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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 4696. Отображено 100.
31-05-2012 дата публикации

Fungicidal diphenyl-substituted pyridazines

Номер: US20120135995A1
Автор: Paula Louise Sharpe
Принадлежит: EI Du Pont de Nemours and Co

Disclosed are compounds of Formula 1, including all stereoisomers, N-oxides, and salts thereof, wherein R 1 , R 2 , R 3 , R 4a , R 4b , R 5 , W, m and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling plant disease caused by a fungal pathogen comprising applying an effective amount of a compound or a composition of the invention.

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Номер записи: 1
22-11-2012 дата публикации

Pyridazine derivatives, processes for their preparation and their use as fungicides

Номер: US20120295876A1
Автор: Clemens Lamberth, Stephan Trah
Принадлежит: SYNGENTA CROP PROTECTION LLC

The present invention relates to novel pyridazine derivatives of formula (I) wherein R 1 is methyl or ethyl; R 2 is H or chloro; R 3 is fluoro or chloro; R 4 is fluoro or methoxy; and R 5 is chloro or methoxy or an agrochemically usable salt from thereof, as active ingredients which have microbiodidal activity, in particular fungicidal activity.

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Номер записи: 2
03-01-2013 дата публикации

Method for the detection of prediabetes

Номер: US20130004972A1
Автор: Toshiaki Watanabe
Принадлежит: Fukuoka University

Provided is a method for prediabetes screening by means of methylglyoxal-modified arginine derivative assay, with which it is possible to treat many samples as simply and as safely as with blood sugar assay, and to collect a blood sample taken during a primary health screening in one procedure without imposing any time restraints, complications or risks on the subject. The method for prediabetes screening by means of methylglyoxal-modified arginine derivative assay comprises assaying the methylglyoxal-modified arginine derivative in blood using an assay system which employs an antibody that specifically recognizes methylglyoxal-modified arginine derivative.

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Номер записи: 3
28-03-2013 дата публикации

Electroluminescent Device

Номер: US20130079517A1
Автор: Bardon Kristina, Bujard Patrice, Rogers Jonathan, Schafer Thomas
Принадлежит: BASF SE

Disclosed are electroluminescent devices that comprise organic layers that contain certain organic compounds containing one or more pyrimidine moieties. The organic compounds containing one or more pyrimidine moieties are suitable components of blue-emitting, durable, organo-electroluminescent layers. The electroluminescent devices may be employed for full color display panels in for example mobile phones, televisions and personal computer screens. 10. An electroluminescent device comprising the compound of .11. An electroluminescent device comprising the compound of .12. An electroluminescent device comprising the compound of .13. An electroluminescent device comprising the compound of .14. An electroluminescent device comprising the compound of .15. An electroluminescent device comprising the compound of .16. An electroluminescent device comprising the compound of . This application is a continuation of pending U.S. application Ser. No. 12/794,828 filed Jun. 7, 2010, which is a continuation of U.S. application Ser. No. 10/531,780 filed Apr. 19, 2005 and issued as U.S. Pat. No. 8,012,602 on Sep. 6, 2011, which is a national stage of PCT/EP 2003/11637, filed Oct. 21, 2003, the contents of all foregoing documents are herein incorporated by reference.The present invention relates to organo-electroluminescent (EL) devices, in particular EL devices that comprise durable, blue-emitting organo-electroluminescent layers. The organo-electroluminescent layers comprise certain organic compounds containing one or more pyrimidine moieties.Progress has been made towards developing organic-based electroluminescent devices suitable for full color displays. Generally, an EL device is comprised of a light-emitting layer or layers and a pair of facing electrodes sandwiching the light-emitting layer(s). Application of an electric field between the electrodes results in the injection of electrons and holes to the system, resulting in the release of energy as light.However, organo EL ...

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Номер записи: 4
28-03-2013 дата публикации

REGIOSELECTIVE PREPARATION OF SUBSTITUTED PYRIMIDINES

Номер: US20130079519A1
Автор: DURAN Adil, GOEPPER Stefan, HALMER Joerg, Konrad Michael
Принадлежит:

The present invention relates to a method of making pyrimidines of formula (III) wherein X1, X2, R1 and R2 have the meanings as defined herein. 2. The method of wherein X1 and X2 are the same or different leaving groups independently selected from halide claim 1 , arylsulfonate claim 1 , alkylsulfonate claim 1 , perfluoroalkylsulfonate claim 1 , arylsulfinate and alkylsulfinate.3. The method of wherein X1 and X2 are the same or different leaving groups and are each independently halides.4. The method of wherein X1 and X2 are chloride.5. The method of wherein one of R1 and R2 is hydrogen and the other is an aromatic group claim 1 , such as e.g. optionally substituted phenyl.6. The method of wherein said non-nucleophilic auxiliary base is N claim 1 ,N-diisopropyl-ethylamine.7. The method of wherein said non-nucleophilic alcohols are tert-butanol claim 1 , tert-pentanol claim 1 , neo-pentanol claim 1 , sec-pentanol and sec-isoamylalcohol.8. The method of wherein said reaction is conducted in tert-butanol as reaction solvent.9. The method of wherein said reaction is conducted at a reaction temperature from about room temperature to about boiling temperature of the solvent(s) used.10. The method of wherein said reaction is conducted at a reaction temperature from about 40° C. to about 80° C.11. The method of wherein said reaction is conducted at about 80° C.12. The method of characterized in that said reaction is conducted without any Lewis acidic metal cation.13. The method of further comprising the steps of precipitating the compound of formula III from the reaction mixture claim 1 , collecting the precipitate claim 1 , washing the precipitate and drying the precipitate.14. The method of further comprising the step of reacting said compound of formula III with an oxygen claim 1 , sulphur or nitrogen nucleophile.15. The method of further comprising suspending the precipitate in water after it is precipitated from the reaction mixture.16. The method of characterized in ...

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Номер записи: 5
09-05-2013 дата публикации

Triazolium carbene catalysts and processes for asymmetric carbon-carbon bond formation

Номер: US20130116445A1
Автор: Daniel Dirocco, Joseph Guiles, Tomislav Rovis
Принадлежит: COLORADO STATE UNIVERSITY RESEARCH FOUNDATION

Provided herein are chiral triazolium catalysts useful for asymmetric C—C bond formation and processes for their preparation. Also provided are synthetic reactions in which these catalysts are used, in particular, in asymmetric C—C bond formation.

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Номер записи: 6
16-05-2013 дата публикации

MODULATORS OF CENTRAL NERVOUS SYSTEM NEUROTRANSMITTERS

Номер: US20130123253A1
Автор: CASHMAN John
Принадлежит: HUMAN BIOMOLECULAR RESEARCH INSTITUTE

Disclosed are agents having pharmacological activity against cellular receptors and intracellular signaling, particularly receptors and signaling pathways of central nervous system (CNS) neurotransmitters. Also disclosed are related methods and compositions for the treatment or prevention of diseases or disorders using the agents. 3. A compound of claim 2 , wherein G is hydrogen or combined with Rto form a 5-6 membered heterocylcoalkyl containing 1-2 heteroatoms each independently selected from the group consisting of N and 0; and subscript b is 1-3.4. A compound of claim 3 , wherein D is a member selected from the group consisting of optionally substituted phenyl claim 3 , optionally substituted naphthyl and optionally substituted bi-phenyl; and subscript a is 0-3.5. A compound of claim 3 , selected from the group consisting of:2-(aminomethyl)-5-phenyltetrahydrofuran,2-(aminomethyl)-5-(4′-chlorophenyl)tetrahydrofuran,2-(aminomethyl)-5-(4-bromophenyl)tetrahydrofuran,2-(aminomethyl)-5-(4-methoxyphenyl)tetrahydrofuran,2-(aminomethyl)-5-(4′-t-butylphenyl)tetrahydrofuran,trans-2-(aminomethyl)-5-(2′-methoxy-5′-fluorophenyl)tetrahydrofuran,cis-2-(aminomethyl)-5-(2′-methoxy-5-fluorophenyl)tetrahydrofuran,2-(aminomethyl)-5-(3′-fluoro-4′-methylphenyl)tetrahydrofuran,2-(aminomethyl)-5-cyclohexyltetrahydrofuran,2-(aminomethyl)-5-(1′-naphthyl)tetrahydrofuran,2-(aminomethyl)-5-(2′-naphthyl)tetrahydrofuran,2-(aminomethyl)-5-(2′-naphthyl)tetrahydrofuran,2-(aminoethyl)-5-phenyltetrahydrofuran,2-(aminoethyl)-5-(4′-fluorophenyl)tetrahydrofuran,2-(aminoethyl)-5-(4′-bromophenyl)tetrahydrofuran,2-(aminoethyl)-5-(4′-t-butylphenyl)tetrahydrofuran,trans-7 aminoethyl)-5-(2′-methoxy-5′-fluorophenyl)tetrahydrofuran,cis-2-(aminoethyl)-5-(2′-methoxy-5′-fluorophenyl)tetrahydrofuran,2-(aminoethyl)-5-cyclohexyltetrahydrofuran,2-(aminoethyl)-5-(2′-furyl)tetrahydrofuran,2-(aminomethyl)-5-benzyltetrahydrofuran,2-(aminoethyl)-5-benzyltetrahydrofuran,trans-2-(aminomethyl)-5-(2′-methoxy-5′-fluorobenzyl) ...

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Номер записи: 7
16-05-2013 дата публикации

TREATMENT OF A PATHOLOGY LINKED TO AN EXCESSIVE EFFECT OF TNF WITH A BENZENE SULPHONAMIDE COMPOUND

Номер: US20130123266A1
Автор: Guillemain Hélène, Montes Matthieu, Mouhsine Hadley, ZAGURY Jean-François
Принадлежит: VAX-CONSULTING

A benzene sulphonamide compound of formula I 2. A sulphonated compound as defined in for its use in a method for treating a non-cancer pathology linked to an excessive effect of TNF-alpha chosen from the inflammatory diseases of the intestine claim 1 , inflammation claim 1 , chronic inflammatory diseases claim 1 , rheumatoid arthritis claim 1 , juvenile rheumatoid arthritis claim 1 , psoriatic arthritis claim 1 , arthrosis claim 1 , refractory rheumatoid arthritis claim 1 , non-rheumatoid chronic arthritis claim 1 , bone resorption/osteoporosis claim 1 , Crohn's disease claim 1 , haemorrhagic rectocolitis claim 1 , septic shock claim 1 , endotoxin shock claim 1 , atherosclerosis claim 1 , ischaemia-reperfusion lesions claim 1 , coronary heart disease claim 1 , vasculitis claim 1 , amydoloidosis claim 1 , multiple sclerosis claim 1 , septicaemia claim 1 , chronic recurrent uveitis claim 1 , hepatitis C virus claim 1 , malaria claim 1 , ulcerative colitis claim 1 , cachexia claim 1 , psoriasis claim 1 , endometriosis claim 1 , Behçet's disease claim 1 , Wegener's granulomatosis claim 1 , meningitis claim 1 , AIDS claim 1 , HIV infections claim 1 , auto-immune diseases claim 1 , immunodeficiency claim 1 , common variable immunodeficiency (CVID) claim 1 , chronic graft-versus-host diseases claim 1 , trauma and graft rejections claim 1 , respiratory distress syndrome claim 1 , pulmonary fibrosis claim 1 , diabetes claim 1 , juvenile diabetes claim 1 , ankylosing spondylitis claim 1 , and skin disorders due to delayed-type hypersensitivity reactions claim 1 , Alzheimer's disease claim 1 , disseminated lupus erythematosus claim 1 , and allergic asthma and more generally the inflammatory diseases for which the anti-TNF biotherapies (monoclonal antibodies claim 1 , soluble receptors) are effective.3. A sulphonated compound according to or claim 1 , characterized in that R4 represents a hydrogen atom or a C1-C5 alkyl and', {'claim-ref': {'@idref': 'CLM-00001', 'claims 1'}, ' ...

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Номер записи: 8
16-05-2013 дата публикации

1-PYRIDAZINYL-HYDROXYIMINO-3-PHENYL-PROPANES

Номер: US20130123267A1
Автор: Dehmlow Henrietta, Martin Rainer E., Mattei Patrizio, Obst Sander Ulrike, Richter Hans
Принадлежит: Hoffmann-La Roche Inc.

This invention relates to 1-pyridazinyl-hydroxyimino-3-phenyl-propanes of the formula 2. The compound according to claim 1 , wherein Ris pyridazin-4-yl claim 1 , said pyridazin-4-yl being unsubstituted or substituted by one claim 1 , two or three groups independently selected from the group consisting of C-alkyl claim 1 , halogen claim 1 , halogen-C-alkyl claim 1 , hydroxy claim 1 , hydroxy-C-alkyl claim 1 , C-alkoxy and C-alkoxy-C-alkyl.3. The compound according to claim 1 , wherein Ris 6-oxo-1 claim 1 ,6-dihydropyridazin-3-yl claim 1 , said 6-oxo-1 claim 1 ,6-dihydropyridazin-3-yl being unsubstituted or substituted by one claim 1 , two or three groups independently selected from the group consisting of C-alkyl claim 1 , halogen claim 1 , halogen-C-alkyl claim 1 , hydroxy claim 1 , hydroxy-C-alkyl claim 1 , C-alkoxy and C-alkoxy-C-alkyl.4. The compound according to claim 1 , wherein Ris 3-oxo-2 claim 1 ,3-dihydro-pyridazin-4-yl claim 1 , said 3-oxo-2 claim 1 ,3-dihydro-pyridazin-4-yl being unsubstituted or substituted by one claim 1 , two or three groups independently selected from the group consisting of C-alkyl claim 1 , halogen claim 1 , halogen-C-alkyl claim 1 , hydroxy claim 1 , hydroxy-C-alkyl claim 1 , C-alkoxy and C-alkoxy-C-alkyl.5. The compound according to claim 1 , wherein Ris unsubstituted phenyl or phenyl substituted by one claim 1 , two or three groups independently selected from the group consisting of C-alkyl claim 1 , halogen claim 1 , halogen-C-alkyl claim 1 , halogen-C-alkoxy and C-alkylsulfonyl.6. The compound according to claim 1 , wherein Ris 2-methylphenyl.7. The compound according to claim 1 , wherein Rand Rare hydrogen.8. The compound according to claim 1 , wherein Ris selected from the group consisting of{'sub': '1-7', 'halogen, halogen-C-alkyl,'}{'sub': '1-7', 'cyano, cyano-C-alkyl,'}{'sub': 1-7', '3-7', '1-7, 'C-alkyl, C-alkenyl, C-alkynyl,'}{'sub': 1-7', '1-7', '1-7, 'C-alkoxy, C-alkoxy-C-alkyl,'}{'sub': 1-7', '3-7', '3-7, 'hydroxy, ...

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Номер записи: 9
30-05-2013 дата публикации

DERIVATIVES OF OXADIAZOLE AND PYRIDAZINE, THEIR PREPARATION AND THEIR APPLICATION IN THERAPEUTICS

Номер: US20130137691A1
Автор: Fett Eykmar, Mougenot Patrick, Namane Claudie, Nicolai Eric, Philippo Christophe
Принадлежит: SANOFI

The invention relates to compounds of formula (I): 2. The compound of formula (I) as claimed in claim 1 , wherein:W represents a —CH— group;Y represents a —(C3-C10)cycloalkyl-, aryl or aryloxy group, said groups being optionally substituted with one or more substituents chosen from a halogen atom;Z2 is absent; andZ3 is absent or represents a methylene group.3. The compound of formula (I) as claimed in claim 1 , wherein X1 represents a nitrogen atom claim 1 , and X2 and X3 represent a nitrogen atom or an oxygen atom.4. The compound of formula (I) as claimed in claim 1 , wherein X1 represents —CH═CH— claim 1 , and X2 and X3 represent a nitrogen atom.5. The compound of formula (I) as claimed in claim 1 , selected from the group consisting of:trans{4-[4-(5-benzyl[1.2.4]oxadiazol-3-ylcarbamoyl)phenyl]cyclohexyl}acetic acid,trans{4-[4-(3-benzyl[1.2.4]oxadiazol-5-ylcarbamoyl)phenyl]cyclohexyl}acetic acid,cis-4-[4-(3-benzyl[1.2.4]oxadiazol-5-ylcarbamoyl)phenoxy]cyclohexanecarboxylic acid,cis-4-{4-[3-(3,5-difluorobenzyl)[1.2.4]oxadiazol-5-ylcarbamoyl]phenoxy}cyclohexanecarboxylic acid,cis-4-{4-[3-(1-phenylcyclopropyl)[1.2.4]oxadiazol-5-ylcarbamoyl]phenoxy}-cyclohexanecarboxylic acid,cis-4-{4-[3-(1-methyl-1-phenylethyl)[1.2.4]oxadiazol-5-ylcarbamoyl]phenoxy}-cyclohexanecarboxylic acid,cis-4-[4-(3-phenoxymethyl[1.2.4]oxadiazol-5-ylcarbamoyl)phenoxy]cyclohexanecarboxylic acid,{4-[4-(6-benzylpyridazin-3-ylcarbamoyl)phenyl]cyclohexyl}acetic acid,cis-4-[4-(6-cyclopentylaminopyridazin-3-ylcarbamoyl)phenoxy]cyclohexanecarboxylic acid,cis-4-[5-(3-benzyl[1.2.4]oxadiazol-5-ylcarbamoyl)pyridin-2-yloxy]cyclohexanecarboxylic acid,trans-2-{4-[4-(3-benzyl[1.2.4]oxadiazol-5-ylcarbamoyl)phenyl]cyclohexyl}-cyclopropanecarboxylic acid,trans-(E)-3-{4-[4-(3-benzyl[1.2.4]oxadiazol-5-ylcarbamoyl)phenyl]cyclohexyl}-acrylic acid,trans-3-{4-[4-(3-benzyl[1.2.4]oxadiazol-5-ylcarbamoyl)phenyl]cyclohexyl}-propionic acid,cis-4-[4-(6-phenylaminopyridazin-3-ylcarbamoyl)phenoxy]cyclohexanecarboxylic acid, ...

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Номер записи: 10
30-05-2013 дата публикации

LISOFYLLINE ANALOGS AND METHODS FOR USE

Номер: US20130137693A1
Автор: Cui Peng, Macdonald Timothy L., Nadler Jerry L.
Принадлежит: UNIVERSITY OF VIRGINIA PATENT FOUNDATION

Analogs of a Lisofylline (LSF), and synthetic methods for the preparation of such analogs are provided. The analogs of LSF provided have the ability to protect cell viability, particularly the ability to protect pancreatic β-cells. 2. The compound of claim 1 , wherein Rand Rare the same or different and are selected from hexadecyl claim 1 , 2-hexenyl claim 1 , 3-hexenyl claim 1 , 4-hexenyl claim 1 , 2-hexynyl claim 1 , or 3-hexynyl.3. The compound of claim 2 , wherein Rand Rare hexadecyl.5. A pharmaceutical composition comprising a compound of claim 1 , in combination with a pharmaceutically acceptable carrier.6. A method for preventing or treating a pathological condition or symptom in a mammal claim 1 , wherein the protection of β-cells from Th1 cytokine-induced dysfunction or the onset of Type 1 diabetes can be reduced claim 1 , and such activity is desired claim 1 , comprising administering to said mammal an effective amount of a compound of claim 1 , or pharmaceutically acceptable salt thereof.7. The method of claim 6 , wherein the pathological condition or symptom is Type 1 diabetes.8. The method of claim 6 , wherein the mammal is a human.9. A method for preventing or treating a pathological condition or symptom in a mammal claim 1 , wherein the protection of pancreatic β-cells is desired comprising contacting the cells with an effective protective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.10. The method of claim 9 , wherein the mammal is a human.11. A method for preventing or treating a pathological condition or symptom in a mammal wherein treatment of an inflammatory and autoimmune condition is desired comprising administering to said mammal an effective amount of a compound of claim 1 , or pharmaceutically acceptable salt thereof.12. The method of claim 11 , wherein the inflammatory or autoimmune condition is atherosclerosis claim 11 , type 2 diabetes claim 11 , disorders associated with visceral obesity claim 11 , ...

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Номер записи: 11
30-05-2013 дата публикации

SUBSTITUTED 4-(4-FLUORO-3-(PIPERAZINE-1-CARBONYL)BENZYL)PHTHALAZIN-1(2H)-ONE DERIVATIVES AS POLY (ADP-RIBOSE) POLYMERASE-1 INHIBITORS

Номер: US20130137695A1
Автор: Shrivastava Brijesh Kumar
Принадлежит: CADILA HEALTHCARE LIMITED

Disclosed are compounds of general formula (I), their stereoisomers, regioisomers, tautomeric forms and novel intermediates involved in their synthesis, their pharmaceutically acceptable salts. These compounds are suitable as Poly (ADP-ribose) polymerase-1 inhibitors (PARP-1 inhibitors). 2. The compounds as claimed in claim 1 , wherein substituents on Ris selected from hydroxyl claim 1 , oxo claim 1 , halo claim 1 , thio claim 1 , nitro claim 1 , amino claim 1 , alkyl claim 1 , alkoxy claim 1 , haloalkyl or haloalkoxy groups.3. The compounds as claimed in claim 1 , wherein the aryl group is selected from phenyl claim 1 , naphthyl claim 1 , tetrahydronaphthyl claim 1 , indenyl claim 1 , dihydroindenyl or biphenyl groups.4. The compounds as claimed in claim 3 , wherein the substituents on aryl group is selected from hydrogen claim 3 , halogen claim 3 , alkyl claim 3 , alkoxy claim 3 , hydroxyl claim 3 , haloalkyl claim 3 , haloalkoxy claim 3 , cyano claim 3 , thioalkyl or cycloalkyl groups.5. The compounds as claimed in claim 1 , wherein the heteroaryl group is selected from pyridyl claim 1 , thienyl claim 1 , furyl claim 1 , pyrrolyl claim 1 , indolinyl claim 1 , indolyl claim 1 , pyridofuranyl claim 1 , pyridothienyl claim 1 , thienopyrimidyl claim 1 , quinolinyl claim 1 , pyrimidinyl claim 1 , pyrazolyl claim 1 , quinazolinyl claim 1 , pyridazinyl claim 1 , purinyl groups.6. The compounds as claimed in claim 5 , wherein the substituents on heteroaryl group is selected from hydrogen claim 5 , halogen claim 5 , alkyl claim 5 , alkoxy claim 5 , hydroxyl claim 5 , haloalkyl claim 5 , haloalkoxy claim 5 , aryl claim 5 , aralkyl claim 5 , cyano claim 5 , alkylthio or thioalkyl groups.7. The compounds as claimed in claim 1 , wherein the heterocyclic group is selected from aziridinyl claim 1 , azetidinyl claim 1 , pyrrolidinyl claim 1 , imidazolidinyl claim 1 , piperidinyl claim 1 , piperazinyl claim 1 , 2-oxopiperidinyl claim 1 , 4-oxopiperidinyl claim 1 , 2- ...

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Номер записи: 12
30-05-2013 дата публикации

THERAPEUTIC COMPOUNDS

Номер: US20130137699A1
Автор: Dawson Marcia, Fontana Joseph A., Xia Zebin
Принадлежит:

The invention provides compounds of formula I or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for inducing apoptosis or treating cancer using compounds of formula I. 2. The compound of wherein Zis N claim 1 , Zis CR claim 1 , Zis CRand Zis N.3. The compound of wherein Zis CR claim 1 , Zis CR claim 1 , Zis CRand Zis N.4. The compound of wherein Ris H or halo.56-. (canceled)7. The compound of wherein Zis CR claim 1 , Zis N claim 1 , Zis CRand Zis N.89-. (canceled)10. The compound of wherein Zis CR claim 1 , Zis CR claim 1 , Zis N and Zis N.1112-. (canceled)13. The compound of wherein Zis CR claim 1 , Zis N claim 1 , Zis CRand Zis CR.1416-. (canceled)17. The compound of wherein Zis CR claim 1 , Zis N claim 1 , Zis N and Zis CR.1819-. (canceled)20. The compound of wherein Ris adamantyl wherein any adamantyl of Rmay be optionally substituted with one or more groups selected from —OH and oxo(═O).2123-. (canceled)24. The compound of claim wherein Ris —OH or —OC(═O)R.2527-. (canceled)28. The compound of wherein Ris H or (C-C)alkoxy.2931-. (canceled)32. The compound of wherein Rand Rtogether with the atoms to which they are attached form a alkylenedioxy ring claim 1 , wherein the alkylenedioxy ring is optionally substituted is with one or more (C-C)alkyl.33. (canceled)34. The compound of wherein A is —CR═CR—.35. (canceled)36. The compound of wherein Ris H or (C-C)alkyl.37. (canceled)39. A composition comprising a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable diluent or carrier.40. (canceled)41. A method for inducing apoptosis or cell death in a mammal in need of such treatment comprising administering to the mammal an effective amount of a compound as described in claim 1 , or a ...

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Номер записи: 13
06-06-2013 дата публикации

METHOD FOR PREPARING ROSUVASTATIN CALCIUM INTERMEDIATE

Номер: US20130143908A1
Автор: LIN Wenqing, YANG Peng, ZHENG Hongjie
Принадлежит: PORTON FINE CHEMICALS LTD.

A method for preparing a rosuvastatin calcium intermediate represented by formula I. The method includes: hydrolyzing an ester compound represented by formula II (in which, R represents C1-C5) in the presence of a metal compound to obtain a carboxylic acid compound represented by formula III; and reducing the carboxylic acid compound in the presence of a reductant. 2. The method of claim 1 , wherein in step a) claim 1 , the metallic compound is LiOH or a hydrate thereof.3. The method of claim 1 , wherein in step b) claim 1 , the reductant is a borane or a hydroboron and Lewis acid reduction system.4. The method of claim 3 , wherein the hydroboron and Lewis acid reduction system is selected from the group consisting of a system comprising potassium borohydride and boron trifluoride diethyl etherate; a system comprising sodium borohydride and boron trifluoride diethyl etherate; a system comprising lithium borohydride and boron trifluoride diethyl etherate; a system comprising potassium borohydride and HSO; a system comprising potassium borohydride and ZnCl; a system comprising potassium borohydride and AlCl; a system comprising potassium borohydride and I; a system comprising potassium borohydride and CFCOOH; a system comprising potassium borohydride and HCOOH; a system comprising potassium borohydride and MsOH; a system comprising potassium borohydride and CHCOOH; a system comprising potassium borohydride and NiCl; a system comprising zinc borohydride and HSO; a system comprising zinc borohydride and ZnCl; a system comprising zinc borohydride and AlCl; a system comprising zinc borohydride and I; a system comprising zinc borohydride and CFCOOH; a system comprising zinc borohydride and HCOOH; a system comprising zinc borohydride and MsOH; a system comprising zinc borohydride and CHCOOH; a system comprising zinc borohydride and NiCl; a system comprising sodium borohydride and HSO; a system comprising sodium borohydride and ZnCl; a system comprising sodium borohydride ...

