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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 4373. Отображено 100.
19-07-2012 дата публикации

Novel compounds

Номер: US20120184553A1
Автор: Andrew John Eatherton, Daniele Andreotti, Karamjit Singh Jandu, Oliver James Philps, Paul Bamborough, Paula Louise Nichols
Принадлежит: Glaxo Group Ltd

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

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Номер записи: 1
07-02-2013 дата публикации

Therapeutic peptides

Номер: US20130035296A1
Автор: Martina Havelkova, Morten STRØM, Terkel Hansen, Veronika TØRFOSS
Принадлежит: LYTIX BIOPHARMA AS

The present invention provides a peptide, peptidomimetic or amino acid derivative having a net positive charge of at least +2 and incorporating a disubstituted β amino acid, each of the substituting groups in the β amino acid, which may be the same or different, comprises at least (7) non-hydrogen atoms, is lipophilic and has at least one cyclic group, one or more cyclic groups within a substituting group may be linked or fused to one or more cyclic groups within the other substituting group and where cyclic groups are fused in this way the combined total number of non-hydrogen atoms for the two substituting groups is at least (12), for use as a cytolytic therapeutic agent; as well as non therapeutic uses of these molecules and certain defined novel compounds from within this definition.

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Номер записи: 2
04-04-2013 дата публикации

CARBOXYLATION CATALYSTS

Номер: US20130085276A1
Автор: Cazin Catherine, NOLAN Steven P.
Принадлежит:

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

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Номер записи: 3
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: 4
06-06-2013 дата публикации

Guanidine compound

Номер: US20130143860A1
Автор: Daisuke Suzuki, Hiroyoshi Yamada, Hisashi Mihara, Kousei Yoshihara, Norio Seki, Susumu Yamaki
Принадлежит: Astellas Pharma Inc

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that the compound or a salt thereof of the present invention exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. In addition, the present invention relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound or a salt thereof of the present invention, and an excipient.

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Номер записи: 5
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: 6
25-07-2013 дата публикации

SUBSTITUTED PYRIDAZINE CARBOXAMIDE COMPOUNDS

Номер: US20130190298A1
Автор: Liang Congxin
Принадлежит: Xcovery Holding Company, LLC.

The new pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases especially against ALK and are useful in treating disorders related to abnormal protein kinase activities such as cancer, neurological and psychiatric diseases. 5. A compound of formula I in wherein Rand Rtogether with nitrogen form a bi-cyclic heterocyclyl or heteroaryl optionally substituted by 1-3 groups of Z.6. The compound of claim 3 , wherein Ris hydrogen.7. The compound of claim 4 , wherein Ris hydrogen.8. A compound selected from the following:{5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-aminopyridazin-3-yl}-N-{4-[(4-methylpiperazinyl)carbonyl]phenyl}carboxamide; and{5-[(1S)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-aminopyridazin-3-yl}-N-{4-[(4-methylpiperazinyl)carbonyl]phenyl}carboxamide.9. A compound of wherein the compound is selected from the following:{6-amino-5[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-[4-(morpholin-4-ylcarbonyl)phenyl]carboxamide;{6-amino-5[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-(4-{[4-(2-hydroxyethyl)piperazinyl]carbonyl}phenyl)carboxamide;{6-amino-5[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-{4-[(4-pyrrolidinylpiperidyl)carbonyl]phenyl}carboxamide;{6-Amino-5[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-{4-[(4-ethylpiperazinyl)carbonyl]phenyl}carboxamide;{6-Amino-5[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-{4-[(4-cyclopropylpiperazinyl)carbonyl]phenyl}carboxamide;N-(4-{[(2R)-2-(pyrrolidinylmethyl)pyrrolidinyl]carbonyl}phenyl){6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}carboxamide; andN-{4-[((3S,5R)-3,5-dimethylpiperazinyl)carbonyl]phenyl}{6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}carboxamide.10. The compound of claim 2 , wherein the compound is selected from the following:{5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-aminopyridazin-3-yl}-N-{3-fluoro-4-[(4-methylpiperazinyl)carbonyl]phenyl}carboxamide;{5-[(1R)-1-(2,6-dichloro-3- ...

