unsaturated 4-7 membered nitrogen-containing heterocycle, halogen, or NRR, wherein Ror Ris any one of the following groups: a) a hydrogen; b) a substituted or unsubstituted C1-8 straight-chain or branched alkyl.'}5. The compound according to claim 1 , wherein claim 1 , m in Ris 2-3 claim 1 , and Rmay be a saturated or unsaturated 5-6 membered nitrogen-containing heterocycle claim 1 , halogen claim 1 , or NRR claim 1 , wherein Ror Ris any one of the following groups: a) a hydrogen; b) a substituted or unsubstituted C1-8 straight-chain or branched alkyl.6. The compound according to claim 1 , wherein claim 1 , Ris halo-ethyl claim 1 , dimethylamino-ethyl claim 1 , diethylamino-ethyl claim 1 , piperidyl-ethyl claim 1 , morpholinyl-ethyl claim 1 , pyrrolidinyl-ethyl claim 1 , imidazolyl-ethyl claim 1 , dimethylamino- ...

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Номер записи: 10
25-04-2013 дата публикации

TARGETED NITROXIDE AGENTS

Номер: US20130102626A1
Автор: Frantz Marie Celine, Wipf Peter
Принадлежит:

Provided herein are compositions and related methods useful for free radical scavenging, with particular selectivity for mitochondria. The compounds comprise a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. Also provided herein are methods, for preventing, mitigating and treating damage caused by radiation. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent, mitigate or treat damage caused by radiation. 45-. (canceled)6. The compound of claim 1 , in which R is Ac claim 1 , Boc claim 1 , Cbz claim 1 , or —P(O)-Ph.7. The compound of claim 1 , in which R claim 1 , R claim 1 , Rand Rare independently chosen from hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , 2-propyl claim 1 , butyl claim 1 , t-butyl claim 1 , pentyl claim 1 , hexyl claim 1 , benzyl claim 1 , hydroxybenzyl claim 1 , phenyl and hydroxyphenyl.8. The compound of claim 1 , wherein when X is —CH═CR— claim 1 , Ris hydrogen claim 1 , methyl or ethyl.912-. (canceled)13. The compound of in which R1 claim 1 , R2 and R3 independently are methyl claim 1 , ethyl claim 1 , propyl claim 1 , 2-propyl claim 1 , butyl claim 1 , t-butyl claim 1 , pentyl claim 1 , hexyl claim 1 , benzyl claim 1 , hydroxybenzyl claim 1 , phenyl and hydroxyphenyl.1421-. (canceled)27. A method of making a targeted antioxidant compound claim 1 , comprising:{'sub': 1', '1', '1', '6', '6', '5, 'a. reacting an aldehyde of structure R—C(O)— with (R)-2-methylpropane-2-sulfinamide to form an imine, in which Ris C-Cstraight or branched-chain alkyl, optionally including a phenyl (CH) group, that optionally is methyl-, hydroxyl- or fluoro-substituted;'}{'sub': 2', '2', '2, 'b. reacting a terminal alkyne-1-ol (HCC—R—CH—OH), in which Ris not present or is branched or straight-chained alkylene, with a tert-butyl)diphenylsilane salt to produce an alkyne;'}c. ...

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Номер записи: 11
02-05-2013 дата публикации

ACTIVATORS OF HUMAN PYRUVATE KINASE

Номер: US20130109672A1
Автор: Auld Douglas S., Boxer Matthew B., Shen Min, Thomas Craig J., Walsh Martin J.
Принадлежит: The United States of America,as represented by the Secretary, Department of Health and Human Service

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

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Номер записи: 12
09-05-2013 дата публикации

PROCESSES FOR PRODUCING CAPROLACTAM AND DERIVATIVES THEREOF FROM FERMENTATION BROTHS CONTAINING DIAMMONIUM ADIPATE, MONOAMMONIUM ADIPATE AND/OR ADIPIC ACID

Номер: US20130116398A1
Автор: Albin Brooke A., Clinton Nye A., Dombek Bernard D., Dunuwila Dilum, Fruchey Olan S., Keen Brian T., Manzer Leo E.
Принадлежит: BIOAMBER S.A.S.

Processes for making caprolactam (CL) from monoammonium adipate (MAA) and/or adipic aicd (AA) obtained from a clarified diammonium adipate-containing (DAA-containing) fermentation broth or MAA-containing fermentation broth and converting the MAA or AA to the CL with hydrogen in the presence of a catalyst at selected temperatures and pressures. 1. A process for producing CL from a clarified DAA-containing fermentation broth , comprising:(a) distilling the broth to firm an overhead that comprises water and ammonia, and a liquid bottoms that comprises MAA, at least some DAA, and at least about 20 wt % water;{'sub': 'N', '(b) cooling andfor evarating the bottoms, and optionally adding an antisolvmt to the bottoms, to attain a temperature and composition sufficient to cause the bottoms to separate into a DAA-containing liquid portion and a MAA-containing, solid portion that is substantially free of DAA;'}(c) separating the solid portion from the liquid portion;(d) recovering the solid portion; and(e) contacting at least a portion of the solid portion with hydrogen, optionally in the presence of a solvent, in the presence of to hydrogenation catalyst and, optionally an ammonia source, at a temperature of about 25° C. to about 500° C. and a pressure of about 0.5 to about 40 MPa to produce the CL.2. A process for producing CI from a DAA-comairring fermentation broth , comprising:(a) distilling the broth to form a first overhead that includes water and ammonia, and a first liquid bottoms that includes MAA, at least some DAA, and at least about 20 wt % water;(b) cooling andlor evaporating the bottoms, and optionally adding an antisolvent to the bottoms, to attain a temperature and composition sufficient to cause the bottoms to separate into a DAA-containing liquid portion and a MAA-containing solid portion that is substantially free of DAA;(c) separating the solid portion from the liquid portion;(d) recovering the solid portion;(e) dissolvine the solid portion in Water to ...

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Номер записи: 13
16-05-2013 дата публикации

Process for the asymmetric transfer hydrogenation of ketones

Номер: US20130123490A1
Автор: Jung Joeng, Meudt Andress, Wisdom Richard
Принадлежит: Euticals GmbH

The invention relates to a process for the asymmetric transfer hydrogenation of a ketone substrate to produce as chiral secondary alcohol with an ee of greater than 85% in which an enantio-enriched chiral catalyst containing ruthenium or rhodium is used with a hydrogen donor and in which an anion exchange resin is used as a base. 1. A process for the asymmetric transfer hydrogenation of a ketone substrate to produce as chiral secondary alcohol with an ee of greater than 85% in which an enantio-enriched chiral catalyst containing ruthenium or rhodium is used with a hydrogen donor and in which an anion exchange resin is used as a base.3. A process according to or in which the starting ketone is 10-oxo-10 ,11-dihydro-5H-dibenz[b ,f]azepine-5-carboxamide and the product alcohol is (S)-10 ,11-dihydro-10-hydroxy-5H-dibenz[b ,f]azepine-5-carboxamide.4. A process according to either or or in which formic acid or a salt of formic acid is used as a hydrogen donor.5. A process according to or or or in which the anion exchange resin used is a weak anion exchange resin.6. A process according to in which the weak anion exchange resin used is of a porous acrylate gel structure.7. A process according to or in which the weak anion exchange resin used is formally a copolymer of N claim 5 ,N-dimethylaminopropylacrylamide claim 5 , a vinyl ether derivative and another monomer.8. A process according to in which weak anion exchange resin used is formally a copolymer of N claim 7 ,N-dimethylaminopropylacrylamide claim 7 , di(ethylene glycol) divinyl ether and divinylbenzene.9. A process according to to in which the formed (S)-10 claim 7 ,11-dihydro-10-hydroxy-5H-dibenz[b claim 7 ,f]azepine-5-carboxamide (eslicarbazepine) is of ee greater than 96%.10. A process according to to in which the formed (S)-10 claim 7 ,11-dihydro-10-hydroxy-5H-dibenz[b claim 7 ,f]azepine-5-carboxamide is isolated and then acetylated to produce (S)-10-acetoxy-10 claim 7 ,11-dihydro-5H-dibenz[b claim 7 ,f]azepine-5 ...

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Номер записи: 14
23-05-2013 дата публикации

CATIONIC LIPID

Номер: US20130129811A1
Автор: Era Tomohiro, Kuboyama Takeshi, Naoi Tomoyuki
Принадлежит:

The present invention provides a cationic lipid, which allow nucleic acids to be easily introduced into cells, represented by formula (I) 2. The cationic lipid according to claim 1 , wherein Xand Xare combined together to form a single bond or alkylene.3. The cationic lipid according to claim 1 , wherein Lis a single bond claim 1 , Ris a hydrogen atom claim 1 , methyl claim 1 , pyrrolidin-3-yl claim 1 , piperidin-3-yl claim 1 , piperidin-4-yl claim 1 , or alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s) claim 1 , which is(are) claim 1 , the same or different claim 1 , amino claim 1 , monoalkylamino claim 1 , dialkylamino claim 1 , trialkylammonio claim 1 , hydroxy claim 1 , alkoxy claim 1 , carbamoyl claim 1 , monoalkylcarbamoyl claim 1 , dialkylcarbamoyl claim 1 , pyrrolidinyl claim 1 , piperidyl or morpholinyl claim 1 , and Land Lare —O—.4. The cationic lipid according to claim 1 , wherein Lis —CO— or —CO—O— claim 1 , Ris pyrrolidin-3-yl claim 1 , piperidin-3-yl claim 1 , piperidin-4-yl claim 1 , or alkyl having 1 to 6 carbon atoms or alkenyl having 3 to 6 carbon atoms substituted with 1 to 3 substituent(s) claim 1 , which is(are) claim 1 , the same or different claim 1 , amino claim 1 , monoalkylamino claim 1 , dialkylamino claim 1 , trialkylammonio claim 1 , hydroxy claim 1 , alkoxy claim 1 , carbamoyl claim 1 , monoalkylcarbamoyl claim 1 , dialkylcarbamoyl claim 1 , pyrrolidinyl claim 1 , piperidyl or morpholinyl claim 1 , wherein at least one of the substituents is amino claim 1 , monoalkylamino claim 1 , dialkylamino claim 1 , trialkylammonio claim 1 , pyrrolidinyl claim 1 , piperidyl or morpholinyl claim 1 , and Land Lare identically —CO—O— or —O—CO—.5. The cationic lipid according to any one of to claim 1 , wherein Xis absent claim 1 , or is methyl.64. The cationic lipid according to any one of to claims 1 , wherein Land Lare —O— or —O—CO— claims 1 , and Rand Rare (Z)-hexadec-6-enyl or (Z)-hexadec ...

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Номер записи: 15
23-05-2013 дата публикации

BENZAZEPINE COMPOUND

Номер: US20130131045A1
Автор: Kan Keizo, Ohtani Tadaaki
Принадлежит: OTSUKA PHARMACEUTICAL CO., LTD.

An object of the present invention is to provide a novel benzazepine compound or a salt thereof, which has excellent vasopressin antagonistic activity. 2. A benzazepine compound selected from the group consisting of:(1) N-(4-(7-chloro-5-hydroxy-2,3,4-trihydro-5-deutero-1H-benzo[b]azepine-1-carbonyl)-3-methylphenyl)-2-methylbenzamide,(2) N-(4-(7-chloro-2,3-dihydro-5-hydroxy-4,4,5-trideutero-1H-benzo[b]azepine-1-carbonyl)-3-methylphenyl)-2-methylbenzamide,(3) N-(4-(7-chloro-5-hydroxy-2,2-dideutero-3,4,5-trihydro-1H-benzo[b]azepine-1-carbonyl)-3-methylphenyl)-2-methylbenzamide,(4) N-(4-(7-chloro-5-hydroxy-2,2,4,4,5-pentadeutero-1H-benzo[b]azepine-1-carbonyl)-3-methylphenyl)-2-methylbenzamide, and(5) N- {4-(7-chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carbonyl)-3-methylphenyl} -3,4,5,6-tetradeutero -2-trideutero methylbenzamide,or a salt thereof.3. A pharmaceutical composition or a salt thereof comprising claim 1 , as an active ingredient claim 1 , the benzazepine compound of claim 1 , and a pharmaceutically acceptable carrier.4. Use of the benzazepine compound or a salt thereof of claim 1 , as a drug.5. A vasopressin antagonist comprising claim 1 , as an active ingredient claim 1 , the benzazepine compound or a salt thereof of .6. The pharmaceutical composition according to claim 3 , which is for preventing or treating at least one disease selected from the group consisting of hypertension claim 3 , edema claim 3 , ascites claim 3 , heart failure claim 3 , renal dysfunction claim 3 , syndrome of inappropriate secretion of antidiuretic hormone (SIADH) claim 3 , liver cirrhosis claim 3 , hyponatremia claim 3 , hypokalemia claim 3 , diabetes claim 3 , circulatory failure claim 3 , motion sickness claim 3 , water-metabolism disorder claim 3 , renal failure claim 3 , cerebral infarction claim 3 , cardiac infarction claim 3 , and polycystic kidney disease (PKD).7. The pharmaceutical composition according to claim 3 , which is for use as at least one drug ...

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Номер записи: 16
13-06-2013 дата публикации

PROCESSES FOR THE PRODUCTION OF HYDROGENATED PRODUCTS AND DERIVATIVES THEREOF

Номер: US20130150551A1
Автор: Albin Brooke A., Clinton Nye A., Dombek Bernard D., Dunuwila Dilum, Fruchey Olan S., Keen Brian T., Manzer Leo E.
Принадлежит: BIOAMBER S.A.S.

Processes for making hydrogenated products including caprolactame (CL) caprolactone (CLO) or 1,6-hexanediol (HDO) and derivative thereof from monoammonium adipate (MAA) and/or adipic acid (AA) obtained from a clarified diammonium adipate-containing (DAA-containing) fermentation broth or monoammonium adipate-containing (MAA-containing) fermentation broth. 1. A process for making a hydrogenated product from a clarified DAA-containing fermentation broth comprising;(a) distilling the broth to form an overhead that comprises water and ammonia, and a liquid bottoms that comprises MAA, at least some DAA, and at least about 20 wt % water;(b) cooling and/or evaporating the bottoms, and optionally adding an antisolvent to the bottoms, to attain a temperature and composition sufficient to cause the bottoms to separate into a DAA-containing liquid portion and a MAA-containing solid portion that is substantially free of DAA;(c) separating the solid portion from the liquid portion;(d) recovering the solid portion;(e) hydrogenating the solid portion in the presence of at least one hydrogenation catalyst to produce the hydrogenated product comprising at least one of CL, CLO or HDO; and(f) recovering the hydrogenated product.2. A process for making a hydrogenated product from a DAA-containing fermentation broth comprising:(a) distilling the broth to form a first overhead that includes water and ammonia, and a first liquid bottoms that includes MAA, at least some DAA, and at least about 20 wt % water;(b) cooling and/or evaporating the bottoms, and optionally adding an antisolvent to the bottoms, to attain a temperature and composition sufficient to cause the bottoms to separate into a DAA-containing liquid portion and a MAA-containing solid portion that is substantially free of DAA;(c) separating the solid portion from the liquid portion;(d) recovering the solid portion;(e) dissolving the solid portion in water to produce an aqueous MAA solution;(f) distilling the aqueous MAA ...

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Номер записи: 17
20-06-2013 дата публикации

PROCESSES FOR THE PREPARATION OF 5-HT2C RECEPTOR AGONISTS

Номер: US20130158013A1
Автор: Blackburn Anthony C., Shifrina Anna
Принадлежит:

Processes and intermediates for preparing salts of the 5-HT-receptor agonist (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, and pharmaceutically acceptable solvates and hydrates thereof, that are useful for, inter alia, weight management. 1. A process for preparing (R)-8-chloro-1-methyl-2 ,3 ,4 ,5-tetrahydro-1H-3-benzazepine hydrochloride salt hemihydrate Form III , comprising slurrying a first mixture comprising: (R)-8-chloro-1-methyl-2 ,3 ,4 ,5-tetrahydro-1H-3-benzazepine hydrochloride salt Form IV; and a first solvent; to form said (R)-8-chloro-1-methyl-2 ,3 ,4 ,5-tetrahydro-1H-3-benzazepine hydrochloride salt hemihydrate Form III.2. The process according to claim 1 , wherein said first mixture has a water activity of greater than about 0.15.3. The process according to claim 1 , wherein said first mixture has a water activity of greater than about 0.20.4. The process according to claim 1 , wherein said (R)-8-chloro-1-methyl-2 claim 1 ,3 claim 1 ,4 claim 1 ,5-tetrahydro-1H-3-benzazepine hydrochloride salt Form IV is prepared by slurrying a second mixture comprising: a starting material selected from (R)-8-chloro-1-methyl-2 claim 1 ,3 claim 1 ,4 claim 1 ,5-tetrahydro-1H-3-benzazepine hydrochloride salt Form I claim 1 , (R)-8-chloro-1-methyl-2 claim 1 ,3 claim 1 ,4 claim 1 ,5-tetrahydro-1H-3-benzazepine hydrochloride salt Form II claim 1 , and mixtures thereof; and a second solvent; to form said (R)-8-chloro-1-methyl-2 claim 1 ,3 claim 1 ,4 claim 1 ,5-tetrahydro-1H-3-benzazepine hydrochloride salt Form IV.5. The process according to claim 4 , further comprising isolating said (R)-8-chloro-1-methyl-2 claim 4 ,3 claim 4 ,4 claim 4 ,5-tetrahydro-1H-3-benzazepine hydrochloride salt Form IV.6. The process according to claim 4 , wherein said second mixture further comprises seed crystals claim 4 , wherein said seed crystals comprise (R)-8-chloro-1-methyl-2 claim 4 ,3 claim 4 ,4 claim 4 ,5-tetrahydro-1H-3-benzazepine hydrochloride salt Form IV.7. The process ...

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Номер записи: 18
20-06-2013 дата публикации

PIPERIDINE DERIVATIVES

Номер: US20130158050A1
Автор: Kolczewski Sabine, Pinard Emmanuel, Stalder Henri
Принадлежит: Hoffmann-La Roche Inc.

The present invention relates to a compound of formula I 2. A compound of claim 1 , wherein Ris lower alkyl.3. A compound of claim 2 , wherein the phenyl group for Ar is substituted by at least two CFgroups.4. A compound of claim 3 , selected from the group consisting ofrac-2-fluoro-N-(1-methyl-3-phenyl-piperidin-3-yl)-4,6-bis-trifluoromethyl-benzamide;rac-2-methoxy-N-(1-methyl-3-phenyl-piperidin-3-yl)-4,6-bis-trifluoromethyl-benzamide;rac-2-ethyl-N-(1-methyl-3-phenyl-piperidin-3-yl)-4,6-bis-trifluoromethyl-benzamide;rac-N-[3-(4-fluoro-phenyl)-1-methyl-piperidin-3-yl]-2-methoxy-4,6-bis-trifluoromethyl-benzamide; and2-methoxy-N—((R)-1-methyl-3-phenyl-piperidin-3-yl)-4,6-bis-trifluoromethyl-benzamide.5. A compound of claim 1 , wherein the phenyl group for Ar is substituted by at least one CFgroup.6. A compound of claim 5 , selected from the group consisting ofrac-2-ethyl-N-(1-methyl-3-phenyl-piperidin-3-yl)-4-trifluoromethyl-benzamide;rac-2-bromo-6-methoxy-N-(1-methyl-3-phenyl-piperidin-3-yl)-4-trifluoromethyl-benzamide;rac-N-(1,2-dimethyl-3-phenyl-piperidin-3-yl)-2-methoxy-6-methylsulfanyl-4-trifluoromethyl-benzamide;rac-2-cyclopropyl-N-(1-methyl-3-phenyl-piperidin-3-yl)-4-trifluoromethyl-benzamide;rac-2-methoxy-N-(1-methyl-3-phenyl-piperidin-3-yl)-6-methylsulfanyl-4-trifluoromethyl-benzamide;rac-N-(1-methyl-3-phenyl-piperidin-3-yl)-2-methylsulfanyl-4-trifluoromethyl-benzamide;rac-N-[3-(4-fluoro-phenyl)-1-methyl-piperidin-3-yl]-2-methoxy-6-methylsulfanyl-4-trifluoromethyl-benzamide;rac-N-[3-(4-chloro-phenyl)-1-methyl-piperidin-3-yl]-2-methoxy-6-methylsulfanyl-4-trifluoromethyl-benzamide;2-methoxy-N-((S)-1-methyl-3-phenyl-piperidin-3-yl)-6-methylsulfanyl-4-trifluoromethyl-benzamide;2-methoxy-N—((R)-1-methyl-3-phenyl-piperidin-3-yl)-6-methylsulfanyl-4-trifluoromethyl-benzamide; andrac-2-difluoromethoxy-N-(1-methyl-3-phenyl-piperidin-3-yl)-4-trifluoromethyl-benzamide.7. A compound of claim 5 , selected from the group consisting ofrac-N-[3-(3-chloro-phenyl)-1-methyl- ...

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Номер записи: 19
20-06-2013 дата публикации

PROCESS FOR THE SYNTHESIS OF IVABRADINE AND ADDITION SALTS THEREOF WITH A PHARMACEUTICALLY ACCEPTABLE ACID

Номер: US20130158257A1
Автор: Gaillard Sylvain, Lecouve Jean-Pierre, Pannetier Nicolas, RENAUD Jean-Luc, Vaysse-Ludot Lucile
Принадлежит: LES LABORATOIRES SERVIER

Process for the synthesis of ivabradine of formula (I): 2. The process according to claim 1 , wherein the reductive amination reaction is carried out in the absence of solvent.3. The process according to claim 1 , wherein the amount of formic acid used in the reductive amination reaction is from 2 to 50 equivalents per equivalent of aldehyde.4. The process according to claim 1 , wherein the amount of triethylamine used in the reductive amination reaction is from 2 to 50 equivalents per equivalent of aldehyde.5. The process according to claim 1 , wherein the temperature of the reductive amination reaction is from 30 to 100° C. The present invention relates to a process for the synthesis of ivabradine of formula (I):or 3-{3-[{[7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino]-propyl}-7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one, addition salts thereof with a pharmaceutically acceptable acid, and hydrates thereof.Ivabradine, and its addition salts with a pharmaceutically acceptable acid, and more especially its hydrochloride, have very valuable pharmacological and therapeutic properties, especially bradycardic properties, making those compounds useful in the treatment or prevention of various clinical situations of myocardial ischaemia such as angina pectoris, myocardial infarct and associated rhythm disturbances, and also in various pathologies involving rhythm disturbances, especially supraventricular rhythm disturbances, and in heart failure.The preparation and therapeutic use of ivabradine and its addition salts with a pharmaceutically acceptable acid, and more especially its hydrochloride, have been described in the European patent specification EP 0 534 859. Unfortunately, the ivabradine synthesis route described in that patent specification results in the expected product in a yield of only 1%.Another ivabradine synthesis route, which is based on a reductive amination reaction, has been described in the European patent ...