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Номер записи: 14
20-06-2013 дата публикации

PHENYLAMIDINES HAVING A HIGH FUNGICIDAL ACTIVITY AND USE THEREOF

Номер: US20130157851A1
Автор: Badaracco Christian, BRAVINI Paolo, Elmini Alexia, FILIPPINI Lucio, Gusmeroli Marilena, PELLACINI Franco, VAZZOLA Matteo Santino
Принадлежит: ISAGRO S.P.A.

New phenylamidines are described, having general formula (I): 4. Fungicidal compositions comprising one or more compounds having formula (I) claim 1 , according to claim 1 , a solvent and/or a solid or liquid diluent claim 1 , optionally a surfactant.5. The compositions according to claim 4 , also comprising active principles compatible with the compounds having general formula (I) claim 4 , selected from fungicides other than the compounds having general formula (I) claim 4 , phytoregulators claim 4 , antibiotics claim 4 , herbicides claim 4 , insecticides claim 4 , fertilizers and/or mixtures thereof claim 4 , antifreeze agents claim 4 , adhesion agents.6. The compositions according to claim 4 , wherein the concentration of compounds having general formula (I) ranges from 1 to 90% by weight with respect to the total weight of the composition claim 4 , preferably from 5 to 50% by weight with respect to the total weight of the composition.8. Use of the compounds according to claim 2 , for the control of phytopatogenic fungi in agricultural crops.9. Use of the compositions according to for the control of phytopatogenic fungi in agricultural crops.10PucciniaUstilagoTilletiaUromycesPhakopsoraRhizoctoniaErysipheSphaerothecaPodosphaeraUncinulaHelminthosporiumRhynchosporiumPyrenophoraMoniliniaSclerotiniaSeptoriaMycosphaerellaVenturiaBotrytisAlternariaFusariumCercosporaCercosporella herpotrichoides, ColletotrichumPyricularia oryzae, SclerotiumPhytophtoraPythiumPlasmopara viticola, PeronosporaPseudoperonospora cubensis, Bremia lactucae.. Use according to claim 7 , for the control of phytopatogenic fungi belonging to the group of Basidiomycetes claim 7 , Ascomycetes claim 7 , Deuteromycetes or imperfect fungi claim 7 , Oomycetes: spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. claim 7 , spp. (spp.) claim 7 , ...

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Номер записи: 15
20-06-2013 дата публикации

Tyrosine Kinase Inhibitors

Номер: US20130158041A1
Автор: Daniels Matthew, Wilson Kevin
Принадлежит:

The present invention relates to pyridazinthione derivatives that are useful for treating cellular proliferative diseases, for treating disorders associated with MET activity, and for inhibiting the receptor tyrosine kinase MET. The invention also relates to compositions which comprise these compounds, and methods of using them to treat cancer in mammals. 2. The compound of wherein Ris heteroaryl claim 1 , wherein said heteroaryl group is optionally substituted with one to three groups independently selected from the group consisting of halo claim 1 , cyano claim 1 , Calkyl claim 1 , (Calkyl)R claim 1 , heterocyclyl claim 1 , ORand (C═O)N(R)(R); or a pharmaceutically acceptable salt thereof.3. The compound of wherein Ris heteroaryl claim 2 , wherein said heteroaryl group is optionally substituted with Calkyl claim 2 , or a pharmaceutically acceptable salt thereof.4. The compound of wherein Ris hydrogen claim 2 , and Ris hydrogen claim 2 , or a pharmaceutically acceptable salt thereof.6. The compound of wherein Ris phenyl claim 5 , wherein said phenyl group is substituted with heteroaryl claim 5 , which is optionally substituted with ORor R claim 5 , or a pharmaceutically acceptable salt thereof.7. The compound of wherein X is O.8. The compound of selected from:3-[3-(5-Ethoxypyrimidin-2-yl)benzyl]-1-(1-methyl-1H-pyrazol-4-yl)pyridazin-4(1H)-one;3-[3-(5-methoxypyrimidin-2-yl)benzyl]-1-(1-methyl-1H-pyrazol-4-yl)pyridazin-4(1H)-thione;3-{3-[5-(2-methoxyethoxy)pyrimidin-2-yl]benzyl}-1-(1-methyl-1H-pyrazol-4-yl)pyridazin-4(1H)-thione;3-[3-[3-(5-ethoxypyrimidin-2-yl)benzyl]-4-thioxopyridazin-1(4H)-yl]benzonitrile;1-(1-ethyl-1H-pyrazol-4-yl)-3-[3-(1-propyl-1H-1,2,4-triazol-3-yl)benzyl]pyridazin-4(1H)-thione;3-(3-aminobenzyl)-1-(3,4-difluorophenyl)pyridazine-4(1H)-thione;N-(3-{[1-(3,4-difluorophenyl)-4-thioxo-1,4-dihydropyridazin-3-yl]methyl}phenyl)-2,2,2-trifluoroacetamide;N-(3-{[1-(3,4-difluorophenyl)-4-thioxo-1,4-dihydropyridazin-3-yl]methyl}phenyl)-2,2,2- ...

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Номер записи: 16
27-06-2013 дата публикации

JAK1 Inhibitors

Номер: US20130165440A1
Автор: Anand Neel Kumar, Brown S. David, Tesfai Zerom, Zaharia Cristiana A.
Принадлежит: Exelixis, Inc.

JAK1 inhibitors of structural formula (I), wherein Ar, Ar, Q, W, X, Y, and Z are defined in the specification, pharmaceutically acceptable salts thereof, compositions thereof, and use of the compounds and compositions for treating diseases. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases. 2. The compound according to wherein:{'sup': 1', '1', '2, 'Aris phenyl optionally substituted with 1-2 Rgroups, or heteroaryl optionally substituted with 1-2 Rgroups;'}{'sup': 2', '5, 'Aris phenyl optionally substituted with 1-3 Rgroups;'}{'sup': 1', '3', '3', '4', '3', '4', '3, 'sub': '2', 'each Ris independently —C(O)OR, —C(O)R, —C(O)N(H)alkylR, —N(H)C(O)alkyl, —C(O)N(R)(R), or —SOR;'}{'sup': 2', '3', '4', '3, 'each Ris independently —N(R)(R), alkyl, or —C(O)OR;'}{'sup': '3', 'Ris H or alkyl;'}{'sup': '4', 'Ris H or alkyl optionally substituted with heterocyclyl;'}{'sup': 5', '3', '6', '6', '3', '6', '3, 'each Ris independently halo, —CN, —C(O)OR, R, —OR, —N(R)R, alkyl optionally substituted with 1-3 halo, alkoxy optionally substituted with 1-3 halo, or heterocyclyl optionally substituted with R;'}{'sup': 6', '3', '7, 'Ris alkyl optionally substituted with —NRR;'}{'sup': '7', 'Ris H or alkyl;'}Q is C(H) or N;W is C(H) or N;X is C(H) or N;Y is C(H) or N; andZ is C(H) or N.4. The compound according to claim 3 , wherein:{'sup': 1', '1', '2, 'Aris phenyl optionally substituted with 1-2 Rgroups or heteroaryl optionally substituted with 1-2 Rgroups, wherein the heteroaryl is 1H-indazolyl, pyrazolyl, benzotriazolyl, or benzofuranyl, isoindolyl;'}{'sup': 5', '3', '6', '6', '3', '6', '3, 'sub': 1', '3, 'each Ris independently halo, —CN, —C(O)OR, R, —OR, —N(R)R, (C-C)alkyl optionally substituted with 1-3 halo, alkoxy optionally substituted with 1-3 halo, or heterocyclyl optionally substituted with R; and'}{'sup': '7', 'sub': 1', '3, 'Ris H or (C-C)alkyl.'}12. A composition comprising a compound according to and ...

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Номер записи: 17
04-07-2013 дата публикации

PYRIMIDINE COMPOUNDS AND THEIR USES

Номер: US20130172350A1
Автор: Balasubramanian Gopalan, Parameswaran Venkatesan, Saxena Sanjeev, SHARMA Ganapavarapu, Vishwakarma Santosh
Принадлежит: Orchid Chemicals and Pharmaceuticals Limited

Pyrimidine compounds of the general formula (I), their derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites and prodrugs thereof, are useful are useful as PDE4 inhibitors and are useful for treating PDE4 mediated diseases and in the treatment of immunological diseases, inflammation, pain disorder, rheumatoid arthritis; osteoporosis; multiple myeloma; uveititis; acute and chronic myelogenous leukemia; atherosclerosis; cancer; cachexia; ischemic-induced cell damage; pancreatic beta cell destruction; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; ARDS; psoriasis; Crohn's disease; allergic rhinitis; ulcerative colitis; anaphylaxis; contact dermatitis; muscle degeneration; asthma; COPD; bone resorption diseases; multiple sclerosis; sepsis; septic shock; toxic shock syndrome and fever. 4. The composition of in the form of a tablet claim 3 , capsule claim 3 , powder claim 3 , syrup claim 3 , solution or suspension.6. A method of treatment of rheumatoid arthritis in a mammal comprising administering an effective amount of a compound as claimed in to the mammal in need thereof.7. A method of treatment of osteoporosis in a mammal comprising administering an effective amount of a compound as claimed in to the mammal in need thereof.8. A method of treatment of multiple myeloma in a mammal comprising administering an effective amount of a compound as claimed in to the mammal in need thereof.9. A method of treatment of uveitis in a mammal comprising administering an effective amount of a compound as claimed in to the mammal in need thereof.10. A method of treatment of atheroscelorsis in a mammal comprising administering an effective amount of a compound as claimed in to the mammal in need thereof.11. A method of treatment of osteoarthritis in a mammal comprising administering an effective amount of a compound as claimed in to the ...

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Номер записи: 18
04-07-2013 дата публикации

METHOD FOR PRODUCING PYRIDAZINONE COMPOUNDS AND INTERMEDIATE THEREOF

Номер: US20130172556A1
Автор: ANRYU Mitsuharu, JACHMANN Markus, WAKAMATSU Takayuki
Принадлежит:

The present invention relates to a novel method for producing a pyridazinone compound and an intermediate thereof as shown in the following scheme: wherein the symbols are as defined in the specification. 2. The method according to claim 1 , wherein n is an integer of 2.3. The method according to claim 1 , wherein G is a phenyl group wherein the phenyl group may optionally have one or more substituents selected from the Group R claim 1 , provided that when it has two or more substituents claim 1 , then the substituents may be same or different.4. The method according to claim 1 , wherein the Group Ris Group R;{'sup': '4-1', 'wherein the Group Rconsists of halogen, a cyano group, a nitro group, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C6 cycloalkyl group, a C2-C6 alkynyl group, and a phenyl group;'}{'sup': '4-1', 'in the Group R, the C1-C6 alkyl group, the C1-C6 alkoxy group, the C3-C6 cycloalkyl group, and the C2-C6 alkynyl group may be optionally substituted with one or more halogens, provided that when they are substituted with two or more halogens, then the halogens may be same or different; and'}the phenyl group may optionally have one or more substituents selected from Group 4-1, provided that when it has two or more substituents, then the substituents may be same or different;the Group 4-1 consists of halogen and a C1-C6 alkyl group;in the Group 4-1, the C1-C6 alkyl group may be optionally substituted with one or more halogens, provided that when it is substituted with two or more halogens, then the halogens may be same or different.5. The method according to claim 4 , wherein Ris hydrogen claim 4 , a C1-C6 alkyl group or a phenyl group claim 4 ,{'sup': '2', 'Ris hydrogen, a C1-C6 alkyl group or a phenyl group wherein the C1-C6 alkyl group may be optionally substituted with one or more halogens, provided that when it is substituted with two or more halogens, then the halogens may be same or different, and the phenyl group may optionally have one or more ...

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Номер записи: 19
11-07-2013 дата публикации

PYRIDAZINE AMIDE COMPOUNDS

Номер: US20130178478A1
Автор: Hermann Johannes Cornelius, Kennedy-Smith Joshua, Lucas Matthew C., Padilla Fernando, Soth Michael
Принадлежит: Hoffman-La Roche Inc.

The present invention relates to the use of novel triazolopyridine derivatives of formula I: 2. The compound of claim 1 , wherein B is pyridyl.3. The compound of claim 2 , wherein A is cyclohexyl or tetrahydro pyranyl.4. The compound of claim 3 , wherein m is 1.5. The compound of claim 4 , wherein X is amino.6. The compound of claim 5 , wherein n is 1.7. The compound of claim 6 , wherein Y is lower alkyl claim 6 , cycloalkyl claim 6 , heteroaryl claim 6 , or lower alkyl sulfonyl.8. The compound of claim 7 , wherein Y is lower alkyl.9. The compound of claim 5 , wherein n is 2.10. The compound of claim 9 , wherein one Y is lower alkyl and the other is halo or lower alkyl.11. The compound of claim 1 , wherein B is pyrrolo[2 claim 1 ,3-b]pyridinyl or pyrazolyl.12. A compound selected from the group consisting of:6-(cis-2-Amino-cyclohexylamino)-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide;6-(cis-2-Amino-cyclohexylamino)-4-(6-ethyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide;6-((3R,4R)-3-Amino-tetrahydro-pyran-4-ylamino)-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide;6-((1S,2R)-2-Amino-cyclohexylamino)-4-(6-[1,2,3]triazol-1-yl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide;6-(cis-2-Amino-cyclohexylamino)-4-(5-methanesulfonyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide;6-((1R,2S)-2-Amino-cyclohexylamino)-4-p-tolylamino-pyridazine-3-carboxylic acid amide;6-((1R,2S)-2-Amino-cyclohexylamino)-4-(6-isopropyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide;6-((3R,4R)-3-Amino-tetrahydro-pyran-4-ylamino)-4-(5,6-dimethyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide;6-((1R,2S)-2-Amino-cyclohexylamino)-4-(1-methyl-1H-pyrazol-3-ylamino)-pyridazine-3-carboxylic acid amide;6-((1R,2S)-2-Amino-cyclohexylamino)-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide;6-((1R,2S)-2-Amino-cyclohexylamino)-4-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazine-3-carboxylic acid amide;6-((1R,2S)-2- ...

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Номер записи: 20
01-08-2013 дата публикации

PREPARATION METHOD OF ROSUVASTATIN CALCIUM AND ITS INTERMEDIATES

Номер: US20130197224A1
Автор: CHEN Benshun, JIN Xiaofeng, WANG Bing, ZOU Lin
Принадлежит: CHANGZHOU PHARMACEUTICAL FACTORY

A preparation method of rosuvastatin calcium (Formula 1), which can be used for the production of medicament lowering the levels of LDL-cholesterol and triglycerides in vivo, is provided. Such preparation method is suitable for industrial production. Furthermore, the intermediate crystallines used in the preparation method are provided. 2. The method of claim 1 , wherein the crystalline intermediate is chosen from (3R claim 1 ,5S claim 1 ,6E)-7-[4-(4-fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 1 ,5-dihydroxyl-6-methyl heptenoate claim 1 , (3R claim 1 ,5S claim 1 ,6E)-7-[4-(4fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 1 ,5-dihydroxyl-6-isopentyl heptenoate claim 1 , and (3R claim 1 ,5S claim 1 ,6E)-7-[4-(4-fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 1 ,5-dihydroxyl-6-isopentyl heptenoate3. The method of claim 2 , wherein the crystalline intermediate is (3R claim 2 ,5S claim 2 ,6E)-7-[4-(4-fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 2 ,5-dihydroxyl-6-methyl heptenoate claim 2 , and the crystalline intermediate has a spectrum of powder XRD with peak values at 2θ=8.7 claim 2 , 9.3 claim 2 , 9.6 claim 2 , 17.4 claim 2 , 18.0 claim 2 , 19.5 claim 2 , 21.7 claim 2 , 24.4 claim 2 , 24.7 and 26.3.4. The method of claim 3 , wherein the crystalline intermediate is prepared from (3R claim 3 ,5S claim 3 ,6E)-7-[4-(4-fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 3 ,5-dihydroxyl-6-methyl heptenoate following step (c).5. The method of claim 4 , wherein the crystalline intermediate is prepared by recrystallizing (3R claim 4 ,5S claim 4 ,6E)-7-[4-(4-fluorophenyl)-6-(1-methyl ethyl)-2-[methyl(methyl sulfonyl)amino]-5-pyrimidyl]-3 claim 4 ,5-dihydroxyl-6-methyl heptenoate in the presence of a solvent comprising ethyl ether.6. The crystalline intermediate of being used for the ...

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Номер записи: 21
15-08-2013 дата публикации

Method for determining odor when using a self-tanning agent

Номер: US20130210159A1
Автор: Masayuki Yabuki, Miki Takahashi
Принадлежит: Kao Corp

A method for evaluating an odor generated when using a self-tanning agent, wherein at least one compound selected from pyrazine compounds represented by the following general formula (1) is used as an indicator substance: wherein R 1 represents a methyl group, an ethyl group or an acetyl group, and R 2 , R 3 and R 4 independently represent a hydrogen atom or a methyl group.

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Номер записи: 22
29-08-2013 дата публикации

HETEROCYCLIC DERIVATES, PREPARATION PROCESSES AND MEDICAL USES THEREOF

Номер: US20130224107A1
Автор: Gao Daxin
Принадлежит: SHANGHAI DE NOVO PHARMATECH CO LTD.

Disclosed are heterocyclic derivatives, methods for making them, compositions containing the same and uses thereof. Particularly, their pharmaceutical use as inhibitors of PARP is disclosed. 1. A Compound of the formula (I) , and hydrates , isomers , solvates , prodrugs , and a pharmaceutically acceptable salt thereof:{'br': None, 'B-A-CO-Q-CO—CO—R\u2003\u2003(I)'}Wherein:A is aryl or substituted aryl; heteroaryl or substituted heteroaryl, said substituents are selected from the group consisting of halo, cyano, lower alkyl, amino, lower alkylamino, sulfonamide, lower alkyl alkyoxyl, and alkyl substituted by optionally substituted heterocyclic group or optionally substituted aryl; andB is aryl or substituted aryl; heteroaryl or substituted heteroaryl, said substituents are selected from the group consisting of halo, cyano, lower alkyl, amino, lower alkylamino, sulfonamide, and lower alkyl alkyoxyl, and alkyl substituted by optionally substituted heterocyclic group or optionally substituted aryl;Q is optionally substituted heterocyclic ring which contains at least two nitrogen atoms as a member of the atoms forming the ring wherein the at least two nitrogen atoms independently bind to —CO-A-B group and —CO—CO—R group at the carbon atom of carbonyl, respectively; and is selected from the group consisting of mono-heterocyclic group, bridged-heterocyclic group, bi-heterocyclic group, and spiro-heterocyclic group; andR is selected from the group consisting of alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, and heteroaryl or substituted heteroaryl, said substituents are selected from the group consisting of halo, lower alkyl, amino, lower alkylamino, lower alkyl alkyoxyl, haloalkoxyl, hydroxyl, amido, aminocarbonyl, sulfonamide, cyano, alkynyl, alkoxyl, aryloxyl, carboxylic acid, and carboxylic ester.7. A ...

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Номер записи: 23
29-08-2013 дата публикации

Crystalline Form of Bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] Calcium Salt

Номер: US20130225622A1
Автор: Booth Rebecca Jane, Cittern Peter Anthony, Crabb Jeffrey Norman, Hornbury John, Jones David Wyn Calvert
Принадлежит: AstraZeneca UK Limited

Two polymorphic forms of bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt, processes for making them and their use as HMG Co-A reductase inhibitors are described. 2. The crystalline hydrated form as claimed in with an X-ray powder diffraction pattern with peaks at 2-theta (2θ)=4.3 claim 1 , 8.8 claim 1 , 13.1 claim 1 , 13.7 claim 1 , 21.5 claim 1 , 22.8 and 28.9°.3. The crystalline hydrated form as claimed in with an X-ray powder diffraction pattern with peaks at 2-theta (2θ)=4.3 claim 1 , 8.8 claim 1 , 13.1 claim 1 , 13.7 claim 1 , 15.2 claim 1 , 15.8 claim 1 , 17.5 claim 1 , 21.5 claim 1 , 21.9 claim 1 , 22.8 claim 1 , 24.5 and 28.9°.4. The crystalline hydrated form as claimed in claim 1 , which contains about 9-10% water.5. The crystalline hydrated form as claimed in having an X-ray powder diffraction pattern substantially as shown in .7. The crystalline form as claimed in having an X-ray powder diffraction pattern substantially as shown in .8. A pharmaceutical composition comprising the crystalline form as claimed in and a pharmaceutically acceptable carrier.9. A process for formation and amorphous bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R claim 1 ,5S)-3 claim 1 ,5-dihydroxyhept-6-enoic acid] calcium salt comprising{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'isolating from a solution the crystalline form as claimed in ; and'}subsequently converting the crystalline form to an amorphous form.10. The process as claimed in comprisingmixing a solution contain [(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt with a slurry of the crystalline form of formula 1 having an X-ray powder diffraction pattern with peaks at 2-theta (2θ)=8.8, 13.1 and 21.5° or formula 1 having an X-ray powder diffraction pattern with peaks at 2-theta (2θ)=4.4, 7 ...

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Номер записи: 24
05-09-2013 дата публикации

Compounds and Method for Treatment of Cancer

Номер: US20130231345A1
Автор: Danter Wayne R., Lau Cheuk Kun
Принадлежит: CRITICAL OUTCOME TECHNOLOGIES, INC.

The invention relates to a compound of Formula I: 2. The compound of claim 1 , wherein R claim 1 , Rand Rare each independently selected from H claim 1 , halo claim 1 , hydroxyl claim 1 , cyano claim 1 , substituted or unsubstituted alkyl claim 1 , substituted or unsubstituted alkenyl claim 1 , substituted or unsubstituted alkynyl claim 1 , substituted or unsubstituted haloalkyl claim 1 , substituted or unsubstituted hydroxyalkyl claim 1 , substituted or unsubstituted alkoxy claim 1 , a substituted or unsubstituted heterocyclic group claim 1 , a substituted or unsubstituted aromatic group claim 1 , a substituted or unsubstituted heteroaromatic group claim 1 , carboxyl claim 1 , alkylcarbonyl claim 1 , arylcarbonyl claim 1 , cycloalkylcarbonyl claim 1 , heterocyclylcarbonyl claim 1 , amino claim 1 , aminoalkyl claim 1 , alkylaminoalkyl claim 1 , heterocyclylalkyl claim 1 , aralkyl claim 1 , arylalkenyl claim 1 , arylalkynyl claim 1 , alkylthio claim 1 , alkylamino claim 1 , arylamino claim 1 , heteroarylamino claim 1 , aralkylamino claim 1 , alkylaminoalkylamino claim 1 , arylthio claim 1 , aralkylthio claim 1 , aryloxy claim 1 , aralkoxy claim 1 , heterocyclylalkoxy claim 1 , heterocyclyloxyalkyl claim 1 , cycloalkyl claim 1 , and cycloalkenyl.3. The compound of claim 2 , wherein Ris selected from a substituted or unsubstituted aromatic group claim 2 , or a substituted or unsubstituted heteroaromatic group claim 2 , the substituted aromatic group or heteroaromatic group being substituted with at least one group selected from halo claim 2 , hydroxyl claim 2 , amino claim 2 , nitro claim 2 , a substituted or unsubstituted hydrocarbon group claim 2 , a substituted or unsubstituted heterogeneous group claim 2 , a substituted or unsubstituted carbocyclic group claim 2 , a substituted or unsubstituted heterocyclic group claim 2 , a substituted or unsubstituted aromatic group claim 2 , or a substituted or unsubstituted heteroaromatic group and Ris H or substituted or ...

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Номер записи: 25
12-09-2013 дата публикации

PYRIDAZINE DERIVATIVES, COMPOSITIONS AND METHODS FOR TREATING COGNITIVE IMPAIRMENT

Номер: US20130237545A1
Автор: III John A., Lowe
Принадлежит: AGENEBIO, INC.

This invention relates to pyridazine derivatives, compositions comprising therapeutically effective amounts of those pyridazine derivatives and methods of using those derivatives or compositions in treating central nervous system (CNS) disorders with cognitive impairment that are responsive to agonists of α5 subunit containing GABAreceptor, e.g., age-related cognitive impairment, Mild Cognitive Impairment (MCI), dementia, Alzheimer's Disease (AD), prodromal AD, post traumatic stress disorder (PTSD), schizophrenia and cancer-therapy-related cognitive impairment. 4. The compound according to claim 3 , wherein at least one of Rand Ris hydrogen.5. The compound according to claim 4 , wherein Rand Rare each independently hydrogen.6. The compound according to claim 3 , wherein at least one of Rand Ris (C1-C12)-aliphatic- substituted at each substitutable position with 0-3 substituents independently selected from J.7. The compound according to claim 6 , wherein Rand Rare each independently (C1-C12)-aliphatic- substituted at each substitutable position with 0-3 substituents independently selected from J.8. The compound according to claim 7 , wherein Rand Rare each independently unsubstituted (C1-C4)-aliphatic.9. The compound according to claim 8 , wherein Rand Rare each independently methyl claim 8 , ethyl or allyl.10. The compound according to claim 7 , wherein Rand Rare each independently (C1-C4)-alkyl claim 7 , and wherein at least one of Rand Ris substituted with at least one (C6-C10)-aryl.11. The compound according to claim 10 , wherein Rand Rare each independently substituted with at least one (C6-C10)-aryl.12. The compound according to or claim 10 , wherein the at least one (C6-C10)-aryl is phenyl.13. The compound according to claim 6 , wherein Ris H— and Ris (C1-C12)-aliphatic-substituted at each substitutable position with 0-3 substituents independently selected from J.14. The compound according to claim 13 , wherein Ris unsubstituted (C1-C4)-alkyl.15. The compound ...