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Номер записи: 7
25-07-2013 дата публикации

Pyridazine derivatives and use thereof as medicaments for treating microrna viral infection

Номер: US20130190319A1
Автор: Guoming Zhao, Hongliang Wang, Junhai Xiao, Lili Wang, Song Li, Wu Zhong, Xian Zhang, Xiaokui Wang, Xinbo Zhou, Xingzhou Li, Yunde Xie, Zhibing Zheng
Принадлежит: Institute of Pharmacology and Toxicology of AMMS

Disclosed are pyridazine derivatives represented by Formula I or pharmaceutically acceptable salts or hydrates thereof, pharmaceutical compositions comprising the compounds, methods of treating and/or preventing diseases or disorders associated with viral infections in patients using the compounds, and the use of the compounds in preparing the medicaments for treating and/or preventing diseases or disorders associated with viral infections. The compounds represented by Formula I have antiviral activity, especially anti-microRNA viral activity. Symbols in the compounds represented are described in the specification.

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Номер записи: 8
08-08-2013 дата публикации

Substituted pyridazine carboxamide compounds as kinase inhibitor compounds

Номер: US20130203763A1
Автор: Congxin Liang
Принадлежит: Xcovery Holding Co LLC

The new pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases especially against c-Met and are useful in treating disorders related to abnormal protein kinase activities such as cancer.

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Номер записи: 9
22-08-2013 дата публикации

COMPOUNDS FOR MODULATING RNA BINDING PROTEINS AND USES THEREFOR

Номер: US20130217685A1
Автор: Ryder Sean
Принадлежит: University of Massachusetts

The invention relates to compositions and methods for inhibiting RNA binding proteins (e.g., MEX-3, MEX-5 and POS-1), as well as methods for treating and preventing disorders associated with parasitic infections and inflammatory disorders. 1. A method for treating or preventing a parasitic associated state in a subject comprising administering to said subject an effective amount of an RNA binding modulatory compound , such that said parasitic associate state is treated or prevented.3. The method of claim 1 , wherein the RNA binding modulatory compound is a compound of Table 1 or Table 2 claim 1 , and pharmaceutically acceptable salts thereof.4. The method of claim 1 , wherein said subject is a plant claim 1 , an animal or a human.56-. (canceled)7. The method of claim 1 , wherein said parasitic associated state is a parasitic infestation or parasitic re-infestation or a disease caused by a parasitic infestation.8. (canceled)9. The method of claim 1 , wherein said method includes protecting plants from a parasitic infestation claim 1 , inhibiting embryogenesis in a parasite or in a subject suffering from a parasitic infestation claim 1 , or reducing parasitic burden in soil claim 1 , in plants or in an animal suffering from a parasitic infection.10. The method of claim 1 , wherein said parasite is a helminth.11. The method of claim 10 , wherein said helminth is selected from the group consisting of a cestode claim 10 , a trematode and a nematode.12. (canceled)13. A method for inhibiting embryogenesis in a parasite claim 10 , comprising contacting said parasite with an effective amount of an RNA binding modulatory compound claim 10 , such that said embryogenesis is inhibited.15. The method of claim 13 , wherein the RNA binding modulatory compound is a compound of Table 1 or Table 2 claim 13 , and pharmaceutically acceptable salts thereof.16. The method of claim 13 , wherein the parasite is present in a subject.1719-. (canceled)20. The method of claim 13 , wherein said ...

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Номер записи: 10
29-08-2013 дата публикации

2-(benzyloxy) benzamides as lrrk2 kinase inhibitors

Номер: US20130225584A1
Автор: Andrew John Eatherton, Daniele Andreotti, Karamjit Singh Jandu, Oliver James Philps, Qian Liu, Xuedong Dai
Принадлежит: Individual

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

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Номер записи: 11
05-09-2013 дата публикации

ARYLCYCLOPROPYLAMINE BASED DEMETHYLASE INHIBITORS OF LSD1 AND THEIR MEDICAL USE

Номер: US20130231342A1
Автор: Estirate-Martinez Maria de los Ángeles, Fyfe Matthew Colin Thor, MARTINELL PEDEMONTE Marc, Muñoz Alberto Ortega, TIRAPU FERNANDEZ DE LA CUESTA Iñigo
Принадлежит: Oryzon Fenomics S.A.