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Номер записи: 20
27-06-2013 дата публикации

PROCESSES FOR PREPARING 3-BENZAZEPINES

Номер: US20130165648A1
Автор: AYTES SHELLEY, ESTRADA SCOTT A., GILSON, III Charles A., REY MAX, SENGUPTA DIPANJAN, SMITH BRIAN, WEIGL ULRICH, Wolgast Beverly L.
Принадлежит:

The present invention provides processes and intermediates for the preparation of 3-benzazepines and salts thereof which can be useful as serotonin (5-HT) receptor agonists for the treatment of, for example, central nervous system disorders such as obesity. 1651.-. (canceled)653. A process according to claim 652 , wherein said halogenating/sulfonating reagent is SOBror SOCl.654. A process according to claim 652 , wherein Xis Cl.655. A process according to claim 652 , wherein Xis Br.656. A process according to claim 652 , wherein the reaction of said compound of Formula X with said halogenating/sulfonating reagent is carried out in the presence of solvent claim 652 , and said solvent comprises dimethylformamide or toluene.657. A process according to claim 652 , wherein the reaction of said compound of Formula X with said halogenating/sulfonating reagent is carried out at a temperature of about −40 to about 80° C.658. A process according to claim 652 , wherein Ris H claim 652 , Ris Me claim 652 , Ris H claim 652 , Ris Cl claim 652 , Ris H claim 652 , Ris H claim 652 , Ris H claim 652 , Ris H claim 652 , Ris H claim 652 , and Ris H.660. A compound according to claim 659 , wherein Xis Br.661. A compound according to claim 659 , wherein Xis Cl.662. A compound according to claim 659 , wherein Ris H claim 659 , Ris Me claim 659 , Ris H claim 659 , Ris Cl claim 659 , Ris H claim 659 , Ris H claim 659 , Ris H claim 659 , Ris H claim 659 , Ris H claim 659 , and Ris H.664. A process according to claim 663 , wherein the reaction of said compound of Formula XI to give said compound of Formula X is carried out at a temperature of about 80 to about 110° C.665. A process according to claim 663 , wherein Xis Br.666. A process according to claim 663 , wherein Ris H claim 663 , Ris Me claim 663 , Ris H claim 663 , Ris Cl claim 663 , Ris H claim 663 , Ris H claim 663 , Ris H claim 663 , Ris H claim 663 , Ris H claim 663 , and Ris H.668. A compound according to claim 667 , wherein Ris H ...

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Номер записи: 21
27-06-2013 дата публикации

PRODUCTION METHOD OF INTERMEDIATE COMPOUND FOR SYNTHESIZING MEDICAMENT

Номер: US20130165659A1
Автор: An Ji Eun, KIM Bong Chan, Kim Kyu Young, Lee Hee Bong, Lee Kyu Woong
Принадлежит: LG LIFE SCIENCES LTD.

The present invention relates to a novel method for preparing a compound of formula (2) as the intermediate, which can be effectively used for preparation of a compound of formula (1) exhibiting good inhibitory activity against dipeptidyl peptidase IV enzyme. 3. The method according to claim 1 , wherein Pis t-butyl group claim 1 , and Pis methyl or ethyl group.4. The method according to claim 1 , wherein GO is triflate claim 1 , mesylate claim 1 , tosylate claim 1 , besylate or nonaflate.5. The method according to claim 1 , wherein R3 and R4 are hydrogen claim 1 , and R5 and R6 are fluorine.6. The method according to claim 2 , wherein in step (a) C-Ctrialkylamine is used as the base.7. The method according to claim 2 , wherein in step (b) acetic acid is used as the acid.8. The method according to claim 2 , wherein in the case of the compound of formula (2a) wherein Pis Boc and Pis t-butyl claim 2 , the hydrolysis of said step (c) is conducted under the basic condition to selectively remove only Pamong the protecting groups Pand Pto provide the compound of formula (2).9. The method according to claim 8 , wherein aqueous sodium hydroxide solution is used as the base.11. The method according to claim 10 , wherein in step (a) the reduction is conducted using NaBH.12. The method according to claim 10 , wherein in step (b) the Gcompound is selected from the group consisting of trifluoromethane sulfonic acid anhydride (TfO) claim 10 , trifluoromethane sulfonyl chloride (TfCl) claim 10 , methanesulfonyl chloride (MsCl) claim 10 , toluenesulfonyl chloride (TsCl) claim 10 , bromobenzenesulfonyl chloride (BsCl) claim 10 , (CF(CF)SO)F and (CF(CF)SO)O.14. The method according to claim 13 , wherein Pis Boc claim 13 , Pis i-propyl group or t-butyl group claim 13 , and GO is triflate or nonaflate.17. The method according to claim 16 , wherein Pis Boc claim 16 , and Pis i-propyl or t-butyl.18. The method according to claim 16 , wherein in step (a) chloroformate or BocO is used as ...

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Номер записи: 22
04-07-2013 дата публикации

ANTI-INFLAMMATORY AGENTS

Номер: US20130172318A1
Автор: Fox David John, Grainger David John
Принадлежит:

Disclosed herein are methods of preventing or treating inflammatory diseases using 3-aminolactam compounds, each with aromatic “tail groups”. Compounds as defined by formulae (I) and (I′), and the medical uses of the compounds, are described herein. 3. (canceled)4. (canceled)6. A compound of{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, ','}provided that the compound is not selected from the group consisting of: (S)-3-(4′-methoxybenzoylamino)-caprolactam, (S)-3-(4′-methylbenzoylamino)-caprolactam, (S)-3-(3′-trifluoromethylbenzoylamino)-caprolactam, (S)-3-(2′-carboxybenzoyl-amino)-caprolactam, and (S)-3-(3′,4′,5′-trimethoxybenzoylamino)-caprolactam.7. A pharmaceutical composition comprising claim 5 , as active ingredient claim 5 , a compound as defined in claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , and at least one pharmaceutically acceptable excipient and/or carrier.8. The compound according to claim 1 , wherein n=2.9. The compound according to claim 1 , wherein n=3.10. The compound according to claim 1 , wherein X is haloalkyl.11. The compound according to claim 2 , wherein the compound is selected from the group consisting of:(S)-3-(4′-methylbenzoylamino)-caprolactam, and(S)-3-(3′,5′-dimethylbenzoylamino)-caprolactam,and pharmaceutically acceptable salts thereof.12. A compound according to claim 2 , selected from the group consisting of:(S)-3-fluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-2-fluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-4-fluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)—N-(2-oxopiperidin-3-yl)-4-(trifluoromethyl)benzamide,(S)—N-(2-oxopiperidin-3-yl)-3-(trifluoromethyl)benzamide,(S)—N-(2-oxopiperidin-3-yl)-2-(trifluoromethyl)benzamide,(S)-2,3-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-2,4-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-2,5-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-2,6-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-3,4-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-3,5-difluoro-N-(2-oxopiperidin-3-yl)benzamide,(S)-3 ...

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Номер записи: 23
04-07-2013 дата публикации

Alpha-AminoCycloLactam Ligands for G-Protein Coupled Receptors, and Methods of Using Same

Номер: US20130172319A1
Автор: Fox David John, Grainger David J.
Принадлежит:

The invention relates to the generation of a library of compounds enriched in agonist and antagonists for members of the G-protein coupled class of receptors (GPCRs). 4. A library composed of claim 1 , or enriched in claim 1 , library elements which are compounds according to .5. A method of screening in an assay claim 4 , a library according to claim 4 , to identify agent(s) which modulate signalling through GPCRs.6. The method according to claim 5 , wherein the agent(s) identified are antagonists at one or more GPCRs.7. The method according to claim 5 , wherein the agent(s) identified are agonists at one or more GPCRs.8. The method according to claim 5 , wherein the GPCR is selected from the group consisting of adrenalin receptors claim 5 , endothelin receptors claim 5 , chemokine receptors claim 5 , EDG receptors claim 5 , VIP/PECAP receptors claim 5 , dopamine receptors claim 5 , serotonin receptors claim 5 , purine receptors claim 5 , metabotropic glutamate receptors claim 5 , acetyl choline receptors claim 5 , C5a receptors claim 5 , fMLP receptors claim 5 , glucagon or GLP receptors claim 5 , NPY receptors claim 5 , MSH receptors claim 5 , glycoprotein hormone receptors claim 5 , protease activated receptors (PARs) claim 5 , somatostatin receptors claim 5 , angiotensin receptors claim 5 , cholecystokinin receptors claim 5 , and melatonin receptors. This application is a continuation of application Ser. No. 13/193,274, now U.S. Pat. No. 8,389,279, which is a continuation of application Ser. No. 11/574,656, now U.S. Pat. No. 8,008,289, which is the U.S. national stage of PCT/GB2005/003134, filed Aug. 10, 2005 and published in English as WO 2006/024815 A1 on Mar. 9, 2006, which claims the benefit of priority under 35 U.S.C. §119 to United Kingdom application serial no. 0419517.8, filed Sep. 2, 2004, all of which applications and publications are incorporated herein by reference.The invention relates to the generation of a library of compounds enriched in agonist ...

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Номер записи: 24
11-07-2013 дата публикации

TRICYCLIC COMPOUNDS AND PBK INHIBITORS CONTAINING THE SAME

Номер: US20130178459A1
Автор: AHMED Feryan, CUI Wenge, DECORNEZ Helene, GAUUAN Polivina Jolicia F., GURRAM Mahender, HISADA Shoji, Huntley Raymond, JENKINS David M., KARGBO Robert B., Matsuo Yo, Nakamura Yusuke, SAJJADI-HASHEMI Zohreh, Walker Joel R.
Принадлежит: Oncotherapy Science, Inc.

Tricyclic compounds are provided. These compounds are PBK inhibitors, and are useful for the treatment of PBK related diseases, including cancer. 3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris hydrogen claim 2 , cyano claim 2 , C-Calkyl optionally substituted with hydroxyl or halogen claim 2 , C-Ccycloalkyl claim 2 , C-Calkenyl claim 2 , C-Calkynyl claim 2 , or halogen.4. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris hydrogen claim 2 , hydroxyl claim 2 , halogen claim 2 , C-Calkoxy claim 2 , or C-Caryl optionally substituted with hydroxyl.5. The compound of or a pharmaceutically acceptable salt claim 2 , wherein Ris hydrogen claim 2 , hydroxyl claim 2 , halogen claim 2 , C-Calkoxy claim 2 , or dihydroxyphenyl.6. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein Ris selected from the group consisting of: hydrogen; hydroxyl; C-Calkyl optionally substituted with hydroxyl claim 2 , halogen claim 2 , or hydroxyethylamino; halogen; C-Calkoxy optionally substituted with dimethylamino or morpholinyl; C-Calkylphenyl claim 2 , wherein the aliphatic carbons are optionally substituted with —NRR; cyano; nitro; amino; 3- to 8-membered heterocycloalkyl optionally substituted with amino; heteroaryl; —OSOCH; —OSOCF; —OCOR claim 2 , wherein Rrepresents C-Calkyl; —OCOORwherein Rrepresents C-Calkyl; —OCONRRwherein Rand Reach independently represent hydrogen or C-Calkyl claim 2 , or Rand Rtaken together form morpholinyl; and —CONH.7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein when Ris a 3- to 8-membered heterocycloalkyl claim 6 , the 3- to 8-membered heterocycloalkyl is selected from the group consisting of piperidyl claim 6 , pyrrolidinyl claim 6 , morpholinyl claim 6 , or piperazinyl and optionally substituted with amino; and when Ris heteroaryl claim 6 , the heteroaryl is pyridyl.8. The compound of ...

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Номер записи: 25
11-07-2013 дата публикации

CHIRAL AUXILIARIES

Номер: US20130178612A1
Автор: Shimizu Mamoru, Wada Takeshi
Принадлежит: CHIRALGEN, LTD.

Chiral auxiliaries useful for efficiently producing a phosphorus atom-modified nucleic acid derivative with high stereoregularity, and compounds represented by the following the general formula (I) or the general formula (XI) for introducing the chiral auxiliaries. 2. The compound or a salt thereof according to claim 1 , wherein Rand Rare hydrogen atom or an alkyl group claim 1 , Ris phenyl group claim 1 , Rand Rare hydrogen atom or an alkyl group claim 1 , and Y is —C(R)(R)— (Rand Rare independently hydrogen atom or an alkyl group claim 1 , and when Rrepresents an alkyl group claim 1 , Rmay bind with the phenyl group represented by Rto form a ring) claim 1 , o-phenylene group claim 1 , or naphthalene-1 claim 1 ,2-diyl group.8. The method according to claim 7 , wherein 3% dichloroacetic acid (DCA) in dichloromethane is used for the acidic condition in the step (c).9. The method according to claim 7 , wherein claim 7 , as the modification of phosphorus atom claim 7 , a group represented by X (X represents an alkylthio group which may have a substituent claim 7 , an alkenylthio group which may have a substituent claim 7 , an alkynylthio group which may have a substituent claim 7 , an arylthio group which may have a substituent claim 7 , thiol group claim 7 , an alkoxy group which may have a substituent claim 7 , —BH claim 7 , —Se claim 7 , an alkyl group which may have a substituent claim 7 , an alkenyl group which may have a substituent claim 7 , an alkynyl group which may have a substituent claim 7 , an aryl group which may have a substituent claim 7 , an acyl group which may have a substituent claim 7 , or —N(R)(R) (Rand Rindependently represent hydrogen atom claim 7 , an alkyl group which may have a substituent claim 7 , an alkenyl group which may have a substituent claim 7 , an alkynyl group which may have a substituent claim 7 , or an aryl group which may have a substituent) is introduced on the phosphorus atom.11. The compound or a salt thereof according to ...

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Номер записи: 26
11-07-2013 дата публикации

PROCESSES FOR THE PREPARATION OF 8-CHLORO-1-METHYL-2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPINE AND INTERMEDIATES RELATED THERETO

Номер: US20130178619A1
Автор: Koetz Ulf, Porstmann Frank, Straessler Christoph, Ulmer Lars, WEIGL ULRICH
Принадлежит:

The present invention provides processes, methods and intermediates for the preparation of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, salts, hydrates and crystal forms thereof which are useful as serotonin (5-HT) receptor agonists for the treatment of, for example, central nervous system disorders such as obesity. 127.-. (canceled)29. The method according to claim 28 , wherein the L-(+)-tartaric acid salt of said compound of Formula (Ia) has a chiral purity of greater than 98.0% enantiomeric excess.30. The method according to claim 28 , wherein the L-(+)-tartaric acid salt of said compound of Formula (Ia) has a chiral purity of greater than 99.0% enantiomeric excess.31. The method according to claim 28 , further comprising recrystallizing the L-(+)-tartaric acid salt of said compound of Formula (Ia) from acetone and water.32. The method according to claim 31 , wherein the recrystallized L-(+)-tartaric acid salt of said compound of Formula (Ia) has a chiral purity of greater than 98.0% enantiomeric excess.33. The method according to claim 31 , wherein the recrystallized L-(+)-tartaric acid salt of said compound of Formula (Ia) has a chiral purity of greater than 99.0% enantiomeric excess.35. The method according to claim 34 , wherein the L-(+)-tartaric acid salt of said compound of Formula (Ia) has a chiral purity of greater than 98.0% enantiomeric excess.36. The method according to claim 34 , wherein the L-(+)-tartaric acid salt of said compound of Formula (Ia) has a chiral purity of greater than 99.0% enantiomeric excess.37. The method according to claim 34 , further comprising recrystallizing the L-(+)-tartaric acid salt of said compound of Formula (Ia) from acetone and water.38. The method according to claim 37 , wherein the recrystallized L-(+)-tartaric acid salt of said compound of Formula (Ia) has a chiral purity of greater than 98.0% enantiomeric excess.39. The method according to claim 37 , wherein the recrystallized L-(+)-tartaric acid salt of ...

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Номер записи: 27
25-07-2013 дата публикации

ENZYMATIC CONJUGATION OF POLYPEPTIDES

Номер: US20130189287A1
Автор: Belmant Christian, Bregeon Delphine, Dennler Patrick, Fischer Eliane, Gauthier Laurent, Romagne Francois, Schibli Roger
Принадлежит:

The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions 1. An antibody or antibody fragment comprising a functionalized acceptor glutamine residue , the functionalized acceptor glutamine residue having Formula IVa ,{'br': None, 'sub': n', 'z', 'q', 'q', 'r, '(Q)-NH—(C)—X-L-(V—(Y—(Z))))\u2003\u2003Formula IVa'}or a pharmaceutically acceptable salt or solvate thereof,wherein:Q is glutamine residue present in an antibody or antibody fragment;{'sub': 'n', '(C)is a substituted or unsubstituted alkyl or heteroalkyl chain, optionally wherein any carbon of the chain is substituted with an alkoxy, hydroxyl, alkylcarbonyloxy, alkyl-S—, thiol, alkyl-C(O)S—, amine, alkylamine, amide, or alkylamide;'}n is an integer selected from among the range of 2 to 20;X is NH, O, S, absent, or a bond;L is independently absent, a bond or a continuation of a bond, or a carbon comprising framework of 5 to 200 atoms substituted at one or more atoms;r is an integer selected from among 1, 2, 3 or 4;q is an integer selected from among 1, 2, 3 or 4;z is an integer selected from among 1, 2, 3 or 4; andV is independently absent, a bond or a continuation of a bond, a non-cleavable moiety or a conditionally-cleavable moiety;Y is independently absent, a bond or a continuation of a bond, or a spacer system which is comprised of 1 or more spacers; andZ is a moiety that improves pharmacokinetic properties, a therapeutic moiety or a diagnostic moiety, wherein Z is an organic compound that is electrically negatively charged, hydrophobic and/or that has a molecular weight of at least 400 g/mol.2. The antibody of claim 1 , wherein n is an integer selected from among the range of 10 to 20.3. The antibody of claim 1 , wherein (C)is a heteroalkyl chain that comprises a (CH—CH—O—)group claim 1 , wherein x is ...

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Номер записи: 28
25-07-2013 дата публикации

PROCESS FOR PREPARING TOLVAPTAN INTERMEDIATES

Номер: US20130190490A1
Автор: Krishna Bandi Vamsi, Reddy Bandi Parthasaradhi, Reddy Dasari Muralidhara, Reddy Kura Rathnakar, Reddy Maruthi Janakiram
Принадлежит: HETERO RESEARCH FOUNDATION

The present invention provides a novel process for the preparation of 7-chloro-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one. The present invention also provides an improved process for the preparation of 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine. The present invention further provides an improved process for the preparation of 7-chloro-1-[2-methyl-4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine. 1. A process for the preparation of 7-chloro-5-oxo-2 ,3 ,4 ,5-tetrahydro-1H-1-benzazepine , comprising:a. reacting 7chloro-4-ethoxycarbonyl-5-oxo-N-p-toluenesufonyl-2,3,4,5-tetrahydro-1H-benzazepine with sulfuric acid;b. maintaining the contents obtained in step (a) at above 50° C. to form reaction mass;c. cooling the first reaction mass obtained in step (b) at room temperature;d. pouring the reaction mass into water;e. adjusting the pH of the reaction mass to about 7.0 to 8.5 with a base; andf. isolating 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine from the reaction mass.2. The process of claim 1 , wherein the sulfuric acid is used in step (a) in the form of aqueous sulfuric acid.3. The process of claim 1 , wherein step (b) is carried out at a temperature of about 60 to 100° C.4. The process of claim 1 , wherein the base used in step (e) is an organic base or inorganic base.54. The process of claim 1 , wherein the base is an inorganic base selected from alkali metal hydroxides claim 1 , alkali metal carbonates and alkali metal bicarbonates.6. The process of claim 5 , wherein the inorganic base is sodium hydroxide or potassium hydroxide.7. The process of claim 1 , wherein the pH in step (e) is adjusted to 7.2 to 8.2.8. A process for the preparation of 7-chloro-1-(2-methyl-4-1-nitrobenzoyl)-5-oxo-2 claim 1 ,3 claim 1 ,4 claim 1 ,5-tetrahydro-1H-1-benzazepine claim 1 , comprising reacting 7-chloro-5-oxo-2 claim 1 ,3 claim 1 ,4 claim 1 ,5-tetrahydro-1H-1-benzazepine with 2-methyl-4-nitobenzoyl chloride in the ...

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Номер записи: 29
08-08-2013 дата публикации

ANTI-INFLAMMATORY AGENTS

Номер: US20130203734A1
Автор: Fox David John, Grainger David John
Принадлежит:

Disclosed herein are methods of preventing or treating inflammatory diseases using sulfonamide analogs of 3-aminolactam compounds, each with aromatic “tail groups”. Compounds as defined by formulae (I) and (I′), and the medical uses of the compounds, are described herein. 3. (canceled)4. (canceled)5. A compound according to claim 1 , with the proviso that:{'sub': 2', '6', '1', '7', '1', '7, 'when n =3, then at least one of C-Con the phenyl ring is substituted with a group other than halogen, C-Calkyl, or C-Chaloalkyl; and'}when n =1, 2 or 3, then{'sub': 2', '6, 'Cor Con the phenyl ring are other than hydrogen or fluorine, or'}{'sub': 3', '1', '6, 'Con the phenyl ring is other than hydrogen, halogen, C-Calkyl,'}{'sub': 1', '6', '1', '6, 'C-Calkoxy, or C-Chaloalkyl, or'}{'sub': 4', '1', '6', '1', '6', '1', '6, 'Con the phenyl ring is other than hydrogen, halogen, C-Calkyl, C-Calkoxy, C-Chaloalkyl, amino, aminoalkyl or aminodialkyl, or'}{'sub': '5', 'Con the phenyl ring is other than hydrogen or halogen;'}provided that the compound is neither of:3-(2′-carboxybenzenesulfonylamino)-tetrahydropyridin-2-one, and (R)-3-(4′-methylbenzenesulfonylamino)-caprolactam.6. A compound of claim 2 , with the proviso that:{'sub': 2', '6', '1', '7', '1', '7, 'when n=3, then at least one of C-Con the phenyl ring is substituted with a group other than halogen, C-Calkyl, or C-Chaloalkyl; and'}when n =1, 2 or 3, then{'sub': 2', '6, 'Cor Con the phenyl ring are other than hydrogen or fluorine, or'}{'sub': 3', '1', '6', '1', '6', '1', '6, 'Con the phenyl ring is other than hydrogen, halogen, C-Calkyl, C-Calkoxy, or C-Chaloalkyl, or'}{'sub': 4', '1', '6', '1', '6', '1', '6, 'Con the phenyl ring is other than hydrogen, halogen, C-Calkyl, C-Calkoxy, C-Chaloalkyl, amino, aminoalkyl or aminodialkyl, or'}{'sub': '5', 'Con the phenyl ring is other than hydrogen or halogen;'}provided that the compound is not one of the group consisting of:(S)-3-(4′-methylbenzenesulfonylamino)-tetrahydropyridin-2-one ...