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Номер записи: 26
19-09-2013 дата публикации

AMIDE COMPOUNDS

Номер: US20130245033A1
Автор: HU Wenhui, XU Hongjiang, YANG Ling, Zhong Guifa
Принадлежит: GUANGZHOU INSTITUTES OF BIOMEDICINE AND HEALTH, CHINESE ACADEMY OF SCIENCES

A compound represented by formula (I) and the pharmaceutical acceptable salt thereof are disclosed, 3. The compound represented by formula (I) and the pharmaceutical acceptable salt thereof according to claim 1 , wherein Ris a substituted or unsubstituted C-Calkyl claim 1 , substituted or unsubstituted C-Ccyclic alkyl claim 1 , substituted or unsubstituted C-Caryl claim 1 , or substituted or unsubstituted 5-10 members heterocyclic aryl claim 1 , wherein the substituents are selected from the group consisting of aryl claim 1 , aryl alkyl claim 1 , alkyl claim 1 , alkoxy claim 1 , substituted alkyl claim 1 , halogen claim 1 , hydroxyl claim 1 , azyl claim 1 , and cyano group claim 1 , respectively.4. The compound represented by formula (I) and the pharmaceutical acceptable salt thereof according to claim 1 , wherein Ris a 4-fluoro phenyl claim 1 , 2 claim 1 ,4-bifluoro phenyl claim 1 , pyrimidin-2-yl claim 1 , pyridin-2-yl claim 1 , 5-fluoropyrimidin-2-yl claim 1 , pyrazin-2-yl claim 1 , pyridin-4-yl claim 1 , methyl claim 1 , isopropyl or cyclohexyl.5. The compound represented by formula (I) and the pharmaceutical acceptable salt thereof according to claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , Rare individually hydrogen.6. The compound represented by formula (I) and the pharmaceutical acceptable salt thereof according to claim 1 , wherein Ar is a substituted or unsubstituted pyridazinyl claim 1 , substituted or unsubstituted quinazolinyl claim 1 , substituted or unsubstituted pyrrolyl claim 1 , substituted or unsubstituted thienyl claim 1 , substituted or unsubstituted indazolyl claim 1 , or substituted or unsubstituted pyrazolyl.7. The compound represented by formula (I) and the pharmaceutical acceptable salt thereof according to claim 1 , wherein Ar is a 4-methyl-6-phenylpyridazin-3-yl claim 1 , indol-2-yl claim 1 , 2-phenylquinazolin-4-yl claim 1 , pyrrol-2-yl claim 1 , thien-2-yl claim 1 , indazol-3-yl claim 1 , 5-fluoroindazol-3-yl claim 1 , 4 claim 1 ...

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Номер записи: 27
26-09-2013 дата публикации

METHODS AND COMPOSITIONS FOR WEED CONTROL

Номер: US20130254940A1
Автор: ADER DANIEL, Finnessy John J., Li Zhaolong, Liu Hong, Masucci James D., Shah Ronak Hasmukh, Tao Nengbing, Wang Dafu
Принадлежит:

Provided are novel compositions for use to enhance weed control. Specifically, the present invention provides for methods and compositions that modulate Phytoene desaturase in weed species. The present invention also provides for combinations of compositions and methods that enhance weed control. 1. A method of plant control comprising: treating a plant with a composition comprising a polynucleotide and a transfer agent , wherein said polynucleotide is essentially identical or essentially complementary to a phytoene desaturase (PDS) gene sequence or fragment thereof , or to an RNA transcript of said PDS gene sequence or fragment thereof , wherein said PDS gene sequence is selected from the group consisting of SEQ ID NO:1-78 and 2138 or a polynucleotide fragment thereof , whereby said plant growth or development or reproductive ability is regulated , suppressed , or delayed or said plant is more sensitive to a PDS inhibitor herbicide as a result of said polynucleotide containing composition relative to a plant not treated with said composition.2. The method as claimed in claim 1 , wherein said transfer agent comprises an organosilicone surfactant composition or compound contained therein.3. The method as claimed in claim 1 , wherein said polynucleotide fragment is 18 contiguous claim 1 , 19 contiguous nucleotides claim 1 , 20 contiguous nucleotides or at least 21 contiguous nucleotides in length and at least 85 percent identical to a PDS gene sequence selected from the group consisting of SEQ ID NO:1-78 and 2138.4. The method as claimed in claim 3 , wherein said polynucleotide fragment is selected from the group consisting of sense or anti-sense ssDNA or ssRNA claim 3 , dsRNA claim 3 , or dsDNA claim 3 , or dsDNA/RNA hybrids.5Abutilon theophrasti, Amaranthus chlorostachys, Amaranthus graecizans, Amaranthus palmeri, Amaranthus rudis, Amaranthus hybridus, Amaranthus lividus, Amaranthus spinosus, Amaranthus viridis, Ambrosia artemisiifolia, Ambrosia trifida, Commelina ...

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Номер записи: 28
10-10-2013 дата публикации

DIARYLPYRIDAZINONE DERIVATIVES, PREPARATION THEREOF, AND USE THEREOF FOR THE TREATMENT OF HUMANS

Номер: US20130267520A1
Автор: Dupont-Passelaigue Elisabeth, Le Roy Isabelle, Mialhe Samuel, Pignier Christophe
Принадлежит: PIERRE FABRE MEDICAMENT

The present invention relates to diarylpyridazinone derivatives that block the potassium Kv channels (specifically the Kv1.5, Kv4.3, and Kv11.1 channels) and to the use thereof for the treatment of humans. Said compounds have the general formula (I), where Rand Rare simultaneously or independently one or more groupings such as: halogen, such as F, Br, Cl, a straight or branched C-Calkyl, hydroxy, a straight or branched C-Calkoxy, arylsulfonamido, in which the aryl is optionally replaced with a straight or branched C-Calkyl, or nitrile, as well as the various enantiomers and the mixtures thereof in any proportion, and the pharmaceutically acceptable salts thereof. 5. Compounds of general formula I according to wherein they are chosen from:4,5-Bis-(4-hydroxy-phenyl)-2-(1-phenyl-ethyl)-2H-pyridazin-3-one,.4,5-B is-(4-hydroxy-phenyl)-2-((S)-1-phenyl-ethyl)-2H-pyridazin-3-one4,5-Bi s-(4-hydroxy-phenyl)-2-((R)-1-phenyl-ethyl)-2H-pyridazin-3-one,2,2,′-(6-oxo-1-(1-phenyl-ethyl)-1,6-dihydropyridazine-4,5-diyl)dibenzonitrile,3,3′-(6-oxo-1-(1-phenyl-ethyl)-1,6-dihydropyridazine-4,5-diyl) dibenzonitrile4,5-Bis-(4-methoxy-phenyl)-2-(1-phenyl-ethyl)-2H-pyridazin-3-one,N,N′-(3,3′-(6-oxo-1-(1-phenylethyl)-1,6-dihydropyridazine-4,5-diyl)bis(3,1-pheylee))bis(4-methylbenzenesulfonamide),3-(5-(4-methoxyphenyl)-6-oxo-1-(1-phenylethyl)-1,6-dihydropyridazin-4-yl)-benzonitrile,2-[5-(4-Methoxy-phenyl)-6-oxo-1-(1-phenyl-ethyl)-1,6-dihydro-pyridazin-4-yl]-benzonitrile,N-{3-[5-(3,4-Dimethyl-phenyl)-6-oxo-1-(1-phenyl-ethyl)-1,6-dihydro- pyridazin-4-yl]-phenyl}-4-methyl-benzenesulfonamide, or4,5-Bis-(3,4-dichloro-phenyl)-2-(1-phenyl-ethyl)-2H-pyridazin-3-one,7. Method of treatment of comprising administering to a patient in need thereof a compound according to wherein the s atient suffers from atrial fibrillation claim 1 , auricular and/or ventricular cardiac arrhythmias claim 1 , cancer or inflammation.8. Method of blockin S otassium channels com risin administerin to a patient in need thereof ...

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Номер записи: 29
24-10-2013 дата публикации

PYRIDAZINONE COMPOUND AND HERBICIDE AND NOXIOUS ARTHROPOD CONTROLLING AGENT COMPRISING IT

Номер: US20130281299A1
Автор: Araki Tomohiro, JIN Yoshinobu, KURAGANO Takashi, Souma Shin-ichiro
Принадлежит: SUMITOMO CHEMICAL COMPANY,LIMITED

The present invention relates to a pyridazinone compound of the formula (I): wherein Rrepresents hydrogen, a Calkyl group, and the like, Rrepresents halogen, a cyano group, a nitro group, a Calkoxy group, and the like, G represents hydrogen, and the like, Z represents halogen, a cyano group, a nitro group, a Calkyl group, and the like, and n represents an integer of 1-5 useful as an active ingredient in a herbicideand a noxious arthropod controlling agent. 3. The pyridazinone compound according to wherein Ris a methyl group;{'sup': '2', 'Ris a methoxy group, an ethoxy group, a methylthio group, a methylsulfinyl group, a methylsulfonyl group, a dimethylamino group, a fluorine atom, a chlorine atom, a bromine atom, a cyano group, a nitro group, a cyclopropylmethyl group, a cyclopropylmethyl group, a methylthiomethoxy group, a methoxymethoxy group, an allyloxy group, a propargyloxy group, a cyanomethyloxy group, an amino group, an acetamide group, a hydroxymethyl group, a methoxymethyl group, a cyanomethyl group, a hydroxyiminomethyl group, or a formyl group;'}G is hydrogen, an acetyl group, a propionyl group, a benzoyl group, a methoxycarbonyl group, an ethoxycarbonyl group, an allyloxycarbonyl group, a phenoxycarbonyl group, a methoxymethyl group, or an ethoxymethyl group; andZ is a methyl group, an ethyl group, a vinyl group, or a thinyl group.4. The pyridazinone compound according to wherein G is hydrogen.5. A herbicide comprising the pyridazinone compound according to as an active ingredient.6. A method of controlling a weed which comprises applying an effective amount of the pyridazinone compound according to to a weed or soil where a weed is grown.7. Use of the pyridazinone compound according to for controlling a weed.8. A noxious arthropod controlling agent which comprises the pyridazinone compound according to as an active ingredient.9. A method of controlling a noxious arthropod which comprises applying an effective amount of the pyridazinone compound ...

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Номер записи: 30
24-10-2013 дата публикации

PYRIDAZINONES, THE PREPARATION METHOD AND THE USE THEREOF

Номер: US20130281426A1
Автор: Chao Bo, Hu Youhong, Lin Shijun, Liu Zhende, Lou Liguang, Xu Yongping, Zhao Hongbing
Принадлежит:

The present invention relates to a class of pyridazinones of formula I, which comprises 6-[3-(trifluoromethyl)phenyl]pyridazin-3(2H)-one as a mother nucleus, the preparation method thereof and the use thereof in manufacturing medicaments against tumors, especially liver cancer. 2. The method according to claim 1 , wherein said method comprising administering said pyridazinone having the structure of formula I to said patient;wherein:R is selected from the group consisting of said substituted or unsubstituted heteroaryl group and said substituted or unsubstituted heterocyclic group;wherein said heteroaryl group is a 5- or 6-membered aromatic ring containing 1 to 3 nitrogen atoms; andsaid heterocyclic group is a 3- to 7-membered monocyclic ring or an 8-membered bicyclic ring, wherein the heterocyclic group contains 1 to 3 nitrogen atoms;wherein the heterocyclic group is optionally substituted with said oxo group or said sulfido group.4. The method according to claim 1 , wherein said tumor is liver cancer claim 1 , ovarian cancer claim 1 , cervical carcinoma or nasopharyngeal carcinoma.5. The method according to claim 2 , wherein said tumor is liver cancer claim 2 , ovarian cancer claim 2 , cervical carcinoma or nasopharyngeal carcinoma.6. The method according to claim 3 , wherein said tumor is liver cancer claim 3 , ovarian cancer claim 3 , cervical carcinoma or nasopharyngeal carcinoma.7. The method according to claim 1 , wherein said tumor is liver cancer.8. The method according to claim 1 , wherein said tumor is ovarian cancer.9. The method according to claim 1 , wherein said tumor is cervical carcinoma.10. The method according to claim 1 , wherein said tumor is a nasopharyngeal carcinoma. This application is a continuation-in-part of parent U.S. application Ser. No. 12/933,104, filed on Nov. 17, 2010, as a National Stage Entry based on International Application No. PCT/CN2009/000295, filed on Mar. 18, 2009, which claims priority to Chinese application No. ...

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Номер записи: 31
24-10-2013 дата публикации

METHOD FOR PREPARING ROSUVASTATIN SALTS

Номер: US20130281694A1
Автор: Barkoczy Jozsef, Bartha Ferenc Lorant, Debreczeni Jozsef, Keszthelyi Adrienn, Krasznai Gyorgy, Lukács Gyula, MILEN Mátyás, Molnár Enikö, Pandur Angéla, Pongo Laszlo, Porcs-Makkay Márta, Ruzsics György, SZABÓ Tibor, TOTHNE LAURITZ Maria, Volk Balazs
Принадлежит: EGIS GYOGYSZERGYAR NYILVANOSAN MUKODO RESZVENY-TARSASAG

The present invention is related to methods for the preparation of pharmaceutically acceptable salts of (+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl-amino)-pyrimidin-5-yl]-(3R,5S,6E)-dihydroxy-hept-6-enoic acid, intermediates thereof and methods for producing said intermediates. 5. Method according to claim 19 , which comprises using a compound of general Formula (X) wherein Ris 1-butyl or 2 claim 19 ,2-dimethyl-ethyl and Rand Rare hydrogen claim 19 , respectively.6. Method according to claim 19 , wherein for each mole of the compound of the general Formula (III) claim 19 , 1 to 30 claim 19 , preferably 20 molar equivalents of the compound of the general Formula (X) are used.7. Method according to claim 19 , characterized by that the reaction is carried out at a temperature between 80 and 140° C. claim 19 , preferably between 110 and 130° C.9. Method according to claim 8 , which comprises using a compound of the general Formula (X) claim 8 , wherein Ris 2 claim 8 ,2-dimethylethyl claim 8 , Rand Rare hydrogens.10. Method according to claim 8 , which comprises using a compound of the general Formula (X) wherein Ris 1-butyl claim 8 , Rand Rare hydrogens.12. Method according to claim 11 , characterized by that as a compound of the general Formula (X) claim 11 , the compound is used wherein Ris 2 claim 11 ,2-dimethylethyl claim 11 , Rand Rare each hydrogens.13. Method according to claim 11 , characterized by that as a compound of the general Formula (X) claim 11 , the compound wherein Ris 1-butyl claim 11 , Rand Rare each hydrogens is used.14. Crystalline Form II rosuvastatin t-butylammonium salt of the Formula (IIa) characterized by the following X-ray diffraction lines measured using CuKα radiation: (±0.2° 2Θ): 18.654 degrees 2Θ; or 18.654 and 15.803 degrees 2Θ; or 11.282 claim 11 , 15.803 and 19.832 degrees 2Θ.15. Crystalline Form II rosuvastatin t-butylammonium salt of the Formula (IIa) according to claim 14 , characterized by the following X-ray ...

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Номер записи: 32
12-12-2013 дата публикации

INHIBITORS OF PROTEIN KINASES

Номер: US20130331407A1
Автор: Allgeier Hans, Augustin Martin, Peraus Gisela, Pleiss Michael A., Schauerte Heike, Stumm Gabriele, Wabnitz Philipp
Принадлежит: Ingenium Pharmaceuticals GmbH

The present invention relates to inhibitors of cyclin-dependent kinases and therapeutic applications thereof. Furthermore, the invention relates to methods of preventing and/or treating any type of pain, inflammatory disorders, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases and neurodegenerative diseases comprising the administration of an effective amount of at least one inhibitor of cyclin-dependent kinases. 2. The method of claim 1 , wherein the pain comprises chronic pain claim 1 , inflammatory pain claim 1 , neuropathic pain claim 1 , or a combination thereof.3. A method for treatment of a disease selected from the group of pain claim 1 , an inflammatory disorder claim 1 , an immunological disease claim 1 , a proliferative disease claim 1 , an infectious disease claim 1 , a cardiovascular disease and a neurodegenerative disease claim 1 , comprising administering a therapeutically effective amount of at least one compound represented by general Formula I wherein Ris 1 to 3 substituents independently selected from the group consisting of methyl claim 1 , ethyl claim 1 , hydroxymethyl claim 1 , hydroxy claim 1 , methoxy claim 1 , ethoxy claim 1 , isopropoxy claim 1 , benzyloxy claim 1 , hydrogen claim 1 , fluoro claim 1 , chloro claim 1 , trifluoromethyl claim 1 , 2-methoxy-ethoxy claim 1 , methoxymethyl claim 1 , 2-methoxy-ethyl claim 1 ,{'sub': 3', '2', '3, 'tetrahydro-furan-3-yloxy, tetrahydro-furan-2-yl-methoxy, —N(CH)SOCH, piperidin-1-yl-methyl, 2-hydroxymethyl-piperidin-1-yl-methyl, 3-hydroxymethyl-piperidin-1-yl-methyl, 3-(2-hydroxy-ethyl)-piperidin-1-yl-methyl, 3-aminocarbonyl-piperidin-1-yl-methyl, dimethylaminomethyl, diethylaminomethyl, (ethyl-isopropyl-amino)-methyl, morpholin-4-ylmethyl, 4-methyl-piperazin-1-yl-methyl, [1,2,4]triazol-1-yl-methyl, pyridine-3-yl-methoxy, and pyridine-4-yl-methoxy to a patient suffering from said disease.'}4. The method of claim 3 , wherein the pain comprises chronic pain ...

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Номер записи: 33
19-12-2013 дата публикации

COMPOUNDS FOR TREATING PROLIFERATIVE DISORDERS

Номер: US20130338162A1
Автор: Chen Shoujun, Demko Zachary, Koya Keizo, Sun Lijun, Xia Zhi-Qiang
Принадлежит: Synta Pharmaceuticals Corp.

Disclosed are compounds and methods of using compounds of the invention for treating a subject with a proliferative disorder, such as cancer, and methods for treating disorders responsive to Hsp70 induction and/or natural killer induction. Also, disclosed are pharmaceutical compositions comprising compounds of the invention and a pharmaceutically acceptable carrier. 2. The compound of claim 1 , wherein Xand Xare each an optionally substituted ethylene group.3. The compound of claim 1 , wherein Xand Xare each an optionally substituted ethylene group.5. The compound of claim 4 , wherein:{'sub': 1', '2, 'Rand Rare each an optionally substituted aryl or an optionally substituted heteroaryl;'}{'sub': 5', '6, 'Ris —H and Ris —H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl; and'}{'sub': 3', '4, 'Rand Rare each an alkyl group.'}6. The compound of claim 4 , wherein{'sub': 1', '2, 'Rand Rare both an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl;'}{'sub': '5', 'Ris —H; and'}{'sub': '6', 'Ris —H or an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl.'}7. The compound of claim 4 , wherein{'sub': 13', '7', '8, 'Ris —C(R)(R)—;'}{'sub': 7', '8', '7', '8, 'Rand Rare each independently —H or an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted cycloalkenyl, an optionally substituted heterocyclyl, or Ris —H and Ris an optionally substituted aryl or an optionally ...

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Номер записи: 34
19-12-2013 дата публикации

METHOD FOR THE PREPARATION OF HIGH-PURITY PHARMACEUTICAL INTERMEDIATES

Номер: US20130338360A1
Автор: Bagyinszki Gabor, Barkoczy Jozsef, Bartha Ferenc Lorant, Imre Janos, Keszthelyi Adrienn, Kovanyine Lax Gyorgyi, Krasznai Gyorgy, Morovjan Gyorgy, Nagy Kalman, Ruzsics György, Simig Gyula, Sipos Eva, Volk Balazs
Принадлежит: EGIS Gyogyszergyar Nyilvanosan Mukodo Reszvenytars

The present invention is related to intermediates useful in the preparation of pharmaceutically acceptable salts of (+)-7-[4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl-amino)-pyrimidin-5-yl]-(3R,5S)-dihydroxy-hept-6-enoic acid and polymorphs of said intermediates, methods for preparation thereof and use thereof. 3. A method according to claim 1 , which is a method III for the preparation of amorphous rosuvastatin TBA salt of the Formula (III) claim 1 , which comprises dissolving rosuvastatin TBA salt in a saturated aliphatic alcohol having one to four carbon atoms claim 1 , preferably in methanol claim 1 , removing the solvent and drying the solid residue at room temperature in air.5. Crystalline Form II rosuvastatin TBA salt of the Formula (III) according to claim 4 , having the X-ray diffraction signals measured with CuK radiation exceeding 50% relative intensity during powder X-ray diffraction analysis: 15.803 and 18.651 degrees (+/−0.2°) (2Θ).6. Crystalline Form II rosuvastatin TBA salt of the Formula (III) according to claim 4 , having the X-ray diffraction signals measured with CuK radiation exceeding 25% relative intensity during powder X-ray diffraction analysis at 11.282 claim 4 , 15.803 claim 4 , 18.651 claim 4 , 19.050 claim 4 , 19.832 and 20.512 degrees (+/−0.2°) (2Θ).8. Amorphous rosuvastatin TBA salt according to .10. A method for preparing a rosuvastatin calcium (2:1) salt claim 1 , which includes a reaction involving a rosuvastatin TBA salt of Formula (III) prepared according to claim 1 , which method is one of the methods I to III.11. A method for preparing a rosuvastatin zinc (2:1) salt claim 1 , which includes a reaction involving a rosuvastatin TBA salt of Formula (III) prepared according to claim 1 , which method is one of the methods I to III.12. Crystalline Form II rosuvastatin methylester of the Formula (IIa) according to claim 4 , having the most intense diffraction signals measured in powder X-ray diffractometry using CuK ...

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Номер записи: 35
09-01-2014 дата публикации

Medicine for Treating Ischemic Brain Injury and its Sequelae, and Preparation Method Thereof

Номер: US20140011813A1
Автор: HONG Ying, Lei Haimin
Принадлежит: Haimin Lei

Disclosed in the present invention are a compound of the general structure formula LQC-T as shown below, wherein R represents an aromatic organic acid or phenol or the structural analogue thereof, such as protocatechuic acid, protocatechuic aldehyde, vanillic acid, gallic acid, caffeic acid, ferulic acid etc., and the synthesis and use of the compound. The compounds promote new blood vessel growth in the chick embryo chorioallantoic membrane, wherein LQC-T4 can be used to prepare a medicine for treating ischemic brain injury (stroke) and its sequelae. 2. A method of treating apoplexy caused by ischemic cerebral damage and the sequelae thereof comprising administering to a patient in need thereof an effective amount of a compound according to .4. The compound or the pharmaceutically acceptable salt thereof according to claim 3 , wherein Ris an alkyl which is substituted by pyrazine substituted by multiple methyls claim 3 , Ris an alkyl which is substituted by pyrazine substituted by multiple methyls claim 3 , Ris an alkoxycarbonyl which is substituted by pyrazine substituted by multiple methyls claim 3 , an alkenyl substituted by alkoxycarbonyl which is substituted by pyrazine substituted by multiple methyls claim 3 , or an aldehyde group.5. The compound or the pharmaceutically acceptable salt thereof according to claim 4 , wherein Ris a pyrazine methylene substituted by three methyls claim 4 , Ris a pyrazine methylene substituted by three methyls claim 4 , Ris a pyrazine methyleneoxy carbonyl which is substituted by three methyls claim 4 , an alkenyl substituted by alkoxycarbonyl which is substituted by pyrazine substituted by multiple methyls claim 4 , an aldehyde group.6. The compound according to claim 3 , wherein the compound is selected from the group consisting of:i) (3,5,6-trimethylpyrazin-2-yl)methyl 4-hydroxy-3-methoxybenzoate,ii) (3,5,6-trimethylpyrazine-2-yl)methyl-3,4-bis((3,5,6-trimethylpyrazine-2-yl)methoxy)benzoate,iii) (3,5,6-trimethylpyrazin-2-yl) ...

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Номер записи: 36
30-01-2014 дата публикации

Herbicidal compounds

Номер: US20140031223A1
Автор: Jonathan Dallimore
Принадлежит: Syngenta Ltd

The present invention relates to novel herbicidal compounds of Formula (I), or an agronomically acceptable salt of said compound wherein R 1 , R 2 , A 1 , R a , R b , R c and R d are as defined herein. The invention further relates to compositions which comprise the herbicidal compounds, and to their use for controlling weeds, in particular in crops of useful plants.

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Номер записи: 37
30-01-2014 дата публикации

ASYMMETRICALLY SUBSTITUTED ANTHRAPYRIDAZONE DERIVATIVES AS CYTOSTATICS

Номер: US20140031357A1
Автор: Bontemps-Gracz Maria, Borowski Edward, Cybulski Marcin, Dzieduszycka Maria, Mazerski Jan, Obukowicz Janusz, Punda Pawel, Stefanska Barbara, Szelejewski Wieslaw, Wietrzyk Joanna, Wysocka Malgorzata
Принадлежит: BS-154 SP. Z O.O.

The invention relates to the new, asymmetrically substituted derivatives of 2,7-dihydro-3H-dibenzo[de,h]cinnoline-3,7-dione and their use as cytostatics exhibiting activity against tumor cells, especially against cells with multidrug resistance (MDR). In particular, the invention concerns derivatives of 2,7-dihydro-3H-dibenzo[de,h]cinnoline-3,7-dione represented by the general formula (I). 6. Anthrapyridazone derivatives according to selected from the group comprising:2-[2-(Dimethylamino)ethyl]-6-{[2-(methylamino)ethyl]amino}-2,7-dihydro-3H-dibenzo[de,h]cynnoline-3,7-dione,2-[2-(Dimethylamino)ethyl]-6-[2-(aminoethypamino)-2,7-dihydro-3H-dibenzo [de,h]cynnoline-3,7-dione,2-[2-(Dimethylamino)ethyl]-6-(N-methylamino)-2,7-dihydro-3H-dibenzo[de,h]cynnoline-3,7-dione,2-[2-(Dimethylamino)ethyl]-6-{[2-(ethylamino)ethyl]amino}2,7-dihydro-3H-dibenzo [de,h]cynnoline-3,7-dione,2-[2-(Dimethylamino)ethyl]-6-[(3-aminopropyl)amino]-2,7-dihydro-3H-dibenzo[de,h]cynnoline-3,7-dione,2-[2-(Dimetyloamino)etyl]-6-[(3-acetyloaminopropyl)amino]-2,7-dihydro 3H-dibenzo [de,h]cynnolino-3,7-dione,2-[2-(dimethylamino)ethyl]-6-(acetylamino)-2,7-dihydro-3H-dibenzo[de,h]cynnoline 3,7-dione,2-[2-(Dimethylamino)ethyl]-6-{[(2-diethylamino)ethyl]amino}2,7-dihydro 3H -dibenzo[de,h]cynnoline-3,7-dione,2-[2-(Dimethylamino)ethyl]-6-(N-benzylamino)-2,7-dihydro-3H-dibenzo[de,h]cynnoline-3,7-dione,2-[2-(Dimethylamino)ethyl]-6-[2-(2-aminoethylamino)etanolo]-2,7-dihydro 3H -dibenzo [de,h]cynnoline-3,7-dione,2-[2-(Dimethylamino)ethyl]-6-[(N,N-dimethyloacetamido)amino]-2,7-dihydro-3H-dibenzo [de,h]cynnolin-3,7-dione,2-[2-(Dimethylamino)propyl]-6-{[2-(dimethylamino)propyl]amino}-2,7dihydro-3H-dibenzo[de,h]cynnoline-3,7-dione,2-(2-Morpholinethyl)-6-amino-2,7-dihydro-3H-dibenzo[de,h]cynnoline 3,7-dione,2-[3-(Dimethylamino)propyl]-6-amino-2,7-dihydro-3H-dibenzo[de,h]cynnoline-3,7-dione,2-[2-(Piperidinamino)ethylo]-6-amino-2,7-dihydro-3H-dibenzo[de,h]cynnoline-3,7-dione,{'b': '0', '2-(2-Hydroxyethyl)-6-(2- ...