The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection. Thus, in one specific aspect the invention relates to formulas (II), (III), (IV), (V), (VI), (VII), (VIII), (IX). 2. The compound of wherein (A) is an aryl group or a heteroaryl group claim 1 , wherein said aryl group or said heteroaryl group has n substituents (R3).3. The compound of wherein (A) is phenyl claim 1 , pyridinyl claim 1 , thiophenyl claim 1 , pyrrolyl claim 1 , furanyl claim 1 , or thiazolyl claim 1 , and further wherein (A) has n substituents (R3).4. The compound of wherein (A) is phenyl or pyridyl claim 1 , and further wherein said phenyl or said pyridyl has n substituents (R3).5. The compound of wherein (A) has 0 substituents (R3).6. The compound of wherein (B) is —O—CH-phenyl or phenyl claim 1 , and further wherein said phenyl or the phenyl moiety comprised in said —O—CH-phenyl has n substituents (R2).78-. (canceled)9. The compound of wherein (B) has 0 claim 1 , 1 or 2 substituents (R2).10. (canceled)11. The compound of wherein (D) is thiazolyl claim 1 , oxadiazolyl claim 1 , oxazolyl claim 1 , isoxazolyl claim 1 , thiadiazolyl claim 1 , triazinyl claim 1 , pyridazinyl claim 1 , pyrazinyl claim 1 , pyridinyl or pyrimidinyl claim 1 , and further wherein said thiazolyl claim 1 , said oxadiazolyl claim 1 , said oxazolyl claim 1 , said isoxazolyl claim 1 , said thiadiazolyl claim 1 , said triazinyl claim 1 , said pyridazinyl claim 1 , said pyrazinyl claim 1 , said pyridinyl or said pyrimidinyl has one substituent (R1).12. The compound of wherein (D) is thiazolyl claim 1 , oxadiazolyl or pyrimidinyl claim 1 , and further wherein said thiazolyl claim 1 , said oxadiazolyl or said pyrimidinyl has one substituent (R1).13. The compound of wherein (D) is oxadiazolyl ...

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Номер записи: 12
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: 13
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: 14
03-10-2013 дата публикации

PYRIDAZINYL DERIVATIVES AS SMO INHIBITORS

Номер: US20130261299A1
Автор: CHEN Zhuoliang, HE Feng, LAGU Bharat, Miller-Moslin Karen Marie, PEUKERT Stefan, YUSUFF Naeem
Принадлежит: NOVARTIS AG