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Номер записи: 30
08-08-2013 дата публикации

Preparation of Diazo and Diazonium Compounds

Номер: US20130203974A1
Автор: MYERS Eddie Leonard, Raines Ronald Thaddeus
Принадлежит:

A method for making diazo-compounds, diazonium salts thereof and other protected forms of these compounds. Diaz-compounds are prepared by reaction of a tertiary phosphine reagent carrying a reactive carbonyl group with an azide. The reaction can also generate an acyl triazene which can be converted thermally or by addition of base to form the diazo-compound or the acyl triazene can be isolated. The method is particularly useful for conversion of azides carrying one or more electron withdrawing groups to diazo-compounds. The method can be carried out in aqueous medium under mild conditions and is particularly useful for conversion of azido sugars to diazo-compound and diazonium salts thereof under physiological conditions. Tertiary phosphine reagents, particularly those that are water-soluble, and precursors for preparation of the reagents are provided. 2. The phosphine of wherein —ORis{'sup': 7', '7', '7', '7', '7, 'sub': '2', '(1) a-ON(R)group, a —O—NR′— CO—Rgroup or a —O—N(COR)—COR′, where each Ris an optionally substituted alkyl or aryl, or where the two Rgroups together form an optionally substituted 5-8 member heterocyclic ring having one or more heteroatoms or —CO— groups or both in the ring;'}{'sub': 2', '3', '2', '2, '(2) a phenyloxy group substituted with one or more halogens, hydroxy, nitro, alkyl, alkenyl, alkynyl, aryl, halogenated alkyl, hydroxy-substituted alkyl, amino-substituted alkyl, cyano, isocyano, thiocyano, isothiocyano, —SO, —SOR, —N(R), —COR, —COOR, —CON(R), —NR—CO—NR—, —CO—SR, —OR, or —SR, where each R, independently, is selected from hydrogen, alkyl, halogenated alkyl, alkenyl, alkynyl, aryl, halogenated aryl, heteroaryl, or heterocyclic groups, or two R together form a 5-8 member optionally substituted heterocyclic ring containing one or more heteroatoms, optionally one or more —CO— groups or both;'}{'sup': 5', '5, '(3) —O—Rwhere Ris an optionally substituted heterocylic or heteroaromatic group; or'}{'sub': 2', 'S', 'S', '3', '4', '9, '(4) ...

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Номер записи: 31
15-08-2013 дата публикации

2-ALKOXY-11-HYDROXYAPORPHINE DERIVATIVES AND USES THEREOF

Номер: US20130209362A1
Автор: Neumeyer John L., Si Yu-Gui, Sromek Anna W.
Принадлежит: The McLean Hospital Corporation

The invention features 2-alkoxy-11-hydroxyaporphine derivatives that selectively bind Dreceptors. The compounds are useful for imaging Dreceptors and for the treatment of diseases, such as Parkinson's disease, sexual dysfunction, and depressive disorders. 2. The compound of claim 1 , wherein Ris H claim 1 , CH claim 1 , CHCH claim 1 , CHCHCH claim 1 , CHCH═CH claim 1 , or cyclopropylmethyl.4. The compound of claim 1 , wherein Ris CH claim 1 , CHCH claim 1 , or CHCHCH; and Xis fluoromethyl claim 1 , difluoromethyl claim 1 , trifluoromethyl claim 1 , 2-fluoroethyl claim 1 , 1-fluoroethyl claim 1 , 1 claim 1 ,2-difluoroethyl claim 1 , 2 claim 1 ,2-difluoroethyl claim 1 , 2 claim 1 ,2 claim 1 ,2 claim 1 ,-trifluoroethyl claim 1 , 1 claim 1 ,2-difluoroethylene claim 1 , 2 claim 1 ,2-difluoroethylene claim 1 , pentafluoroethyl claim 1 , 3-fluoro-n-propyl claim 1 , 3 claim 1 ,3-difluoro-n-propyl claim 1 , 3 claim 1 ,3 claim 1 ,3-trifluoro-n-propyl claim 1 , 3 claim 1 ,3 claim 1 ,3 claim 1 ,2 claim 1 ,2-pentafluoro-n-propyl claim 1 , heptafluoro-n-propyl claim 1 , 3 claim 1 ,3 claim 1 ,3-trifluoro-1-propene claim 1 , 3 claim 1 ,3 claim 1 ,3-trifluoro-1-propyne claim 1 , iodomethyl claim 1 , iodoethyl claim 1 , or iodopropyl.5. The compound of claim 1 , wherein said Cfluoroalkyl comprises a radioactive fluorine atom.7. The compound of claim 6 , wherein Rt is H claim 6 , CH claim 6 , CHCH claim 6 , CHCHCH claim 6 , CHCH═CH claim 6 , or cyclopropylmethyl.8. The compound of claim 6 , wherein Zis a radioactive fluorine atom.9. The compound of claim 1 , wherein said compound is selected from R(−2-(trifluoromethoxy)-11-hydroxy-N-methyl-noraporphine claim 1 , R(−)-2-(fluoromethoxy)-11-hydroxy-N-methyl-noraporphine claim 1 , R(−)-2-(2-fluoroethoxy)-11-hydroxy-N-methyl-noraporphine claim 1 , R(−)-2-(3-fluoro-n-propanoxy)-11-hydroxy-N-methyl-noraporphirte claim 1 , R(−)-2-(trifluoromethoxy)-11-hydroxy-N-ethyl-noraporphirte claim 1 , R(−)-2-(fluoromethoxy)-11-hydroxy-N-ethyl- ...

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Номер записи: 32
15-08-2013 дата публикации

HIGH TEMPERATURE LACTAM NEUTRALISATION

Номер: US20130211038A1
Автор: Baur Henricus Anna Christiaan, Guit Rudolf Philippus Maria, Oevering Hendrik
Принадлежит: DSM IP ASSETS B.V.

The invention relates to a method for preparing a lactam in a continuous process, comprising forming the lactam and ammonium sulphate by contacting a lactam sulphate contained in an acidic liquid with ammonia, during which forming of lactam heat of reaction is generated, which heat is partially or fully recovered, wherein ammonia is brought into contact with the acidic liquid as part of a liquid aqueous ammonia solution, and wherein the contacting takes place at a temperature of at least 120° C., and wherein the average residence time at a temperature of at least 120° C. is at most 15 minutes, and wherein the ammonium sulphate remains dissolved in a liquid phase during said residence time. 1. Method for preparing a lactam in a continuous process , comprising forming the lactam and ammonium sulphate by contacting a lactam sulphate contained in an acidic liquid with ammonia , during which forming of lactam heat of reaction is generated , which heat is partially or fully recovered , wherein ammonia is brought into contact with the acidic liquid as part of a liquid aqueous ammonia solution , wherein the contacting takes place at a temperature of at least 120° C. , and wherein the average residence time at a temperature of at least 120° C. is at most 15 minutes , and wherein the ammonium sulphate remains dissolved in a liquid phase during said residence time.2. Method according to claim 1 , wherein the heat is partially or fully used for steam generation claim 1 , preferably steam having a super-atmospheric pressure.3. Method according to claim 2 , wherein the heat is recovered by transferring the heat to a water stream via a heat exchanger claim 2 , which water stream is converted into a steam stream.4. Method according to claim 2 , wherein heat is transferred from product stream comprising lactam and ammonium sulphate claim 2 , and the product stream is thereafter subjected to (further) cooling to a temperature below 120° C. claim 2 , preferably below 100° C. claim 2 , ...

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Номер записи: 33
15-08-2013 дата публикации

New process for the resolution of enantiomers of (3,4 dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl)nitrile and application in the synthesis of ivabradine

Номер: US20130211070A1
Автор: Daniel Dron, Eric Gojon, Jean-Michel Lerestif, Jean-Pierre Lecouve, Maryse Phan
Принадлежит: Laboratoires Servier SAS

Process for the optical resolution of the compound of formula (I): by chiral chromatography. Application in the synthesis of ivabradine, of its addition salts with a pharmaceutically acceptable acid and of their hydrates.

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Номер записи: 34
15-08-2013 дата публикации

METHOD FOR MAKING ALPHA-AMINO-EPSILON-CAPROLACTAM USING MIXED SUPER CRITICAL FLUIDS

Номер: US20130211071A1
Автор: Berry William W., Sutterlin William Rusty, Tegen Mark G.
Принадлежит: INVENTURE RENEWABLES, INC.

The present invention can involve a method of synthesizing α-amino-ε-caprolactam. The method can comprise heating a salt of L-lysine in a solvent comprising an alcohol under Super Critical Fluid conditions. The methods can comprise heating a salt of L-lysine in a solvent comprising an alcohol and deaminating the reaction product. In various embodiments, the invention can include methods of converting biomass into nylon 6. The methods can comprise heating L-lysine in a solvent comprising an alcohol to produce α-amino-ε-caprolactam, deaminating to produce ε-caprolactam and polymerizing into nylon 6, wherein the L-lysine is derived from biomass. In other embodiments, the present invention can include methods of making nylon 6. The methods can comprise synthesizing ε-caprolactam and then polymerizing, wherein the ε-caprolactam is derived from L-lysine. 1. A process for synthesizing a α-amino -ε-caprolactam , the process comprising:heating a salt of lysine in a solvent comprising: an alcohol, a water or an alcohol and a water, without the presence of a catalyst, at a temperature of about 235° C. to about 320° C., to produce the α-amino-ε-caprolactam.2. The process of according to claim 1 , further comprising:(a) purifying the α-amino-ε-caprolactam; or(b) crystallizing the α-amino-ε-caprolactam.3. (canceled)4. The process of claim 1 , wherein the lysine is L-lysine.5. The process of claim 1 , wherein the alcohol has from 2 to 6 carbons.6. The process of claim 1 , wherein the alcohol comprises a diol claim 1 , a triol claim 1 , a glycol claim 1 , or a combination thereof.78and . (canceled)9. The process of claim 1 , wherein the alcohol is selected from the group consisting of an ethanol claim 1 , a 1-propanol claim 1 , a 1-butanol claim 1 , a 1-pentanol claim 1 , a 1-hexanol claim 1 , a 1 claim 1 ,2-propanediol claim 1 , and mixtures thereof.10. The process of claim 1 , wherein the alcohol comprises a methanol claim 1 , an ethanol claim 1 , a butanol or a 1 claim 1 ,2- ...

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Номер записи: 35
15-08-2013 дата публикации

CAPROLACTAM RECOVERY WITH MEMBRANE TREATMENT

Номер: US20130211072A1
Автор: Avramescu Maria Elena, Tinge Johan Thomas
Принадлежит:

The invention relates to a process for treating an aqueous solution containing ε-caprolactam, ammonium sulphate and one or more other impurities, comprising one or more organic impurities from a caprolactam production process and optionally other salts than ammonium sulphate, by means of a membrane process, thereby obtaining a retentate and a permeate, in which process the membrane used is selected from the group of polyether sulphone membranes, sulphonated polyether sulphone membranes, polyester membranes, polysulphone membranes, aromatic polyamide membranes, polyvinyl alcohol membranes, polypiperazine membranes, cellulose acetate membranes, titanium oxide membranes, zirconium oxide membranes and aluminium oxide membranes, having a molecular weight cut off in the range of 100-1000 g/mol; and wherein more than 60 wt. % of the caprolactam in the aqueous solution is passed through a membrane to the permeate side, to obtain a purified caprolactam containing permeate stream, and wherein at least 50 wt. % of the organic impurities are retained in the retentate solution.

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Номер записи: 36
15-08-2013 дата публикации

INDENOPYRIDINE DERIVATIVES

Номер: US20130211089A1
Автор: QU Bo, SAHA Anjan, SAVOIE Jolaine, WEI Xudong
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

Disclosed is a compound of formula (I) 2. The compound of formula (I) of in free-base form.3. The compound of formula (I) of in the form of a salt.4. The compound of formula (I) of claim 3 , wherein the salt is selected from chloride claim 3 , bromide claim 3 , iodide claim 3 , sulfonate claim 3 , triflate claim 3 , and methanesulfonate.5. The compound of formula (I) of in the form of a hydrogen chloride salt.7. The method of claim 7 , wherein the compound of formula (I) is in the form of a hydrogen chloride salt claim 7 , and the salt-forming acid is hydrochloric acid.9. The method claim 8 , wherein the compound of formula (I) is in the form of a hydrogen chloride salt claim 8 , and the salt-forming acid is hydrochloric acid. This application relates to indenopyridine derivatives. The indenopyridine derivatives of the invention are useful as intermediates for the preparation of pharmaceutically active compounds such as 11-β-hydroxysteroid hydrogenase type 1 (11-β-HSD1) inhibitors.Aryl- and heteroarylcarbonyl derivatives of hexahydroindenopyridines are reportedly useful as inhibitors of 11-β-hydroxysteroid hydrogenase type 1 (“11-β-HSD1”) and for treatment of disorders associated with 11β-HSD1 activity including, for example, diabetes mellitus (e.g., type II diabetes), obesity, symptoms of metabolic syndrome, glucose intolerance, hyperglycemica (see, e.g., WO 2011/057054).The aryl- and heteroarylcarbonyl derivatives of hexahydroindenopyridines can be prepared, for example, from nitrile-substituted hexahydroindenopyridines as described in WO 2011/057054. In one method described in WO 2011/057054, the intermediate (4aR,9aS)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridine-6-carbonitrile (A) is allowed to react with 1H-benzoimidazole-5-carboxylic acid (B) followed by reaction with hydrogen chloride to provide the 11-β-HSD1 inhibitor (4a-R,9a-S)-1-(1H-benzoimidazole-5-carbonyl)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridine-6-carbonitrile (C) as depicted below:Methods ...

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Номер записи: 37
22-08-2013 дата публикации

5HT2C RECEPTOR MODULATORS

Номер: US20130217676A1
Автор: SMITH BRIAN, Smith Jeffrey
Принадлежит:

The present invention relates to novel compounds of Formula (I): 112.-. (canceled)13. A composition comprising (R)-8-chloro-1-methyl-2 ,3 ,4 ,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt thereof and ethyl acetate.15. The process of claim 14 , further comprising the step of: forming a pharmaceutically acceptable salt of a compound of Formula H.16. The process of claim 14 , further comprising the step of: preparing a composition comprising a compound of Formula H.17. The process of claim 15 , further comprising the step of: preparing a composition comprising a pharmaceutically acceptable salt of a compound of Formula H.18. A process for preparing 8-chloro-1-methyl-2 claim 15 ,3 claim 15 ,4 claim 15 ,5-tetrahydro-1H-3-benz azepine comprising the step of: deprotecting N-trifluoroacetyl-8-chloro-1-methyl-2 claim 15 ,3 claim 15 ,4 claim 15 ,5-tetrahydro-1H-3-benzazepine to form 8-chloro-1-methyl-2 claim 15 ,3 claim 15 ,4 claim 15 ,5-tetrahydro-1H-3-benzazepine.19. The process of claim 18 , wherein the N-trifluoroacetyl-8-chloro-1-methyl-2 claim 18 ,3 claim 18 ,4 claim 18 ,5-tetrahydro-1H-3-benzazepine is prepared by a process comprising the step of: hydrogenating N-trifluoroacetyl-8-chloro-1-methylene-2 claim 18 ,3 claim 18 ,4 claim 18 ,5-trihydro-1H-3-benzazepine.20. The process of claim 19 , wherein the N-trifluoroacetyl-8-chloro-1-methylene-2 claim 19 ,3 claim 19 ,4 claim 19 ,5-trihydro-1H-3-benzazepine is prepared by a processing the step of: reacting N-allyl claim 19 , N-trifluoroacetyl-2-iodo-4-chlorophenethylamine under conditions suitable for a Heck coupling reaction.21. The process of claim 18 , further comprising the step of: forming a pharmaceutically acceptable salt of the 8-chloro-1-methyl-2 claim 18 ,3 claim 18 ,4 claim 18 ,5-tetrahydro-1H-3-benzazepine.22. The process of claim 18 , further comprising the step of: preparing a composition comprising the 8-chloro-1-methyl-2 claim 18 ,3 claim 18 ,4 claim 18 ,5-tetrahydro-1H-3-benzazepine. ...

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Номер записи: 38
29-08-2013 дата публикации

CARBOXAMIDE BIOISOSTERES OF OPIATES

Номер: US20130225628A1
Автор: WENTLAND Mark P
Принадлежит: RENSSELAER POLYTECHNIC INSTITUTE

A compound of formula I is disclosed. 111-. (canceled)13. A method according to wherein said disease or condition is chosen from the group consisting of pain claim 12 , pruritis claim 12 , diarrhea claim 12 , irritable bowel syndrome claim 12 , gastrointestinal motility disorder claim 12 , obesity claim 12 , respiratory depression claim 12 , convulsions claim 12 , coughing claim 12 , hyperalgesia claim 12 , inflammation claim 12 , osteoarthritis and drug addiction.14. A method according to wherein said drug addiction is selected from heroin claim 13 , cocaine claim 13 , nicotine claim 13 , amphetamine and alcohol addiction.15. A method according to claim 13 , wherein the condition is pain and the composition further comprises an effective amount of an opioid.16. A method according to claim 13 , wherein the condition is osteoarthritis and the composition further comprises an effective amount of an opioid.1732-. (canceled)33. A method according to claim 12 , wherein Rand Rare hydrogen.34. A method according to claim 12 , wherein Ris —OH claim 12 , —CHO claim 12 , —CONH claim 12 , —CON(H)CHCONH claim 12 , —CON(H)CHCHCONH claim 12 , —CON(H)CHCOOH claim 12 , or —CON(H)CHCHCOOH; or Rand Rtogether with the atoms to which they are attached forms a —OCHO— fused ring.35. A method according to claim 12 , wherein Ris H.39. A method according to wherein Ris in the para position relative to B and Ris hydrogen or methyl; or Rand Rtogether with the atoms to which they are attached claim 38 , and a fragment selected from —OCHO— or —OCHCHO— claim 38 , form a ring.44. A method according to wherein Ris in the para position relative to B and Ris hydrogen.45. A method according to claim 12 , wherein Aris phenyl and one of Ror Ris in the para position relative to B. This application is a divisional application of U.S. patent application Ser. No. 13/069,104, filed Mar. 22, 2011, now allowed. U.S. patent application Ser. No. 13/069,104 claims priority of U.S. provisional applications 61/316 ...

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Номер записи: 39
29-08-2013 дата публикации

PRODUCTION OF CAPROLACTAM FROM ADIPIC ACID

Номер: US20130225785A1
Автор: DIAS ERIC L., Jiang Hong, Longmire James, Murphy Vincent J.
Принадлежит: Rennovia, Inc.

Processes are disclosed for the conversion of adipic acid to caprolactam employing a chemocatalytic reaction in which an adipic acid substrate is reacted with ammonia and hydrogen, in the presence of particular heterogeneous catalysts and employing unique solvents. The present invention also enables the conversion of other adipic acid substrates, such as mono-esters of adipic acid, di-esters of adipic acid, mono-amides of adipic acid, di-amides of adipic acid, and salts thereof to caprolactam. Solvents useful in the process that do not react with ammonia are also disclosed. Catalyst supports are disclosed which catalyze the reaction of the substrate with ammonia in the absence of added metal. Metals on the catalyst supports comprise ruthenium (Ru), rhodium (Rh), palladium (Pd), osmium (Os), iridium (Ir), and/or platinum (Pt). Heterogeneous catalysts comprising ruthenium (Ru) and rhenium (Re) on titania and/or zirconia supports are also disclosed. Further, disclosed are products produced by such processes, as well as products producible from such products. 1. A process for preparing a caprolactam product , the process comprising chemocatalytically converting an adipic acid substrate to a caprolactam product , wherein the step of chemocatalytically converting the adipic acid substrate to the caprolactam product comprises reacting the adipic acid substrate with hydrogen and ammonia in the presence of a heterogeneous catalyst and a solvent comprising tert-butanol.3. The process of or , wherein reacting the adipic acid substrate with hydrogen and ammonia in the presence of the heterogeneous catalyst and solvent comprises:a) combining the adipic acid substrate, the ammonia, the heterogeneous catalyst, and solvent; and,b) contacting the combined adipic acid substrate, ammonia, heterogeneous catalyst, and solvent with hydrogen.4. The process of or , wherein reacting the adipic acid substrate with hydrogen and ammonia in the presence of the heterogeneous catalyst and solvent ...