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Номер записи: 38
06-02-2014 дата публикации

CXCR4 ANTAGONISTS FOR THE TREATMENT OF MEDICAL DISORDERS

Номер: US20140039187A1
Автор: Liang Zhongxing, Liotta Dennis C., Shim Hyunsuk, Snyder James P., Zhan Weiqiang
Принадлежит:

The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor for the treatment of proliferative conditions mediated by CXCR4 receptors. The compounds provided interfere with the binding of SDF1 to the receptor. These compounds are particularly useful for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis. 2. The method of claim 1 , wherein the reducing agent is sodium triacetoxyborohydride.4. The method of claim 3 , wherein the carboxylic acid is tartaric acid. This application claims priority to U.S. Provisional Application No. 60/642,375, filed Jan. 7, 2005 and U.S. Provisional Application No. 60/642,374, filed Jan. 7, 2005.The invention provides compounds, pharmaceutical compositions and methods of use of certain compounds that are antagonists of the chemokine CXCR4 receptor. The compounds are useful to mediate any medical condition that is modulated by CXCR4 receptor signaling, and in particular for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis.Cancer is currently the second leading cause of death in developed nations. In 2004, the American Cancer Society estimated that approximately 1.37 million new cases were diagnosed in the U.S. alone, and approximately 550,000 deaths occurred due to cancer (American Cancer Society, Cancer Facts & Figures 2004, see URL: http://www.cancer.org/docroot/STT/stt0.asp).Metastasis, the spread and growth of tumor cells to distant organs, is the most devastating attribute of cancer. Most morbidity and mortality associated with certain types of cancer, such as breast cancer, is associated with disease caused by metastatic cells rather than by the primary tumor. Therapy for metastasis currently relies on a combination of early diagnosis and aggressive treatment of the primary tumor.The establishment and growth of metastases at distant sites is thought to depend ...

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Номер записи: 39
03-04-2014 дата публикации

Ssh-2 (slingshot-2) inhibitors and methods for making and using them

Номер: US20140094466A1
Автор: Jason H. Haga, Marshall J. LEVESQUE, Matt Mui, Phillip D. Pham, Shu Chien
Принадлежит: UNIVERSITY OF CALIFORNIA

In alternative embodiments, the invention provides compositions that inhibit the polypeptide SSH-2, or SlingSHot-2, a phosphatase enzyme that regulates actin filaments, and methods for making and using them, including methods comprising administering compositions of the invention to regulate or modify actin filament polymerization by inhibiting SSH-2, where in one embodiment compositions of the invention slow or inhibit F-actin depolymerization and severing. In alternative embodiments, compositions and methods of the invention are used to slow or inhibit cell motility and/or internal remodeling. In alternative embodiments, compositions and methods of the invention are used to slow or inhibit, or reverse, or ameliorate the progression of a cancer or a metastasis or other uncontrolled or unregulated cell growth, and/or Alzheimer's disease.

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Номер записи: 40
03-01-2019 дата публикации

PLANT DISEASE CONTROL COMPOSITION AND PLANT DISEASE CONTROL METHOD

Номер: US20190000081A1
Автор: HIROTOMI Dai, Kiguchi So
Принадлежит: Sumitomo Chemical Company, Limited

The present invention provides a plant disease control composition that has excellent plant disease controlling effects and that contains a pyridazine compound represented by formula (1) 3. The composition for controlling a plant disease described in wherein the compound represented by the formula (2a) is the compound wherein Yrepresents a chlorine atom in the formula (2a).4. The composition for controlling a plant disease described in wherein the compound represented by the formula (1) is the compound wherein X represents a hydrogen atom in the formula (1).5. The composition for controlling a plant disease described in wherein a weight ratio of the compound represented by the formula (1) to the compound represented by the formula (2) is 1:0.0125 to 1:500.7. The method for controlling a plant disease described in wherein the step of application to a plant or a soil for cultivating the plant is a step of application to a seed. This application claims priority to and the benefit of Japanese Patent Application Nos. 2015-158973 filed on Aug. 11, 2015 and 2015-253222 filed on Dec. 25, 2015, the entire contents of which are incorporated herein by reference.The present invention relates to a composition for controlling plant diseases and a method for controlling plant diseases.Hitherto, some compounds have been known as active ingredient for a composition for controlling plant diseases (see Patent Documents 1 and 2).Patent Document 1: WO 2012/020772 pamphletPatent Document 2: WO 2012/169516 pamphletAn object of the present invention is to provide a composition for controlling plant diseases and a method for controlling plant diseases, each having an excellent control efficacy on plant disease.The present inventors have intensively studied to find out a composition for controlling plant diseases and a method for controlling plant diseases, each having an excellent control efficacy on plant diseases. As a result, they have found that a composition comprising a pyridazine ...

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Номер записи: 41
03-01-2019 дата публикации

Compounds and Compositions That Bind and Stabilize Transthyretin and Their Use for Inhibiting Transthyretin Amyloidosis and Protein-Protein Interactions

Номер: US20190000805A1
Автор: Alhamadsheh Mamoun M., Graef Isabella A.
Принадлежит:

Disclosed herein are compounds and compositions thereof which find use in increasing stability of proteins particularly proteins that tend to misfold and form aggregates. Also provided herein are methods for using these compounds and compositions for increasing stability of proteins and thereby decreasing aggregate formation by these proteins. Also disclosed herein are heterobifunctional compounds that include a TTR binding compound connected to a targeting moiety via a linker, for use in disrupting PPIs of a target protein. 132-. (canceled)34. The kit of claim 33 , further comprising a package insert describing the use of Compound VIIa.35. The kit of claim 33 , wherein Ris selected from the group consisting of COOH CONH claim 33 , CONH(OH) claim 33 , COOR claim 33 , and CONHR. This application claims the benefit of U.S. Provisional Patent Application No. 61/745,089, filed Dec. 21, 2012, which application is incorporated herein by reference in its entirety.Protein aggregation underlies a large number of human disorders, including some of the most common diseases observed in the aging population, including systemic and CNS amyloidoses (Selkoe et al. 6:1054-1061 (2004); Falk et al., 337:898-909 (1997)). Recently this process has also been implicated as an important mechanism in cellular senescence (Haigis et al., 40:333-344 (2010)). Aggregation of disease-associated peptides or proteins can occur in different sub-cellular compartments and either affect specific tissues or spread systemically (Stefani et al., 1739:5-25 (2004)). Data from biophysical, cellular and animal models indicate that a number of genetic and environmental factors contribute to in vivo protein misfolding, aggregation and amyloid fibril formation (amyloidogenesis). Protein misfolding and amyloid formation is believed to be intimately involved in the pathogenic mechanisms of human amyloid diseases based on the demonstrated cytotoxicity of in vitro aggregated proteins/peptides. A number of ...

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Номер записи: 42
05-01-2017 дата публикации

CRYSTALLINE FORMS OF A HISTONE DEACETYLASE INHIBITOR

Номер: US20170001965A1
Автор: Liu Gui, SEYEDI Farzaneh, van Duzer John H.
Принадлежит:

This disclosure provides solid forms of 2-((2-chlorophenyl)(phenyl)amino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide, and methods of manufacturing and using these forms. 1. A crystalline form of 2-((2-chlorophenyl)(phenyl)amino)-N-(7-(hydroxyamino)-7-oxoheptyl)pyrimidine-5-carboxamide.2. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees-2-theta at angles 8.3±0.2° claim 1 , 10.6±0.2° claim 1 , 16.6±0.2° claim 1 , 21.3±0.2° claim 1 , and 25.0±0.2° (Form I).3. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2-Theta at angles 11.6±0.2° claim 1 , 19.5±0.2° claim 1 , 20.2±0.2° claim 1 , 23.3±0.2° claim 1 , and 23.8±0.2° (Form II).4. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2-Theta at angles 8.3±0.2° claim 1 , 11.7±0.2° claim 1 , 13.5±0.2° claim 1 , 13.7±0.2° claim 1 , and 23.6±0.2° (Form III).5. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2-Theta at angles 11.8±0.2° claim 1 , 13.6±0.2° claim 1 , 13.8±0.2° claim 1 , 23.7±0.2° claim 1 , and 30.6±0.2° (Form IV).6. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2-Theta at angles 7.6±0.2° claim 1 , 15.1±0.2° claim 1 , 21.1±0.2° claim 1 , and 24.8±0.2° (Form V).7. The crystalline form of claim 1 , wherein the crystalline form is characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2-Theta at angles 8.2±0.2° claim 1 , 20.0±0.2° claim 1 , 22.2±0.2° claim 1 , and 24.9±0.2° (Form VI).8. The crystalline form of claim 1 , wherein the crystalline form is ...

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Номер записи: 43
05-01-2017 дата публикации

BICYCLOAMINE-SUBSTITUTED-N-BENZENESULFONAMIDE COMPOUNDS WITH SELECTIVE ACTIVITY IN VOLTAGE-GATED SODIUM CHANNELS

Номер: US20170002008A1
Автор: Egbertson Melissa, Jones Kristen L. G., Layton Mark E., Li Dansu, Peng Xuanjia, Roecker Anthony J., Wang Xiu
Принадлежит: Merck Sharp & Dohme Corp.

Disclosed are compounds of Formula A-a, or a salt thereof: Where “B” and “R” through “R” are as defined herein, which compounds have properties for blocking Na1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A-a or their salts, and methods of treating neuropathic pain disorders using the same. 2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': 4', '5, 'Rand Rare independently: —H; or a cyclic-, branched- or linear-alkyl moiety of up to 6 carbon atoms; and'}{'sup': 1', '2, 'sub': '3', 'Rand Rare independently: —H; —F; —Cl; —Br; —CN; a cyclic-, branched, or linear-alkyl moiety comprising up to 6 carbon atoms; or —CF.'}34-. (canceled)5. A compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein:{'sup': '1', 'sub': '3', 'Ris: —H; —F; —Cl; —Br; —CN; or —CH;'}{'sup': '2', 'sub': 3', '2', '3', '3, 'Ris: —H; —F; —Cl; —Br; —CN; CH; —CHCH; or —CF; and'}{'sup': 4', '5, 'sub': '3', 'Rand Rare independently: (i) —H; or (ii) —CH.'}6. (canceled)8. A compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein:{'sup': 3', '4', '5, 'sub': '2', 'A, Aand Aare each [—CH—]; and'} [{'sup': '1', 'sub': '3', 'Ris independently: —H; —F; —Cl; —Br; —CN; or CH;'}, {'sup': '2', 'sub': 3', '3', '2', '3, 'Ris independently: —H; —F; —Cl; —Br; —CN; —CF, —CH; or —CHCH.'}], 'in the structure of Formula A-a9. (canceled)10. A compound of claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein:{'sup': 10a2', '11a2, 'claim-text': [{'sup': 10a2', '11a2, 'claim-text': (a) hydrogen;', '(b) halogen;', {'sub': 1-6', '3-6', '3-6', '1-4', '3-4, '(c) an alkyl moiety which is —C-linear-alkyl, —C-branched-alkyl, or —C-cycloalkyl, which alkyl moiety is optionally substituted with one or more: (i) halogen; (ii) an aryl moiety optionally substituted with C-linear-alkoxy or C-branched-alkoxy; or (iii) —OH; ...

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Номер записи: 44
02-01-2020 дата публикации

PRMT5 INHIBITORS

Номер: US20200002355A1
Автор: Camerino Michelle Ang, Stupple Paul Anthony, Walker Scott Raymond
Принадлежит:

A compound of formula (Ia), (Ib) or (Ic) wherein: n is 1 or 2; Ris H or Me; Ris optionally one or more halo or methyl groups; Rand Rare independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CHOH; Rand R(if present) are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CHOH; Rand Rare independently selected from H and Me; Ris selected from OH, —NH, —C(═O)NH, and —CHOH; Ris either H or Me; X is either N or CH; Ris selected from H and Calkyl; (a) one of R, R, Rand Ris selected from H, halo, Calkyl, Calkoxy, NHCalkyl; (b) another of R, R, Rand Ris selected from H, Calkyl, Cfluoroalkyl, Ccycloalkyl, Cheteroaryl, Cheteroaryl methyl, Cheterocyclyl, Cheterocyclyl methyl, phenyl, benzyl, halo, amido, amidomethyl, acylamido, acylamidomethyl, Calkyl ester, Calkyl ester methyl, Calkyl carbamoyl, Calkyl carbamoyl methyl, Calkylacyl, Calkylacyl methyl, phenylcarbonyl, carboxy, carboxymethyl, ether, amino, amino methyl, sulfonamido, sulfonamino, sulfone, sulfoxide, nitrile and nitrilemethyl; (c) the others of R, R, Rand Rare H. 2. A compound according to claim 1 , wherein n is 1.3. (canceled)4. A compound according to claim 1 , wherein Ris H.5. (canceled)6. A compound according to claim 1 , wherein there are no Rsubstituents.7. (canceled)8. A compound according to claim 1 , wherein R claim 1 , R claim 1 , Rand R(if present) are all H.919-. (canceled)20. A compound according to claim 1 , wherein Rand Rare both Me.21. A compound according to claim 1 , wherein Ris OH.22. A compound according to claim 1 , wherein Ris H.23. (canceled)25. (canceled)26. A compound according to claim 1 , wherein the compound is a racemate at the carbon atom to which Rand Rare attached.2728-. (canceled)2927. A compound according to claim claim 1 , wherein the compound is the (S)-enantiomer at the carbon atom to which Rand Rare attached.30. A compound according to wherein X is N.3132-. (canceled)33. A compound according to claim 1 , ...

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Номер записи: 45
07-01-2021 дата публикации

SULPHONYL UREA DERIVATIVES AS NLRP3 INFLAMMASOME MODULATORS

Номер: US20210002261A1
Автор: BOCK Mark G., HARRISON David, WATT Alan Paul
Принадлежит:

The present disclosure relates to compounds of Formula (I): 2. The compound of any one of the preceding claims , wherein Ris C-Cbicyclic cycloalkyl.6. The compound of any one of the preceding claims , wherein Ris C-Ctricyclic cycloalkyl.9. The compound of any one of the preceding claims , wherein , Ris C-Caryl optionally substituted by one or more R.10. The compound of any one of the preceding claims , wherein Ris phenyl is substituted by one , two , or three R.15. The compound of any one of the preceding claims , wherein Ris cyclopentyl , cyclohexyl , or cycloheptyl , wherein the cyclopentyl , cyclohexyl , or cycloheptyl is optionally substituted by one or more R.17. The compound of any one of the preceding claims , wherein at least one Ris methyl , ethyl , isopropyl , isobutyl , secbutyl , methoxy , ethoxy , —CF , —OCF , —OCHCF , F , or Cl.18. The compound of any one of the preceding claims , wherein Ris —R.19. The compound of any one of the preceding claims , wherein Ris —(CXX)—R.20. The compound of any one of the preceding claims , wherein Ris —(CXX)—R.21. The compound of any one of the preceding claims , wherein each Xis H.22. In some embodiments , at least one Xis C-Calkyl , C-Calkenyl , or C-Calkynyl , wherein the C-Calkyl , C-Calkenyl , or C-Calkynyl is optionally substituted with one or more halo , —CN , —OH , —O(C-Calkyl) , —NH , —NH(C-Calkyl) , —N(C-Calkyl) , or oxo.23. The compound of any one of the preceding claims , wherein Ris 4- to 8-membered heterocycloalkyl optionally substituted with one or more C-Calkyl , C-Calkenyl , C-Calkynyl , C-Chaloalkyl , halo , —CN , —OH , —O(C-Calkyl) , —NH , —NH(C-Calkyl) , —N(C-Calkyl) , or oxo.24. The compound of any one of the preceding claims , wherein Ris 4- to 8-membered heterocycloalkyl.25. The compound of any one of the preceding claims , wherein Ris 5- to 8-membered heterocycloalkyl.26. The compound of any one of the preceding claims , wherein Ris 5- to 7-membered heterocycloalkyl.27. The compound of any one of ...

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Номер записи: 46
01-01-2015 дата публикации

COMPOSITION FOR CONTROLLING PLANT DISEASES AND USE THEREOF

Номер: US20150005495A1
Автор: Matsuzaki Yuichi
Принадлежит:

A composition for controlling plant diseases, containing a pyridazine compound represented by Formula (I) and fipronil, exhibits an excellent control effect against plant diseases. The present invention provides a composition for controlling plant diseases, containing the pyridazine compound represented by Formula (I) and fipronil, and a method for controlling plant diseases, including a step of applying an effective amount of the pyridazine compound represented by Formula (I) and fipronil to a plant or soil for cultivating a plant. 2. The composition for controlling plant diseases according to claim 1 , wherein a weight ratio of the pyridazine compound to fipronil (the pyridazine compound/fipronil) is 1/1 to 1/100.4. The method for controlling plant diseases according to claim 3 , wherein a weight ratio of the pyridazine compound to fipronil (the pyridazine compound/fipronil) is 1/1 to 1/100.5. The method for controlling plant diseases according to claim 3 , wherein the plant or the soil for cultivating a plant is wheat or soil for cultivating wheat.6. The method for controlling plant diseases according to claim 3 , wherein the plant or the soil for cultivating a plant is plant seeds. The present invention relates to a composition for controlling plant diseases and a use thereof.In the related art, many compounds have been developed for controlling plant diseases, and put into practical use (for example, refer to PTLs 1 and 2).[Patent Document 1] Pamphlet of International Publication No. 2005/121104[Patent Document 2] Pamphlet of International Publication No. 2006/001175An object of the present invention is to provide a composition having an excellent control effect against plant diseases.The present inventor has studied to find a composition having an excellent controlling effect against plant diseases, and as a result, has found that a composition for controlling plant diseases containing a pyridazine compound represented by the following Formula (I) and fipronil ...

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Номер записи: 47
14-01-2016 дата публикации

Lipophilic Curcumin Analogs And Methods Of Inhibiting HIV-1, Treating Latent HIV In The Brain, And Preventing HIV-Mediated Cognitive Decline And HIV Dementia

Номер: US20160009623A1
Автор: Kulkarni Amol, Nwulia Evaristus A.
Принадлежит:

Compounds having formulas (I) to (VIII), salts thereof, or combinations thereof and pharmaceutical compositions comprising one or more these compounds are described herein for the treatment of HIV and neurodegenerative effects caused by HIV. Also provided herein are methods and a kit for inhibiting HIV-1, treating latent HIV in the brain, and preventing HIV-mediated cognitive decline and HIV dementia comprising administering the compounds having the formulas (I) to (VIII) and pharmaceutical compositions comprising the compounds having these formulas. The compounds having formulas I through VIII are curcumin analogs which are advantageously characterized as having anti-retroviral, neuroprotective, anti-glucosidase, and anti-HIV integrase properties. In one aspect, the pharmaceutical composition is delivered intranasally. 114-. (canceled)16. The compound according to claim 15 , wherein the compound is of formula (II) or pharmaceutically acceptable salt thereof.17. The compound according to claim 15 , wherein the compound is of formula (III) or pharmaceutically acceptable salt thereof.18. The compound according to claim 15 , wherein the compound is of formula (IV) or pharmaceutically acceptable salt thereof.19. The compound according to claim 15 , wherein the compound is of formula (V) or pharmaceutically acceptable salt thereof.20. The compound according to claim 15 , wherein the compound is of formula (VI) or pharmaceutically acceptable salt thereof.21. The compound according to claim 15 , wherein the compound is of formula (VII) or pharmaceutically acceptable salt thereof.22. The compound according to claim 15 , wherein the compound is of formula (VIII) or pharmaceutically acceptable salt thereof.23. A pharmaceutical composition comprising at least one compound of any of formulas (II) through (VIII) or a pharmaceutically acceptable salt thereof as defined in .24. The pharmaceutical composition according to claim 23 , further comprising a pharmaceutically acceptable ...

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Номер записи: 48
11-01-2018 дата публикации

CONTRAST AGENTS FOR MYOCARDIAL PERFUSION IMAGING

Номер: US20180009763A1
Автор: Casebier David S., Purohit Ajay, Radeke Heike S.
Принадлежит: Lantheus Medical Imaging, Inc.

The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging. 125-. (canceled)27. A composition , comprising:{'claim-ref': {'@idref': 'CLM-00026', 'claim 26'}, 'the compound of and a solvent.'}29. A composition comprising:{'claim-ref': {'@idref': 'CLM-00028', 'claim 28'}, 'the compound of and a solvent.'}31. The precursor compound of claim 30 , wherein the precursor compound is provided in a solution.32. The precursor compound of claim 30 , wherein the precursor compound is provided as a solid preparation.33. The precursor compound of claim 32 , wherein the solid preparation is a lyophilized solid. The present application claims the benefit of priority under 35 U.S.C. §119(e) from the provisional application 60/544,861 filed Feb. 13, 2004, the contents of which are herein incorporated by reference.The present disclosure relates to novel compounds comprising imaging moieties, and their use for diagnosing certain disorders in a patient.Mitochondria are membrane-enclosed organelles distributed through the cytosol of most eukaryotic cells. Mitochondria are especially concentrated in myocardium tissue.Complex 1 (“MC-1”) is a membrane-bound protein complex of 46 dissimilar subunits. This enzyme complex is one of three energy-transducing complexes that constitute the respiratory chain in mammalian mitochondria. This NADH-ubiquinone oxidoreductase is the point of entry for the majority of electrons that traverse the respiratory chain, eventually resulting in the reduction of oxygen to water (1992, 25, 253-324).Known inhibitors of MC-1 include deguelin, piericidin A, ubicidin-3, rolliniastatin-1, rolliniastatin-2 (bullatacin), capsaicin, pyridaben, fenpyroximate, amytal, MPP+, quinolines, and quinolones (1998, 1364, 222-235).The present disclosure is based, in ...

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Номер записи: 49
08-01-2015 дата публикации

Inhibitors of Protein Kinases

Номер: US20150011576A1
Автор: Allgeier Hans, Augustin Martin, Peraus Gisela, Pleiss Michael A., Schauerte Heike, Stumm Gabriele, Wabnitz Philipp
Принадлежит:

The present invention relates to inhibitors of cyclin-dependent kinases and therapeutic applications thereof. Furthermore, the invention relates to methods of preventing and/or treating any type of pain, inflammatory disorders, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases and neurodegenerative diseases comprising the administration of an effective amount of at least one inhibitor of cyclin-dependent kinases. 2. The method of claim 1 , wherein the pain comprises chronic pain claim 1 , inflammatory pain claim 1 , neuropathic pain claim 1 , or a combination thereof.4. The method of claim 3 , wherein the pain comprises chronic pain claim 3 , inflammatory pain claim 3 , neuropathic pain claim 3 , or a combination thereof.6. The method of claim 5 , wherein the pain comprises chronic pain claim 5 , inflammatory pain claim 5 , neuropathic pain claim 5 , or a combination thereof.7. A method for treatment of a disease selected from the group of pain claim 5 , an inflammatory disorder claim 5 , an immunological disease claim 5 , a proliferative disease claim 5 , an infectious disease claim 5 , a cardiovascular disease and a neurodegenerative disease claim 5 , comprising administering a therapeutically effective amount of at least one compound selected from the group consisting of:{4-[4-(2-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-methanesulfonamide (Compound 1);C-{4-[4-(2-Methoxy-phenyl)-pyrimidin-2-ylamino]-phenyl}-N-methyl-methanesulfonamide (Compound 2); and{4-[4-(2-Methoxy-phenyl)-6-methyl-pyrimidin-2-ylamino]-phenyl}-methanesulfonamide (Compound 3)to a patient suffering from said disease.8. The method of claim 7 , wherein the pain comprises chronic pain claim 7 , inflammatory pain claim 7 , neuropathic pain claim 7 , or a combination thereof. This application is a division of U.S. patent application Ser. No. 12/451,041, filed on Mar. 3, 2010, which is a U.S. National Stage of PCT/EP2008/054977, filed on Apr. 24, 2008, ...

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Номер записи: 50
14-01-2021 дата публикации

HERBICIDAL COMPOUNDS

Номер: US20210009530A1
Автор: "ORIORDAN Timothy Jeremiah Cornelius", KITSIOU Christiana, LING Kenneth Bruce, Mathews Christopher John, SEDEN Peter Timothy, SHANAHAN Stephen Edward, TATE Joseph Andrew
Принадлежит: SYNGENTA PARTICIPATIONS AG

The present invention relates to herbicidal substituted phenyl-pyridazine-diones and substituted phenyl-pyridazinone derivatives of formula (I), as well as to processes and intermediates used for the preparation of such derivatives. The invention further extends to herbicidal compositions comprising such derivatives, as well as to the use of such compounds and compositions in controlling undesirable plant growth: in particular the use in controlling weeds, such as broad-leaved dicotyledonous weeds, in crops of useful plants. 2. The compound according to claim 1 , wherein G is hydrogen or —C(O)R claim 1 , and Ris C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , —C-Calkoxy claim 1 , —NRRwherein Rand Rtogether form a morpholinyl ring claim 1 , or phenyl3. The compound according to claim 1 , wherein G is hydrogen or C(O)Rwherein Ris isopropyl claim 1 , t-butyl claim 1 , methyl claim 1 , ethyl claim 1 , propargyl claim 1 , methoxy claim 1 , ethoxy claim 1 , or tert-butoxy.4. The compound of wherein X is hydrogen claim 1 , halogen claim 1 , or Chaloalkyl.5. The compound of wherein Y is hydrogen claim 1 , C-Calkyl claim 1 , C-Chaloalkyl claim 1 , or halogen.6. The compound according to wherein Ris methyl claim 1 , ethyl claim 1 , n-propyl claim 1 , cyclopropyl claim 1 , propargyl claim 1 , or Chaloalkyl.7. The compound according to wherein Ris selected from the group consisting of hydrogen claim 1 , C-Calkyl claim 1 , C-Chaloalkyl claim 1 , C-Calkoxy claim 1 , C-Calkoxy-C-Calkyl claim 1 , C-Ccycloalkyl claim 1 , C-Calkenyl claim 1 , C-Chaloalkenyl claim 1 , C-Calkynyl and C-Chaloalkynyl.8. The compound according to wherein D is a substituted or unsubstituted9. The compound according to wherein each Ris independently.10. The compound according to wherein D is Dp and each Z is independently selected from hydrogen claim 1 , cyano claim 1 , halogen claim 1 , methyl claim 1 , methoxy claim 1 , and trifluoromethyl.11. The compound according to wherein W is W1 and ...