The present invention relates to compounds of formula I: 1. A compound , or a pharmaceutically acceptable salt thereof , selected from: (R)-4-(4 ,5-Dimethyl-6-phenoxy-pyridazin-3-yl)-2-methyl-3 ,4 ,5 ,6-tetrahydro-2H-[1 ,2′]bipyrazinyl-5′-carboxylic methyl ester; (R)-4-(4 ,5-Dimethyl-6-phenylamino-pyridazin-3-yl)-2-methyl-3 ,4 ,5 ,6-tetra-hydro-2H-[1 ,2′]bipyrazinyl-5′-carboxylic acid methyl ester; (R)-4-(4 ,5-Dimethyl-6-phenylamino-pyridazin-3-yl)-2-methyl-3 ,4 ,5 ,6-tetra-hydro-2H-[1 ,2′]bipyrazinyl-5′-carboxylic acid phenylamide; 2-[(R)-4-(4 ,5-Dimethyl-6-phenylamino-pyridazin-3-yl)-2-methyl-3 ,4 ,5 ,6-tetrahydro-2H-[1 ,2′]bipyrazinyl-5′-yl]-propan-2-ol; (R)-4-[6-(4-fluoro-phenyl)-4 ,5-dimethyl-pyridazin-3-yl]-2-methyl-3 ,4 ,5 ,6-tetrahydro-2H-[1 ,2′]bipyrazinyl-5′-carboxylic acid methyl ester; (R)-4-[6-(4-trifluoromethyl-phenyl)-4 ,5-dimethyl-pyridazin-3-yl]-2-methyl-3 ,4 ,5 ,6-tetrahydro-2H-[1 ,2′]bipyrazinyl-5′-carboxylic acid methyl ester; (R)-4-[6-(4-trifluoromethyl-phenyl)-4 ,5-dimethyl-pyridazin-3-yl]-2-methyl-3 ,4 ,5 ,6-tetrahydro-2H-[1 ,2′]bipyrazinyl-5′-carboxylic acid; (R)-4-[6-(4-fluoro-phenyl)-4 ,5-dimethyl-pyridazin-3-yl]-2-methyl-3 ,4 ,5 ,6-tetrahydro-2H-[1 ,2′]bipyrazinyl-5′-carboxylic acid; Methyl 5-(4-(6-benzyl-4 ,5-dimethylpyridazin-3-yl)piperidin-1-yl)pyrazine-2-carboxylate; 2-{5-[4-(6-Benzyl-4 ,5-dimethyl-pyridazin-3-yl)-piperidin-1-yl]-pyrazin-2-yl}-propan-2-ol; 3-Benzyl-6-{1-[5-(1-methoxy-1-methyl-ethyl)-pyrazin-2-yl]-piperidin-4-yl}-4 ,5-dimethyl-pyridazine; 3-Benzyl-6-{1-[5-(trifluoromethyl)pyridin-2-yl]-piperidin-4-yl}-4 ,5-dimethyl-pyridazine; (R)-4-(6-Benzoyl-4 ,5-dimethyl-pyridazin-3-yl)-2-methyl-3 ,4 ,5 ,6-tetrahydro-2H-[1 ,2′]bipyrazinyl-5′-carboxylic acid methyl ester; (6-{(R)-4-[4-(1-Hydroxy-1-methyl-ethyl)-phenyl]-3-methyl-piperazin-1-yl}-4 ,5-dimethyl-pyridazin-3-yl)-phenyl-methanone; (R)-4[6-(hydroxyl-phenyl-methyl)-4 ,5-dimethyl-pyridazin-3-yl]-2-methyl-3 ,4 ,5 ,6-tetrahydro-2H-[1 ,2′]bipyrazinyl-5′-carboxylic acid methyl ...

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Номер записи: 15
10-10-2013 дата публикации

1,2-pyridazines, 1,6-pyridazines and pyrimidines

Номер: US20130267519A1
Автор: Hans Richter, Henrietta Dehmlow, Patrizio Mattei, Shawn David Erickson
Принадлежит: Hoffmann La Roche Inc

This invention relates to novel 1,2-pyridazines, 1,6-pyridazines or pyrimidines of the formula wherein B 1 to B 3 and R 1 to R 7 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may therefore be useful as medicaments for the treatment of diseases such as type II diabetes.

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Номер записи: 16
09-01-2014 дата публикации

NEPRILYSIN INHIBITORS

Номер: US20140011997A1
Автор: Fleury Melissa, Gendron Roland, Hudson Ryan, Hughes Adam D., Smith Cameron
Принадлежит: THERAVANCE, INC.