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Номер записи: 40
05-09-2013 дата публикации

4-HYDROXYBENZOMORPHANS

Номер: US20130231361A1
Автор: WENTLAND Mark P.
Принадлежит: Rensselaer Polytechnic Institue

4-Hydroxybenzomorphans containing carboxamide or thiocarboxamide at the 3-position are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications. A compound of formula This application is a continuation application of U.S. application Ser. No. 11/760,039, filed Jun. 8, 2007, which was a divisional application of U.S. application Ser. No. 11/266,651, filed Nov. 3, 2005, and issued as U.S. Pat. No. 7,262,298 on Aug. 28, 2007. U.S. application Ser. No. 11/266,651 claims priority from U.S. Provisional Application 60/625,348 filed Nov. 5, 2004. The entire disclosures of each of the prior applications are hereby incorporated herein by reference.The invention relates to 4-hydroxybenzomorphans substituted at the 3-position with carboxamide or thiocarboxamide. The compounds are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives, anti-cocaine, and anti-addiction medications.Opiates have been the subject of intense research since the isolation of morphine in 1805, and thousands of compounds having opiate or opiate-like activity have been identified. Many opioid receptor-interactive compounds including those used for producing analgesia (e.g., morphine) and those used for treating drug addiction (e.g., naltrexone and cyclazocine) have been employed in human therapy. Almost all therapeutically useful opioids in the benzazocine and morphinane classes have a phenolic hydroxyl group (OH) at a position which is numbered “8” in the numbering system used for 2,6-methano-3-benzazocines [e.g., cyclazocine and EKC (ethylketocyclazocine)] and which is numbered “3” in the numbering system used for morphinanes (e.g., morphine).Although the compounds of the present invention do not possess the furan ring of the morphinans, the morphinan numbering system will be used:2,6-Methano-3-benzazocines are also known as benzomorphans, and this terminology will be used interchangeably herein.Until the publications of Wentland et al ...

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Номер записи: 41
12-09-2013 дата публикации

LACTAM DERIVATIVES USEFUL AS OREXIN RECEPTOR ANTAGONISTS

Номер: US20130237525A1
Автор: Aissaoui Hamed, Boss Christoph, Brotschi Christine, Heidmann Bibia, Sifferlen Thierry, Williams Jodi T.
Принадлежит: ACTELION PHARMACEUTICALS LTD.

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

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Номер записи: 42
12-09-2013 дата публикации

PREPARATION OF 6-AMINOCAPROIC ACID FROM ALPHA-KETOPIMELIC ACID

Номер: US20130237698A1
Автор: Menke Hildegard Henna, Raemakers-Franken Petronella Catharina, Schürmann Martin, Trefzer Axel Christoph, Turk Stefanus Cornelis Hendrikus
Принадлежит: DSM IP ASSETS B.V.

The invention is directed to a method for preparing 6-aminocaproic acid, comprising decarboxylating alpha-aminopimelic acid, using at least one biocatalyst comprising an enzyme having alpha-aminopimelic acid decarboxylase activity. The invention is further directed to a method for preparing caprolactam from 6-aminocaproic acid prepared by said method, to a host cell suitable for use in a method according to the invention and to a polynucleotide encoding a decarboxylase that may be used in a method according to the invention. 1. Method for preparing 6-aminocaproic acid , comprising decarboxylating alpha-aminopimelic acid , using at least one biocatalyst comprising an enzyme having alpha-aminopimelic acid decarboxylase activity , wherein said enzyme comprises an amino acid sequence selected from the group of sequences represented by any of the SEQUENCE ID NO's: 2 , 5 , 8 and 11 and homologues of said sequences having alpha-aminopimelic acid decarboxylase activity.2. Method according to claim 1 , wherein said enzyme comprises a homologue having at least 40% claim 1 , preferably at least 60% claim 1 , in particular at least 80% claim 1 , more in particular at least 90% sequence identity with any of the SEQUENCE ID NO's: 2 claim 1 , 5 claim 1 , 8 and 11.3. Method according to claim 1 , comprising preparing alpha-aminopimelic acid from alpha-ketopimelic acid.4. Method according to claim 3 , wherein the preparation of alpha-aminopimelic acid is catalysed by a biocatalyst in the presence of an amino donor claim 3 , said biocatalyst having catalytic activity with respect to the transamination or the reductive amination of alpha-ketopimelic acid.5. Method according to claim 4 , wherein the biocatalyst comprises an enzyme having catalytic activity with respect to the transamination or the reductive amination of alpha-ketopimelic acid selected from the group of aminotransferases (E.C. 2.6.1) and amino acid dehydrogenases (E.C. 1.4.1).6. Method according to claim 5 , wherein the ...

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Номер записи: 43
19-09-2013 дата публикации

Novel Antiviral Compounds

Номер: US20130245049A1
Автор: Chaltin Patrick, Christ Frauke, De Maeyer Marc, Debyser Zeger, Marchand Arnaud, Marchand Damien, Voet Arnout
Принадлежит: Katholieke Universiteit Leuven

The present invention relates to compounds of formula (A), as further defined herein, having antiviral activity, more specifically HIV (Human Immunodeficiency Virus) replication inhibiting properties. The invention also relates to pharmaceutical compositions comprising an effective amount of such compounds as active ingredients. The invention further relates to the use of such compounds, optionally combined with one or more other drugs having antiviral activity, for the treatment of animals suffering from viral infections, in particular HIV infection. 13. A compound according to wherein Ris COOR claim 1 , wherein Ris selected from hydrogen and alkyl.14. A compound according to wherein Ris COOH.15. A compound according to wherein Ris selected from alkyl claim 1 , aryl; heterocycle or arylalkyl; wherein in the alkyl moiety of said arylalkyl one —CH— is optionally replaced by —NH— claim 1 , —O— claim 1 , or —S—; and wherein said aryl claim 1 , heterocycle claim 1 , or arylalkyl can be unsubstituted or substituted with one or more halogen claim 1 , OH or alkyl.16. A compound according to wherein Ris selected from C-Calkyl claim 1 , phenyl; phenylalkyl claim 1 , heteroaryl claim 1 , O-phenyl; S-phenyl or NH-phenyl and wherein said phenyl; phenylalkyl claim 1 , heteroaryl claim 1 , O-phenyl; S-phenyl or NH-phenyl can be unsubstituted or substituted with one or more halogen claim 1 , OH or C-Calkyl.17. A compound according to wherein one of Rand Ris hydrogen and the other one of Rand Ris selected from the group consisting of C-Calkyl and C-C-alkoxy claim 1 , said C-Calkyl and C-Calkoxy being optionally substituted with up to three F atoms.18. A compound according to wherein the dotted line “a” forms a double bond claim 1 , the dotted line “b” does not form a double bond claim 1 , Ris not present and Ris selected from hydrogen claim 1 , hydroxyl claim 1 , alkyl or aryl claim 1 , wherein said alkyl and aryl can be unsubstituted or substituted with one or more halogens.19. A ...

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Номер записи: 44
03-10-2013 дата публикации

NITRIC OXIDE AND ITS BIOMEDICAL SIGNIFICANCE

Номер: US20130261146A1
Автор: Kream Richard M., Mantione Kirk, Stefano George B., Zhu Wei
Принадлежит: THE RESEARCH FOUNDATION OF STATE UNIVERSITY OF NEW YORK

A pharmaceutical composition for stimulating nitric oxide production in mammalian cells, the pharmaceutical composition including at least one compound selected from a group consisting of: 2,3-dihydroxypropyl oleate; bis(m-phenoxyphenyl) ether; 6-acetyl-5,6,6a,7-tetrahydro-4H-dibezo(de,g)quinoline; and (+)-N-(p-(2-methylbutoxy)benzylidene)-4-(2-methylbutyl)aniline. 1. A pharmaceutical composition for stimulating nitric oxide production in mammalian cells , the pharmaceutical composition comprising:at least one compound selected from a group consisting of: 2,3-dihydroxypropyl oleate; bis(m-phenoxyphenyl)ether; 6-acetyl-5,6,6a,7-tetrahydro-4H-dibezo(de,g)quinoline; and (+)-N-(p-(2-methylbutoxy)benzylidene)-4-(2-methylbutyl)aniline.2. The pharmaceutical composition of claim 1 , wherein the at least one compound includes 2 claim 1 ,3-dihydroxypropyl oleate.3. The pharmaceutical composition of claim 1 , wherein the at least one compound includes bis(m-phenoxyphenyl)ether.4. The pharmaceutical composition of claim 1 , wherein the at least one compound includes 6-acetyl-5 claim 1 ,6 claim 1 ,6a claim 1 ,7-tetrahydro-4H-dibezo(de claim 1 ,g)quinoline.5. The pharmaceutical composition of claim 1 , wherein the at least one compound includes (+)-N-(p-(2-methylbutoxy)benzylidene)-4-(2-methylbutyl)aniline.6Allium vineale, Salix alba, AgropyrumPetroselinium crispum, Taraxacum officinale, Sesamum indicum, MedicagoPiper methysticum, AnthemisTurnera diffusa, Verbascum densiflorum, OcimumMaranta arundinaceae, Coriandrum sativum, Artemesia dracunculus, Lavendula augustifolia, Mentha pulegium, Centella asiatica, Ginko bilobaVitis vinifera.. The pharmaceutical composition of claim 1 , wherein the at least one compound is derived/extracted from at least one plant species selected from the group consisting of spp. claim 1 , spp. claim 1 , spp. claim 1 , spp. claim 1 , and7. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has the ability to stimulate ...

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Номер записи: 45
03-10-2013 дата публикации

CATALYST COMPLEX WITH CARBENE LIGAND

Номер: US20130261296A1
Автор: HUANG Jinkun, NOLAN Steven P.
Принадлежит:

Catalytic complexes including a metal atom having anionic ligands, at least one nucleophilic carbene ligand, and an alkylidene, vinylidene, or allenylidene ligand. The complexes are highly stable to air, moisture and thermal degradation. The complexes are designed to efficiently carry out a variety of olefin metathesis reactions. 2. A catalytic complex according to wherein Ar is η—CHN or an alkyl substituted derivative thereof claim 1 , p-cymene claim 1 , fluorene claim 1 , or indene.3. A catalytic complex according to wherein the complex is linked to a solid support by means of a link between said anionic ligand and said solid support.4. A catalytic complex according to wherein the complex is linked to a solid support by means of a link between said nucleophilic carbene and said solid support.5. A method of performing ring closing metathesis claim 1 , said method comprising contacting a diene with a catalytic complex of under conditions appropriate claim 1 , and for a time sufficient to produce a cyclic alkene.6. A method according to wherein Ar is η—CHN or an alkyl substituted derivative thereof claim 5 , p-cymene claim 5 , fluorene claim 5 , or indene.8. A method as in wherein the terminal acetylene is substituted at the y-position with hydrogen claim 7 , a vinyl claim 7 , group or a phenyl group claim 7 , wherein the vinyl or phenyl group is optionally substituted with one or more moieties selected from C-Calkyl claim 7 , C-Calkoxy claim 7 , phenyl claim 7 , or a functional group selected from chloride claim 7 , bromide claim 7 , iodide claim 7 , fluoride claim 7 , nitro claim 7 , or dimethylamine.9. A method as in wherein the precursor species is formed from a dimer of the formula [ArMXX]by exposing the dimer to a nucleophilic carbene in a suitable solvent. This application is a continuation of application Ser. No. 13/041,573, filed Mar. 7, 2011, which is continuation of U.S. Pat. No. 7,902,389, issued Mar. 8, 2011, which is a continuation of U.S. Pat. No. 7, ...

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Номер записи: 46
03-10-2013 дата публикации

PROCESS FOR THE SYNTHESIS OF IVABRADINE AND ADDITION SALTS THEREOF WITH A PHARMACEUTICALLY ACCEPTABLE ACID

Номер: US20130261298A1
Автор: Grandjean Mathieu, LE FLOHIC Alexandre
Принадлежит: LES LABORATOIRES SERVIER

Process for the synthesis of ivabradine of formula (I): 2. The process according to claim 1 , wherein the coupling agent used to carry out the reaction for lactamisation of the compound of formula (VI) is selected from oxalyl chloride claim 1 , thionyl chloride claim 1 , N claim 1 ,N-dicyclohexylcarbodiimide (DCC) claim 1 , 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) claim 1 , N claim 1 ,N-carbonyldiimidazole (CDI) claim 1 , 1-propanephosphonic acid cyclic anhydride (T3P) and 1-(methylsulphonyl)-1H-benzotriazole.3. The process according to claim 2 , wherein the coupling agent used to carry out the reaction for lactamisation of the compound of formula (VI) is thionyl chloride.4. The process according to claim 3 , wherein the amount of thionyl chloride used to carry out the reaction for lactamisation of the compound of formula (VI) is between 1 and 5 equivalents claim 3 , inclusive.5. The process according to claim 1 , wherein the base used to carry out the reaction for lactamisation of the compound of formula (VI) is selected from triethylamine claim 1 , diisopropylethylamine and pyridine.6. The process according to claim 5 , wherein the base used to carry out the reaction for lactamisation of the compound of formula (VI) is triethylamine.7. The process according to claim 1 , wherein the organic solvent used to carry out the reaction for lactamisation of the compound of formula (VI) is selected from dichloromethane claim 1 , tetrahydrofuran claim 1 , acetonitrile claim 1 , acetone and toluene.8. The process according to claim 7 , wherein the organic solvent used to carry out the reaction for lactamisation of the compound of formula (VI) is dichloromethane.9. The process according to claim 1 , wherein the reaction for lactamisation of the compound of formula (VI) is carried out at a temperature between 0° C. and 40° C. claim 1 , inclusive.12. The process according to claim 10 , wherein the base used to carry out the alkylation reaction between the compound of ...

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Номер записи: 47
17-10-2013 дата публикации

Compound Having Activity Of Blocking NMDA Receptor Channel, and Pharmaceutical Agent Using The Same

Номер: US20130274248A1
Автор: Igarashi Kazuei, Takayama Hiromitsu
Принадлежит:

[PROBLEMS] To provide a novel compound having NMDA receptor channel blocking activity, and also a pharmaceutical agent comprising the compound. 23-. (canceled)56-. (canceled)11. (canceled) This application is a continuation of U.S. patent application Ser. No. 12/298,564, filed Oct. 27, 2008, which in turn is a National Stage Application of PCT/JP2007/059108, filed Apr. 26, 2007, which claims priority to JP 2006-124858 filed Apr. 28, 2006.The present invention relates to compounds having activity of blocking an NMDA receptor channel, and pharmaceutical agents using the same.Cerebrovascular disorders such as cerebral infarction and cerebral hemorrhage, and diseases that strongly affect higher brain functions such as Alzheimer's disease exhibit poor prognosis, and bring decreased QOL (Quality of Life) on elderly people and further psychological stress on caretakers. Several pharmaceutical agents for improving brain functions have been developed and marketed to date. However, a sufficient therapeutic effect has not yet been obtained by using any of them. Thus, new and more effective agents for improving brain functions and agents for preserving brain functions are expected to be developed rapidly.Meanwhile, N-methyl-D-aspartic acid (hereafter referred to as “NMDA”) receptor, which is one kind of receptor for glutamic acid that is an excitatory neurotransmitter, is known to transport Ca to neuron and thereby strongly participate in memory formation and in development of symptoms in cerebral ischemia.The present inventors already reported in the Non-Patent Document 1 shown below that NMDA receptors expressed on followed by contacting with a plurality of polyamine derivatives and measuring a change in electric potential resulted in a finding that a polyamine derivative having an anthraquinone skeleton showed a significant channel blocking activity (see Non-Patent Document 1 shown below).However, even in the technology described in the above-mentioned Non-Patent Document 1, ...

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Номер записи: 48
17-10-2013 дата публикации

PREMATURE-TERMINATION-CODONS READTHROUGH COMPOUNDS

Номер: US20130274283A1
Автор: BERTONI Carmen, DAMOISEAUX Robert, DU Liutao, GATTI Richard A., Jung Michael, KU Jin-Mo, LAI Chih-Hung
Принадлежит: The Regents of the University of California

Premature termination codons readthrough compounds, composition thereof, and methods of making and using the same are provided. 1. A system for high throughput assay for readthrough compound having the ability to read through premature termination codons (PTCs) in RNA , comprising high throughput reading trays and wells containing a plasmid ,wherein the plasmid comprises a fragment of ATM gene that contains a PTC mutation, which fragment being flanked by a sequence that initiates transcription of:a) a myc epitope,b) the ATM fragment, andc) a V5 epitope;wherein the assay is based on a coupled protein transcription/translation (PTT) reaction that is driven by the plasmid;wherein the reading trays are coated with an antibody to the myc epitope; andwherein an antibody to V5 is provided for attaching to readthrough proteins expressing the V5 epitope.2. The system of claim 1 , wherein the V5 epitope is conjugated to horseradish peroxidase.3. The system of claim 1 , further comprising a robot.4. A method of screening for readthrough compounds having the ability to read through premature termination codons (PTCs) in RNA claim 1 , comprising: a) a myc epitope,', 'b) the ATM fragment, and', 'c) a V5 epitope;, 'providing a plasmid template to a reaction well having a test compound to cause a coupled protein transcription/translation (PTT) reaction to occur to generate a PTT reaction product, the plasmid template comprising a fragment of ATM gene that contains a PTC mutation, which fragment being flanked by a sequence that initiates transcription ofadding the PTT reaction product to high throughput reading trays, which are coated with an antibody to the myc epitope to capture a protein fragment of the fragment of ATM gene,adding an antibody to the V5 epitope (V5 antibody) to wells in the reading trays,detecting the attachment of the V5 antibody to proteins in the PTT product, andidentifying the test compound as a readthrough compound if the attachment of the V5 antibody to ...

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Номер записи: 49
17-10-2013 дата публикации

PHENYL-TETRAHYDROISOQUINOLINE DERIVATIVES

Номер: US20130274287A1
Автор: Aebi Johannes, Amrein Kurt, Hornsperger Benoit, Kühn Bernd, Liu Yongfu, Maerki Hans P., Martin Rainer E., Mayweg Alexander V., Mohr Peter, Tan Xuefei
Принадлежит: Hoffmann-La Roche Inc.

The invention provides novel compounds having the general formula (I) 3. A compound according to claim 1 , wherein R claim 1 , R claim 1 , Rand Rare independently selected from H claim 1 , halogen claim 1 , cyano claim 1 , alkyl and haloalkyl.4. A compound according to claim 1 , wherein Ris H or halogen.5. A compound according to claim 1 , wherein Ris H claim 1 , alkyl or halogen.6. A compound according to claim 1 , wherein Ris H or halogen.7. A compound according to claim 1 , wherein Ris halogen claim 1 , cyano or haloalkyl.8. A compound according to claim 1 , wherein Ris cyano or haloalkyl.9. A compound according to claim 1 , wherein Ris haloalkyl.10. A compound according to claim 1 , wherein Ris H or halogen.11. A compound according to claim 1 , wherein Ris H.12. A compound according to claim 1 , wherein Ris H.13. A compound according to claim 1 , wherein Ris H or aryl substituted with R claim 1 , Rand R.14. A compound according to claim 1 , wherein Ris H.15. A compound according to claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare independently selected from H and alkyl.16. A compound according to claim 1 , wherein Ris H or alkyl.17. A compound according to claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , Rand Rare H.18. A compound according to claim 1 , wherein A is —(CRR)—NRR.19. A compound according to claim 1 , wherein A is —(CRR) claim 1 , —OR.20. A compound according to claim 1 , wherein Ris H.21. A compound according to claim 1 , wherein Ris H claim 1 , alky claim 1 , —S(O)R claim 1 , —S(O)NRR claim 1 , —C(O)R claim 1 , —C(O)ORor —C(O)NRR.22. A compound according to claim 1 , wherein in case A is{'sup': 13', '14', '15', '16', '16', '17', '17', '18', '17', '17', '17', '18, 'sub': p', '2', '2, '—(CRR)—NRR, then Ris H, —S(O)R, —S(O)NRR, —C(O)R, —C(O)ORor —C(O)NRR.'}23. A compound according to claim 1 , wherein in case A is{'sup': 13', '14', '16', '16', '17', '18, 'sub': 'p', '—(CRR)—OR, then Ris H, alkyl or —C(O)NRR.'}24. A ...

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Номер записи: 50
24-10-2013 дата публикации

Carbonyl propyl sulfuryl anthrapyridone sulfonic acid compounds and their preparation methods and applications

Номер: US20130276667A1
Автор: Feng Wang, Fengling Song, Jiangli Fan, Jinhe WU, Licheng Wang, Rong Zhang, Shaolei Li, Shiguo Sun, Xiaojun Peng, Zhi LONG
Принадлежит: Dalian University of Technology, Zhuhai Ninestar Management Co Ltd

The present invention relates to compounds shown in the general formula (I) or (III), the salts thereof or their mixtures, as well as their preparation method and application. In the general formula (I), X 1 is H or CO 2 H; X 2 is OH or phenyl group with 0-2 sulfonic acid substituents, and the sulfonic acid substituents are located at random positions of a benzene ring; when X 2 is OH, X 1 is H; when X 2 is phenyl group with 0-2 sulfonic acid substituents, X 1 is H or CO 2 H; n is an integer of 0-2; and in the general formula (III), n and m are respectively an integer of 0-2. The compounds and the mixtures not only have improved light resistance, ozone resistance and water resistance, but also have excellent water solubility and long-term stability in ink-jet ink.

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Номер записи: 51
24-10-2013 дата публикации

Modulators of Muscarinic Receptors

Номер: US20130281476A1
Автор: Bergeron Daniele M., Blanco Miguel Garcia-Guzman, Drutu Ioana, Hurley Dennis J., Makings Lewis R., Nakatani Akiko, Raffai Gabriel, Silina Alina, Termin Andreas P.
Принадлежит:

The present invention relates to modulators of muscarinic receptors. The present invention also provides compositions comprising such modulators, and methods therewith for treating muscarinic receptor mediated diseases. 171-. (canceled)73. The method according to claim 72 , wherein G is an optionally substituted bicyclic group of formula (III) in which ring B is absent.74. The method according to claim 73 , wherein Xis —(CH)—.75. The method according to claim 74 , wherein G is optionally substituted bicyclo[2.2.1]heptyl claim 74 , bicyclo[3.2.1]octyl claim 74 , bicyclo[3.3.1]nonyl claim 74 , bicyclo[2.2.2]octyl claim 74 , or bicyclo[2.2.1]heptanyl.76. The method according to claim 75 , wherein G is substituted with 1 to 2 substituents independently selected from Q claim 75 , and —C(O)—X-aliphatic claim 75 , where Xis absent claim 75 , —O— claim 75 , —NH— claim 75 , or —NQ- claim 75 , and the aliphatic group is optionally substituted with 1-3 substituents independently selected from Q.77. The method according to claim 73 , wherein Xis —N(Q)— or —N(C(O)—X-aliphatic) claim 73 , where Xis absent claim 73 , —O— claim 73 , —NH— claim 73 , or —NQ- claim 73 , and the aliphatic group is optionally substituted with 1-3 substituents independently selected from Q.78. The method according to claim 77 , wherein G is an optionally substituted tropane.79. The method according to claim 78 , wherein the tropane is substituted with Q claim 78 , or —C(O)—X-aliphatic claim 78 , where Xis absent claim 78 , —O— claim 78 , —NH— claim 78 , or —NQ- claim 78 , and the aliphatic group is optionally substituted with 1-3 substituents independently selected from Q.80. The method according to claim 78 , wherein the tropane is substituted at the tropane ring nitrogen atom with alkoxycarbonyl claim 78 , alkoxyalkoxycarbonyl claim 78 , heterocycloalkoxy carbonyl claim 78 , cycloalkoxycarbonyl claim 78 , alkoxyaryloxycarbonyl claim 78 , alkylaminocarbonyl claim 78 , haloalkoxy carbonyl claim 78 , ...