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Номер записи: 51
10-01-2019 дата публикации

PERK INHIBITORS AND USES THEREOF IN TREATING DISEASES ASSOCIATED WITH AGGREGATION-PRONE PROTEINS

Номер: US20190010130A1
Автор: EIGER Hagit, Ganz Javier, LEDERKREMER Gerardo Zelmar, LEITMAN Julia, Offen Daniel, PORTNOY Moshe
Принадлежит: Ramot at Tel-Aviv University Ltd.

Compounds represented by Formula I are disclosed herein, 116-. (canceled)19. The method of claim 18 , wherein Rand Rare each other than bromo.20. The method of claim 18 , wherein when R is OR′ claim 18 , and R′ is methyl claim 18 , Rand Rare each other than bromo.21. The method of claim 18 , wherein Ra is methyl.22. The method of claim 18 , wherein Rand Rare each hydrogen.23. The method of claim 18 , wherein R-Rare each hydrogen.24. The method of claim 18 , wherein R-Rare each hydrogen.25. The method of claim 18 , wherein R is OR′.26. The method of claim 25 , wherein R′ is methyl.28. The method of claim 18 , wherein R is OH.31. The method of claim 30 , wherein Ra is methyl.32. The method of claim 30 , wherein Rand Rare each hydrogen.33. The method of claim 30 , wherein R-Rare each hydrogen.34. The method of claim 30 , wherein R-Rare each hydrogen.35. The method of claim 30 , wherein R is OR′.36. The method of claim 35 , wherein R′ is methyl.38. The method of claim 30 , wherein R is OH. The present invention, in some embodiments thereof, relates to therapy, and more particularly, but not exclusively, to compounds which inhibit pancreatic endoplasmic reticulum kinase (PERK) activity and which are usable in treating diseases associated with aggregation-prone proteins, such as Huntington's disease.Protein aggregation is a biological phenomenon in which misfolded proteins form, either intracellularly or extracellularly, aggregates which are often toxic. Aggregation-prone proteins produce cellular stress, toxicity and death and are the cause of many of the neurodegenerative diseases, including, for example, ALS, Alzheimer's, Parkinson's and prion disease.Proteins fold into their native conformation and undergo a series of post-translational modifications in the endoplasmic reticulum (ER) as part of the normal process of cellular homeostasis. Disruption of cellular protein folding results in ER stress. Cells respond to ER stress by activation of the unfolded protein ...

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Номер записи: 52
10-01-2019 дата публикации

COMPOSITION AND LIGHT EMITTING ELEMENT DEVICE USING THE SAME

Номер: US20190010134A1
Автор: ANRYU Makoto, KURAGANO Takashi, SAITO Takakazu, SASADA Toshiaki, TSUBATA Yoshiaki
Принадлежит:

A composition which is useful for production of a light emitting device excellent in light emission efficiency is provided. In particular, provided is a composition containing a compound represented by formula (1) and a phosphorescent compound, wherein Rand Reach independently represent a substituent, nrepresents an integer of 1 to 14, and Arrepresents an arylene group or a divalent heterocyclic group, and at least one of one or more groups Aris a group represented by the formula (1-A), wherein the variable groups Rto R, R, and Rare as defined in the specification. 2. The composition according to claim 1 , wherein one of Rand Ris a connecting bond claim 1 , and one of Rand Ris a connecting bond.3. The composition according to claim 1 , wherein Ris an alkyl group optionally having a substituent or a cycloalkyl group optionally having a substituent.4. The composition according to claim 1 , wherein Ris an aryl group optionally having a substituent.9. The composition according to claim 1 , wherein all of ngroups Arare groups represented by the formula (1-A).12. The composition according to claim 1 , further comprising at least one material selected from the group consisting of a hole transporting material claim 1 , a hole injection material claim 1 , an electron transporting material claim 1 , an electron injection material claim 1 , a light emitting material and an antioxidant.13. The composition according to claim 1 , further comprising a solvent.14. A light emitting device comprising the composition according to . The present invention relates to a composition and a light emitting device using the same.Light emitting devices such as an organic electroluminescent device can be suitably used for applications of display and illumination. As the light emitting material used in a light emitting layer of a light emitting device, for example, a composition comprising a fluorene compound 1 represented by the following formula and Ir (ppy)represented by the following formula ...

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Номер записи: 53
03-02-2022 дата публикации

INTERMEDIATES FOR PREPARING HERBICIDAL PYRIDAZINONES

Номер: US20220033361A1
Автор: McCann Stephen Frederick, STEVENSON Thomas Martin
Принадлежит:

Disclosed is a compound of Formula I, including N-oxides, and salts thereof, wherein R, Rand Rare defined as set forth in the disclosure. Also disclosed is a process for preparing a compound of Formula I. A compound of Formula I can also be used as a synthetic intermediate to prepare pyridazinone-based herbicides. 3. The compound of wherein{'sup': '1', 'sub': 1', '4, 'Ris C-Calkyl; and'}{'sup': '4', 'Ris methyl, ethyl, n-propyl or i-propyl.'}4. The compound of wherein{'sup': '1', 'Ris methyl; and'}{'sup': '4', 'Ris methyl.'}6. The compound of wherein{'sup': '1', 'sub': 1', '4, 'Ris C-Calkyl; and'}{'sup': '4', 'Ris methyl, ethyl, n-propyl or i-propyl.'}7. The compound of wherein{'sup': '1', 'Ris methyl; and'}{'sup': '4', 'Ris methyl.'}9. The process of wherein Ris methyl.11. The process of wherein Ris methyl.12. The process of wherein Ris methyl. The present disclosure provides pyridazinones and a process for preparing pyridazinones. The pyridazinones disclosed herein can be used as synthetic intermediates to prepare pyridazinone-based herbicides. WO 2015/168010 and WO 2017/074988 disclose herbicidal pyridazinones and synthetic intermediates used to prepare herbicidal pyridazinones. There exists a need for improved methods of preparing herbicidal pyridazinones.In one aspect, the present disclosure provides a compound of Formula I and N-oxides or salts thereof,whereinIn another aspect, the present disclosure provides a process for preparing a compound of Formula I-A,whereinwhereinIn another aspect, the present disclosure provides a process for preparing a compound of Formula I-BwhereinAs used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains”, “containing,” “characterized by” or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a process or method that comprises a list of elements is not necessarily limited to only those elements but ...

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Номер записи: 54
19-01-2017 дата публикации

DISUBSTITUTED 5-FLUORO PYRIMIDINE DERIVATIVES CONTAINING A SULFONDIIMINE GROUP

Номер: US20170015634A1
Автор: BOHLMANN Rolf, Bömer Ulf, Lienau Philip, Lucking Ulrich, SCHOLZ Arne, Siemeister Gerhard
Принадлежит: BAYER PHARMA AKTIENGESELLSCHAFT

The present invention relates to 5-fluoro pyrimidine derivatives containing a sulfondiimine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I). 3. The compound of general formula (I) according to claim 1 , wherein{'sup': 9a', '9b, 'Rand Rrepresent a hydrogen atom,'}or an enantiomer, diastereomer, salt, solvate or salt of solvate thereof.7. The compound of general formula (I) according to claim 1 , wherein{'sup': '6', 'Rrepresents a fluoro atom;'}{'sup': '7', 'Rrepresents a hydrogen atom,'}or an enantiomer, diastereomer, salt, solvate or salt of solvate thereof.8. The compound of general formula (I) according to claim 1 , wherein{'sup': '3', 'sub': '5', 'Rrepresents a group selected from a fluoro atom and —SF;'}or an enantiomer, diastereomer, salt, solvate or salt of solvate thereof.11. The compound according to claim 1 , which is5-Fluoro-4-(4-fluoro-2-methoxyphenyl)-N-{3-fluoro-5-[(S-methylsulfonodiimidoyl)methyl]phenyl}pyrimidin-2-amine;(rac)-N-{3-[(N,S-Dimethylsulfonodiimidoyl)methyl]-5-fluorophenyl}-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-amine;(rac)-5-Fluoro-4-(4-fluoro-2-methoxyphenyl)-N-{3-fluoro-5-[(S-methyl-N-phenylsulfonodiimidoyl)methyl]phenyl}pyrimidin-2-amine;(rac)-5-Fluoro-4-(4-fluoro-2-methoxyphenyl)-N-(3-fluoro-5-{[S-methyl-N-(prop-2-yn-1-yl)sulfonodiimidoyl]methyl}phenyl)pyrimidin-2-amine;{'sup': '6', '(rac)-[(3-Fluoro-5-{[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino}benzyl)(imino)methyl-λ-sulfanylidene]cyanamide;'}{'sup': '6', '(rac)-3-{[(3-Fluoro-5-{[5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-yl]amino}benzyl)(imino)methyl-λ-sulfanylidene]amino}propan-1-ol;'}{'sup': '6', '4 ...

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Номер записи: 55
21-01-2016 дата публикации

COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CANCER

Номер: US20160016913A1
Автор: De Waal Lucian, Gechijian Lara Nicole, Greulich Heidi, Lewis Timothy A., Meyerson Matthew, Munoz Benito
Принадлежит: THE BROAD INSTITUTE, INC.

Disclosed are compounds, such as pyridazinones, that can be, inter alia, used for treating cancer.

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Номер записи: 56
18-01-2018 дата публикации

IMPROVED PROCESS FOR PREPARING STATIN PRECURSOR

Номер: US20180016241A1
Автор: Bessembinder Karin Henderika Maria, De Lange Ben, Heemskerk Dennis
Принадлежит:

The present invention relates to a process for preparing a statin precursor, which process comprises a first reaction step, wherein a hydroxy-pyrimidine-carbonitrile is reacted with an organic sulfonyl halide to form the sulfonate-pyrimidine-carbonitrile; a second reaction step, wherein the sulfonate-pyrimidine-carbonitrile is reacted with N-methylmethane sulfonamide to form a pyrimidinyl-sulfonamide; and optionally a third reaction step, wherein the pyrimidinyl-sulfonamide is reacted with a reducing agent. All steps are conducted in toluene as the main solvent. 2. The process according to wherein toluene is present in steps (a) claim 1 , (b) and (c).4. The process according to claim 1 , wherein the first and second temperature are independently chosen to lie in the range of 50 to 110° C.5. The process according to claim 1 , wherein the intermediate mixture is contacted with N-methylmethane sulfonamide by adding the intermediate mixture to a sulfonamide mixture comprising N-methylmethane sulfonamide in toluene.6. The process according to claim 5 , wherein the intermediate mixture is added to the mixture comprising N-methylmethane sulfonamide over a period of at least 1 hour.7. The process according to claim 5 , wherein the mixture comprising N-methylmethane sulfonamide further comprises a base.8. The process according to claim 5 , wherein the sulfonamide mixture comprises 1-60 wt. % N-methylmethane sulfonamide claim 5 , relative to the total weight of toluene in the sulfonamide mixture.9. The process according to claim 1 , wherein the organic sulfonyl halide is selected from the group consisting of methanesulfonyl chloride claim 1 , ethanesulfonyl chloride claim 1 , trifluoromethanesulfonyl chloride claim 1 , methanesulfonyl bromide claim 1 , benzenesulfonyl chloride claim 1 , benzenesulfonyl bromide claim 1 , p-toluenesulfonyl chloride claim 1 , p-toluenesulfonyl bromide claim 1 , p-toluenesulfonyl fluoride claim 1 , 4-chlorobenzenesulfonyl chloride claim 1 , 2- ...

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Номер записи: 57
17-01-2019 дата публикации

PYRIDAZINONE HERBICIDES

Номер: US20190016712A1
Автор: DeBergh John Robbins, Deprez Nicholas Ryan, SELBY Thomas Paul, STEVENSON Thomas Martin, Taggi Andrew Edmund
Принадлежит:

Disclosed are compounds of Formula 1, including all stereoisomers, N-oxides, and salts thereof, 123.-. (canceled)25. The compound of wherein{'sub': 3', '3, 'X is O, S, —CH═CH—, —C(CH)═CH—, —CH═CF—, —CH═CCl— or —CH═C(CH)—;'}{'sup': '1', 'sub': 1', '7', '3', '8', '3', '8', '4', '7', '3', '7', '3', '7', '3', '7', '4', '7', '2', '3', '1', '4', '2', '7', '1', '7', '3', '7', '2', '7', '3', '7', '1', '7, 'Ris H, C-Calkyl, C-Calkylcarbonylalkyl, C-Calkoxycarbonylalkyl, C-Calkylcycloalkyl, C-Calkenyl, C-Calkynyl, C-Ccycloalkyl, C-Ccycloalkylalkyl, C-Ccyanoalkyl, C-Cnitroalkyl, C-Chaloalkoxyalkyl, C-Chaloalkyl, C-Chaloalkenyl, C-Calkoxyalkyl, C-Calkylthioalkyl, C-Calkoxy, benzyl or phenyl;'}{'sup': '2', 'sub': 1', '7', '3', '8', '3', '8', '2', '4', '2', '7', '4', '7', '3', '7', '3', '7', '1', '4', '1', '4', '1', '4', '2', '8', '3', '7', '4', '7', '2', '3', '1', '4', '2', '7', '1', '7', '3', '7', '2', '7', '1', '7', '1', '5, 'Ris H, halogen, —CN, —CHO, C-Calkyl, C-Calkylcarbonylalkyl, C-Calkoxycarbonylalkyl, C-Calkylcarbonyl, C-Calkylcarbonyloxy, C-Calkylcycloalkyl, C-Calkenyl, C-Calkynyl, C-Calkylsulfinyl, C-Calkylsulfonyl, C-Calkylamino, C-Cdialkylamino, C-Ccycloalkyl, C-Ccycloalkylalkyl, C-Ccyanoalkyl, C-Cnitroalkyl, C-Chaloalkoxyalkyl, C-Chaloalkyl, C-Chaloalkenyl, C-Calkoxyalkyl, C-Calkoxy or C-Calkylthio;'}{'sup': '3', 'sub': 1', '3', '2', '4', '2', '4', '3', '4', '1', '3', '1', '3', '1', '2', '1', '2', '1', '2, 'each Ris independently halogen, —CN, C-Calkyl, C-Calkenyl, C-Calkynyl, C-Ccycloalkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, C-Calkylthio or C-Chaloalkylthio;'}{'sup': '4', 'sub': 1', '3', '2', '4', '2', '4', '3', '4', '1', '3', '1', '3', '1', '2', '1', '2', '1', '2, 'Ris halogen, —CN, C-Calkyl, C-Calkenyl, C-Calkynyl, C-Ccycloalkyl, C-Chaloalkyl, C-Calkoxy, C-Chaloalkoxy, C-Calkylthio or C-Chaloalkylthio; and'}n is 0, 1, 2 or 3.26. The compound of wherein{'sub': 3', '3, 'X is —CH═CH—, —C(CH)═CH—, —CH═CF—, —CH═CCl— or —CH═C(CH)—;'}{'sup': '1', 'sub': 1', '7', ' ...

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Номер записи: 58
21-01-2021 дата публикации

STABILISED RADIOLABELLING REACTION

Номер: US20210017098A1
Автор: CLARKE Alan P., Engell Torgrim, Grigg Julian, Jackson Alexander, KAHN Alexander Imtiaz, MCROBBIE Walter Graeme
Принадлежит:

The present invention provides a method for the synthesis of an injectable composition comprising a [F]-labelled pyridaben derivative that is advantageous over prior methods. In particular, the method of the present invention comprises a method of radiosynthesis that permits a more facile purification using solid phase extraction (SPE). 1. A method comprising reacting a precursor compound with F-fluoride in the presence of (2 ,2 ,6 ,6-Tetramethylpiperidin-1-yl)oxyl (TEMPO) to obtain an F-labelled compound wherein: {'br': None, 'BTM-LINKER-LG \u2003\u2003(I)'}, 'said precursor compound is of Formula Iwherein:BTM is an analogue of pyridaben;LINKER is an alkylene or an alkoxyalkylene; and,LG is a sulfonate-containing leaving group; and{'sup': '18', 'claim-text': {'br': None, 'sup': '18', 'BTM-LINKER-F \u2003\u2003(II)'}, 'said F-labelled compound is of Formula IIwherein BTM and LINKER are as defined for Formula I.3. The method as defined in wherein Ris Calkyl.4. The method as defined in wherein Ris methyl claim 2 , ethyl claim 2 , propyl claim 2 , n-butyl claim 2 , s-butyl claim 2 , or t-butyl.5. The method as defined in wherein Ris halo.6. The method as defined in wherein Ris chloro.7. The method as defined in wherein W is heteroalkylene.8. The method as defined in wherein W is alkoxyalkylene.11. The method as defined in wherein LG is selected from mesylate claim 1 , tosylate claim 1 , triflate claim 1 , nosylate claim 1 , or 1 claim 1 ,2-cyclic sulfate.12. The method as defined in wherein LG is tosylate.13. The method as defined in wherein said precursor compound is dissolved in acetonitrile.14. The method as defined in wherein said TEMPO is present in a molar ratio to the precursor compound of between 0.01:1 and 5:1.15. The method as defined in wherein the starting radioactivity is at least 100 GBq.16. The method as defined in wherein the starting radioactivity is between 100-1000 GBq.17. The method as defined in wherein the starting radioactivity is between 100-750 ...

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Номер записи: 59
16-01-2020 дата публикации

HETEROCYCLIC INHIBITORS OF THE SODIUM CHANNEL

Номер: US20200017488A1
Автор: III Glenn F., Lee Margaret S., Romero Donna L., Short
Принадлежит:

The invention relates to compounds useful in treating conditions associated with voltage-gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention concerns heterocyclic compounds (e.g., compounds according to any of Formulas (I)-(III) or Compounds (1)-(65) of Table 1) that are that are useful in treatment of conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotropic lateral sclerosis, glaucoma, ischaemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome. This application is a continuation of U.S. patent application Ser. No. 15/122,085 filed Aug. 26, 2016 which is a national phase application of PCT/US2015/017806 filed Feb. 26, 2014 which claims benefit to U.S. Provisional Patent Application No. 61/945,309 filed Feb. 27, 2014, and which is hereby incorporated by reference in its entirety.The invention relates to compounds useful in treating conditions associated with voltage-gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention relates to heterocyclic compounds (e.g., compounds according to any of Formulas (I)-(III) or Compounds (1)-(65) of Table 1) that are that are useful in treatment of diseases and conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotropic lateral sclerosis, glaucoma, ischaemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome.Voltage-gated sodium (Nav) channels are present in neurons and excitable tissues where they contribute to processes such as membrane excitability and muscle contraction (Ogata et al., 88:365-77, 2002). Nine different transmembrane 3-subunits (Nav1.1-1.9) from a single Nav1 family combine with auxiliary β-subunits that modify channel ...

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Номер записи: 60
28-01-2016 дата публикации

HISTONE DEACETYLASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF

Номер: US20160024019A1
Автор: Beaumont Vahri, Beconi Maria, Bürli Roland W., Dominguez Celia, Haughan Alan F., Luckhurst Christopher A., Muñoz-Sanjuán Ignacio, Raphy Gilles, Thomas Beth, Wall Michael
Принадлежит:

Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, compositions thereof, and methods of their use. 3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein n is 1.5. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein each Ris independently C-Calkyl or C-Chaloalkyl.6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein each Ris independently methyl or trifluoromethyl.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein m is 1.9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein at least one Ris halo.10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof claim 9 , wherein at least one Ris fluoro.11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof claim 10 , wherein m is 1 claim 10 , and Ris 2-fluoro.13. A pharmaceutically acceptable composition comprising a pharmaceutically acceptable carrier and at least one compound of claim 1 , or a pharmaceutically acceptable salt thereof.14. A pharmaceutical composition of claim 13 , wherein the composition is formulated in a form chosen from tablets claim 13 , capsules claim 13 , powders claim 13 , liquids claim 13 , suspensions claim 13 , suppositories claim 13 , and aerosols.15. A method for treating a condition or disorder mediated by at least one histone deacetylase in a patient in need of such a treatment which method comprises administering to the patient a therapeutically effective amount of at least one compound of claim 1 , or a pharmaceutically acceptable salt thereof.16. A method for treating a condition or disorder responsive to inhibition of at least one histone deacetylase in a patient in need of such a treatment which method comprises administering to the patient an effective amount of at least one compound of claim 1 , or a pharmaceutically acceptable salt ...

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Номер записи: 61
26-01-2017 дата публикации

INTERMEDIATE COMPOUND FOR PREPARING ROSUVASTATIN CALCIUM AND METHOD FOR PREPARING ROSUVASTATIN CALCIUM THEREFROM

Номер: US20170022169A1
Автор: DONG Changming, GAGE James, HONG Hao, LI Jiuyuan, SHEN Litao, ZHANG LEI
Принадлежит:

Provided are an intermediate compound for preparing rosuvastatin calcium and a preparation method of the rosuvastatin calcium. The method comprises: using the foregoing intermediate compound as a raw material, and subjecting the raw material to a step of Wittig reaction, a step of protecting group removal and hydrolysis and a step of calcium salt formation, so as to obtain the rosuvastatin calcium. The product, which is prepared from the intermediate compound, can be substantially enhanced in stereoselectivity and also notably improved in purity and yield; in addition, the method for preparing rosuvastatin calcium from the intermediate compound is simple, convenient and low in cost. 3. The method according to claim 2 , wherein Ris tert-butyl claim 2 , tert-pentyl claim 2 , cyclopentyl or cyclohexyl.4. The method according to claim 2 , wherein the step of combining formula (I) with formula (II) comprises: adding the intermediate compound formula (I) into an organic solvent claim 2 , cooling down to −80 to −20° C. claim 2 , then adding an alkali claim 2 , adding dropwise a solution of formula (II) at −80 to −20° C. claim 2 , reacting at −80 to −20° C. for 1 to 3 hours after the addition is completed claim 2 , warming up to −45 to 25° C. and reacting until the reaction is completed claim 2 , quenching the reaction claim 2 , extracting claim 2 , concentrating the extraction solution claim 2 , and adding a solvent to the crude product obtained by concentrating claim 2 , and crystallizing formula (III).5. The method according to claim 2 , wherein the alkali is selected from the group consisting of sodium hydride claim 2 , butyllithium claim 2 , lithium diisopropylamide claim 2 , lithium hexamethyldisilazide claim 2 , sodium hexamethyldisilazide claim 2 , 2 claim 2 ,2 claim 2 ,6 claim 2 ,6-tetramethylpiperidinylmagnesium chloride claim 2 , 2 claim 2 ,2 claim 2 ,6 claim 2 ,6-tetramethylpiperidine lithium claim 2 , potassium hexamethyldisilazide claim 2 , lithium ...

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Номер записи: 62
17-04-2014 дата публикации

Benzamides

Номер: US20140107340A1
Автор: Chen Bin, Eldemenky Eman Mohammed, Hopper Allen T., Jessing Mikkel, Jiang Yu, Kilburn John Paul, Rasmussen Lars Kyhn
Принадлежит: H. Lundbeck A/S

The present invention is directed to benzamide containing compounds which inhibit the P2X7 receptor 2. The compound of claim 1 , wherein Ris optionally substituted phenyl.3. The compound of claim 1 , wherein Ris optionally substituted pyridyl.4. The compound of claim 1 , wherein Ris optionally substituted pyrazinyl.5. The compound of claim 1 , wherein Ris optionally substituted pyrimidyl.6. The compound of claim 1 , wherein Ris optionally substituted 5 membered heteroaryl.7. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted piperazinyl.8. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted piperidinyl.9. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted morpholinyl.10. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted pyrrolidinyl.11. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted pyrrolo.12. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted imidazo.13. The compound of anyone of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted homomorpholinyl14. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted homopiperidinyl15. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted homopiperazinyl16. The compound of claim 1 , wherein Rand Rcombine with the nitrogen to which they are attached to form optionally substituted azetidinyl.17. The compound of claim 1 , wherein Ris chlorine claim 1 , methyl or trifluorormethyl.18. The compound of claim 1 ...

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Номер записи: 63
10-02-2022 дата публикации

PYRIDAZINONE HERBICIDES AND PYRIDAZINONE INTERMEDIATES USED TO PREPARE A HERBICIDE

Номер: US20220041560A1
Автор: CHEN Yuzhong, Marshall Eric Allen, McCann Stephen Frederick, SELBY Thomas Paul, STEVENSON Thomas Martin
Принадлежит:

Disclosed are compounds of Formula I and N-oxides or salts thereof, wherein Ris C-Calkyl or C-Ccycloalkyl; Ris H, Cl, Br or I; Ris Cl or OR; Ris H or C-Calkyl; Ris H, F, Cl or CH; and Ris H or Cl. Also disclosed is a composition containing a compound of Formula I, and methods for controlling undesired vegetation comprising contacting the undesired vegetation or its environment with an effective amount of a compound of Formula I or a composition thereof. Also disclosed are methods for preparing a compound of Formula I. 2. The compound of wherein{'sup': '2', 'Ris Cl;'}{'sup': 3', '4, 'Ris OR;'}{'sup': '4', 'Ris H or methyl; and'}{'sup': '5', 'sub': '3', 'Ris F, Cl or CH;'}{'sup': '6', 'Ris H or Cl.'}3. The compound of any one of to wherein Ris CH.4. The compound of any one of to wherein Ris Cl.5. The compound of selected from the group consisting of6-chloro-4-(2,7-dimethyl-1-naphthalenyl)-5-hydroxy-2-methyl-3(2H)-pyridazinone;6-chloro-4-(7-fluoro-2-methyl-1-naphthalenyl)-5-hydroxy-2-methyl-3(2H)-pyridazinone;6-chloro-4-(7-chloro-2-methyl-1-naphthalenyl)-5-hydroxy-2-methyl-3(2H)-pyridazinone; and6-chloro-4-(4-chloro-2-methyl-1-naphthalenyl)-5-hydroxy-2-methyl-3(2H)-pyridazinone.12. A herbicidal composition comprising the compound of and at least one component selected from the group consisting of surfactants claim 1 , solid diluents claim 1 , and liquid diluents.13. A herbicidal composition comprising a compound of claim 1 , at least one additional active ingredient selected from the group consisting of other herbicides and herbicide safeners claim 1 , and at least one component selected from the group consisting of surfactants claim 1 , solid diluents and liquid diluents.14. A herbicidal mixture comprising (a) a compound of claim 1 , and (b) at least one additional active ingredient.15. A method for controlling the growth of undesired vegetation comprising contacting the vegetation or its environment with a herbicidally effective amount of a compound of . The present ...