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Номер записи: 52
24-10-2013 дата публикации

PERIPHERAL OPIOID RECEPTOR ANTAGONISTS AND USES THEREOF

Номер: US20130281483A1
Автор: Lokhnauth John, Melucci Charles K.
Принадлежит: WYETH LLC

The present invention provides a compound of formula I: 118-. (canceled)20. The composition of claim 19 , wherein X is selected from the group consisting of the anion of a suitable BrØnsted acid claim 19 , a hydrogen halide claim 19 , a carboxylic acid claim 19 , a sulfonic acid claim 19 , a sulfuric acid claim 19 , a phosphoric acid claim 19 , chloride claim 19 , bromide claim 19 , iodide claim 19 , fluoride claim 19 , bisulfate claim 19 , tartrate claim 19 , nitrate claim 19 , citrate claim 19 , bitartrate claim 19 , carbonate claim 19 , phosphate claim 19 , malate claim 19 , maleate claim 19 , fumarate sulfonate claim 19 , methylsulfonate claim 19 , formate claim 19 , carboxylate claim 19 , sulfate claim 19 , methylsulfate and succinate.21. The composition of claim 19 , wherein Ris Caliphatic and Ris lower alkyl;{'sup': '1', 'optionally wherein Ris a (cycloalkyl)alkyl group or alkenyl group, or'}{'sup': 1', '2, 'optionally wherein Ris cyclopropyl methyl or allyl and Ris methyl.'}24. The composition of claim 23 , wherein X is selected from the group consisting of the anion of a suitable BrØnsted acid claim 23 , a hydrogen halide claim 23 , a carboxylic acid claim 23 , a sulfonic acid claim 23 , a sulfuric acid claim 23 , a phosphoric acid claim 23 , chloride claim 23 , bromide claim 23 , iodide claim 23 , fluoride claim 23 , bisulfate claim 23 , tartrate claim 23 , nitrate claim 23 , citrate claim 23 , bitartrate claim 23 , carbonate claim 23 , phosphate claim 23 , malate claim 23 , maleate claim 23 , fumarate sulfonate claim 23 , methylsulfonate claim 23 , formate claim 23 , carboxylate claim 23 , sulfate claim 23 , methylsulfate and succinate.25. The composition of claim 23 , wherein Ris Caliphatic and Ris lower alkyl;{'sup': '1', 'optionally wherein Ris a (cycloalkyl)alkyl group or alkenyl group, or'}{'sup': 1', '2, 'optionally wherein Ris cyclopropyl methyl or allyl and Ris methyl.'}28. The compound of claim 27 , wherein X is selected from the group consisting ...

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Номер записи: 53
07-11-2013 дата публикации

QUINOLINE DERIVATIVE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME

Номер: US20130296571A1
Автор: Baek Nam Joon, Choi Sang Zin, KIM Ki Hyun, Kim Soon Hoe, Lee Kang Ro, LEE Tae Ho, Son Miwon
Принадлежит: Dong-A ST Co., Ltd.

The present invention relates to a novel quinoline derivative compound, an optical isomer thereof, a pharmaceutically acceptable salt thereof, and a hydrate or a solvate thereof. The novel quinoline derivative compound, the optical isomer thereof, the pharmaceutically acceptable salt thereof, and the hydrate or the solvate thereof accelerates gastrointestinal movement, and thus can effectively prevent or treat gastrointestinal motility disorders.

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Номер записи: 54
21-11-2013 дата публикации

Salts of lorcaserin with optically active acids

Номер: US20130310369A1
Автор: Anna Shifrina, Anthony C. Blackburn, Jaimie Karyn Rueter, Scott Stim, William Lucas Betts, III, YUN Shan
Принадлежит: Arena Pharmaceuticals Inc

Salts of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine with optically active acids, and pharmaceutical compositions comprising them that are useful for, inter alia, weight management.

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Номер записи: 55
21-11-2013 дата публикации

Synthesis of therapeutic and diagnostic drugs centered on regioselective and stereoselective ring opening of aziridinium ions

Номер: US20130310555A1
Автор: Hyun-Soon Chong
Принадлежит: Illinois Institute of Technology

Stereoselective and regioselective synthesis of compounds via nucleophilic ring opening reactions of aziridinium ions for use in stereoselective and regioselective synthesis of therapeutic and diagnostic compounds.

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Номер записи: 56
21-11-2013 дата публикации

Methods including latent 1,3-dipole-functional compounds and materials prepared thereby

Номер: US20130310570A1
Автор: Frederic Friscourt, Geert-Jan Boons, Ngalle Eric Mbua, Petr A. Ledin
Принадлежит: University of Georgia Research Foundation Inc UGARF

Methods that include latent 1,3-dipole-functional compounds are disclosed herein. The latent 1,3-dipole-functional compound (e.g., an oxime) can be used to form an active 1,3-dipole-functional compound (e.g., a nitrile oxide) that can be used to react with a cyclic alkyne in a dipolar cycloaddition reaction.

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Номер записи: 57
28-11-2013 дата публикации

NON-HYGROSCOPIC SALTS OF 5-HT2C AGONISTS

Номер: US20130317005A1
Автор: Blackburn Anthony C., Shan Yun, Shifrina Anna, Stirn Scott
Принадлежит:

Salts of the 5-HT2C-receptor agonist (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, and dosage forms comprising them that are useful for, inter alia, weight management. 1. A salt selected from:(R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hemi-edisylate salt;(R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine phosphate salt;(R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine citrate salt;(R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hemi-oxalate salt;(R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine succinate salt; and(R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine oxoglutarate salt; andpharmaceutically acceptable salts, solvates and hydrates thereof.2. The salt according to claim 1 , that is (R)-8-chloro-1-methyl-2 claim 1 ,3 claim 1 ,4 claim 1 ,5-tetrahydro-1H-3-benzazepine hemi-edisylate salt.3. The salt according to claim 2 , having an X-ray powder diffraction pattern comprising peaks claim 2 , in terms of 20 claim 2 , at about 23.12° claim 2 , about 6.00° claim 2 , and about 19.70°.4. The salt according to claim 2 , having an X-ray powder diffraction pattern substantially as shown in .5. The salt according to claim 1 , that is (R)-8-chloro-1-methyl-2 claim 1 ,3 claim 1 ,4 claim 1 ,5-tetrahydro-1H-3-benzazepine phosphate salt.6. The salt according to claim 5 , having an X-ray powder diffraction pattern comprising peaks claim 5 , in terms of 20 claim 5 , at about 19.27° claim 5 , about 25.06° claim 5 , and about 25.77°.7. The salt according to claim 5 , having an X-ray powder diffraction patter substantially as shown in .8. The salt according to claim 1 , that is (R)-8-chloro-1-methyl-2 claim 1 ,3 claim 1 ,4 claim 1 ,5-tetrahydro-1H-3-benzazepine citrate salt hemihydrate.9. The salt according to claim 8 , having an X-ray powder diffraction pattern comprising peaks claim 8 , in terms of 20 claim 8 , at about 11.93° claim 8 , about 18.64° claim 8 , and about 24.52°.10. The salt according to claim 8 , ...

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Номер записи: 58
28-11-2013 дата публикации

TETRAHYDROISOQUINOLINE DERIVATIVE

Номер: US20130317010A1
Автор: HAMAGUCHI Wataru, KANEKO Osamu, KINOYAMA Isao, KOGANEMARU Yohei, MIYAZAKI Takehiro, SEKIOKA Ryuichi, WASHIO Takuya
Принадлежит: Astellas Pharma Inc

To provide an excellent agent for preventing or treating dementia and schizophrenia based on serotonin 5-HTreceptor regulating action, it was found that a tetrahydroisoquinoline derivative characterized by a structure in which an acylguanidino group binds to a N atom of a tetrahydroisoquinoline ring or the like, and a cyclic group binds to an unsaturated ring has a potent 5-HTreceptor regulating action and an excellent pharmacological action based on the regulating action and also discovered that the tetrahydroisoquinoline derivative is useful as an agent for treating or preventing dementia, schizophrenia, and the like, whereby the present invention has been completed. 2. The compound according to or a pharmaceutically acceptable salt thereof claim 1 ,{'sup': 1', '1', '2', '3', '4, 'wherein Rrepresents phenyl, pyridyl, or cycloalkyl which may be respectively substituted with group(s) selected from G, Rrepresents halogen, m represent 1, n represents 1, and both Rand Rrepresent H.'}3. The compound according to or a pharmaceutically acceptable salt thereof claim 1 ,{'sup': 1', '2', '3', '4, 'wherein Rrepresents phenyl which may be substituted with halogen or —O-(lower alkyl), Rrepresents H, F, Cl, or methyl, m represents 1, n represents 1, and both Rand Rrepresent H.'}4. The compound according to or a pharmaceutically acceptable salt thereof claim 1 ,{'sup': 1', '2', '3', '4, 'wherein Rrepresents pyridyl which may be substituted with halogen or —O-(lower alkyl), Rrepresents H, F, Cl, or methyl, m represents 1, n represents 1, and both Rand Rrepresent H.'}5. The compound according to or a pharmaceutically acceptable salt thereof claim 1 ,{'sup': 1', '2', '3', '4, 'wherein Rrepresents phenyl which may be substituted with halogen or —O-(lower alkyl), Rrepresents H, F, Cl, or methyl, m represents 1, n represents 1, and Rand Rform cyclopropane-1,1-diyl or cyclobutane-1,1-diyl together with the carbon atom binding thereto, as ethylene or trimethylene.'}6. A compound selected ...

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Номер записи: 59
12-12-2013 дата публикации

CROSS-LINKED CYCLIC AMINE COMPOUNDS AND AGENTS FOR PEST CONTROL

Номер: US20130331569A1
Автор: HAMAMOTO Isami, HANAI Daisuke, IWASA Takao, Kawaguchi Masahiro, Takahashi Jun, YANO Makio
Принадлежит: NIPPON SODA CO., LTD.

Cyclic amine compounds represented by formula (1) 116-. (canceled)19. Cyclic amine compounds according to claim 17 , wherein Cyrepresents a pyridazyl group substituted by halogen claim 17 , nitro claim 17 , or haloalkyl.20. Agents for pest control comprising at least one of the cyclic amine compounds of . The present invention relates to novel cyclic amine compounds and agents for pest control which contain these cyclic amine compounds or the like as active ingredients.Priority is claimed on Japanese Patent Application No. 2005-294126, filed Oct. 6, 2005, Japanese Patent Application No. 2005-294127, filed Oct. 6, 2005, Japanese Patent Application No. 2005-297803, filed Oct. 12, 2005, Japanese Patent Application No. 2005-297804, filed Oct. 12, 2005, Japanese Patent Application No. 2006-016877, filed Jan. 25, 2006, and Japanese Patent Application No. 2006-182314, filed Jun. 30, 2006, the contents of which are incorporated herein by reference.Although many compounds which have insecticidal/acaricidal activities are conventionally known, there are problems such as insufficient effect thereof, limitation of use thereof because of drug resistance problems, occurrence of phytotoxicity or contamination in plant bodies, or strong toxicity against mammalians, fish, or the like.As compounds with backbones similar to those of the compounds of the present invention, compounds represented by the formula below are known.In the formula, X represents —O—, —N(R)—, —S—, or the like and Rrepresents a substituted saturated heterocyclic group or the like. As a representative of such compounds, the compound represented by the formula below is known (refer to Patent document 1).Moreover, the compounds represented by the formula below are known.In the formula, X represents —CH— or the like; Z represents a bonding or the like; Rrepresents an optionally substituted aryl or an optionally substituted heteroaryl; and Rand Rrepresent —(CH)— or the like together. However, when Rand Rrepresent —(CH ...

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Номер записи: 60
19-12-2013 дата публикации

NOVEL MORPHINANS USEFUL AS ANALGESICS

Номер: US20130338182A1
Автор: Lawson John
Принадлежит: PHEONIX PHARMALABS, INC.

Compounds of Formula (I) are disclosed. 2. A compound or salt of claim 1 , wherein{'sub': 1', '2', '3', '4', '5', '6', '6a', '7', '8', '9', '11, 'R, R, R, R, R, R, R, R, R, R, and Rare independently selected from'}(i) hydrogen, hydroxyl, cyano, and halogen; and{'sub': 11', '12', '2', '11', '12', '11', '12', '11', '12', '1', '6, '(ii) hydrocarbyl and heteroatom-containing hydrocarbyl, each of which (ii) is unsubstituted or substituted with one or more substituents independently chosen from hydroxyl, amino, cyano, halogen, oxo, —COOH, —CONRR, —SONRR, and —NRCOR, where Rand Rare independently hydrogen and C-Calkyl; and'}{'sub': 10', '10', '11', '12', '2', '11', '12', '11', '12', '11', '12', '1', '6, 'Ris hydrocarbyl or carbon-linked, heteroatom-containing hydrocarbyl, which Ris unsubstituted or substituted with one or more substituents independently chosen from hydroxyl, amino, cyano, halogen, oxo, —COOH, —CONRR, —SONRR, and —NRCOR, where Rand Rare independently chosen from hydrogen and C-Calkyl.'}7. A compound or salt of claim 1 , where{'sub': 1', '2', '4', '5', '6', '6a', '7', '8', '9', '11, 'R, R, R, R, R, R, R, R, R, and Rare independently selected from'}(i) hydrogen, hydroxyl, cyano, and halogen; and{'sub': 1', '8', '2', '8', '3', '7', '0', '4', '11', '12', '2', '11', '12', '11', '12', '11', '12', '1', '6, '(ii) C-Calkyl, C-Calkenyl, and (C-Ccycloalkyl)C-Calkyl, each containing zero or one or two heteroatoms independently chosen from N, O, and S, each of which (ii) is unsubstituted or substituted with one or more substituents independently chosen from hydroxyl, amino, cyano, halogen, oxo, —COOH, —CONRR, —SONRR, and —NRCOR, where Rand Rare independently chosen from hydrogen and C-Calkyl;'}{'sub': '3', 'Ris'}(i) hydroxyl, halogen, or{'sub': 1', '8', '2', '8', '3', '7', '0', '4', '11', '12', '2', '11', '12', '11', '12', '11', '12', '1', '6, '(ii) C-Calkoxy, C-Calkenyloxy, and (C-Ccycloalkyl)C-Calkoxy, each containing zero or one or two heteroatoms independently ...

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Номер записи: 61
26-12-2013 дата публикации

PROCESS FOR THE PREPARATION OF (S)-(+)- OR (R)-(-)-10-HYDROXY DIHYDRODIBENZ[B,F]AZEPINES BY ENANTIOSELECTIVE REDUCTION OF 10,11-DIHYDRO-10-OXO-5H-DIBENZ[B,F]AZEPINES AND POLYMORPHS THEREOF

Номер: US20130345198A1
Автор: Bansal Vikas, BISWAS Sujay, Dubey Shailendra Kumar, MASAND Mukesh, VIR Dharam
Принадлежит: Jubilant Life Sciences Limited

The present invention provides a novel process for the preparation of substituted optically pure (S)-(+)- or (R)-(−)-10-hydroxy-dihydrodibenz[b,f]azepines or derivatives thereof, starting from 10,11-dihydro-10-oxo-5H-dibenz[b,f]azepines using boronate esters or their derivatives. The present invention also provides use of thus prepared (S)-(+)- or (R)-(−)-10-hydroxy-dihydrodibenz[b,f]azepines for the preparation of their ester such as (S)-(−)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide or (R)-(+)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide. The present invention also provides novel solid state crystalline forms J, J, J, Jand amorphous form of eslicarbazepine and the process for the preparation thereof. Also, the present invention provides novel solid state crystalline form and amorphous form of eslicarbazepine acetate and the process for the preparation thereof. The novel solid state forms of eslicarbazepine are useful for the preparation of derivatives of eslicarbazepine such as eslicarbazepine acetate. 153-. (canceled)54. A process for preparing (S)-(+)-10 ,11-dihydro-10-hydroxy-5H-dibenz[b ,f]azepines or (R)-(−)-10 ,11-dihydro-10-hydroxy-5H-dibenz[b ,f]azepines or derivatives thereof , by enantioselective reduction of 10 ,11-dihydro-10-oxo-5H-dibenz[b ,f]azepines or derivatives thereof in presence of boronate esters.55. The process according to claim 54 , wherein (S)-(+)-10 claim 54 ,11-dihydro-10-hydroxy-5H-dibenz[b claim 54 ,f]azepines and (R)-(−)-10 claim 54 ,11-dihydro-10-hydroxy-5H-dibenz[b claim 54 ,f]azepines are (S)-(+)-10 claim 54 ,11-dihydro-10-hydroxy-5H-dibenz[b claim 54 ,f]azepine-5-carboxamide and (R)-(−)-10 claim 54 ,11-dihydro-10-hydroxy-5H-dibenz[b claim 54 ,f]azepine-5-carboxamide respectively.56. The process according to claim 54 , wherein (S)-(+)-10 claim 54 ,11-dihydro-10-hydroxy-5H-dibenz[b claim 54 ,f]azepines claim 54 , (R)-(−)-10 claim 54 ,11-dihydro-10-hydroxy-5H-dibenz[b claim 54 ,f]azepines and 10 ...

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Номер записи: 62
26-12-2013 дата публикации

LARGE SUBSTITUENT, NON-PHENOLIC OPIOIDS AND METHODS OF USE THEREOF

Номер: US20130345251A1
Автор: WENTLAND Mark P.
Принадлежит: RENSSELAER POLYTECHNIC INSTITUTE

8-Substituted-2,6-methano-3-benzazocines of general structure This application is a divisional of allowed U.S. application Ser. No. 13/215,392, filed Aug. 23, 2011; which is a continuation of U.S. application Ser. No. 12/477,223, filed Jun. 3, 2009, and issued as 8,026,252 on Sep. 27, 2011; which is a continuation of U.S. application Ser. No. 11/459,203, filed Jul. 21, 2006, and issued as 7,557,119 on Jul. 7, 2009; and claims priority of U.S. provisional application 60/701,407, filed Jul. 21, 2005. The entire disclosures of each of the prior applications are hereby incorporated herein by reference.The following invention was made with Government support under contract number 5 R01 DA12180 awarded by U.S. Dept of Health and Human Services. The Government has certain rights in this invention.The invention relates to opioid receptor binding compounds containing carboxamides that have large substitutents on the nitrogen of the carboxamide. The compounds are useful as analgesics, anti-diarrheal agents, anticonvulsants, anti-obesity agents, antitussives, anti-cocaine, and anti-addiction medications.Opiates have been the subject of intense research since the isolation of morphine in 1805, and thousands of compounds having opiate or opiate-like activity have been identified. Many opioid receptor-interactive compounds including those used for producing analgesia (e.g., morphine) and those used for treating drug addiction (e.g., naltrexone and cyclazocine) in humans have limited utility due to poor oral bioavailability and a very rapid clearance rate from the body. This has been shown in many instances to be due to the presence of the 8-hydroxyl group (OH) of 2,6-methano-3-benzazocines, also known as benzomorphans [(e.g., cyclazocine and EKC (ethylketocyclazocine)] and the corresponding 3-OH group in morphinanes (e.g., morphine).The high polarity of these hydroxyl groups retards oral absorption of the parent molecules. Furthermore, the 8-(or 3-)OH group is prone to ...

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Номер записи: 63
26-12-2013 дата публикации

Synthesis and use of dual tyrosyl-dna phosphodiesterase i (tdp1)- topoisomerase i (top1) inhibitors

Номер: US20130345252A1
Автор: Mark S. Cushman, Martin M. Conda-Sheridan, Trung X. Nguyen
Принадлежит: PURDUE RESEARCH FOUNDATION

The invention described herein pertains to the synthesis and use of certain N-substituted indenoisoquinoline compounds which inhibit the activity Tyrosyl-DNA Phosphodiesterase I (Tdp1) or Topoisomerase I (Top1) or both, or otherwise demonstrate anticancer activity. Also disclosed are novel N-substituted indenoisoquinoline compounds and pharmaceutical compositions comprising the novel N-substituted indenoisoquinoline compounds.

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Номер записи: 64
02-01-2014 дата публикации

Substituted Aromatic Sulfur Compounds and Methods of Their Use

Номер: US20140005175A1
Автор: DORSEY Bruce D., Kuwada Scott K., Theroff Jay P., ZIFICSAK Craig A.
Принадлежит:

Compounds of formula II are described: 2. The compound of claim 1 , wherein A is at the 4-position of the phenyl ring.4. The compound of claim 1 , wherein Rand Rare each —CH.5. The compound of claim 3 , wherein Ris —OH.6. The compound of claim 3 , wherein Ris substituted or unsubstituted heterocycloalkyl.7. The compound of claim 3 , wherein Ris —NRR.8. The compound of claim 7 , wherein Ris H.9. The compound of claim 8 , wherein Ris substituted or unsubstituted alkyl.10. The compound of claim 8 , wherein Ris substituted or unsubstituted aryl.11. The compound of claim 8 , wherein Ris substituted or unsubstituted aralkyl.12. The compound of claim 8 , wherein Ris substituted or unsubstituted heteroaryl.13. The compound of claim 8 , wherein Ris substituted or unsubstituted heteroaralkyl.14. The compound of claim 8 , wherein Ris substituted or unsubstituted cycloalkyl.15. The compound of claim 8 , wherein Ris substituted or unsubstituted heterocycloalkyl.16. The compound of claim 8 , wherein Ris substituted or unsubstituted alkyene oxide.17. The compound of claim 8 , wherein Ris —NHCOcycloalkyl.18. The compound of claim 8 , wherein Rand R claim 8 , together with the atoms through which they are attached claim 8 , form a substituted or unsubstituted heterocycloalkyl ring.19. The compound of claim 3 , wherein Ris —CH.20. The compound of claim 19 , wherein Ris substituted or unsubstituted alkyl.21. The compound of claim 19 , wherein Ris substituted or unsubstituted aryl.22. The compound of claim 19 , wherein Ris substituted or unsubstituted aralkyl.23. The compound of claim 19 , wherein Ris substituted or unsubstituted heteroaryl.24. The compound of claim 19 , wherein Ris substituted or unsubstituted heteroaralkyl.25. The compound of claim 19 , wherein Ris substituted or unsubstituted cycloalkyl.26. The compound of claim 19 , wherein Ris substituted or unsubstituted heterocycloalkyl.27. The compound of claim 19 , wherein Ris substituted or unsubstituted alkyene oxide.28. The ...