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Номер записи: 64
22-01-2015 дата публикации

Benzamide Compounds and Related Methods of Use

Номер: US20150025235A1
Автор: Kazantsev Aleksey G., Khanfar Mohammad, Silverman Richard B., Wang Hua
Принадлежит:

Benzamide compounds and derivatives thereof, as can be used for selective inhibition of the SIRT2 enzyme and/or therapeutic use in the treatment of Huntington's disease. 3. The compound of wherein each of Eand Eis CH.4. The compound of wherein n is 0.5. The compound of wherein o is 1-2.6. The compound of wherein Ris selected from benzyl and mono- and disubstituted benzyl moieties.7. The compound of selected from compounds B wherein m is 1-2.8. The compound of wherein Ris selected from phenyl and mono- and disubstituted phenyl moieties.9. The compound of wherein Eis CH claim 8 , and Eis selected from CH and N.10. The compound of wherein n is 0. This application is a continuation of and claims priority benefit of application Ser. No. 14/139,763 filed Dec. 23, 2013 which claimed priority from application Ser. No. 61/745,056 filed Dec. 21, 2012—each of which is incorporated herein by reference in its entirety.This invention was made with government support under grant number 5 U01 NS066912 awarded by the National Institutes of Health. The government has certain rights in the invention.Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is characterized by progressive motor dysfunction, emotional disturbances, dementia, and weight loss. There currently is no treatment for delaying the onset of the disease or for slowing the progression of HD. Management of HD is focused on symptom reduction, and the only drug approved by the FDA is tetrabenazine, which is indicated to suppress involuntary movements (chorea) but does not slow the disease progression. The disease is caused by an elongated CAG trinucleotide repeat expansion located within exon 1 of the IT-15 gene encoding huntingtin, a 350-kDa protein of unknown function. The CAG repeat is translated into a polyglutamine (polyQ) stretch. In HD patients, huntingtin is expressed with 38-180 glutamine residues, whereas in healthy individuals the protein is synthesized with 8-37 ...

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Номер записи: 65
22-01-2015 дата публикации

ARYLALKYL ESTERS OF 4-AMINO-6-(SUBSTITUTED PHENYL)-PICOLINATES AND 6-AMINO-2-(SUBSTITUTED PHENYL)-PYRIMIDINECARBOXYLATES AND THEIR USE AS SELECTIVE HERBICIDES FOR CROPS

Номер: US20150025238A1
Автор: Eckelbarger Joseph D., Epp Jeffrey B., Guenthenspberger Katherine A., Lowe Christian T., Schmitzer Paul R., Siddall Thomas L., Yerkes Carla N.
Принадлежит: DOW AGROSCIENCES LLC

Arylalkyl esters of 4-aminopicolinic acids and 6-amino-4-pyrimidinecarboxylates are herbicides for control of weeds especially those species common to rice and wheat cropping systems and in pasture management programs. 2. The compound of in which Y represents substituted phenyl.3. The compound of in which Z represents Cl claim 1 , —CH═CHor OCH.4. The compound of in which Rand Rrepresent H.5. The compound of in which Rrepresents a benzyl.6. The compound of in which Rrepresents an unsubstituted or ortho- claim 1 , meta- or para-monosubstituted benzyl. This application is a divisional of U.S. Non-Provisional application Ser. No. 13/356,668 filed Jan. 24, 2012 which claims the benefit of U.S. Provisional Patent Application Ser. No. 61/435,925 filed Jan. 25, 2011.This invention relates to certain novel esters of 4-amino-6-(substituted phenyl)-picolinic acids and 6-amino-2-(substituted phenyl)-4-pyrimidinecarboxylic acids and to the use of these compounds as herbicides for control of weeds especially those species common to rice and wheat cropping systems and in pasture management programs.A number of picolinic acids and their pesticidal properties have been described in the art. U.S. Pat. No. 6,784,137 B2 and U.S. Pat. No. 7,314,849 B2 disclose a genus of 4-amino-6-arylpicolinic acids and their derivatives and their use as selective herbicides, particularly for rice and cereals such as wheat and barley. WO 2005/063721 A1, WO 2007/082076 A1, U.S. Pat. No. 7,863,220 B2, U.S. Pat. No. 7,300,907 B2, U.S. Pat. No. 7,642,220 B2, and U.S. Pat. No. 7,786,044 B2 disclose certain 6-amino-2-substituted-4-pyrimidinecarboxylic acids and their derivatives and their use as herbicides. It has now been discovered that certain esters of 4-amino-6-(substituted phenyl)picolinic acids and of 6-amino-2-(substituted phenyl)-4-pyrimidinecarboxylic acids can provide superior weed control especially in rice and wheat cropping systems and in pasture management programs.Certain arylalkyl esters of ...

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Номер записи: 66
10-02-2022 дата публикации

OREXIN 1 RECEPTOR ANTAGONISTS

Номер: US20220041573A1
Автор: Brown Giles Albert, Bucknell Sarah Joanne, Christopher John Andrew, Congreve Miles Stuart, Mills Mark, PATEL ANIL, Stephenson Anne Mary, Swain Nigel Alan, TEHAN Benjamin Gerald
Принадлежит:

The disclosures herein relate to novel compounds of formula (I): and salts thereof, wherein W; X; Y; Z; R; R; Rand Rare defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of neurological or psychiatric disorders associated with orexin receptors. 3. The compound according to or wherein X is CR.4. The compound according to wherein W is N.5. The compound according to or wherein Ris selected from H claim 3 , F claim 3 , OMe claim 3 , OCHF claim 3 , OCDor CHOMe.6. The compound according to or wherein W is CR.7. The compound according to wherein X is N.8. The compound according to or wherein Ris H claim 6 , Me claim 6 , CHOMe or OMe.9. The compound according to any one of - wherein Z is CH.10. The compound according to any one of - wherein Ris H.11. The compound according to any one of - wherein Ris a 1 claim 6 ,2 claim 6 ,3-triazole ring optionally substituted with one or more fluorine atoms; a pyrimidine ring optionally substituted with one or more fluorine atoms; or a pyrazine ring optionally substituted with one or more fluorine atoms.14. The compound according to any one of - wherein Ris H.15. The compound according to any one of - wherein Ris F.16. The compound according to or which is selected from the group consisting of:N-[(1S,2S)-2-[(4-fluorophenoxy)methyl]cyclopentyl]-2-(triazol-2-yl)benzamide;N-[(1S,2S)-2-[(4-fluorophenoxy)methyl]cyclopentyl]-5-methyl-2-pyrimidin-2-yl-benzamide;N-[(1S,2S)-2-[(4-fluorophenoxy)methyl]cyclopentyl]-5-methyl-2-(triazol-2-yl)benzamide;2-fluoro-N-[(1S,2S)-2-[(4-fluorophenoxy)methyl]cyclopentyl]-6-(triazol-2-yl)benzamide;N-[(1S,2S)-2-[(4-fluorophenoxy)methyl]cyclopentyl]-2-methoxy-6-(triazol-2-yl)benzamide;N-[(1S,2S)-2-[(4-chlorophenoxy)methyl]cyclopentyl]-2-methoxy-6-(triazol-2-yl)benzamide;N-[(1S,2S)-2-[dideuterio-(4-fluorophenoxy)methyl]cyclopentyl]-2-methoxy-6-(triazol-2-yl)benzamide;2-(difluoromethoxy)-N-[(1S,2S)-2-[(4-fluorophenoxy)methyl]cyclopentyl]-6-(triazol-2-yl)benzamide;N ...

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Номер записи: 67
28-01-2021 дата публикации

SOLID PHASE EXTRACTION

Номер: US20210023558A1
Автор: CLARKE Alan P., Engell Torgrim, Grigg Julian, Jackson Alexander, KAHN Alexander Imtiaz, MCROBBIE Walter Graeme
Принадлежит:

The present invention provides a method for the synthesis of an injectable composition comprising a [F]-labelled pyridaben derivative that is amenable to automation. In particular, the method of the present invention comprises a method of purification carried out by means of solid phase extraction (SPE) alone. 1. A method comprising: [{'br': None, 'BTM-LINKER-LG\u2003\u2003(I)'}, 'wherein:', 'BTM is a biological targeting moiety;', 'LINKER is an alkylene or an alkoxyalkylene; and,', 'LG is a sulfonate-containing leaving group, '(a) reacting in acetonitrile a precursor compound of Formula I{'sup': 18', '18, 'claim-text': {'br': None, 'sup': '18', 'BTM-LINKER-F\u2003\u2003(II)'}, 'with F-fluoride to obtain a crude reaction mixture comprising an F-labelled compound of Formula IIwherein BTM and LINKER are as defined for Formula I;(b) diluting the crude reaction mixture obtained in step (a) to obtain a diluted crude reaction mixture; (i) transferring said diluted crude reaction mixture to an SPE cartridge;', '(ii) optionally passing water through said SPE cartridge;', '(iii) passing a wash solution comprising an organic solvent through said SPE cartridge;', '(iv) optionally passing water through said SPE cartridge to remove said organic solvent; and,', '(v) passing an elution solution comprising ethanol through said SPE cartridge to elute said compound of Formula I from said SPE cartridge;, '(c) purifying the diluted crude reaction mixture obtained in step (b) by means of one or more solid phase extraction (SPE) cartridges to obtain a purified compound of Formula II where said purifying comprises the sequential steps ofwherein step (b) includes adding a hydrolyzing reagent to said crude reaction mixture and/or said water of step (ii) and/or step (iv) comprises a hydrolyzing reagent.2. The method as defined in wherein said BTM is a small molecule.3. The method as defined in wherein said small molecule is an analogue of pyridaben.5. The method as defined in wherein Ris ...

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Номер записи: 68
28-01-2021 дата публикации

PROCESS FOR PRODUCING HERBICIDAL PYRIDAZINONE COMPOUNDS

Номер: US20210024470A1
Автор: DIECKMANN Michael Christian, GODINEAU EDOUARD, Gribkov Denis, ROBINSON ALAN JAMES, SCARBOROUGH Christopher Charles, SMITS HELMARS
Принадлежит: SYNGENTA PARTICIPATIONS AG

The present invention provides, inter alia, a process for producing a compound of Formula (I): wherein A, R, R, R, R, Rand Rare as defined herein. The present invention further provides intermediate compounds utilised in said process, and methods for producing said intermediate compounds. 2. A process according to claim 1 , wherein Ris an optionally substituted heteroaryl.3. A process according to claim 1 , wherein Ris an optionally substituted phenyl.4. A process according to claim 3 , wherein Ris phenyl optionally substituted by one or more substituents selected from the group consisting of halo claim 3 , C-Calkyl claim 3 , C-Chaloalkyl claim 3 , C-Calkoxy claim 3 , cyano and nitro.5. A process according to claim 4 , wherein Ris 3 claim 4 ,4-dimethoxyphenyl.6. A process according to claim 1 , wherein Ris methyl.7. A process according to claim 1 , wherein X is selected from the group consisting of Br claim 1 , Cl and I.8. A process according to claim 1 , wherein X is Br.9. A process according to claim 1 , wherein Ais CRRand R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare hydrogen.10. A process according to claim 1 , wherein the reaction medium further comprises (v) a solvent.11. A process according to claim 10 , wherein the solvent is acetonitrile.14. A process according to claim 13 , wherein Compound (X) and Compound (XI) are reacted using a photochemical catalysed procedure. The present invention relates to a process for producing herbicidal pyridazinone compounds. Such compounds are known, for example, from WO 2012/136703 and WO2017/178582. As explained therein, such compounds are typically produced by forming an acid chloride of the corresponding pyridazinone acid and coupling it with the cyclohexanedione in the presence of base. This reaction first produces an enol ester which can be rearranged to a compound of Formula (I) using a catalytic amount of cyanide source, for example acetone cyanohydrin. However the yields obtained are not ideal for a ...

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Номер записи: 69
28-01-2021 дата публикации

PROCESS FOR PRODUCING HERBICIDAL PYRIDAZINONE COMPOUNDS

Номер: US20210024531A1
Автор: Dumeunier Raphael, GODINEAU EDOUARD, LEHMANN MATTHIAS, MILNER HARRY JOHN, ROBINSON ALAN JAMES, SMITS HELMARS
Принадлежит: SYNGENTA PARTICIPATIONS AG

The present invention provides, inter alia, a process for producing a compound of Formula (I): wherein A, R, R, R, R, Rand Rare as defined herein. The present invention further provides intermediate compounds utilised in said process, and methods for producing said intermediate compounds. 2. A process according to claim 1 , wherein Ris an optionally substituted heteroaryl.3. A process according to claim 1 , wherein Ris an optionally substituted phenyl.4. A process according to claim 1 , wherein Ris phenyl optionally substituted by one or two substituents independently selected from the group consisting of halo claim 1 , C-Calkyl claim 1 , C-Chaloalkyl claim 1 , C-Calkoxy claim 1 , cyano and nitro.5. A process according to claim 1 , wherein Ais CRRand R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare hydrogen.6. A process according to claim 1 , wherein steps (i) claim 1 , (ii) and (iii) are performed in a single operation.9. A process according to claim 1 , wherein Ris 3 claim 1 ,4-dimethoxyphenyl.10. A process according to claim 1 , wherein Ris methyl. The present invention relates to a process for producing herbicidal pyridazinone compounds. Such compounds are known, for example, from WO 2012/136703 and WO2017/178582. As explained therein, such compounds are typically prepared by reacting an acid chloride of the corresponding pyridazinone with cyclohexanedione in the presence of a base to first make an enol ester which is then rearranged to the pyridazinone triketone using a catalytic amount of cyanide source, typically acetone cyanohydrin. This reaction is understood to proceed via an intermediate acyl cyanide as described in, for example, Montes, I. F.; Burger, U. Tetr. Lett. 1996, 37, 1007. However the yields achieved using such a cyanide rearrangement procedure are not ideal for a large scale production and the use of toxic cyanides in commercial manufacturing remains undesirable. Therefore a new, more efficient synthesis method not involving the use of ...

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Номер записи: 70
29-01-2015 дата публикации

PYRIDAZINONE COMPOUNDS AND THEIR USE AS DAAO INHIBITORS

Номер: US20150030704A1
Автор: Farnaby William, Fieldhouse Charlotte, Hazel Katherine, Kerr Catrina, Kinsella Natasha, Livermore David, Merchant Kevin, MILLER DAVID
Принадлежит: Takeda Pharmaceutical Company Limited

The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein Rand Rare as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy. 2. The compound according to claim 1 , wherein Rrepresents a hydrogen atom.3. The compound according to claim 1 , wherein Y is chosen from a bond or —CRR—.5. The compound according to claim 4 , wherein each Rindependently is chosen from a hydrogen atom or methyl group.6. The compound according to claim 1 , wherein Ris chosen from phenyl claim 1 , pyridinyl claim 1 , oxazolyl claim 1 , pyrazinyl claim 1 , cyclopropyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , tetrahydropyranyl claim 1 , 2 claim 1 ,3-dihydrobenzofuranyl claim 1 , pyrimidinyl claim 1 , imidazo[1 claim 1 ,2-a]pyridinyl claim 1 , pyrazolyl claim 1 , thiazolyl or piperidinyl claim 1 , and wherein the ring system is unsubstituted or substituted.7. The compound according to claim 1 , wherein Ris chosen from an unsubstituted or substituted 3- to 6-membered saturated or unsaturated carbocyclic or heterocyclic ring system.8. The compound according to claim 7 , wherein Ris chosen from a 5- or 6-membered unsaturated carbocyclic or heterocyclic ring system claim 7 , wherein the heterocyclic ring system comprises one or two ring heteroatoms independently chosen from nitrogen and oxygen claim 7 , and{'sub': 1', '4', '2', '4', '1', '2', '1', '2', '1', '4', '1', '2', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '3', '6', '3', '6', '3', '6', 'p', '2', 'q, 'sup': '7', 'wherein the carbocyclic or heterocyclic ring system is unsubstituted or substituted by one, two, three or four substituents independently chosen from fluorine, chlorine, bromine, hydroxyl, cyano, oxo, C-Calkyl, C-Calkenyl, C-Chaloalkyl, C-Chydroxyalkyl, C-Calkoxy, C-Chaloalkoxy, C-Calkylthio, C-Calkylsulphinyl, C-Calkylsulphonyl, C-Calkylcarbonyl, C- ...

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Номер записи: 71
02-02-2017 дата публикации

LABILE ESTERS OF AGROCHEMICALS FOR CONTROLLED RELEASE AND REDUCTION OF OFF-SITE MOVEMENT

Номер: US20170029355A1
Автор: Morgenstern David A.
Принадлежит:

The present invention relates to esters of carboxylic acid agrochemicals comprising a labile protecting group and having formula (I). Certain of the esters of carboxylic acid agrochemicals do not undergo hydrolysis to a significant degree in the dark, but are cleaved to regenerate the parent carboxylic acid agrochemical when exposed to light. Others of the esters of carboxylic acid agrochemicals undergo hydrolysis under both light and dark conditions. The present invention further relates to methods for the controlled release of a carboxylic acid agrochemicals, and to methods of controlling unwanted plants comprising applying to the unwanted plants an ester of a carboxylic acid agrochemical. 2. The ester of a carboxylic acid agrochemical of claim 1 , wherein the carboxylic acid agrochemical is a herbicide claim 1 , a fungicide claim 1 , an insecticide claim 1 , a plant health agent claim 1 , or a plant growth regulator.3. The ester of a carboxylic acid agrochemical of claim 2 , wherein the carboxylic acid agrochemical is a herbicide selected from the group consisting of dicamba claim 2 , 2 claim 2 ,4-dichlorophenoxyacetic acid (2 claim 2 ,4-D) claim 2 , fenoxaprop claim 2 , fenoxaprop-P claim 2 , desmedipham claim 2 , cyhalofop claim 2 , carfentrazone claim 2 , flufenpyr claim 2 , fluthiacet claim 2 , fluroglycofen claim 2 , pyraflufen claim 2 , flumiclorac claim 2 , 4-(4-chloro-2-methylphenoxy)butanoic acid (MCPB) claim 2 , fluroxypyr claim 2 , picloram claim 2 , quinclorac claim 2 , benazolin claim 2 ,clodinafop, 4-(2,4-dichlorophenoxy)butanoic acid (2,4-DB), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), dichlorprop, dichlorprop-P, diethatyl, endothall, fluazifop, flufenpyr, flumiclorac, fluoroglycofen, haloxyfop, indole-3-acetic acid, indole-3-butyric acid, mecoprop, mecoprop-P, pyrafluren, fenoprop, triclopyr, aminopyralid, bispyribac, chlorthal, imazamethabenz, pyrothiobac, quinmerac, quizalofop, quizalofop-P, diclofop, and lactofen.4. The ester of a carboxylic ...

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Номер записи: 72
17-02-2022 дата публикации

HERBICIDAL CINNOLINIUM COMPOUNDS

Номер: US20220046923A1
Автор: NG Sean, Scutt James Nicholas, WILLETTS Nigel James
Принадлежит: SYNGENTA CROP PROTECTION AG

Compounds of the formula (I) wherein the substituents are as defined in claim , useful as a pesticides, especially as herbicides. 3. The compound of formula (I) according to claim 2 , wherein Rand Rare independently selected from the group consisting of hydrogen and C-Calkyl.4. The compound of formula (I) according to claim 2 , wherein each Rand Rare independently selected from the group consisting of hydrogen claim 2 , C-Calkyl claim 2 , —OH and —NH.5. The compound of formula (I) according to claim 2 , wherein m is 1 or 2.6. The compound of formula (I) according to claim 2 , wherein Ris selected from the group consisting of hydrogen claim 2 , halogen and C-Calkyl.7. The compound of formula (I) according to claim 2 , wherein Ris selected from the group consisting of hydrogen claim 2 , —NH claim 2 , —NRR claim 2 , —OR claim 2 , —S(O)R claim 2 , C-Calkyl claim 2 , C-Chaloalkyl claim 2 , C-Ccycloalkyl claim 2 , C-Calkenyl claim 2 , C-Calkynyl claim 2 , C-Chaloalkoxy claim 2 , C-Calkylaminocarbonyl and phenyl claim 2 , wherein said phenyl is optionally substituted by 1 claim 2 , 2 or 3 Rsubstituents claim 2 , which may be the same or different.8. The compound of formula (I) according to claim 2 , wherein when k is 1 or 2 claim 2 , each Ris independently selected from the group consisting of halogen claim 2 , cyano claim 2 , —NH claim 2 , —NRR claim 2 , —OH claim 2 , —OR claim 2 , C-Calkyl claim 2 , C-Chaloalkyl claim 2 , C-Ccycloalkyl claim 2 , C-Chaloalkoxy claim 2 , C-Calkenyl claim 2 , C-Calkynyl claim 2 , C-Calkoxycarbonyl claim 2 , C-Calkylaminocarbonyl claim 2 , di-C-Calkylaminocarbonyl and phenyl claim 2 , wherein said phenyl is optionally substituted by 1 claim 2 , 2 or 3 Rsubstituents claim 2 , which may be the same or different.9. The compound of formula (I) according to claim 2 , wherein k is 0 or 1.10. The compound of formula (I) according to claim 2 , wherein Z is selected from the group consisting of —C(O)OR claim 2 , —CHOH claim 2 , —C(O)NHOR claim 2 , —C ...

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Номер записи: 73
01-02-2018 дата публикации

PHARMACEUTICALLY ACTIVE COMPOUNDS

Номер: US20180029985A1
Автор: Londesbrough Derek, NAYLOR Alan, Onions Stuart Thomas, QUDDUS Mohammed Abdul, Sambrook-Smith Colin Peter, SHIERS Jason John, Watts John Paul, WRIGGLESWORTH Joseph William
Принадлежит: BERGENBIO AS

The invention is directed to compounds of general formula (I), and pharmaceutical compositions containing such compounds. The compounds and compositions have valuable pharmaceutical properties. In particular, they may be used for the treatment of cancer. Novel intermediates and novel methods of preparation are also disclosed. 2. A compound according to claim 1 , wherein Qrepresents a nitrogen atom claim 1 , and Qand Qrepresent CH.3. A compound according to claim 1 , wherein Qand Qrepresent CH and Qrepresents a nitrogen atom.4. A compound according to claim 1 , wherein Qand Qboth represent nitrogen atoms claim 1 , and Qrepresents CH.5. A compound according to claim 1 , wherein Q claim 1 , Qand Qrepresent nitrogen atoms.6. A compound according to any preceding claim claim 1 , wherein A represents an optionally substituted five- or six-membered heterocyclic ring.7. A compound according to claim 6 , wherein A contains one claim 6 , two or three heteroatoms claim 6 , which may be the same or different.8. A compound according to claim 7 , wherein the one claim 7 , two or three heteroatoms which may be the same or different are selected from N claim 7 , O and/or S.9. A compound according to any preceding claim claim 7 , wherein A represents optionally substituted pyridyl claim 7 , pyrimidinyl claim 7 , thienyl claim 7 , oxadiazolyl or pyridazinyl.10. A compound according to any of to claim 7 , wherein A represents optionally substituted phenyl.11. A compound according to any preceding claim claim 7 , wherein A is optionally substituted by halo or Calkoxy.12. A compound according to claim 11 , wherein halo is F.13. A compound according to claim 11 , wherein Calkoxy is —OCH.14. A compound according to any preceding claim claim 11 , wherein Rrepresents a six-membered aliphatic carbocyclic or heterocyclic ring claim 11 , optionally substituted by —(C═O)NRR claim 11 , —OR claim 11 , —SORor optionally substituted alkyl.15. A compound according to any of to claim 11 , wherein ...

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Номер записи: 74
04-02-2021 дата публикации

COMPOSITIONS AND METHODS OF MODULATING 15-PGDH ACTIVITY

Номер: US20210032265A1
Автор: Antczak Monika, Bae KiBeom, Desai Amar, Gerson Stanton, Markowitz Sanford, Posner Bruce, Ready Joseph, Tai Hsin-Hsiung, Willson James K.V., Yang Sung Yeun, Zhang Yongyou
Принадлежит:

Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors and 15-PGDH activators described herein. 181-. (canceled)82: A method of treating oral and/or gastrointestinal diseases associated with inflammation and/or ulcers in a subject in need thereof , the method comprising:administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor.83: The method of claim 82 , wherein the ulcer comprises at least one of a mucosal or submucosal ulcer.84: The method of claim 82 , wherein the gastrointestinal disease comprises at least one of oral ulcers or gastrointestinal ulcers.85: The method of claim 82 , wherein the gastrointestinal disease comprises at least one of colitis claim 82 , gastritis claim 82 , or cryptitis.86: The method of claim 82 , wherein the gastrointestinal disease comprises ulcerative colitis.87: The method of claim 82 , wherein the gastrointestinal disease comprises inflammatory bowel disease.88: The method of wherein the 15-PGDH inhibitor is administered at an amount effective to increase prostaglandin levels in blood or tissue of the subject89: The method of claim 82 , wherein the 15-PGDH inhibitor is administered to the subject at an amount effective to inhibit or treat at least one of oral or gastrointesintal ulcer formation.90: The method of claim 82 , wherein the 15-PGDH inhibitor is administered to the subject at an amount effective to inhibit or treat at least one of oral or gastrointesintal inflammation.92: A method of treating oral and/or gastrointestinal inflammation and/or ulcers in a subject in need thereof claim 82 , the method comprising:administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor.93: The method of claim 92 , wherein the subject has at least one of oral ulcers or gastrointestinal ulcers ...

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Номер записи: 75
05-02-2015 дата публикации

Composition for controlling plant diseases and use thereof

Номер: US20150038327A1
Автор: Yuichi Matsuzaki
Принадлежит: Sumitomo Chemical Co Ltd

A composition for controlling plant diseases containing a pyridazine compound represented by Formula (I) and one or more compounds selected from a group (A) exhibits an excellent control effect against plant diseases. The present invention provides a composition for controlling plant diseases containing the pyridazine compound represented by Formula (I) and one or more compounds selected from a group (A), and a method for controlling plant diseases containing a step of applying an effective amount of the pyridazine compound represented by Formula (I) and one or more compounds selected from a group (A) to a plant or soil for cultivating a plant. Group (A): a group consisting of chlorantraniliprole and cyantraniliprole. [In the formula, R 1 represents a chlorine atom, a bromine atom, cyano group, or a methyl group, and R 2 represents a hydrogen atom or a fluorine atom.]

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Номер записи: 76
05-02-2015 дата публикации

COMPOSITION FOR CONTROLLING PLANT DISEASES AND USE THEREOF

Номер: US20150038328A1
Автор: Matsuzaki Yuichi
Принадлежит:

A composition for controlling plant diseases, containing a pyridazine compound represented by Formula (I) and ethaboxam, exhibits an excellent control effect against plant diseases. The present invention provides a composition for controlling plant diseases, containing the pyridazine compound represented by Formula (I) and ethaboxam, and a method for controlling plant diseases, including a step of applying an effective amount of the pyridazine compound represented by Formula (I) and ethaboxam to a plant or soil for cultivating a plant. 2. The composition for controlling plant diseases according to claim 1 , wherein a weight ratio of the pyridazine compound to ethaboxam (the pyridazine compound/ethaboxam) is 0.1/1 to 10/1.4. The method for controlling plant diseases according to claim 3 , wherein a weight ratio of the pyridazine compound to ethaboxam (the pyridazine compound/ethaboxam) is 0.1/1 to 10/1.5. The method for controlling plant diseases according to claim 3 , wherein the plant or the soil for cultivating a plant is wheat or soil for cultivating wheat.6. The method for controlling plant diseases according to claim 3 , wherein the plant or the soil for cultivating a plant is plant seeds. The present invention relates to a composition for controlling plant diseases and a use thereof.In the related art, many compounds have been developed for controlling plant diseases, and put into practical use (for example, refer to Patent Documents 1 and 2).[Patent Document 1] Pamphlet of International Publication No. 2005/121104[Patent Document 2] Pamphlet of International Publication No. 2006/001175An object of the present invention is to provide a composition having an excellent control effect against plant diseases.The present inventor has studied to find a composition having an excellent controlling effect against plant diseases, and as a result, has found that a composition for controlling plant diseases containing a pyridazine compound represented by the following ...