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Номер записи: 65
09-01-2014 дата публикации

Papaver bracteatum with modified alkaloid content

Номер: US20140013465A1
Автор: Damien Lightfoot, Deepa Jha, Jarrod David Ritchie, Justin Taylor Coombs, Mark Alfred Tester
Принадлежит: TPI Enterprises Ltd

The present invention relates to genetically modified plants of the species Papaver bracteatum wherein the type or amount of one or more alkaloids produced by the plants has been modified. Specifically, the genetically modified plants have an increased expression of one or more of thebaine 6-O-demethylase, codeine O-demethylase and/or codeinone reductase relative to wild type P. bracteatum such that the genetically modified poppy plants produce an increased quantity of an alkaloid selected from codeine, oripavine and/or morphine relative to a wild type P. bracteatum . Also provided are progeny plants having the genetically modified poppy plants described above as a parent; mutant or derivative plants of the aforementioned plants; reproductive material derived from, straw produced from, straw concentrate produced from, latex derived from, or one or more isolated cells derived from, the aforementioned plants. Methods for producing an alkaloid from the aforementioned plants are also provided, together with nucleic acid and amino acid sequence variants of the 6-O-demethylase and codeine O-demethylase genes.

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Номер записи: 66
23-01-2014 дата публикации

Patch preparation

Номер: US20140023695A1
Автор: Hiroo Maeda, Katsuhiro Okada, Kazumitsu Yamamoto, Masato Nishimura, Masayasu Tanaka, Yasuaki Okada, Yuji KAWAHARADA
Принадлежит: Nitto Denko Corp, Sumitomo Dainippon Pharma Co Ltd

A patch preparation containing a support and an adhesive layer formed on one surface of the support, wherein the adhesive layer contains 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine or a physiologically acceptable acid addition salt thereof, an acrylic polymer, lactic acid, sesame oil and one or more kinds of stabilizers selected from 2-mercaptobenzimidazole, 2,6-di-tert-butyl-4-methylphenol and propyl gallate. A patch preparation containing a support and an adhesive layer containing lactic acid and magnesium aluminometasilicate and formed on at least one surface of the support, which preparation is superior in both skin permeability and adhesiveness in the presence of water.

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Номер записи: 67
23-01-2014 дата публикации

Benzazepine Derivatives Useful as Vasopressin Antagonists

Номер: US20140024619A1
Автор: KATO Yusuke, KONDO Kazumi, MATSUDA Takakuni, MENJO Yasuhiro, Miyamura Shin, TOMOHIRA Yuso, TOMOYASU Takahiro, YAMADA Keigo
Принадлежит: OTSUKA PHARMACEUTICAL CO., LTD.

The present invention provides a benzazepine compound that can maintain for a long period of time the blood level of tolvaptan enabling to provide the desired pharmaceutical effects. The benzazepine compound of the present invention is represented by general formula (1) 2. The compound according to claim 1 , wherein claim 1 , in formula (1) claim 1 , Ris a group of (1-5) claim 1 , or a salt thereof.3. The compound according to claim 2 , wherein claim 2 , in formula (1) claim 2 , Ris a —CO—Rwherein Ris an alkyl group claim 2 , or a salt thereof.4. (canceled)5. A pharmaceutical preparation comprising the benzazepine compound of or a pharmacologically acceptable salt thereof claim 1 , and a pharmacologically acceptable diluent and/or carrier.6. The pharmaceutical preparation according to which is used as a vasodilator claim 5 , hypotensive drug claim 5 , aquaretic agent claim 5 , or platelet aggregation inhibitor. The present invention relates to a novel benzazepine compound and a pharmaceutical preparation.Tolvaptan represented by the following formula (2) is a known compound, and is disclosed, for example, in U.S. Pat. No. 5,258,510 (Example 1199).Tolvaptan is known to be useful as a vasopressin antagonist having aquaretic efficacy (Circulation, 107, pp. 2690-2696 (2003)). However, because of its low water solubility, tolvaptan has problems in that it is poorly absorbed from the gastrointestinal tract, and its dosage form and administration route are limited. From the viewpoint of medical treatment, the development of a new drug that can maintain for a long period of time the blood level of tolvaptan enabling to provide the desired pharmaceutical effects has been desired.An object of the present invention is to provide a novel benzazepine compound that has excellent properties, such as the maintenance of the blood level of tolvaptan for a long period of time enabling to provide the desired pharmaceutical effects.The present inventors carried out extensive research to ...

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Номер записи: 68
23-01-2014 дата публикации

INHIBITORS OF THE INFLUENZA A VIRUS M2 PROTON CHANNEL

Номер: US20140024635A1
Автор: DeGrado William F., Wang Jun
Принадлежит: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

Provided are compounds that are capable of modulating the activity of the influenza A virus via interaction with the M2 transmembrane protein. Also provided are methods for treating an influenza A-affected disease state or infection comprising administering a composition comprising one or more compounds that have been identified as being capable of interaction with the M2 protein. 2. The compound according to wherein X and Y are each independently methylene or ethylene.3. The compound according to wherein X is methylene and Y is ethylene.4. The compound according to wherein at least one of Rand Ris hydrogen.5. The compound according to wherein one of Rand Ris carbonyl claim 4 , amino claim 4 , carboxyl claim 4 , cyano claim 4 , or —CH(R)(R).6. The compound according to wherein n is 1 or 2 claim 5 , except that if n is 1 claim 5 , both X and Y are methylene claim 5 , and both Rand Rare hydrogen claim 5 , then one of Rand Ris not carbonyl.7. The compound according to wherein one of Rand Ris —CH(R)(R).8. The compound according to wherein one of Rand Ris amino10. A composition comprising a compound according to and a pharmaceutically acceptable carrier claim 1 , diluent claim 1 , or excipient. This application is a divisional of U.S. Ser. No. 12/848,197, filed Aug. 1, 2010 (now allowed), the entire contents of which are hereby incorporated herein by reference.The present invention pertains to, among other things, compounds and methods for modulating the activity of the influenza virus.The M2 protein is found in the viral envelope of influenza A virus and functions as a highly selective, pH-regulated proton channel important for the life cycle of the virus. Unlike neuraminidase inhibitors, rimantadine and amantadine are anti-viral agents capable of blocking the tetrameric M2 channel. In 2006, the CDC issued an alert instructing clinicians to avoid using M2 ion-channel inhibitors during influenza season due to the extraordinarily high frequency of amantadine resistance in ...

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Номер записи: 69
23-01-2014 дата публикации

Benzazepine Derivatives Useful as Vasopressin Antagonists

Номер: US20140024640A1
Автор: KATO Yusuke, KONDO Kazumi, MATSUDA Takakuni, MENJO Yasuhiro, Miyamura Shin, TOMOHIRA Yuso, TOMOYASU Takahiro, YAMADA Keigo
Принадлежит: OTSUKA PHARMACEUTICAL CO., LTD.

The present invention provides a benzazepine compound that can maintain for a long period of time the blood level of tolvaptan enabling to provide the desired pharmaceutical effects. The benzazepine compound of the present invention is represented by general formula (1) 2. The compound according to claim 1 , wherein claim 1 , in formula (1) claim 1 , Ris a —CO—(CH)—COOH group wherein n is an integer of 1 to 4; or a salt thereof.3. (canceled)4. (canceled)5. A pharmaceutical preparation comprising the benzazepine compound of or a pharmacologically acceptable salt thereof claim 1 , and a pharmacologically acceptable diluent and/or carrier.6. The pharmaceutical preparation according to which is used as a vasodilator claim 5 , hypotensive drug claim 5 , aquaretic agent claim 5 , or platelet aggregation inhibitor. The present invention relates to a novel benzazepine compound and a pharmaceutical preparation.Tolvaptan represented by the following formula (2) is a known compound, and is disclosed, for example, in U.S. Pat. No. 5,258,510 (Example 1199).Tolvaptan is known to be useful as a vasopressin antagonist having aquaretic efficacy (Circulation, 107, pp. 2690-2696 (2003)). However, because of its low water solubility, tolvaptan has problems in that it is poorly absorbed from the gastrointestinal tract, and its dosage form and administration route are limited. From the viewpoint of medical treatment, the development of a new drug that can maintain for a long period of time the blood level of tolvaptan enabling to provide the desired pharmaceutical effects has been desired.An object of the present invention is to provide a novel benzazepine compound that has excellent properties, such as the maintenance of the blood level of tolvaptan for a long period of time enabling to provide the desired pharmaceutical effects.The present inventors carried out extensive research to overcome the above problem, and as a result found that benzazepine compounds represented by general ...

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Номер записи: 70
30-01-2014 дата публикации

INSECTICIDAL SPIRONINDANE DERIVATIVES

Номер: US20140031378A1
Автор: CASSAYRE Jerome, Cederbaum Fredrik, MAIENFISCH, MOLLEYRES Louis-Pierre, V Peter
Принадлежит:

An insecticidal compound of formula I 2. A compound according to claim 1 , wherein X is NH and Y is a single bond or C═O.3. A compound according to claim 1 , wherein each Ra is hydrogen and Rand Rare each independently hydrogen claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Calkoxy or cyano.4. A compound according to claim 1 , wherein{'sup': 1', '13', '14, 'sub': 1-6', '1-6', '1-6', '3-7', '1-4', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-4', '1-4', '1-4', '1-4', '2', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '2-6', '2-6', '3-6', '5-7', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6, 'Ris hydrogen; Calkyl; Ccyanoalkyl; Chaloalkyl; Ccycloalkyl(C)alkyl; Calkoxy(C)alkyl; heteroaryl(C)alkyl wherein the heteroaryl group may be optionally substituted by halo, nitro, cyano, Calkyl, Chaloalkyl, Calkoxy, Chaloalkoxy, Calkylsulfonyl, Calkylsulfinyl, Calkylthio, Calkoxycarbonyl, Calkylcarbonylamino, or arylcarbonyl, or two adjacent positions on the heteroaryl ring may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen; aryl(C)alkyl wherein the aryl group may be optionally substituted by halo, nitro, cyano, Calkyl, Chaloalkyl, Calkoxy, Chaloalkoxy, Calkylsulfonyl, Calkylsulfinyl, Calkylthio, Calkoxycarbonyl, Calkylcarbonylamino, or arylcarbonyl, or two adjacent positions on the aryl ring may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen; Calkylcarbonylamino(C)alkyl; aryl which may be optionally substituted by halo, nitro, cyano, Calkyl, Chaloalkyl, Calkoxy, Chaloalkoxy, Calkylsulfonyl, Calkylsulfinyl, Calkylthio, Calkoxycarbonyl, Calkylcarbonylamino, or arylcarbonyl, or ...

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Номер записи: 71
06-02-2014 дата публикации

Boron containing perylene monoimides, a process for their production, their use as building blocks for the production of perylene monoimide derivatives, monoimide derivatives and their use in dye-sensitized solar cells

Номер: US20140039193A1
Автор: Chen Li, Glauco BATTAGLIARIN, Henrike WONNEBERGER, Ingmar Bruder, Klaus Muellen, Robert SEND
Принадлежит: BASF SE, Max Planck Gesellschaft zur Foerderung der Wissenschaften eV

Boron-comprising perylene monoimides and a process for producing the boron-comprising perylene monoimides are provided. The boron-comprising perylene monoimides are useful as building blocks for producing perylene monoimide derivatives and monoimide derivatives. The boron-comprising perylene monoimides are also useful for preparing dye-sensitized solar cells.

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Номер записи: 72
13-02-2014 дата публикации

ANTIDIABETIC TRICYCLIC COMPOUNDS

Номер: US20140045746A1
Автор: Biju Purakkattle, Blizzard Timothy A., CHEN Zhengxia, Cui Mingxiang, Dang Qun, Hagmann William K., Hao Jinglai, Hu Bin, Josien Hubert, Li Bing, Lin Linus S., Nargund Ravi P., Plummer Christopher W.
Принадлежит: Merck Sharp & Dohme Corp.

Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia. 2. The compound according to wherein n is 1; or a pharmaceutically acceptable salt thereof.3. The compound according to wherein X is oxygen; or a pharmaceutically acceptable salt thereof.4. The compound according to wherein T is CH claim 3 , U is N or N-oxide claim 3 , and V is CH; or a pharmaceutically acceptable salt thereof.5. The compound according to wherein T is CH claim 3 , U is N claim 3 , and V is CH; or a pharmaceutically acceptable salt thereof.6. The compound according to wherein A is selected from the group consisting of: phenyl and pyridine claim 5 , wherein A is unsubstituted or substituted with one to five substituents selected from R; or a pharmaceutically acceptable salt thereof.7. The compound according to wherein A is phenyl claim 5 , wherein phenyl is unsubstituted or substituted with one to five substituents selected from R; or a pharmaceutically acceptable salt thereof.8. The compound according to wherein B is selected from the group consisting of: aryl and heteroaryl claim 7 , wherein B is unsubstituted or substituted with one to five substituents selected from R; or a pharmaceutically acceptable salt thereof.9. The compound according to wherein B is selected from the group consisting of: phenyl claim 7 , pyridine claim 7 , pyrimidine claim 7 , thiazole claim 7 , benzimidazole claim 7 , benzthiazole claim 7 , benzoxazole claim 7 , and benzisoxazole claim 7 , wherein B is ...

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Номер записи: 73
13-02-2014 дата публикации

METHOD FOR PRODUCING COMPLEX CRYSTAL AND METHOD FOR SCREENING COMPLEX CRYSTAL

Номер: US20140045824A1
Автор: Fukuda Mamoru, Goto Akinori
Принадлежит:

The present invention relates to a method for producing a complex crystal composed of two or more different compounds, comprising crystallizing the two or more different compounds under a condition at which menthol is heat melted, and a method for screening a complex crystal. In accordance with the method for producing a complex crystal of the present invention, a complex crystal capable of being used as a drug material can be produced rapidly, simply and efficiently. In addition, in accordance with the method for screening a complex crystal of the present invention, a stable complex crystal can be searched, which is industrially useful. 1. A method for producing a complex crystal composed of two or more different compounds , comprising crystallizing the two or more different compounds under a condition at which menthol is heat melted.2. A method for producing a complex crystal , comprising the following steps (i) and (ii):(i) a step of preparing a mixture composed of two or more different compounds and menthol, and(ii) a step of heat melting the menthol contained in the mixture.3. A method for screening a complex crystal , comprising the following steps (I) and (II):(I) a step of preparing plural mixtures each containing two or more different compounds and menthol, and(II) a step of heat melting the menthol contained in the mixture.4. A method for producing a complex crystal composed of two or more different compounds and water , comprising crystallizing the two or more different compounds under a humidified condition and under a condition at which menthol is heat melted.5. The method according to claim 1 , comprising a step of subsequently evaporating the heat melted menthol.6. The method according to claim 1 , wherein the content of each of the two or more different compounds contained in the mixture is an equimolar amount in the mixture.7. The method according to claim 1 , wherein the complex crystal is a cocrystal.8. The method according to claim 2 , comprising ...

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Номер записи: 74
13-02-2014 дата публикации

Fused and Spirocycle Compounds and the Use Thereof

Номер: US20140045875A1
Автор: CHEN Zhengming, ISLAM Khondaker, TAFESSE Laykea, Yao Jiangchao
Принадлежит: Purdue Pharma L.P.

The invention relates to fused and spirocycle compounds of Formula (I), or a pharmaceutically acceptable salt, prodrug, or solvate thereof, wherein R, R, Q-Q, and Z are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat, prevent or ameliorate a disorder responsive to the blockade of calcium channels, and particularly N-type calcium channels. Compounds of the present invention are especially useful for treating pain. 2. (canceled)4. The compound of claim 3 ,{'sup': 1', '2', '3', '4', '5, 'wherein Z is Z, Z, Z, Zor Z.'}5. The compound of claim 3 ,{'sup': '26', 'wherein Rare both hydrogen.'}6. The compound of claim 3 , wherein Ris hydrogen or unsubstituted benzyl.7. The compound of claim 1 , wherein{'sup': 3', '4', '1, 'a) Rand Rtogether form ═O and Z is Z; or'}{'sup': 3', '4', '2, 'b) Rand Rare both hydrogen, Z is Zand n is 0.'}9. The compound of claim 4 , wherein{'sup': 1', '5', '6', '7', '8, 'a) Z is Zand R, R, Rand Rare each independently selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, haloalkyl, hydroxy, cyano, amino, alkylamino, and dialkylamino; or'}{'sup': '2', 'claim-text': [{'sup': '9', 'i. Ris phenyl optionally substituted with one or two substituents independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, aminoalkyl, alkylamino, and dialkylamino; or'}, {'sup': '9', 'ii. Ris pyridyl optionally substituted with one or two substituents independently selected from the group consisting of alkyl, haloalkyl, halogen, haloalkoxy, and alkoxy; or'}], 'b) Z is Zand'}{'sup': '3', 'claim-text': [{'sup': '10', 'i. Ris phenyl optionally substituted with one or two substituents independently selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, haloalkoxy, amino, alkylamino, dialkylamino, and alkylcarbonylamino; or'}, {'sup': '10', 'ii. Ris 1,2,3,4-tetrahydroquinolinyl or 1,2,3,4- ...

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Номер записи: 75
20-02-2014 дата публикации

CRYSTALLINE FORMS OF (R)-8-CHLORO-1-METHYL-2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPINE HYDROCHLORIDE

Номер: US20140051684A1
Автор: Agarwal Rajesh K., BETTS, Henshilwood James A., III William L., Kiang Yuan-Hon, Post Noah
Принадлежит:

The present invention is directed to crystalline forms of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, compositions containing the same and uses thereof. 140.-. (canceled)41. A method of treatment of obesity comprising administering to an individual in need of such treatment a therapeutically effective amount of (R)-8-chloro-1-methyl-2 ,3 ,4 ,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate.42. A method of decreasing food intake comprising administering to an individual in need of such administration a therapeutically effective amount of (R)-8-chloro-1-methyl-2 ,3 ,4 ,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate.43. A method of inducing satiety comprising administering to an individual in need of such administration a therapeutically effective amount of (R)-8-chloro-1-methyl-2 ,3 ,4 ,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate.44. A method of controlling weight gain comprising administering to an individual in need of such administration a therapeutically effective amount of (R)-8-chloro-1-methyl-2 ,3 ,4 ,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate.45. A method of treatment of a disorder of the central nervous system , damage to the central nervous system , a cardiovascular disorder , a gastrointestinal disorder , diabetes insipidus , or sleep apnea comprising administering to an individual in need of such treatment a therapeutically effective amount of (R)-8-chloro-1-methyl-2 ,3 ,4 ,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate.46. A method of treatment of depression , atypical depression , a bipolar disorder , an anxiety disorder , an obsessive-compulsive disorder , a social phobia or panic state , a sleep disorder , sexual dysfunction , a psychosis , schizophrenia , migraine or a condition associated with cephalic pain or other pain , raised intracranial pressure , epilepsy , a personality disorder , an age-related behavioral disorder , a behavioral disorder associated with dementia , organic ...

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Номер записи: 76
27-02-2014 дата публикации

LPA2 Receptor-Specific Benzoic Acid Derivatives

Номер: US20140057936A1
Автор: Fells James, Miller Duane D., Patil Renukadevi, Tigyi Gabor
Принадлежит: UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION

Disclosed are compounds effective for inhibiting cellular apoptosis and for protecting cells and tissues from the apoptotic effects of chemotherapeutic agents and/or ionizing radiation. Compounds of the invention act as agonists of the LPAreceptor. Compounds of the invention comprise non-lipid benzoic acid derivatives. This application claims the benefit of priority of U.S. Provisional Patent Application No. 61/693,731, filed Aug. 27, 2012, the contents of which are incorporated herein by reference.The invention relates to compositions comprising new benzoic acid derivatives. More specifically, the invention relates to compounds comprising new sulfamoyl benzoic acid derivatives, these compounds acting as LPAreceptor agonists.The growth factor-like lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) regulate many fundamental cellular responses, including cell survival, cell proliferation, cellular motility and migration. LPA has been shown to have profound activity in preventing apoptosis and rescuing cells from the progression of the apoptotic cascade. An LPA mimic, octadecenyl thiophosphate (OTP) (Durgam et al., Synthesis and pharmacological evaluation of second-generation phosphatidic acid derivatives as lysophosphatidic acid receptor ligands. (2006) 16(3): 633-640), has demonstrated superior efficacy in vitro and in vivo, as compared to LPA, in rescuing cells and animals from radiation-induced apoptosis (Deng et al., The lysophosphatidic acid type 2 receptor is required for protection against radiation-induced intestinal injury. (2007) 132(5): 1834-1851).The G protein-coupled lysophosphatidic acid 2 (LPA) receptor elicits prosurvival responses to prevent and rescue cells from apoptosis. LPAstimulation provides protection from chemotherapeutic agent-induced apoptosis and radiation-induced apoptosis. Highly effective LPA-specific agonists may therefore have significant therapeutic value.Development of LPA-based drug candidates has thus ...

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Номер записи: 77
13-03-2014 дата публикации

Azide Substituted Naphthylene or Rylene Imide Derivatives and their Use as Reagents in Click-Reactions

Номер: US20140073059A1
Автор: Gessner Thomas, Könemann Martin, Manetto Antonio, Münster Ingo, PSCHIRER Neil Gregory, Qu Jianqiang, Reichelt Helmut, Schwögler Anja, Sens Rüdiger
Принадлежит: BASF SE

Novel mono-azide substituted rylene-imide derivatives, their use in methods for the detection of analytes and reagents kits for the detection of analytes comprising said novel mono-azide substituted rylene-imide derivatives. 6. A reagent kit for detecting an analyte in a sample , comprising:(a) a functionalized compound comprising at least one functional group which is a first reaction partner for a click reaction,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(b) a second reaction partner for a click reaction, wherein the second reaction partner further comprises a marker group said second reaction partner being selected from the mono-azide substituted naphthylene or rylene-imide derivative in accordance with .'}7. A method for detecting an analyte comprising the steps of(i) providing a sample;(ii) contacting the sample with a functionalized compound comprising at least one functional group which is a first reaction partner for a click reaction under conditions wherein said compound forms an association product with the analyte to be detected,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(iii) contacting the association product with a second reaction partner for a click reaction under conditions wherein a click reaction between the first and second reaction partner occurs, wherein the second reaction partner is a monoazide substituted naphthylene or rylene-imide derivative in accordance with , and'}{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(iv) detecting the marker groups in the compounds in the mono-azide substituted naphthylene or rylene-imide derivative in accordance with .'} This application is a divisional of application Ser. No. 13/006,572, filed on Jan. 14, 2011, which is incorporated by reference herein in its entirety. Application Ser. No. 13/006,572 is a continuation-in-part of application Ser. No. 12/180,071 filed on Jul. 25, 2008 which is incorporated by reference in its entirety.The present invention relates to new mono-azide ...

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Номер записи: 78
13-03-2014 дата публикации

Spirocyclic nitriles as protease inhibitors

Номер: US20140073662A1
Автор: Bauer Armin, Kohlmann Anna, SCHUDOK Manfred, Wagner Michael
Принадлежит: SANOFI

The invention relates to substituted carbo- and heterocyclic spiro compounds of the formula Ia which inhibit thiol proteases, to processes for their preparation and to the use thereof as medicaments. 2. A pharmaceutical composition comprising a therapeutically effective amount of the compound of or a physiologically tolerated salt thereof and a pharmaceutically acceptable carrier.4. The method of claim 3 , wherein the condition or disorder is osteoarthritis.5. The method of claim 3 , wherein the condition or disorder is bone loss. This application is a continuation of U.S. application Ser. No. 13/248,366, filed Sep. 29, 2011, which is a divisional of U.S. application Ser. No. 12/277,880, filed Nov. 25, 2008, which is a continuation of International Application No. PCT/EP2007/004550, filed May 23, 2007, which are incorporated herein by reference in their entirety; and claims the benefit of priority of German Patent Application No. 102006025630.1, filed Jun. 1, 2006.The invention relates to substituted carbo- and heterocyclic spiro compounds of the formula Ia which inhibit thiol proteases, to processes for their preparation and to the use thereof as medicaments.Proteolytic enzymes, known as proteases and peptidases, are very important enzymes which make up about 2% of the genes in the human organism, pathogenic microorganisms and also other life forms. Their particular significance is that they influence many physiological processes by playing an important role in the activation, synthesis or degradation of other proteins. This inevitably gives rise to a crucial regulatory function starting at conception, birth, growth, maturation, aging, diseases up to death.The balance of the different processes is of crucial significance for the life and survival of the organism. When there is an imbalance of protease-catalyzed processes as a result of endogenous or exogenous factors such as genetic predisposition or environmental factors, massive disruption can occur in the normal ...

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Номер записи: 79
20-03-2014 дата публикации

Azide Substituted Naphthylene or Rylene Imide Derivatives and their Use as Reagents in Click-Reactions

Номер: US20140080220A1
Автор: Gessner Thomas, Könemann Martin, Manetto Antonio, Münster Ingo, PSCHIRER Neil Gregory, Qu Jianqiang, Reichelt Helmut, Schwögler Anja, Sens Rüdiger
Принадлежит: BASF SE

Novel mono-azide substituted rylene-imide derivatives, their use in methods for the detection of analytes and reagents kits for the detection of analytes comprising said novel mono-azide substituted rylene-imide derivatives. 6. A reagent kit for detecting an analyte in a sample , comprising:(a) a functionalized compound comprising at least one functional group which is a first reaction partner for a click reaction,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(b) a second reaction partner for a click reaction, wherein the second reaction partner further comprises a marker group said second reaction partner being selected from the mono-azide substituted naphthylene or rylene-imide derivative in accordance with .'}7. A method for detecting an analyte comprising the steps of(i) providing a sample;(ii) contacting the sample with a functionalized compound comprising at least one functional group which is a first reaction partner for a click reaction under conditions wherein said compound forms an association product with the analyte to be detected,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(iii) contacting the association product with a second reaction partner for a click reaction under conditions wherein a click reaction between the first and second reaction partner occurs, wherein the second reaction partner is a mono-azide substituted naphthylene or rylene-imide derivative in accordance with , and'}{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(iv) detecting the marker groups in the compounds in the mono-azide substituted naphthylene or rylene-imide derivative in accordance with .'} This application is a divisional of application Ser. No. 13/006,572, filed on Jan. 14, 2011, which is incorporated by reference herein in its entirety. Application Ser. No. 13/006,572 is a continuation-in-part of application Ser. No. 12/180,071 filed on Jul. 25, 2008 which is incorporated by reference in its entirety.The present invention relates to new mono-azide ...

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Номер записи: 80
27-03-2014 дата публикации

AGENTS FOR TREATING NEURODEGENERATIVE DISORDERS

Номер: US20140088063A1
Автор: "Petukhova Vera Yurevna", Makhova Nina Nikolayevna, Novakovskiy Vladimir Vladimirovich, Shevtsov Alexander Vladimirovich
Принадлежит: Pharmdiscovery LLP

The present invention relates to compounds of formula (I) or (I′), use of these compounds to treat mental disorders, especially depressions of different etiology, and methods for their preparation. The compounds that are provided for the treatment of mental disorders can be presented by a general formula (I) as meso-form—S,2S,1′R,2′R-1-[ω-(3,3-dialkyldiaziridin-1-yl)alkyl]-3,3-dialkyldiaziridines: 2. The compound according to claim 1 , wherein the compound is selected from the group consisting of:meso-1S,2S,1′R,2′R-1-[2-(1,2-diazaspiro[12.51]oct-1-yl)ethyl]-1,2-diazaspiro[12.51]octane;meso-1S,2S,1′R,2′R-1-[3-(3,3-dimethyldiaziridin-1-yl)propyl]-3,3-dimethyldiaziridine;meso-1S,2S,1′R,2′R-1-[4-(3,3-dimethyldiaziridin-1-yl)butyl]-3,3-dimethyldiaziridine;meso-1S,2S,1′R,2′R-1-[5-(3,3-dimethyldiaziridin-1-yl)pentyl]-3,3-dimethyldiaziridine;meso-1S,2S,1′R,2′R-1-[2-(3,3-dimethyldiaziridin-1-yl)ethyl]-1,2-diazaspiro[2.5]octane;meso-1S,2S,1′R,2′R-1-[2-(1,2-diazaspiro[2.4]hept-1-yl)ethyl]-1,2-diazaspiro[2.4]heptane;meso-1S,2S,1′R,2′R-1-[2-(3,3-dimethyldiaziridin-1-yl)ethyl]-1,2-diazaspiro[2.4]heptane;meso-1S,2S,1′R,2′R-1-[2-(1,2-diazaspiro[2.4]hept-1-yl)ethyl]-1,2-diazaspiro[2.5]octane;meso-1S,2S,1′R,2′R-1-[2-(3-methyl-3-propyldiaziridin-1-yl)ethyl]-3-methyl-3-propyldiaziridine;meso-1S,2S,1′R,2′R-1-[2-(3-isopropyl-3-methyl-diaziridin-1-yl)ethyl]-3-methyl-3-isopropyldiaziridine;3. The compound according to claim 1 , wherein the compound is selected from the group consisting of:meso-1S,2S,1′R,2′R-1-[2-(3,3-diethyldiaziridin-1-yl)ethyl]-3,3-diethyldiaziridine;meso-1S,2S,1′R,2′R-1-[2-(3,3-dipropyldiaziridin-1-yl)ethyl]-3,3-dipropyldiaziridine;meso-1S,2S,1′R,2′R-1-[2-(3,3-dibutyldiaziridin-1-yl)ethyl]-3,3-dibutyldiaziridine;meso-1S,2S,1′R,2′R-1-[2-(3,3-dipentyldiaziridin-1-yl)ethyl]-3,3-dipentyldiaziridine;meso-1S,2S,1′R,2′R-1-[2-(3,3-dihexyldiaziridin-1-yl)ethyl]-3,3-dihexyldiaziridine;meso-1S,2S,1′R,2′R-1-[2-(3,3-diheptyldiaziridin-1-yl)ethyl]-3,3-diheptyldiaziridine;meso-1S,2S,1 ...

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Номер записи: 81
27-03-2014 дата публикации

Substituted Benzoazepines As Toll-Like Receptor Modulators

Номер: US20140088085A1
Автор: Burgess Laurence E., Doherty George A., Eary C. Todd, Groneberg Robert D., Hershberg Robert, Howbert James Jeffry, Jones Zachary, Lyssikatos Joseph P., Yang Hong Woon
Принадлежит:

Provided are compositions and methods useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compositions and methods have use in treating or preventing disease, including cancer, autoimmune disease, fibrotic disease, cardiovascular disease, infectious disease, inflammatory disorder, graft rejection, or graft-versus-host disease. 3. The compound of claim 1 , wherein at least one of Rand Ris not hydrogen claim 1 , or one of Rand Ris alkyl and the other of Rand Ris hydrogen claim 1 , or one of Rand Ris alkyl substituted with R claim 1 , or both Rand Rare alkyl.46-. (canceled)7. The compound of claim 1 , wherein one of Rand Ris R claim 1 , and the other of Rand Ris hydrogen.8. The compound of claim 1 , wherein Ris not hydrogen.9. The compound of claim 1 , wherein Nand one of Ror Rare connected to form a saturated claim 1 , partially unsaturated claim 1 , or unsaturated heterocycle having 5-7 ring members and the other of Ror Ris hydrogen claim 1 , or absent as necessary to accommodate ring unsaturation.10. (canceled)12. The compound of claim 1 , wherein at least one of Rand Ris not hydrogen claim 1 , or Rand Rare connected to form a saturated carbocycle.1314-. (canceled)15. The compound of claim 1 , Z is N.17. The compound of claim 16 , wherein Rand Rtogether with the nitrogen atom to which they are attached form a saturated heterocyclic ring.18. The compound of claim 17 , wherein Rand Rtogether with the nitrogen atom to which they are attached form pyrrolidine.19. The compound of claim 1 , wherein Ris —ORand Ris alkyl or Ris —NRRin which Rand Rare both alkyl.20. The compound of claim 19 , wherein Ris —O-ethyl or —N(propyl).2122-. (canceled)23. The compound of claim 16 , wherein at least one of Ror Ris alkyl substituted with one —OH.26. (canceled)27. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier.28. A method of treating a TLR7- ...

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Номер записи: 82
03-04-2014 дата публикации

Anti-fibrotic pyridinones

Номер: US20140094456A1
Автор: Brad Owen BUCKMAN, John Beamond Nicholas, Johnnie Y. Ramphal, Kumaraswamy EMAYAN, Scott D. Seiwert
Принадлежит: Intermune Inc

Disclosed are pyridinone compounds, method for preparing these compounds, and methods for treating fibrotic disorders.

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Номер записи: 83
04-01-2018 дата публикации

FACTOR XIa INHIBITORS

Номер: US20180000795A1
Автор: Ali Amjad, Brockunier Linda L., Edmondson Scott D., Gao Ying-Duo, Hruza Alan, Liu Weiguo, Mertz Eric, Moningka Remond, Neelamkavil Santhosh F., So Sung-Sau, Sun Wanying
Принадлежит: Merck Sharp & Dohme Corp.

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein. 3. The compound of wherein Ris phenyl claim 1 , which optionally is substituted with two or three substituents independently selected from the group consisting of halo and heteroaryl; or a pharmaceutically acceptable salt thereof.4. The compound of wherein Ris phenyl claim 1 , which optionally is substituted with halo and tetrazolyl; or a pharmaceutically acceptable salt thereof.5. The compound of where in Ris phenyl claim 1 , which optionally is substituted with three halo; or a pharmaceutically acceptable salt thereof.6. The compound of wherein Ris hydroxy; or a pharmaceutically acceptable salt thereof.7. The compound of wherein Ris phenyl claim 1 , which is optionally substituted with one to three substituents independently selected from the group consisting of (C═O)ORand NH(C═O)R; or a pharmaceutically acceptable salt thereof.8. The compound of wherein Ris phenyl claim 1 , which is substituted with (C═O)OR; or a pharmaceutically acceptable salt thereof.10. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.11. A method for inhibiting thrombus formation in blood or treating thrombus formation in blood comprising administering a composition of to a mammal in need of thereof.12. A method for preventing thrombus formation in blood comprising administering a composition of to a mammal in need thereof.13. A method of treating venous thromboembolism and pulmonary embolism in a mammal comprising administering a composition of to a mammal in need thereof.14. A method of treating deep vein thrombosis in a mammal comprising ...

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Номер записи: 84
07-01-2016 дата публикации

PRODRUGS OF MULTIFUNCTIONAL NITROXIDE DERIVATIVES AND USES THEREOF

Номер: US20160002171A1
Автор: Jagtap Prakash, Salzman Andrew Lurie, Southan Garry John
Принадлежит:

Prodrugs of compounds comprise a nitric oxide donor and a reactive oxygen species (ROS) degradation catalyst, in particular, 1-pyrrolidinyloxy, 1-piperidinyloxy, and 1-azepanyloxy derivatives, and pharmaceutical compositions thereof. These compounds and pharmaceutical compositions are useful in prevention, treatment or management of diseases, disorders or conditions associated with oxidative stress or endothelial dysfunction. 2. The compound of claim 1 , wherein Reach independently is H claim 1 , —COOR claim 1 , —CON(R) claim 1 , or a nitric oxide donor group; and Ris H.3. The compound of claim 1 , wherein Reach independently is (C-C)alkyl.4. The compound of claim 3 , wherein Rare identical.5. The compound of claim 1 , wherein Ris (C-C)alkyl claim 1 , (C-C)alkylene-OH claim 1 , (C-C)alkylene-N(R) claim 1 , or (C-C)alkylene-COOR claim 1 , wherein Reach independently is (C-C)alkyl claim 1 , or H.6. The compound of claim 1 , wherein in said nitric oxide donor group claim 1 , Xis absent or —O—; Xis absent or (C-C)alkylene; Xis —NO or —ONO; and said alkylene is optionally substituted by one or more —ONOgroups.7. The compound of claim 1 , wherein Reach independently is H claim 1 , —COOR claim 1 , —CON(R) claim 1 , or a nitric oxide donor group; Reach independently is (C-C)alkyl; Ris (C-C)alkyl claim 1 , (C-C)alkylene-OH claim 1 , (C-C)alkylene-N(R) claim 1 , or (C-C)alkylene-COOR; Ris H; Reach independently is (C-C)alkyl claim 1 , or H; and in said nitric oxide donor group claim 1 , Xis absent or —O—; Xis absent or (C-C)alkylene optionally substituted by one or more —ONOgroups; and Xis —NO or —ONO.8. The compound of claim 1 , wherein (i) n is 1; and one or two of the carbon atoms at positions 3 or 4 of the pyrrolidine ring are linked to a nitric oxide donor group; (ii) n is 2; and one or more of the carbon atoms at positions 3 to 5 of the piperidine ring are linked to a nitric oxide donor group; or (iii) n is 3; and one or more of the carbon atoms at positions 3 to 6 of ...

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Номер записи: 85
03-01-2019 дата публикации

MATERIALS FOR ELECTRONIC DEVICES

Номер: US20190002417A1
Автор: Kaufhold Oliver, MEYER Sebastian, RIEDMUELLER Stefan
Принадлежит: Merck Patent GmBH

The present invention relates to compounds according to formula (I), which are suitable for use in electronic devices, preferably organic electroluminescent devices. 118-. (canceled)20. The compound of claim 19 , wherein the compound of formula claim 19 , (1) contains exactly one Y wherein a group of formula (N) is bonded thereto instead of R.21. The compound of claim 19 , wherein in the group of formula (N) claim 19 , Aris the same or different in each instance and is selected from the group consisting of phenyl claim 19 , naphthyl claim 19 , phenanthrenyl claim 19 , biphenyl claim 19 , terphenyl claim 19 , quaterphenyl claim 19 , fluorenyl claim 19 , indenofluorenyl claim 19 , carbazolyl claim 19 , dibenzothiophenyl claim 19 , dibenzofusanyl claim 19 , benzofuranyl claim 19 , benzothiophenyl claim 19 , indolyl claim 19 , triazinyl claim 19 , pyrimidinyl claim 19 , pyridyl claim 19 , and pyridazinyl claim 19 , each of which is optionally substituted by one or more radicals R.22. The compound of claim 19 , wherein Aris the same in each instance.25. The compound of claim 19 , wherein all Y are CR.26. The compound of claim 19 , wherein X is C(R).27. The compound of claim 19 , wherein the radicals Rof X are the same or different in each instance and are selected from the group consisting of straight-chain alkyl groups having 1 to 12 carbon atoms claim 19 , branched or cyclic alkyl groups having 3 to 12 carbon atoms claim 19 , and aromatic ring systems having 6 to 20 aromatic ring atoms; wherein the alkyl groups and aromatic ring systems are each optionally substituted by one of more radicals R.28. The compound of claim 19 , Therein the radicals Rin Y are the same or different each instance and are selected from the group consisting of H claim 19 , D claim 19 , F claim 19 , CN claim 19 , straight-chain alkyl groups having 1 to 20 carbon atoms claim 19 , branched or cyclic alkyl groups having 3 to 20 carbon atoms claim 19 , aromatic ring systems having 6 to 40 aromatic ...

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Номер записи: 86
07-01-2021 дата публикации

HYBRID MU OPIOID RECEPTOR AND NEUROPEPTIDE FF RECEPTOR BINDING MOLECULES, THEIR METHODS OF PREPARATION AND APPLICATIONS IN THERAPEUTIC TREATMENT

Номер: US20210002231A1
Автор: Ballet Steven, BIHEL FRÉDÉRIC, Drieu la Rochelle Armand, SIMONIN Frédéric
Принадлежит:

Molecules binding the mu opioid receptor (MOR) and the neuropeptide FF receptor (NPFFR), in particular molecules having a MOR agonist and NPFFR modulatory activity, and pharmaceutical compositions useful in the treatment of pain and/or hyperalgesia. 11. The molecule of wherein said terminal group T is selected from the group consisting of:{'sub': 2', 'n, 'H, Alkyl, (CH)-Aryl (when X6 is a bridged amino acid), and'}{'sub': 2', '1', '2', '1', '2', '2', 'n, 'NH, NH—R or cyclic/acyclic NRRwherein R, R, Ris H, Alkyl or (CH)-Aryl.'}12. The molecule of wherein said molecule comprises from 6 to 10 amino acid residues or derivative thereof.13. The molecule of wherein X1-X2-X3-X4 represent a opioid peptide-based peptide analogue structure or a dermophin peptide based peptide analogue structure.14. A molecule according to claim 1 , wherein said molecule is binding MOR and NPFFR.15. A molecule according to claim 1 , wherein said molecule is an NPFFR1 or NPFFR2 antagonist claim 1 , and in particular a NPFFR1 and NPFFR2 antagonist.16. A method of treating an animal or human body claim 1 , said method comprising administering to said animal or human body of an effective amount of at least one molecule as defined in .17. The method according to claim 16 , wherein said method is a method of treatment of pain and/or hyperalgesia.18. The method according to claim 16 , wherein said method is a method of treatment of a disease or condition associated with MOR.19. The method according to claim 16 , wherein said method is a method of treatment of a disease or condition associated with NPFFR1 and/or NPFFR2.20. The method according to claim 16 , wherein said method is method of treatment of behavioral and somatic signs of opioid withdrawal syndrome.21. A pharmaceutical composition comprising at least one molecule according to and one or more pharmaceutically acceptable excipients.22. A pharmaceutical composition comprising at least one molecule according to and one or more pharmaceutically ...

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Номер записи: 87
05-01-2017 дата публикации

SULFONIC ACID DERIVATIVE COMPOUNDS AS PHOTOACID GENERATORS IN RESIST APPLICATIONS

Номер: US20170003587A1
Автор: GREENE Daniel, Sharma Ram B., Zhang Yongqiang
Принадлежит:

Novel photoacid generator compounds are provided. Photoresist compositions that include the novel photoacid generator compounds are also provided. The invention further provides methods of making and using the photoacid generator compounds and photoresist compositions disclosed herein. The compounds and compositions are useful as photoactive components in chemically amplified resist compositions for various microfabrication applications. 2. A photoresist composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(i) at least one sulfonic acid derivative compound according to ;'}(ii) at least one polymer or copolymer which is capable of being imparted with an altered solubility in an aqueous solution in the presence of an acid;(iii) an organic solvent; and, optionally,(iv) an additive.3. The composition according to claim 2 , wherein the organic solvent is propylene glycol monomethyl ether acetate (PGMEA).4. The composition according to comprising:0.05 to 15 wt. % of the sulfonic acid derivative compound;5 to 50 wt. % of the at least one polymer or copolymer;0 to 10 wt. % of the additive; andreminder is propylene glycol monomethyl ether acetate.5. A process of producing a patterned structure on the surface of a substrate claim 3 , the process comprising the steps of{'claim-ref': {'@idref': 'CLM-00004', 'claim 4'}, '(a) applying a layer of the composition according to onto the surface of the substrate and at least partial removal of the organic solvent (iv);'}(b) exposing the layer to electromagnetic radiation, thereby releasing an acid from the sulfonic acid derivative compound (i) in the areas exposed to the electromagnetic radiation;(c) optionally heating the layer to impart compound (ii) in the areas in which the acid has been released with an increased solubility in an aqueous solution; and(d) at least partial removal of the layer with an aqueous solution in these areas.6. The composition according to wherein claim 2 , during the exposure step ...