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Номер записи: 77
09-02-2017 дата публикации

FUNGICIDAL PYRAZOLES

Номер: US20170037014A1
Автор: Long Jeffrey Keith, Taggi Andrew Edmund
Принадлежит:

Disclosed are compounds of Formula 1, including all geometric and stereoisomers, N-oxides, and salts thereof, 2. A compound of wherein:{'sup': 1', '4, 'Qis a phenyl or pyridinyl ring substituted with 1 to 3 substituents independently selected from R;'}X is O, NH or CHOH;{'sup': '1', 'sub': 1', '3, 'Ris H or C-Calkyl;'}{'sup': '1a', 'Ris H;'}{'sup': '2', 'Ris Br, Cl or methyl;'}{'sup': 3', '7, 'sub': 1', '6', '1', '6', '2', '6', '3', '6', '2', 'n', '3', '6', '4', '7, 'Ris C-Calkyl, C-Chaloalkyl, C-Calkenyl, C-Ccycloalkenyl or —(CH)W; or C-Ccycloalkyl or C-Ccycloalkylalkyl, each optionally substituted with up to 1 substituent selected from R;'}{'sup': 8', '9, 'W is a 5- to 6-membered saturated or partially unsaturated heterocyclic ring containing ring members selected from carbon atoms and 1 to 2 heteroatoms independently selected from up to 2 O, up to 2 S and up to 2 N atoms, the ring optionally substituted with up to 2 substituents independently selected from Ron carbon atom ring members and Ron nitrogen atom ring members;'}{'sup': '4', 'each Ris independently halogen;'}{'sup': '7', 'sub': 2', '4, 'each Ris independently halogen, methyl, halomethyl, cyclopropyl, methoxy or C-Calkoxyalkyl;'}{'sup': '8', 'sub': 2', '4, 'each Ris independently halogen, methyl, halomethyl, methoxy or C-Calkoxyalkyl; and'}{'sup': '9', 'each Ris methyl.'}3. A compound of wherein{'sup': 1', '4, 'Qis a phenyl ring substituted with 1 to 3 substituents independently selected from R;'}{'sup': '1', 'Ris H;'}{'sup': '2', 'Ris methyl;'}{'sup': 3', '7, 'sub': 1', '6', '1', '6', '2', '6', '3', '6', '3', '6', '4', '7, 'Ris C-Calkyl, C-Chaloalkyl, C-Calkenyl, C-Ccycloalkenyl; or C-Ccycloalkyl or C-Ccycloalkylalkyl, each optionally substituted with up to 1 substituent selected from R;'}{'sup': '4', 'each Ris independently Cl, F or Br; and'}{'sup': '7', 'each Ris independently halogen, methyl, halomethyl or methoxy.'}4. A compound of wherein{'sup': 1', '4', '4', '4, 'Qis a phenyl ring substituted at ...

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Номер записи: 78
09-02-2017 дата публикации

NOVEL PHENOL DERIVATIVES AND PHARMACEUTICAL OR COSMETIC USE THEREOF

Номер: US20170037015A1
Автор: Collette Pascal, Linget Jean-Michel, Mauvais Pascale, Poinsard Cédric, Rethore Sandrine
Принадлежит:

The present invention relates to novel compounds of general formula: 29.-. (canceled) The present invention relates to novel compounds of general formula:and to the cosmetic or pharmaceutical use thereof.The present invention proposes to provide novel phenolic derivatives which are powerful androgen receptor modulators.Among the prior art documents describing molecules which modulate androgen receptor activity, mention may, for example, be made of the phenylimidazolines described in patent application EP 580 459, or application WO 2005/42464.The invention relates to novel phenolic derivatives that correspond to general formula (I) below:in which:The compounds of formula (I) may comprise one or more asymmetric carbon atoms. They may thus exist in the form of a mixture of enantiomers or of diastereoisomers. These enantiomers and diastereoisomers, and also mixtures thereof, including racemic mixtures, form part of the invention.The compounds of formula (I) may exist in the form of bases or of acid-addition salts. Such addition salts form part of the invention. These salts are advantageously prepared with pharmaceutically acceptable acids, but the salts of other acids that are useful, for example for purifying or isolating the compounds of formula (I), also form part of the invention. These acids may be, for example, picric acid, oxalic acid or an optically active acid, for example a tartaric acid, a dibenzoyltartaric acid, a mandelic acid or a camphorsulphonic acid, and those that form physiologically acceptable salts, such as hydrochloride, hydrobromide, sulphate, hydrogen sulphate, dihydrogen phosphate, maleate, fumarate, 2-naphthalenesulphonate or para-toluenesulphonate. For a review of physiologically acceptable salts, see the Handbook of Pharmaceutical Salts: Properties, Selection and Use by Stahl and Wermuth (Wiley-VCH, 2002).The solvates or hydrates may be obtained directly after the synthesis process, compound (I) being isolated in the form of a hydrate, for ...

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Номер записи: 79
24-02-2022 дата публикации

COMPOUNDS AND METHODS FOR TREATING AUTOIMMUNE DISORDERS BY TARGETING HLA-DQ2

Номер: US20220055994A1
Автор: Ghevde Asha, Perni Robert B., Schutte Ryan, Siedlecki James M.
Принадлежит:

Compounds and compositions useful in methods of treating, ameliorating, or inhibiting the development of an autoimmune disease by modulating the T cell response to antigenic peptide or fragments of antigenic peptides presented by the major histocompatibility (MHC) class II molecule, DQ2. 2. (canceled)3. (canceled)4. The compound of claim 1 , wherein Ris optionally substituted C-C-alkyl; optionally substituted phenyl claim 1 , optionally substituted naphthyl claim 1 , or optionally substituted quinolyl.9. (canceled)10. (canceled)11. The pharmaceutical composition of wherein Ris optionally substituted C-C-alkyl; optionally substituted phenyl claim 8 , optionally substituted naphthyl claim 8 , or optionally substituted quinolyl.15. The pharmaceutical composition of claim 8 , wherein the composition is formulated for oral or parenteral administration.17. (canceled)18. (canceled)19. The method of claim 16 , wherein Ris optionally substituted C-C-alkyl; optionally substituted phenyl claim 16 , optionally substituted naphthyl claim 16 , or optionally substituted quinolyl.22. The method of claim 16 , wherein the administration alters the presentation of a gluten protein claim 16 , a deaminated gluten protein claim 16 , and/or fragments thereof claim 16 , to T cells by DQ2 MHC class II molecules.23. The method of claim 16 , wherein the compound is administered orally to the subject.24. The method of claim 16 , wherein the autoimmune disease is selected from the group consisting of celiac disease claim 16 , type 1 diabetes (T1D) claim 16 , Stiff-person syndrome (SPS) claim 16 , Addison's disease (AD) claim 16 , Schmidt syndrome (SS) claim 16 , and Myasthenia gravis (MG).25. The method of claim 16 , wherein the subject has been determined to have anti-transglutaminase antibodies claim 16 , antibodies against deamidated gliadin peptides claim 16 , antibodies against acetylcholine receptor claim 16 , antibodies against insulin (IAA) claim 16 , antibodies against beta cell- ...

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Номер записи: 80
18-02-2021 дата публикации

PYRIDAZINONE-SUBSTITUTED KETOXIMES AS HERBICIDES

Номер: US20210045385A1
Автор: DAO Rachel Tran, DeBergh John Robbins, Marshall Eric Allen
Принадлежит:

Disclosed are compounds of Formula 1, including all stereoisomers, N-oxides, and salts thereof, 2. The compound of wherein{'sup': '1', 'sub': 1', '7', '2', '7', '3', '7', '1', '7', '2', '7', '4', '8', '2', '7, 'Ris H, C-Calkyl, C-Calkenyl, C-Calkynyl, C-Chaloalkyl, C-Chaloalkenyl, C-Calkylcycloalkyl or C-Ccyanoalkyl;'}A is selected from the group consisting of A-1, A-2, A-3, A-4, A-6, A-7, A-8 and A-9;{'sup': 'A', 'sub': 1', '5', '3', '5', '4', '5', '1', '5', '2', '5', '1', '5', '1', '5', '1', '4, 'each Ris independently halogen, cyano, C-Calkyl, C-Ccycloalkyl, C-Ccycloalkylalkyl, C-Chaloalkyl, C-Calkoxyalkyl, C-Calkoxy, C-Calkylthio or C-Calkylsulfonyl;'}n is 0, 1 or 2;{'sub': 1', '2', '2', '3, 'L is a direct bond, C-Calkanediyl or C-Calkenediyl;'}{'sup': 2', '5', '5', '6', '6', '7', '8', '9', '10, 'sub': 2', '1', '4', '2', '4', '2', '4', '1', '4', '2', '4', '2', '4', '2', '4, 'Ris H, C(═O)R, C(═S)R, COR, C(═O)SR, CON(R)Ror P(═O)(R)R; or C-Calkyl, C-Calkenyl, C-Calkynyl, C-Chaloalkyl, C-Chaloalkenyl, C-Chaloalkynyl or C-Calkoxyalkyl;'}{'sup': '3', 'sub': 1', '7', '3', '8', '3', '8', '1', '4', '2', '7', '4', '7', '3', '7', '3', '7', '1', '4', '1', '4', '1', '4', '2', '8', '3', '7', '4', '7', '2', '3', '1', '4', '2', '7', '1', '7', '3', '7', '2', '7', '1', '7', '1', '5, 'Ris H, halogen, cyano, —CHO, C-Calkyl, C-Calkylcarbonylalkyl, C-Calkoxycarbonylalkyl, C-Calkylcarbonyl, C-Calkylcarbonyloxy, C-Calkylcycloalkyl, C-Calkenyl, C-Calkynyl, C-Calkylsulfinyl, C-Calkylsulfonyl, C-Calkylamino, C-Cdialkylamino, C-Ccycloalkyl, C-Ccycloalkylalkyl, C-Ccyanoalkyl, C-Cnitroalkyl, C-Chaloalkoxyalkyl, C-Chaloalkyl, C-Chaloalkenyl, C-Calkoxyalkyl, C-Calkoxy or C-Calkylthio;'}{'sup': '4', 'sub': 1', '7', '3', '8', '3', '8', '4', '7', '3', '7', '3', '7', '3', '7', '4', '7', '2', '3', '1', '4', '2', '7', '1', '7', '3', '7', '2', '7', '3', '7', '1', '7', '1', '4', '1', '4, 'Ris H, C-Calkyl, C-Calkylcarbonylalkyl, C-Calkoxycarbonylalkyl, C-Calkylcycloalkyl, C-Calkenyl, C-Calkynyl, C- ...

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Номер записи: 81
18-02-2016 дата публикации

N-ALKYL-2-PHENOXYETHANAMINES, THEIR PREPARATION AND USE

Номер: US20160046649A1
Автор: Chen Ping, Cioffi Christopher, Conlon Michael, DOBRI Nicoleta, Freeman Emily, Johnson Graham, Petrukhin Konstantin, Zhu Lei
Принадлежит: The Trustees of Columbia University in the City of New York

The present invention provides a compound having the structure: (structurally represented) wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl; R6 is alkyl; A is absent or present, and when present is —C(O)— or —C(O)NH—; B is substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, benzyl, CO2H or (C1-C4 alkyl)-CO2H, wherein when B is CO2H, then A is present and is —C(O)—, or a pharmaceutically acceptable salt thereof. 1118.-. (canceled)121. The compound of claim 120 , wherein B is a substituted or unsubstituted heterobicycle.122. The compound of claim 121 , wherein B has the structure:132. The compound of claim 120 , wherein B is a substituted or unsubstituted monocycle or heteromonocycle.137. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.138. A method for treating a disease characterized by excessive lipofuscin accumulation in the retina in a mammal afflicted therewith comprising administering to the mammal an effective amount of the compound of . This application claims priority of U.S. Provisional Application No. 61/785,415, filed Mar. 14, 2013, the contents of which are hereby incorporated by reference.Throughout this application, certain publications are referenced in parentheses. Full citations for these publications may be found immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to describe more fully the state of the art to which this invention relates.The invention was made with government support under Grant numbers NS067594 and NS074476 awarded by the National Institutes of Health. The government has certain rights in the invention.Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. It is estimated that 62.9 million individuals worldwide have the most prevalent atrophic (dry) form of AMD; 8 ...

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Номер записи: 82
01-05-2014 дата публикации

METHOD FOR PREPARATION OF 5-SUBSTITUTED PYRIMIDINES

Номер: US20140121375A1
Автор: Vartak Ashish P., Vince Robert
Принадлежит: Regents of the University of Minnesota

The present invention provides a method to prepare 5-substituted pyrimidines by reacting a 5-acylpyrimidine with a suitable nucleophile to afford a 5-methanolpyrimidine, such as flurprimidol. 3. The method of wherein X is halo.4. The method of wherein X is Br or Cl.5. The method of wherein M in compound (III) is Mg(II) claim 1 , Zn(II) claim 1 , Mn(II) claim 1 , Cr(I) claim 1 , Sn(IV) or Li(I).6. The method of wherein Y in formula (IV) is methoxy.7. The method of wherein M in compound (V) is Zn.8. The method of wherein Ris aryl or (substituted)aryl.9. The method of wherein Ris (substituted)phenyl.10. The method of wherein the metal in the complexed metal is palladium claim 1 , nickel or iron.11. The method of wherein the metal is complexed with triphenyphosphine or acetylacetone.12. The method of wherein the catalyst is (PhP)Pd claim 11 , (PPh)NiClor Fe(acac).13. The method of wherein the compound of formula (VI) is oxidized with SeO claim 2 , KMnOor CrO.14. The method of wherein the solvate is THF or diethyl ether.15. The method of wherein Ris phenyl claim 1 , 4-trifluorophenyl claim 1 , 4-methoxyphenyl or 4-halophenyl or 4-trifluoromethylphenyl.16. The method of wherein Ris 4-chlorophenyl.17. The method of wherein Ris isopropyl claim 16 , halo-substituted phenyl or cyclopropyl.18. The method of wherein Ris 2-chlorophenyl or 3 claim 17 ,5-dichlorophenyl.19. The method of wherein Ris 4-trifluoromethylphenyl and Ris isopropyl.20. The method of wherein Ris 4-chlorophenyl or 4-fluorophenyl and Ris 2-chlorophenyl.21. The method of wherein Ris 4-methoxyphenyl and Ris cyclopropyl.22. The method of wherein Ris phenyl and Ris 3 claim 2 ,4-dichlorophenyl.24. The compound of wherein Z is FC—.25. The compound of wherein Z is Cl.26. The compound of wherein R is methoxy. This application claims priority to U.S. Provisional Patent Application Ser. No. 61/466,276 filed Mar. 22, 2011, which application is incorporated herein by reference.The 5-pyrimidinemethanol, flurprimidol (1, ...

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Номер записи: 83
16-02-2017 дата публикации

Pyrimidine Compounds and Use as Anti-Cervical Cancer Thereof

Номер: US20170044110A1
Автор: CHEN Qianming, He Yang, Jiang Lu, ZHAO Hang
Принадлежит:

Provided is use of a pyrimidine compound or a pharmaceutically acceptable salt thereof in preparation of an anti-cervical cancer medicament. Research of the present invention has found that the above-mentioned pyrimidine compound can be effective against cervical cancer, and has a good inhibition effect on E6 and E7 of HPV16, and indicates that the above-mentioned pyrimidine compound also has a good anti-human papilloma virus effect, providing a new choice for clinical medication. 2. The medicament according to claim 1 , characterized in that said cervical cancer is in presence of an infection by human papilloma virus.3. The medicament according to claim 2 , characterized in that said cervical cancer is caused by human papilloma virus.4. (canceled)5. The medicament according to claim 3 , characterized in that said human papilloma virus is HPV16 claim 3 , HPV18 claim 3 , HPV31 or HPV33.6. (canceled)7. The medicament according to claim 1 , characterized in that said medicament is an inhibitor of E6 and/or E7 proteins in HPV16.8. The medicament according to claim 1 , characterized in that R is chosen from substituted or unsubstituted C4-6 aryl or heterocyclic aryl claim 1 , in which claim 1 , said heterocyclic aryl is an oxygenousor nitrogenous group.9. The medicament according to claim 1 , characterized in that said substituents are chosen from C1-4 alkyl claim 1 , C1-2 alkoxyl claim 1 , C1-2 aminoalkyl claim 1 , amino claim 1 , or halogens.11. The pyrimidine compound according to claim 10 , characterized in that Rto Rare chosen from C1-4 alkyl claim 10 , C1-2alkoxyl claim 10 , C1-2aminoalkyl claim 10 , amino or H.12. The pyrimidine compound according to claim 11 , characterized in that Rto Rare chosen from C1-4 alkyl or C1-2alkoxyl.13. The pyrimidine compound according to claim 12 , characterized in that Rand Rare H; Rand Rare chosen from H or C1-2 alkoxyl with the proviso that Rand Rare not simultaneously H; and Ris C1-4 alkyl.14. The pyrimidine compound according ...

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Номер записи: 84
15-02-2018 дата публикации

New Pyridinones and Isoquinolinones as Inhibitors of the Bromodomain BRD9

Номер: US20180044335A1
Автор: COCKCROFT Xiao-Ling, MARTIN Laetitia, Steurer Steffen
Принадлежит:

The present invention encompasses compounds of general formula (I) wherein the groups Rto R, Xand Xhave the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation, e.g. cancer, pharmaceutical preparations containing such compounds and their uses as a medicament. 5. A compound or its salts according to claim 1 , wherein Ris selected from —CH claim 1 , —CHCHand cyclopropyl.6. A compound or its salts according to claim 1 , wherein Ris selected from —CH claim 1 , —Br claim 1 , —I claim 1 , —CHF claim 1 , —NH claim 1 , —NHCHand —OH.7. A compound or its salts according to claim 6 , wherein Ris selected from —CHand —I.8. A compound or its salts according to claim 1 , wherein Xis —CRand Ris selected from —H claim 1 , —CH.9. A compound or its salts according to claim 1 , wherein Xis —CRand Ris selected from —H claim 1 , —CH.12. A compound or its salts according to claim 1 , wherein Xis CRand Rand Rtaken together form a benzene or a 5-6 membered nitrogen containing heteroarene ring claim 1 , each of which rings is optionally and independently substituted with one or two halogen claim 1 , —OH claim 1 , —NH claim 1 , —NH—Calkyl and —Calkyl claim 1 , wherein the —Calkyl group can be optionally substituted with a 6 membered aryl or 5-6 membered heteroaryl.13. A compound or its salts according to wherein Xis CRand Rand Rtaken together form a benzene or a 5-6 membered nitrogen containing heteroarene ring claim 1 , each of which rings is optionally and independently substituted with one or two halogen claim 1 , —NH claim 1 , —NH—Calkyl and —Calkyl claim 1 , wherein the —Calkyl group can be optionally substituted with a 6 membered aryl or 5-6 membered heteroaryl.16. A compound or its salts according to claim 4 , wherein R claim 4 , R claim 4 , Rand Rare —H.17. A compound or its salts according to claim 4 , wherein one group selected from R claim 4 , R ...

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Номер записи: 85
19-02-2015 дата публикации

POLY (ADP-RIBOSE) POLYMERASE INHIBITOR

Номер: US20150051211A1
Автор: Chen Xin, Guo Na, Ji Jianxin, Kang Bingqiang, XUE Ting, Ye Xinfa, Zhang Tao
Принадлежит: CHENGDU DI'AO PHARMACEUTICAL GROUP CO., LTD.

Disclosed are a phthalic hydrazide (phthalazine ketone) compound, and a pharmaceutical composition comprising the same. As a DNA repair enzyme poly (ADP-ribozyme) polymerase inhibitor, the compound and the pharmaceutical composition can effectively treat diseases involving PARP enzymatic activity, including cancer, neural degenerative diseases, inflammation and the like. 19-. (canceled)10. The compound 4-(3-(4-(1-(dimethylamino)cyclopropanecarbonyl)piperazine-1-carbonyl)-4-fluorophenoxy)2H-phthalazin-1-one pharmaceutically acceptable salt , hydrate , solvate or stereoisomer thereof.11. A method for treating a disease mediated by PARP claim 10 , said method comprising: administering the compound claim 10 , pharmaceutically acceptable salt claim 10 , hydrate claim 10 , solvate or stereoisomer thereof claim 10 , of to a subject.12. The method of claim 11 , wherein the disease mediated by PARP is selected from a cancer claim 11 , a neurodegenerative disease claim 11 , a cardiovascular disease claim 11 , diabetes and inflammation.13. The method of claim 12 , wherein the cancer is histiocytic lymphoma claim 12 , non-small cell lung cancer claim 12 , small-cell lung cancer claim 12 , lung adenocarcinoma claim 12 , lung squamous carcinoma claim 12 , pancreatic cancer claim 12 , breast cancer claim 12 , prostate cancer claim 12 , liver cancer claim 12 , gastric cancer claim 12 , colon cancer claim 12 , colorectal cancer claim 12 , ovarian cancer claim 12 , cervical cancer claim 12 , brain cancer claim 12 , esophageal cancer claim 12 , bone cancer claim 12 , testicular cancer claim 12 , melanoma claim 12 , skin cancer claim 12 , epithelial cell cancer claim 12 , nasopharyngeal cancer claim 12 , oral cancer claim 12 , leukemia claim 12 , and any one of brain tumor claim 12 , reproductive system tumor claim 12 , lymphatic system tumor claim 12 , digestive system tumor claim 12 , respiratory system tumor and skin tumor.14. A pharmaceutical composition comprising an effective ...

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Номер записи: 86
14-02-2019 дата публикации

BIARYL KINASE INHIBITORS

Номер: US20190048006A1
Автор: Luo Guanglin
Принадлежит:

The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1. 1. A compound which is:or a pharmaceutically acceptable salt thereof. This Continuation application claims the benefit of U.S. Ser. No. 15/865,848 filed Jan. 9, 2018, now allowed, which claims the benefit of U.S. Ser. No. 15/300,618 filed Sep. 29, 2016, now U.S. Pat. No. 9,902,722, which is a 371 of PCT/US2015/023805 filed Apr. 1, 2015, now pending, which claims the benefit of Provisional application U.S. Ser. No. 61/973,942 filed Apr. 2, 2014, now expired and Provisional application U.S. Ser. No. 61/061,591 filed Oct. 8, 2014, now expired, hereby incorporated by reference in their entireties.The present disclosure is generally directed to compounds which can inhibit adaptor associated kinase 1 (AAK1), compositions comprising such compounds, and methods for inhibiting AAK1.Adaptor associated kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases. AAK1 mRNA exists in two splice forms termed short and long. The long form predominates and is highly expressed in brain and heart (Henderson and Conner, 2007, 18, 2698-2706). AAK1 is enriched in synaptosomal preparations and is co-localized with endocytic structures in cultured cells. AAK1 modulates clatherin coated endocytosis, a process that is important in synaptic vesicle recycling and receptor-mediated endocytosis. AAK1 associates with the AP2 complex, a hetero-tetramer which links receptor cargo to the clatherin coat. The binding of clatherin to AAK1 stimulates AAK1 kinase activity (Conner et. al., 2003, 4, 885-890; Jackson et. al., 2003, 163, 231-236). AAK1 phosphorylates the mu-2 subunit of AP-2, which promotes the binding of mu-2 to tyrosine containing sorting motifs on cargo receptors (Ricotta et. al., 2002, 156, 791-795; Conner and Schmid, 2002, 156, 921-929). Mu2 phosphorylation is not required for ...

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Номер записи: 87
08-05-2014 дата публикации

BRIDGED BICYCLIC HETEROARYL SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS

Номер: US20140128400A1
Автор: Goff Dane, Heckrodt Thilo J., Holland Sacha, Litvak Joane, Singh Rajinder, Zhang Jing
Принадлежит: Rigel Pharmaceuticals, Inc.

Bridged bicyclic heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl activity are also disclosed. 2. The compound of selected from the group consisting of:{'sup': '3', '1-(6,9-ethano-4-phenyl-6,7,8,9-tetrahydro-5H-pyrido[3,2-c]azepin-2-yl)-N-(4-(4-(pyrrolidin-1-yl)piperidinyl)-3-fluorophenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-(4-fluorophenyl)-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(4-(4-(pyrrolidin-1-yl)piperidinyl)-3-fluorophenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-(3-fluorophenyl)-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(4-(4-(pyrrolidin-1-yl)piperidinyl)-3-fluorophenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(4-(4-(pyrrolidin-1-yl)piperidinyl)-3-fluorophenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(1,4-ethano-8-(3-methoxyphenyl)-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(4-(4-(pyrrolidin-1-yl)piperidinyl)-3-fluorophenyl)-1H-1,2,4-triazole-3,5-diamine; and'}{'sup': '3', '1-(1,4-ethano-8-(2-methylphenyl)-1,2,3,4-tetrahydro-1,5-naphthyridin-6-yl)-N-(4-(4-(pyrrolidin-1-yl)piperidinyl)-3-fluorophenyl)-1H-1,2,4-triazole-3,5-diamine.'}6. The compound of selected from the group consisting of:{'sup': '3', '1-(4-chloro-5,8-ethano-5,6,7,8-tetrahydrophthalazine-1-yl)-N-(4-(4-(pyrrolidin-1-yl)piperidinyl)-3-fluorophenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(4-(2-chlorophenyl)-5,8-ethano-5,6,7,8-tetrahydrophthalazine-1-yl)-N-(4-(4-(pyrrolidin-1-yl)piperidinyl)-3-fluorophenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup': '3', '1-(4-(3-cyanophenyl)-5,8-ethano-5,6,7,8-tetrahydrophthalazine-1-yl)-N-(4-(4-(pyrrolidin-1-yl)piperidinyl)-3-fluorophenyl)-1H-1,2,4-triazole-3,5-diamine;'}{'sup ...

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Номер записи: 88
08-05-2014 дата публикации

CRYSTALS OF GLYCINE DERIVATIVE AND PHARMACEUTICAL USE THEREOF

Номер: US20140128605A1
Автор: Nogami Tsutomu, Shiraki Motohiro, Takahashi Hirozumi
Принадлежит: Toray Industries, Inc.

A crystal of (S,E)-2-(2,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid has excellent chemical and physical stability, and a medical use thereof. 1. A crystal of (S ,E)-2-(2 ,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid.2. The crystal according to claim 1 , which exhibits peaks at 2θ (°) of 17.1 claim 1 , 17.7 claim 1 , 18.7 claim 1 , 19.9 and 21.0° in powder X-ray diffraction.3. The crystal according to claim 2 , which exhibits an endothermic peak in the range of 178 to 182° C. in thermogravimetric-differential thermal analysis.4. The crystal according to claim 1 , which exhibits peaks at 2θ (°) of 5.9 claim 1 , 8.3 claim 1 , 11.8 claim 1 , 13.2 and 21.7° in powder X-ray diffraction.5. The crystal according to claim 4 , which exhibits an endothermic peak in the range of 167 to 171° C. in thermogravimetric-differential thermal analysis.6. The crystal according to claim 1 , which exhibits peaks at 2θ (°) of 6.6 claim 1 , 8.3 claim 1 , 11.1 claim 1 , 14.6 and 18.2° in powder X-ray diffraction.7. The crystal according to claim 6 , which exhibits an endothermic peak in the range of 100 to 104° C. in thermogravimetric-differential thermal analysis.8. The crystal according to claim 1 , which is a non-solvate or a hydrate.9. A pharmaceutical comprising as an effective component said crystal according to .10. A therapeutic or prophylactic agent for inflammatory bowel disease claim 1 , allergic dermatitis claim 1 , multiple sclerosis or leukemia claim 1 , comprising as an effective component said crystal according to . This disclosure relates to a crystal of glycine derivative and a medical use thereof.Pharmaceuticals are required to maintain the quality thereof for a long time during distribution, storage and the like, and high chemical and physical stability is demanded for compounds as effective components. Thus, for the effective components of pharmaceuticals, crystals which are expected to have high ...

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Номер записи: 89
23-02-2017 дата публикации

Benzamide Compounds and Related Methods of Use

Номер: US20170050926A1
Автор: Kazantsev Aleksey G., Khanfar Mohammad, Silverman Richard B., Wang Hua
Принадлежит:

Benzamide compounds and derivatives thereof, as can be used for selective inhibition of the SIRT2 enzyme and/or therapeutic use in the treatment of Huntington's disease. 3. The compound of wherein Ris selected from phenyl claim 2 , 2- claim 2 , 3- claim 2 , and 5-pyridinyl claim 2 , 2-pyrimidinyl claim 2 , 3-pyridazinyl claim 2 , 2-thiazolyl claim 2 , methylene-2-thiazolyl claim 2 , 2-oxadiazolyl claim 2 , 5-isoxazolyl claim 2 , 2-nicotintate and 2-nicotinamide moieties; and Ris selected from phenyl and 2-pyridinyl moieties.4. The compound of wherein a least one of Rand Ris substituted claim 3 , said substituents independently selected from halo claim 3 , cyano claim 3 , C-Calkyl claim 3 , substituted alkyl claim 3 , alkoxy claim 3 , methylsulfinyl claim 3 , hydroxy claim 3 , methylsulfonyl claim 3 , amino claim 3 , alkylamino claim 3 , dialkylamino claim 3 , aceto claim 3 , acetamido claim 3 , nitro claim 3 , aminoalkyl claim 3 , methylthio and 1-hydroxyethyl substituents and combinations thereof.6. The compound of wherein Y is alkyl-substituted methylene and Z is O claim 5 , said alkylene moiety providing a chiral center.7. The compound of wherein said methylene substituent is methyl claim 6 , said compound selected from the (R) and (S) enantiomers.9. The compound of wherein Z is selected from amino claim 8 , alkylamino claim 8 , thio claim 8 , sulfinyl and sulfonyl moieties. This application is a continuation of and claims priority to and the benefit of application Ser. No. 14/139,763 filed on Dec. 23, 2013 and issued as U.S. Pat. No. 9,371,277 on Jun. 21, 2016, which claimed priority to and the benefit of application Ser. No. 61/745,056 filed Dec. 21, 2012—each of which is incorporated herein by reference in its entirety.This invention was made with government support under grant number NS066912 awarded by the National Institutes of Health. The government has certain rights in the invention.Huntington's disease (HD) is an autosomal dominant inherited ...

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Номер записи: 90
22-02-2018 дата публикации

CRYSTALLINE FORMS OF OLAPARIB AND MANUFACTURING PROCESSES THEREFOR

Номер: US20180050991A1
Автор: Hu Tsung-Cheng, Huang Yuan-Chang, Lin Wen-Wei
Принадлежит:

In certain aspects, the invention provides crystalline forms of olaparib (4-[(3-[(4-cyclopropylcarbonyl)piperazin-4-yl]carbonyl)-4-fluorophenyl]methyl(2H)phthalazin-1-one). In related aspects, the invention provides processes for preparing the crystalline forms of olaparib. The processes include: forming a solution comprising crude olaparib and an organic solvent; adding an anti-solvent to the solution to form a slurry comprising a precipitate; isolating the precipitate; and drying the precipitate to obtain a crystalline form I of olaparib or a crystalline form II of olaparib. 1. Crystalline form II of olaparib , characterized by an X-ray powder diffraction pattern comprising peaks at 6.8 , 11.3 , 14.4 , 20.9 , 21.7 , and 25.0 degrees 2θ (±0.2 degrees 2θ); wherein the crystalline form II of olaparib is an anhydrous form.2. The crystalline form II of olaparib according to claim 1 , wherein the X-ray powder diffraction pattern further comprises peaks at 10.4 claim 1 , 12.3 claim 1 , 14.5 claim 1 , 20.4 claim 1 , 23.4 claim 1 , and 26.4 degrees 2θ (±0.2 degrees 2θ).3. The crystalline form II of olaparib according to claim 1 , wherein the X-ray powder diffraction pattern further comprises peaks at 16.0 claim 1 , 17.4 claim 1 , 18.5 claim 1 , 24.0 claim 1 , 25.7 claim 1 , 28.2 claim 1 , and 34.3 degrees 2θ (±0.2 degrees 2θ).4. Crystalline form II of olaparib according to claim 1 , characterized by a powder X-ray diffraction pattern substantially in accordance with .5. The crystalline form II of olaparib according to claim 1 , further characterized by essentially no weight loss upon heating to around 200° C. claim 1 , as measured by thermal gravimetric analysis.6. The crystalline form II of olaparib according to claim 1 , further characterized by a differential scanning calorimetry thermogram comprising endothermic peaks at about 171.3° C. and 210.7° C.7. The crystalline form II of olaparib according to claims 6 , wherein the differential scanning calorimetry thermogram ...

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Номер записи: 91
10-03-2022 дата публикации

6-OXO-1,6-DIHYDROPYRIDAZINE DERIVATIVE, PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF

Номер: US20220073471A1
Автор: CHI Jiangtao, HE Feng, Tao Weikang, Yang Fanglong, Yu Nan
Принадлежит:

A 6-oxo-1,6-dihydropyridazine derivative, a preparation method therefor and medical use thereof, in particular, a 6-oxo-1,6-dihydropyridazine derivative represented by general formula (I), a preparation method therefor, and a pharmaceutical composition containing the derivative, and use thereof as a Nav inhibitor and use thereof in the preparation of a drug for the treatment and/or prevention of pain and pain-related diseases. Each substituent in general formula (I) is the same as defined in the description. 3. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein M is selected from the group consisting of O atom claim 1 , CHand S atom.6. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein each Ris identical or different and each is independently selected from the group consisting of hydrogen atom claim 1 , halogen claim 1 , alkyl claim 1 , alkoxy claim 1 , haloalkyl and haloalkoxy.7. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim 1 , or mixture thereof claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein each Ris identical or different and each is independently selected from the group consisting of hydrogen atom claim 1 , halogen claim 1 , alkyl claim 1 , deuterated alkyl claim 1 , alkoxy claim 1 , deuterated alkoxy claim 1 , hydroxy claim 1 , haloalkyl claim 1 , haloalkoxy claim 1 , cycloalkyl and cycloalkyloxy.8. The compound of formula (I) or the tautomer claim 1 , mesomer claim 1 , racemate claim 1 , enantiomer claim 1 , diastereomer thereof claim ...

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Номер записи: 92
20-02-2020 дата публикации

HERBICIDAL PYRIDAZINONE COMPOUNDS

Номер: US20200054012A1
Автор: BURTON Paul Matthew, EMMETT Edward John, SMITH Alexander Martin Richard, Whalley Louisa
Принадлежит: SYNGENTA PARTICIPATIONS AG

The present invention relates to compounds of Formula (I), or an agronomically acceptable salt of said compounds wherein R, R, R, X, A, R, R, R, Rand m are as defined herein. The invention further relates to herbicidal compositions which comprise a compound of Formula (I), to their use for controlling weeds. The invention further relates to intermediate compounds used to produce compounds of Formula (I). 2. A compound according to claim 1 , wherein X is selected from the group consisting of O claim 1 , —CF— and —CH—;3. A compound according to claim 1 , wherein X is O.4. A compound according to claim 1 , wherein X is —CH—.5. A compound according to claim 1 , wherein Ris methyl.6. A compound according to claim 1 , wherein Rand Rare both C-Calkyl.7. A compound according to claim 1 , wherein Ais (CRR).8. A compound according to claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare hydrogen.9. A compound according to claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rare hydrogen and Ris methyl.10. A herbicidal composition comprising a compound according to and an agriculturally acceptable formulation adjuvant.11. A herbicidal composition according to claim 10 , further comprising at least one additional pesticide.12. A herbicidal composition according to claim 11 , wherein the additional pesticide is a herbicide or herbicide safener.13. A method of controlling weeds at a locus comprising application to the locus of a weed controlling amount of a composition according to .14. Use of a compound of Formula (I) as defined in as a herbicide. The present invention relates to novel herbicidal compounds, to herbicidal compositions which comprise the novel compounds, and to their use in controlling weeds.Herbicidal pyridazinone derivatives are disclosed in WO2012/136703. The present invention relates to novel herbicidal pyridazinone derivatives, which are shown to exhibit improved crop selectivity.Thus, according to the present invention ...

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Номер записи: 93
03-03-2016 дата публикации

Method of manufacturing pyridazinone compound

Номер: US20160060225A1
Автор: Akio Manabe
Принадлежит: Sumitomo Chemical Co Ltd

A compound represented by formula (2) wherein X represents a hydrogen atom, a fluorine atom, a chlorine atom or a bromine atom, and Y represents a hydrogen atom, a fluorine atom, a chlorine atom or a bromine atom, is reacted with a brominating agent and an alkanol having 1 to 6 carbon atoms in the presence of a base to obtain a compound represented by formula (3) wherein R represents a C1 to C6 alkyl group, and X and Y represent the same meaning as described above, and then the compound represented by the formula (3) is reacted with hydrazine, whereby a compound represented by formula (1) wherein X and Y represent the same meaning as described above, which is useful as a production intermediate of a fungicide, can be obtained.

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Номер записи: 94
01-03-2018 дата публикации

PROCESSES FOR PREPARING OLAPARIB

Номер: US20180057464A1
Автор: CHANG Yung-Hung, HSIAO Tsung-Yu
Принадлежит:

Provided herein are novel processes and methods for making 4-[(3-[(4-cyclopropylcarbonyl)piperazin-1-yl]carbonyl)-4-fluorophenyl]methyl(2H)phthalazin-1-one (Olaparib) and intermediates thereof. Olaparib is a poly ADP ribose polymerase (PARP) inhibitor useful in the treatment of cancers. Benefits of the present disclosure include the use of less toxic compounds and improved yields. 24-. (canceled)5. The process of claim 1 , wherein the tertiary amine is selected from the group consisting of trimethylamine claim 1 , N claim 1 ,N-diisopropylethylamine (DIPEA) claim 1 , N-methylmorpholine (NMM) claim 1 , tributylamine claim 1 , 2 claim 1 ,2 claim 1 ,6 claim 1 ,6-tetramethylpiperidine (TMP) claim 1 , pempidine (PMP) claim 1 , 2 claim 1 ,6-dimethylpyridine claim 1 , and 2 claim 1 ,4 claim 1 ,6-trimethylpyridine.6. The process of claim 5 , wherein the tertiary amine is N claim 5 ,N-diisopropylethylamine (DIPEA).7. The process of claim 1 , wherein the first organic solvent is a dialkyl ketone selected from the group consisting of acetone claim 1 , acetophenone claim 1 , butanone claim 1 , diethyl ketone claim 1 , ethyl isopropyl ketone claim 1 , 2-hexanone claim 1 , isophorone claim 1 , mesityl oxide claim 1 , methyl isobutyl ketone claim 1 , methyl isopropyl ketone claim 1 , 3-methyl-2-pentanone claim 1 , 2-pentanone claim 1 , cyclohexanone claim 1 , and cyclopentanone.8. (canceled)9. The process of claim 7 , wherein the dialkyl ketone is acetone.10. The process of claim 1 , wherein the acid used in step (b) is p-toluenesulfonic acid.11. The process of claim 1 , wherein the anion is tosylate.12. The process of claim 1 , wherein the inorganic base used in step (c) is selected from the group consisting of an alkali metal carbonate claim 1 , an alkali metal bicarbonate claim 1 , and combinations thereof.13. The process of claim 12 , wherein the alkali metal carbonate is selected from the group consisting of LiCO claim 12 , NaCO claim 12 , KCO claim 12 , and combinations ...

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Номер записи: 95
15-05-2014 дата публикации

ISOXAZOLINE-SUBSTITUTED BENZAMIDE COMPOUND AND PESTICIDE

Номер: US20140135496A1
Автор: FURUKAWA Yuki, Ikeda Eitatsu, KOMODA Mitsuaki, MASUZAWA Yoshihide, MITA Takeshi, Toyama Ken-ichi, YAOSAKA Manabu
Принадлежит: NISSAN CHEMICAL INDUSTRIES, LTD.

An isoxazoline-substituted benzamide compound of formula (1) or a salt thereof: 117-. (canceled)19. 4-Hydroxyiminomethyl substituted benzamide compound or the salt thereof according to claim 18 , wherein{'sup': '1', 'Ais carbon atom,'}W is oxygen atom,{'sub': 1', '6', '1', '6, 'sup': 5', '7', '6, 'Y is halogen atom, cyano, nitro, C-Calkyl, C-Chaloalkyl, —ORor —N(R)R,'}{'sup': 1', '1a, 'Ris —CH═NOR,'}{'sup': '1a', 'sub': 1', '6, 'Ris C-Calkyl,'}{'sup': 2', '14a, 'sub': 2', '3', '6', '1', '6, 'Ris hydrogen atom, —CHR, C-Calkynyl or C-Calkoxycarbonyl,'}{'sup': '5', 'sub': 1', '6', '1', '6, 'Ris C-Calkyl or C-Chaloalkyl,'}{'sup': '6', 'sub': 1', '6', '1', '6, 'Ris —CHO, C-Calkylcarbonyl or C-Calkoxycarbonyl,'}{'sup': 14a', '25, 'Ris cyano or —OR,'}{'sup': 25', '32, 'sub': 1', '4', '1', '4, 'Ris C-Calkyl, C-Chaloalkyl or —C(O)OR, and'}{'sup': '32', 'sub': 1', '6, 'Ris C-Calkyl.'}20. 4-Hydroxyiminomethyl substituted benzamide compound or the salt thereof according to claim 18 , wherein{'sup': '1', 'Ais carbon atom,'}W is oxygen atom,{'sub': 1', '6', '1', '6, 'sup': 5', '7', '6, 'Y is halogen atom, cyano, nitro, C-Calkyl, C-Chaloalkyl, —ORor —N(R)R,'}{'sup': 1', '1c, 'Ris —C(O)OR,'}{'sup': '1c', 'sub': 1', '6', '3', '6, 'Ris C-Calkyl or C-Ccycloalkyl,'}{'sup': 2', '14a', '5, 'sub': 1', '6', '2', '1', '6', '1', '6', '1', '6, 'Ris hydrogen atom, C-Calkyl, —CHR, E-5, —C(O)R, C-Calkoxycarbonyl, C-Chaloalkoxycarbonyl or C-Chaloalkylthio,'}{'sup': '5', 'sub': 1', '6', '1', '6, 'Ris C-Calkyl or C-Chaloalkyl,'}{'sup': '6', 'sub': 1', '6', '1', '6, 'Ris —CHO, C-Calkylcarbonyl or C-Calkoxycarbonyl,'}{'sup': 14a', '25', '32, 'Ris cyano, —OR, or —NHC(O)OR,'}{'sup': '15', 'sub': 1', '6', '1', '6', '1', '4', '1', '4', '1', '4', '1', '4', '3', '6, 'Ris C-Calkyl, C-Chaloalkyl, C-Calkoxy C-Calkyl, C-Calkylthio C-Calkyl or C-Ccycloalkyl,'}{'sup': 25', '32, 'sub': 1', '4', '1', '4, 'Ris C-Calkyl, C-Chaloalkyl or —C(O)OR,'}{'sup': '32', 'sub': 1', '6, 'Ris C-Calkyl,'}n is an integer of 0 or 1 ...

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Номер записи: 96
20-02-2020 дата публикации

BENZAMIDES-CONTAINING COMPOUNDS AND THEIR USE IN THE TREATMENT OF DEPRESSION

Номер: US20200054630A1
Автор: Chen Bin, Eldemenky Eman Mohamed, Hopper Allen T., Jessing Mikkel, Jiang Yu, Kilburn John Paul, Rasmussen Lars Kyhn
Принадлежит:

The present invention is directed to benzamide-containing compounds of formula I 118-. (canceled)20. The method of claim 19 , wherein the depression is major depressive disorder (MDD) including mild claim 19 , moderate and severe depression.21. The method of claim 19 , wherein the depression is treatment-resistant depression.22. The method of claim 19 , wherein the depression is catatonic depression claim 19 , melancholic depression claim 19 , atypical depression claim 19 , psychotic depression claim 19 , postpartum depression. bipolar depression claim 19 , mild claim 19 , moderate or severe depression claim 19 , wherein bipolar depression includes bipolar I and bipolar II.23. The method of claim 19 , wherein the depression is associated with inflammatory disease.24. The method of claim 19 , wherein the compound is 2-chloro-N-[3-cyclopropyl-2-[2-(trifluoromethyl)pyrimidin-5-yl]propyl]benzamide or a pharmaceutically acceptable salt thereof.25. The method of claim 24 , wherein the depression is major depressive disorder (MDD) including mild claim 24 , moderate and severe depression.26. The method of claim 24 , wherein the depression is treatment-resistant depression.27. The method of claim 24 , wherein the depression is catatonic depression claim 24 , melancholic depression claim 24 , atypical depression claim 24 , psychotic depression claim 24 , postpartum depression. bipolar depression claim 24 , mild claim 24 , moderate or severe depression claim 24 , wherein bipolar depression includes bipolar I and bipolar II.28. The method of claim 24 , wherein the depression is associated with inflammatory disease.29. The method of claim 19 , wherein the compound is (−)2-chloro-N-[3-cyclopropyl-2-[2-(trifluoromethyl)pyrimidin-5-yl]propyl]benzamide or a pharmaceutically acceptable salt thereof.30. The method of claim 29 , wherein the depression is major depressive disorder (MDD) including mild claim 29 , moderate and severe depression.31. The method of claim 29 , wherein the ...

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Номер записи: 97
02-03-2017 дата публикации

BIPHENYL AND PHENYL-PYRIDINE AMIDES AS P2X3 AND P2X2/3 ANTAGONISTS

Номер: US20170057932A1
Автор: Broka Chris Allen, Hawley Ronald Charles
Принадлежит: Roche Palo Alto LLC

Compounds of the formula I: 2. The compound of wherein R claim 1 , Rand Rare hydrogen.3. The compound of wherein Ris pyrimidin-2-yl substituted at the 5-position with methyl or halo.4. The compound of wherein Ris 5-methyl-pyrimidin-2-yl.5. The compound of wherein Ris pyrimidin-2-yl substituted with halo at the 5-position.6. The compound of wherein Ris hydrogen.7. The compound of wherein Ris methyl.8. The compound of wherein Ris Calkyl claim 2 , hydroxy-Calkyl claim 2 , Calkylsulfanyl-Calkyl claim 2 , Calkylsulfonyl-Calkyl claim 2 , amino-Calkyl claim 2 , N—Calkyl-amino-Calkyl claim 2 , N claim 2 ,N claim 2 ,-di-Calkyl-amino-Calkyl claim 2 , Ccycloalkyl claim 2 , optionally substituted phenyl claim 2 , heteroaryl claim 2 , or heterocyclyl-Calkyl.9. The compound of wherein Ris Calkyloxy-Calkyl claim 8 , hydroxy-Calkyl claim 8 , heteroaryl or heterocyclyl-Calkyl.10. The compound of wherein Ris methoxymethyl.11. The compound of wherein Ris hydroxymethyl.12. The compound of wherein Ris heteroaryl selected from pyridinyl claim 9 , pyrimidinyl claim 9 , or pyrazinyl claim 9 , each of which may be optionally substituted once or twice with methyl.13. The compound of wherein Ris hydroxymethyl claim 9 , methoxymethyl claim 9 , pyrazin-2-yl or 5-methyl-pyrazin-2-yl.14. The compound of wherein Ris pyridazin-3-yl.15. The compound of wherein Ris pyridazin-3-yl substituted at the 6-position with methyl or halo.16. The compound of wherein Ris thienyl.17. A pharmaceutical composition comprising a compound of and at least one pharmaceutical acceptable carrier claim 1 , diluent or excipient.18. A method of modulating P2Xand P2Xreceptor activity in a subject claim 1 , said method comprising administering to a subject in need thereof an effective amount of a compound of .19. A method of wherein the subject suffers from a pain condition selected from the group consisting of poisoning claim 18 , neuritis claim 18 , neuralgias claim 18 , interstitial cystitis claim 18 , nerve injury claim ...

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Номер записи: 98
04-03-2021 дата публикации

METHOD FOR SOLUBILIZING 5-AMINO-2,3-DIHYDRO-1,4-PHTHALAZINEDIONE

Номер: US20210061771A1
Автор: Brysch Wolfgang, Saar Ingo
Принадлежит: Metriopharm AG

The present invention relates to a method for solubilizing 5-amino-2,3-dihydro-1,4-phthalazinedione or salts thereof, to the solubilisate produced by this method and respective uses in pharmaceutical dosage forms. A phosphatidylcholine-based solubilization method is disclosed. 1. A method for solubilizing 5-amino-2 ,3-dihydro-1 ,4-phthalazinedione , comprising the following steps:a) Providing 5-amino-2,3-dihydro-1,4-phthalazinedione in the overall range of 0.1% to 25% per weight at room temperature and a pressure of 0.2 bar to 1 bar; at least one medium-chained triglyceride in the overall range of 10% to 70% per weight,', 'at least one lysophosphatidylcholine in the overall range of 1% to 15% per weight,', {'sub': 2', '4', '14', '20, 'at least one Cto Calcohol in the overall range of 1% to 20% per weight, and at least one of glyceryl stearate and/or a saturated or unsaturated Cto Cfatty acid in the overall range of 0.5% to 10% per weight, respectively,'}, 'wherein the relative weight percentages of all ingredients add up to 100% and all solubilization agents are independently from one another a food additive and/or a pharmaceutically acceptable excipient;, 'b) Adding in any sequence the solubilization agents of at least one phosphatidylcholine in the overall range of 20% to 80% per weight,'}c) Cautiously heating the resulting mixture by continuously increasing the temperature with a continuous temperature increment of 0.5° C./min-3° C./min over a period of 20-60 minutes;d) Stopping the temperature increase in a temperature range of 30° C. to 125° C. as soon as a clear solution is reached; ande) Letting the resulting solubilisate cool down to room temperature.3. The method according to claim 1 , wherein said at least one saturated or unsaturated Cto Cfatty acid is oleic acid.4. The method according to claim 1 , wherein said at least one Cto Calcohol is ethanol.5. The method according to claim 1 , wherein additionally in step b) at least one antioxidant in the overall ...

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Номер записи: 99
05-03-2015 дата публикации

NEW COMPOUNDS

Номер: US20150065517A1
Автор: KWAK Young-shin, Liu Wenming, SERRANO-WU Michael H.
Принадлежит: NOVARTIS AG

The present invention provides organic compounds of the following structure; 137-. (canceled)39. The compound according to claim 38 , wherein the divalent residue —[R]—[R]—[C(O)]—[N(R)]—[R]—[R]— is selected from the group consisting of:a divalent alkyl group having from 1 to 4 carbon atomsa divalent alkenyl group having from 2 to 3 carbon atomsa —C(O)— group{'sup': 4', '5, 'sub': 'e', 'claim-text': [{'sup': '5', 'sub': 1', '4', '4', '8, 'e is 0 and Ris selected from the group consisting of a divalent substituted or unsubstituted C-Calkyl group, C-Ccycloalkyl group, phenyl group or 5- or 6-membered heterocyclyl group, or'}, {'sup': 4', '5, 'sub': 1', '4', '4', '8, 'e is 1, Ris a divalent substituted or unsubstituted C-Calkyl group, and Ris a divalent substituted or unsubstituted C-Ccycloalkyl cycloalkyl group, phenyl group or 5- or 6-membered heterocyclyl group,'}], 'a —C(O)—[R]—R— group wherein'}{'sup': 1', '2', '1', '2, 'sub': 1', '4', '4', '8, 'a —R—R— group, wherein Ris a divalent substituted or unsubstituted C-Calkyl group and Ris a divalent substituted or unsubstituted C-Ccycloalkyl group, phenyl group or 5- or 6-membered heterocyclyl group,'}a —C(O)—NH— group,{'sub': 2', '1-3', '2', '1-3, 'a —(CH)—C(O)—NH—(CH)— group,'}{'sup': 4', '4, 'sub': '1-7', 'a —C(O)—NH—R— group, wherein Ris selected from a divalent substituted or unsubstituted Calkyl group, cyclohexyl group or cyclopentyl group,'}{'sup': 3', '4', '3', '4, 'a —C(O)—N(R)—R— group, wherein Rand Rand the N-atom together form a pyrrolidine ring or a piperidine ring, or a pharmaceutically acceptable salt thereof.'}40. The compound according to claim 38 , wherein the alkylidenyl group is ═CH— claim 38 , or a pharmaceutically acceptable salt thereof.41. The compound according to claim 38 , wherein the L1 group is an amine group —NH— claim 38 , or a pharmaceutically acceptable salt thereof.42. The compound according to claim 38 , wherein the L1 group is an amide group —C(O)NH— or —NHC(O)— claim 38 , or a ...

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Номер записи: 100