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Номер записи: 88
07-01-2021 дата публикации

N AND P ACTIVE MATERIALS FOR ORGANIC PHOTOELECTRIC CONVERSION LAYERS IN ORGANIC PHOTODIODES

Номер: US20210005827A1
Автор: CHERCKA Dennis, Danner David, DEICHMANN Vitor, FORD William E., Knorr Nikolaus, MITEVA Tzenka, Nelles Gabriele, Rosselli Silvia, SCHELLER Lars Peter, Yakutkin Vladimir
Принадлежит: SONY CORPORATION

The field of the DISCLOSURE lies in active materials for organic image sensors. The present disclosure relates to transparent N materials and/or to transparent P materials and their use in absorption layer(s), photoelectric conversion layer(s) and/or an organic image sensor and methods for their synthesis. The present disclosure also relates to photoelectric conversion layer(s) including an active material according to the present disclosure, to a device, including active material(s) according to the present disclosure or photoelectric conversion layer(s) according to the present disclosure. Moreover, the present disclosure relates to an organic image sensor including photoelectric conversion layer(s) according to the present disclosure. 2. The organic image sensor according to claim 1 , wherein the naphthalene dimide based material dissociates excitons created on colored N or a mixture of colored N materials (N1:N2) or of another colored P or mixture of colored P and N materials (P2:N or P2:N1:N2) via a process of HOMO dissociation in a P:N heterojunction or P:N bilayer or multilayer junction claim 1 , where transparent refers to an absorption coefficient of less than about 60 claim 1 ,000 cmin the visible wavelength range in the region from about 400 to about 700 nm claim 1 , or to an extinction coefficient of less than about 60 claim 1 ,000 Mcmin toluene claim 1 , and colored refers to an absorption coefficient of more than about 60 claim 1 ,000 cmin the visible wavelength range in the region from about 400 nm to about 700 nm.3. The organic image sensor according to claim 1 , wherein the naphthalene dimide based material has an absorption coefficient of less than about 60 claim 1 ,000 cmin the visible wavelength range in the region from about 400 to about 700 nm claim 1 , or an extinction coefficient of less than about 60 claim 1 ,000 Mcmin toluene claim 1 , and is forming homogenous films formed by a deposition method.5. The organic image sensor according to ...

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Номер записи: 89
12-01-2017 дата публикации

METHOD FOR PREPARING CAPROLACTAM BY USING A MICROREACTOR UNDER LEWIS ACID CATALYSIS

Номер: US20170008850A1
Автор: FANG Zheng, Guo Kai, Li Xin, OUYANG Pingkai, Yu Qi, ZHANG KAI
Принадлежит: NANJING TECH UNIVERSITY

A method for preparing caprolactam by using a microreactor under Lewis acid catalysis, wherein a hydroxyl group in a cyclohexanone oxime is activated to obtain a cyclohexanone oxime sulfonates intermediate, then rearranged under Lewis acid catalysis to prepare the caprolactam. The method of this invention has a simple process and a high operation safety and selectivity, the reaction condition is mild, an efficient reaction can take place even at room temperature, the reaction time is short, the conversion of the cyclohexanone oxime can reach 100% within a short time, the selectivity of the caprolactam can reach 99%, the energy consumption is greatly reduced in the premise of maintaining a high yield, and the production cost is reduced, being an efficient and green and environmentally friendly method of for synthesizing the caprolactam. 1. A method for preparing caprolactam by using a microreactor under Lewis acid catalysis , comprising the following steps:(1) cyclohexanone oxime is dissolved in an organic solvent, an organic acid binding agent is added, and homogeneously mixed, to obtain a homogeneous solution;(2) a sulfonyl chlorides compound is dissolved in an organic solvent, and homogeneously mixed, to obtain a homogeneous solution;(3) a Lewis acid is dissolved in an organic solvent, and homogeneously mixed, to obtain a homogeneous solution;(4) the homogeneous solution obtained in step (1) and the homogeneous solution obtained in step (2) are concurrently and respectively pumped into a first microchannel reactor of a microreactor, and completely reacted, to obtain a cyclohexanone oxime sulphonates intermediate;(5) a mixed system obtained in step (4) and the homogeneous solution obtained in step (3) are concurrently and respectively pumped into a second microchannel reactor of the microreactor, and completely reacted, a outflow liquid is collected, to obtain the caprolactam.2. The method for preparing caprolactam by using a microreactor under Lewis acid catalysis ...

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Номер записи: 90
12-01-2017 дата публикации

PROCESS FOR ISOCYANATE MODIFICATION USING SPIROCYCLIC AMMONIUM SALTS AS CATALYST

Номер: US20170008995A1
Автор: Richter Frank
Принадлежит:

The Invention relates to a process for modifying isocyanates, in which at least one monomeric organic isocyanate having an NCO functionality>1 is oligomerized in the presence of at least one spirocyclic ammonium salt having a cation of the formula I as catalysts for the isocyanate modification, where substituents X and Y in the N positions are identical or different, substituted or unsubstituted C2-C20-alkylene chains optionally interrupted by heteroatoms (0, N, S) and by aromatic rings. The invention further relates to the use of such a catalyst. 2. The process according to claim 1 , wherein X and/or Y are each independently optionally substituted C4-C6-alkylene chains.3. The process according to claim 1 , wherein an anion of the at least one spirocyclic ammonium salt is selected from the group consisting of hydroxide claim 1 , alkanoate claim 1 , carboxylate claim 1 , heterocycles having at least one negatively charged nitrogen atom in the ring.4. The process according to claim 1 , wherein the oligomerization is conducted in the presence of a solvent and/or an additive.5. The process according to claim 1 , wherein the monomeric organic isocyanate is selected from aliphatic diisocyanates.6. The process according to wherein the catalyst of the formula I is used in an amount of 0.001 to 5 mol % claim 1 , based on the sum total of the molar amounts of the monomeric organic isocyanate used and the catalyst.7. The process according to claim 1 , wherein the process is conducted within the temperature range from 0° C. to +250° C.8. The process according to claim 1 , wherein the oligomerization is stopped after 5% to 80% by weight of the monomeric organic isocyanate has been converted.9. The process according to claim 8 , wherein the oligomerization is stopped by deactivating the catalyst.10. The process according to claim 8 , wherein unconverted monomeric organic isocyanate is separated from the reaction mixture.12. The process according to claim 2 , wherein the C4-C6- ...

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Номер записи: 91
11-01-2018 дата публикации

GLUCOCEREBROSIDASE MODULATORS AND USES THEREOF

Номер: US20180009761A1
Автор: Kaul Ramesh, McEachern Ernest J., Sun Jianyu, Vocadlo David J., Zhou Yuanxi, Zhu Yongbao
Принадлежит:

The invention provides compounds for modulating glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. 2. The method of wherein the compound is one or more of the compounds described in Table 1.4. The method of wherein the condition is Parkinson's disease claim 3 , Dementia with Lewy bodies claim 3 , Multiple system atrophy claim 3 , Pick's disease claim 3 , Corticobasal degeneration claim 3 , Alzheimer's disease claim 3 , Amyotrophic lateral sclerosis claim 3 , Amyotrophic lateral sclerosis with cognitive impairment claim 3 , Argyrophilic grain dementia claim 3 , Bluit disease claim 3 , Dementia pugilistica claim 3 , Diffuse neurofibrillary tangles with calcification claim 3 , Down's syndrome claim 3 , Familial British dementia claim 3 , Familial Danish dementia claim 3 , Frontotemporal dementia with parkinsonism linked to chromosome 17 claim 3 , Gerstmann-Straussler-Scheinker disease claim 3 , Guadeloupean parkinsonism claim 3 , Hallevorden-Spatz disease claim 3 , neurodegeneration with brain iron accumulation type 1 claim 3 , Myotonic dystrophy claim 3 , Multi-infarct dementia claim 3 , Niemann-Pick disease type C claim 3 , Pallido-ponto-nigral degeneration claim 3 , Parkinsonism-dementia complex of Guam claim 3 , Post-encephalitic parkinsonism claim 3 , Prion diseases claim 3 , Creutzfeldt-Jakob Disease claim 3 , Variant Creutzfeldt-Jakob Disease claim 3 , Fatal Familial Insomnia claim 3 , Kuru claim 3 , Progressive supercortical gliosis claim 3 , Progressive supranuclear palsy claim 3 , Richardson's syndrome claim 3 , Subacute sclerosing panencephalitis claim 3 , Tangle-only dementia claim 3 , Huntington's disease claim 3 , Schizophrenia claim 3 , Mild Cognitive Impairment claim 3 , Neuropathy claim 3 , or Glaucoma.5. The method of wherein the condition is Parkinson's disease.6. The method of wherein the condition is Gaucher's disease.7. The method of wherein the compound is one or more of ...

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Номер записи: 92
14-01-2021 дата публикации

POLYURETHANE POWDER COATING MATERIAL

Номер: US20210009850A1
Автор: Grahl Michael, Laas Hans-Josef, Latorre Martinez Irene Cristina, Pires Raul
Принадлежит:

The invention relates to a polyurethane powder coating material, to the use of such a polyurethane powder coating material, to a method for producing a coating, and to coated substrates. 2. The powder coating material according to claim 1 , wherein component A) comprises at least one polyester which contains hydroxyl groups and has an OH number of 25 to 200 and a number-average molecular weight of 1000 to 5000.3. The powder coating material according to claim 1 , wherein component A) comprises at least one polyester which contains hydroxyl groups claim 1 , has a softening temperature (Tg) within the temperature range from 40 to 120° C. and/or is semicrystalline with a melting point in the range from 40 to 130° C.4. The powder coating material according to claim 1 , wherein component C) comprises at least one polyaddition compound which contains uretdione groups and optionally free isocyanate groups and which is based on one selected from the group consisting of pentamethylene 1 claim 1 ,5-diisocyanate (PDI) claim 1 , hexamethylene 1 claim 1 ,6-diisocyanate (HDI) claim 1 , 1-isocyanato-3 claim 1 ,3 claim 1 ,5-trimethyl-5-isocyanatomethylcyclohexane (isophorone diisocyanate claim 1 , IPDI) claim 1 , 4 claim 1 ,4′- and/or 4 claim 1 ,2′-diisocyanatodicyclohexylmethane (H-MDI) claim 1 , and mixtures of these diisocyanates.5. The powder coating material according to claim 1 , wherein component C) comprises at least one polyaddition compound which contains uretdione groups and optionally free isocyanate groups and which has a minimum carboxylic ester (calculated as CO; molecular weight=44) and/or carbonate (calculated as CO; molecular weight=60) group content of 1 wt %.6. The powder coating material according to claim 1 , wherein curing catalyst D) comprises salt-like compounds comprising a structural element of the general formulae (I) or (II) in which{'sup': 1', '2, 'Rand Rindependently of one another are identical or different radicals which denote saturated or ...

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Номер записи: 93
14-01-2016 дата публикации

Photoelectric conversion element and method of using same, optical sensor and image sensor

Номер: US20160013424A1
Автор: Takahiko Ichiki, Tomoaki Yoshioka, Yosuke Yamamoto
Принадлежит: Fujifilm Corp

A photoelectric conversion element exhibiting excellent responsiveness and high photoelectric conversion efficiency, a method of using the photoelectric conversion element, and an optical sensor and an image sensor including the photoelectric conversion element are provided. The photoelectric conversion element includes a conductive film, a photoelectric conversion film containing a photoelectric conversion material and a transparent conductive film. The conductive film, the photoelectric conversion film and the transparent conductive film are formed in this order. The photoelectric conversion material contains a compound (A) represented by formula (1):

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Номер записи: 94
19-01-2017 дата публикации

CONSTRAINED TRICYCLIC SULFONAMIDES

Номер: US20170015630A1
Автор: KASTRINSKY David, OHLMEYER Michael
Принадлежит: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

Tricyclic chemical modulators of protein phosphatase 2A are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of the following phenothiazine and dibenzoazepine compounds and similar genera: 3. (canceled)4. (canceled)5. A compound according to claim 1 , wherein B is —(CH—CH)—.6. A compound according to claim 1 , wherein B is —S—.7. A compound according to claim 1 , wherein B is —CH═CH—.8. A compound according to claim 1 , wherein A is N.9. A compound according to claim 8 , wherein B is —(CH—CH)— and A is N.10. A compound according to claim 1 , wherein A is —CH.11. A compound according to claim 1 , wherein n is 1.12. (canceled)13. (canceled)14. A compound according to claim 1 , wherein Xand Xare both H.15. (canceled)16. (canceled)17. A compound according to claim 1 , wherein one instance of Y is H or Cl claim 1 , and another instance of Y is selected from —H claim 1 , —F claim 1 , —(C-C)haloalkyl claim 1 , —(C-C)haloalkoxy claim 1 , —(C-C)alkoxy claim 1 , —C(═O)(C-C)alkyl claim 1 , —C(═O)H claim 1 , —(C-C)hydroxyalkyl claim 1 , —(C-C)haloalkylthio claim 1 , —N claim 1 , and —CN.18. A compound according to claim 17 , wherein one instance of Y is H or Cl claim 17 , and another instance of Y is —OCF.19. (canceled)20. A compound according to claim 11 , wherein B is —(CH—CH)— and n is 1.21. (canceled)23. (canceled)25. (canceled)26. (canceled)2837-. (canceled)38. A method for restoring sensitivity to one or more chemotherapeutic agents in the treatment of cancer claim 1 , the method comprising administering an effective amount of a compound according to .39. A method for treating a disease or disorder in a patient where the disease or disorder involves the dysregulation of the PI3K-AKT-FOXO signaling pathway claim 1 , the method comprising administering to the patient a therapeutically effective amount of a compound according to .40. A pharmaceutical composition comprising a ...

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Номер записи: 95
18-01-2018 дата публикации

Morphan And Morphinan Analogues, And Methods Of Use

Номер: US20180016237A1
Автор: Blumberg Laura Cook, Deaver Daniel R., Eyerman David J., Wynn Thomas Andrew
Принадлежит:

The present application relates to analogues of morphan and morphinan, compositions thereof, and methods for treating a disease or condition comprising administering an effective amount of the compounds or compositions to a subject in need thereof. 19-. (canceled)11. The compound of claim 10 , wherein Ris C-Calkenyl or cycloalkyl.12. The compound of claim 10 , wherein Rand R claim 10 , together with the carbon atoms to which they are attached claim 10 , form a 6-membered unsubstituted carbocyclic ring or a 6-membered carbocyclic ring substituted with a hydroxyl or a ketone.13. The compound of claim 10 , wherein Rand R claim 10 , taken together with the carbon atom to which they are attach to claim 10 , form a C═O group.14. The compound of claim 10 , wherein Ris substituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N claim 10 , O and S.16. The compound of claim 15 , wherein Ris cyclopropyl.17. The compound of claim 15 , wherein X is H or hydroxyl.18. The compound of claim 15 , wherein Y and Z are each claim 15 , independently claim 15 , H or hydroxyl claim 15 , or alternatively claim 15 , Y and Z claim 15 , together with the carbon atom to which they are attached claim 15 , form C═O.19. The compound of claim 15 , wherein Ris —C(O)NH.2128-. (canceled)29. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of .30. A method of treating a depressive symptom in a subject in need thereof claim 10 , the method comprising administering to the subject an effective amount of a compound of claim 10 , wherein the compound is a μ opioid receptor agonist having an Emax of 5% to 45% in a GTPγS binding assay.31. (canceled)32. The method of claim 30 , wherein said agonist has a low risk of opioid dependence claim 30 , opioid addiction claim 30 , and/or symptoms of opioid withdrawal.33. A method of treating a depressive symptom in a subject in need thereof claim 10 , the method comprising ...

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Номер записи: 96
21-01-2021 дата публикации

CHROMANE, ISOCHROMANE AND DIHYDROISOBENZOFURAN DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE

Номер: US20210015800A1
Автор: Arasappan Ashok, Basile Anthony S., Bueters Tjerk Johannes Helena, Eagan Michael F., Kim Nancy Dohee, Marshall Fiona Hamilton, Mukai Yuki, Struyk Arie, Uslaner Jason Martin
Принадлежит:

The present invention provides certain substituted chromane, isochromane, and dihydroisobenzofuran compounds of formula (I): 130-. (canceled)321. The composition of claim , wherein the additional therapeutic agent is an acetylcholinesterase inhibitor.331. The composition of claim , wherein the acetylcholinesterase inhibitor is donepezil.35. The composition of claim 34 , wherein the additional therapeutic agent is an acetylcholinesterase inhibitor.365. The composition of claim claim 34 , wherein the acetylcholinesterase inhibitor is donepezil.38. The method of claim 37 , wherein the treating is for Alzheimer's Disease.39. The method of claim 38 , wherein the treating is for mood disorder.40. The method of claim 39 , wherein the mood disorder is depression.41. The method of claim 38 , further comprising administration of an acetylcholinesterase inhibitor.42. The method of claim 41 , wherein the acetylcholinesterase inhibitor is donepezil.44. The method of claim 43 , wherein the treating is for Alzheimer's Disease.45. The method of claim 43 , wherein the treating is for mood disorder.46. The method of claim 45 , wherein the mood disorder is depression.47. The method of claim 44 , further comprising administration of an acetylcholinesterase inhibitor.48. The method of claim 47 , wherein the acetylcholinesterase inhibitor is donepezil. The invention is directed to certain chromane, isochromane, and dihydroisobenzofuran derivatives, their salts, pharmaceutical compositions comprising them and their use in therapy of the human body. The compounds of the invention have been found to modulate the metabotropic glutamate receptor 2 (mGluR2), and hence are expected to be useful in the treatment of Alzheimer's Disease and other diseases mediated by the mGuR2 receptor.The metabotropic glutamate receptors are known to contain one or more allosteric sites, which may alter the affinity with which glutamate and other metabotropic glutamate (mGuR) ligands bind to the primary binding ...

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Номер записи: 97
21-01-2021 дата публикации

Polycyclic aromatic compounds and methods for making and using the same

Номер: US20210017110A1
Автор: Khagendra HAMAL, Paban SITAULA, Wenlong Yang, Wesley CHALIFOUX
Принадлежит: Nevada System of Higher Education NSHE

Disclosed herein are embodiments of polycyclic aromatic compounds and methods of making and using the same. Various different types of polycyclic ring systems are disclosed, including, but not limited to, polymeric aromatic compounds (e.g., nanographene compounds), pentacene-like compounds, chiral aromatic compounds, asymmetric arene compounds formed from naphthalene-, anthracene-, phenanthrene-, and pyrene-based starting compounds, and dimerized aromatic compounds. Also disclosed herein are novel benzannulation-based methods for making the disclosed polycyclic aromatic compounds.

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Номер записи: 98
21-01-2021 дата публикации

SUBSTITUTED 2-PYRIDONE TRICYCLIC COMPOUNDS, ANALOGUES THEREOF, AND METHODS USING SAME

Номер: US20210017186A1
Автор: Chen Shuai, DORSEY Bruce D., Fan Yi, GOTCHEV Dimitar B., Quintero Jorge
Принадлежит: Arbutus Biopharma Corporation

The present invention includes in one aspect substituted 2-oxo-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carboxylic acids, analogues thereof, and compositions comprising the same, which can be used to treat and/or prevent hepatitis B virus (HBV) infection and/or hepatitis D virus (HDV) in a patient. In certain embodiments, the invention provides a compound of formula (I), or a salt, solvate, geometric isomer, stereoisomer, tautomer, and any mixtures thereof: 3. (canceled)5. (canceled)7. The compound of claim 1 , wherein at least one applies:{'sup': 1', '2', '3', '4, '(a) at least one of X, X, X, and Xis N;'}{'sup': 3a', '3b, 'sub': 1', '6', '3', '8, '(b) at least one of Ror Ris independently selected from the group consisting of optionally substituted C-Calkyl and optionally substituted C-Ccycloalkyl;'}{'sup': 6I', '6II', '6III', '6IV, '(c) none of R, R, Rand R, if present, are N-linked;'}{'sup': 6I', '6II', '6III', '6IV, '(d) none of R, R, Rand R, if present, comprise a basic nitrogen group;'}{'sup': 6II', '6III, '(e) at least one of Rand R, if present, is O-linked;'}{'sup': 6II', '6III, '(f) both of Rand R, if present, are O-linked.'}8. The compound of claim 1 , wherein each occurrence of alkyl claim 1 , alkenyl claim 1 , or cycloalkyl is independently optionally substituted with at least one substituent selected from the group consisting of C-Calkyl claim 1 , halo claim 1 , —OR″ claim 1 , phenyl claim 1 , and —N(R″)(R″) claim 1 , wherein each occurrence of R″ is independently H claim 1 , C-Calkyl claim 1 , or C-Ccycloalkyl.9. The compound of claim 1 , wherein each occurrence of aryl or heteroaryl is independently optionally substituted with at least one substituent selected from the group consisting of C-Calkyl claim 1 , C-Chaloalkyl claim 1 , C-Chaloalkoxy claim 1 , halo claim 1 , —CN claim 1 , —OR″ claim 1 , —N(R″)(R″) claim 1 , —NO claim 1 , —S(═O)N(R″)(R″) claim 1 , acyl claim 1 , and C-Calkoxycarbonyl claim 1 , wherein each occurrence of R″ is independently H ...

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Номер записи: 99
21-01-2021 дата публикации

Isomer-enriched 3-caranlactams and polyamides based thereon with high optical purity and adjustable crystallinity for high-performance applications

Номер: US20210017332A1
Автор: Claudia Falcke, Harald Strittmatter, Paul Stockmann, Volker Sieber
Принадлежит: Fraunhofer Gesellschaft zur Forderung der Angewandten Forschung eV

The present invention relates to a process for the preparation of an isomer-enriched mixture of 3S- and 3R-caranone from 3-carane epoxide, a 3S-caranone obtained therefrom, a process for the production of 3S-caranlactam from 3-carene, a process for the production of 3R-caranlactam from 3-carene, a 3S-caranoxime, a 3S-caranlactam, a 3S-polycaranamide, a 3R-polycaranamide, a 3S/3R-co-polycaranamide, a 3S-caranlactam-laurolactam co-polycaranamide, a 3R-caranlactam-laurolactam co-polycaranamide, a 3S-caranlactam-3R-caranlactam-laurolactam co-polycaranamide, a 3S-caranlactam-caprolactam co-polycaranamide, a 3R-caranlactam-caprolactam co-polycaranamide, as well as a 3S/3R-caranlactam-caprolactam co-polycaranamide.

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Номер записи: 100