In one aspect, the invention relates to compounds having the formula: 1. (canceled)2. The process of claim 18 , where X is selected from pyrazole claim 18 , imidazole claim 18 , triazole claim 18 , benzotriazole claim 18 , furan claim 18 , pyrrole claim 18 , tetrazole claim 18 , pyrazine claim 18 , thiophene claim 18 , oxazole claim 18 , isoxazole claim 18 , thiazole claim 18 , isothiazole claim 18 , oxadiazole claim 18 , thiadiazole claim 18 , pyridazine claim 18 , pyridine claim 18 , pyrimidine claim 18 , pyran claim 18 , benzimidazole claim 18 , benzoxazole claim 18 , benzothiazole claim 18 , pyridylimidazole claim 18 , and pyridyltriazole.3. The process of claim 2 , where X is selected from pyrazole claim 2 , triazole claim 2 , benzotriazole claim 2 , tetrazole claim 2 , oxazole claim 2 , isoxazole claim 2 , thiazole claim 2 , pyridazine claim 2 , pyrimidine claim 2 , and pyridyltriazole.4. The process of claim 18 , where Ris selected from —ORand —NRR claim 18 , where Ris H claim 18 , Ris H or —OH claim 18 , and Ris H.7. The process of claim 18 , where Ris H.8. The process of claim 18 , where Ris absent or is selected from H; halo; —Calkylene-OH; —NH; —Calkyl; —CF; —Ccycloalkyl; —Calkylene-O—Calkyl; —C(O)R; —Calkylene-COOR; —C(O)NRR; —NHC(O)R; ═O; —NO; —C(CH)═N(OH); phenyl optionally substituted with one or two groups independently selected from halo claim 18 , —OH claim 18 , —CF claim 18 , —OCH claim 18 , —NHC(O)CH claim 18 , and phenyl; naphthalenyl; pyridinyl; pyrazinyl; pyrazolyl optionally substituted with methyl; thiophenyl optionally substituted with methyl or halo; furanyl; and —CH-morpholinyl; and Ris H.10. The process of claim 18 , where Ris absent or is selected from H; halo; —Calkylene-OH; —Calkyl; —Ccycloalkyl; —Calkylene-O—Calkyl; —C(O)R; —Calkylene-COOR; —C(O)NRR; —NHC(O)R; —NHC(O)R; ═O; phenyl optionally substituted with one or two groups independently selected from halo claim 18 , —OH claim 18 , and —OCH; pyridinyl; and pyrazinyl; Ris —Calkyl; ...

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Номер записи: 17
23-01-2014 дата публикации

NEW PYRIDAZINONE AND PYRIDONE COMPOUNDS

Номер: US20140024648A1
Автор: Fulop Ferenc, Juhakoski Auni, Kiss Lorand, Lazar Laszlo, Miklos Ferenc, Palko Marta, Pihlavisto Marjo, Smith David, Szakonyi Zsolt, Szatmari Istvan
Принадлежит: BIOTIE THERAPIES CORPORATION

The invention relates to pyridazinone and pyridone compounds having formula (I) or (I′), and pharmaceutically acceptable salts, hydrates, and solvates thereof (I) wherein R/Rand X and Xare as defined in the claims. The invention further relates to their use as inhibitors of copper-containing amine oxidases. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds, pharmaceutically acceptable salts, hydrates, or solvates thereof. 3. The pyridazinone compound according to claim 1 , wherein X is N or pharmaceutically acceptable salt claim 1 , hydrate claim 1 , or solvate thereof.4. The pyridone compound according to claim 1 , wherein X is CH or pharmaceutically acceptable salt claim 1 , hydrate claim 1 , or solvate thereof.5. The pyridazinone or pyridone compound according to claim 1 , wherein Ris hydrogen claim 1 , or pharmaceutically acceptable salt claim 1 , hydrate claim 1 , or solvate thereof.6. The pyridazinone or pyridone compound according to claim 1 , wherein Ris unsubstituted phenyl claim 1 , or pharmaceutically acceptable salt claim 1 , hydrate claim 1 , or solvate thereof.7. The pyridazinone or pyridone compound according to claim 1 , wherein Xis O and forms together with Ra group selected from the group consisting of methoxy claim 1 , ethoxy claim 1 , and phenoxy claim 1 , wherein said phenoxy is optionally substituted with R claim 1 , or pharmaceutically acceptable salt claim 1 , hydrate claim 1 , or solvate thereof.8. The pyridazinone or pyridone compound according to claim 1 , wherein Xis NR′.9. The pyridazinone or pyridone compound according to claim 8 , wherein NR′ forms together with Ra group selected from the group consisting of N-methyl piperazinyl claim 8 , pyrrolidinyl claim 8 , and optionally substituted 1 claim 8 ,2 claim 8 ,3-triazolyl.10. The pyridazinone or pyridone compound according to claim 9 , ...

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Номер записи: 18
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: 19
20-02-2014 дата публикации

1,4-DISUBSTITUTED PYRIDAZINE ANALOGS THERE OF AND METHODS FOR TREATING SMN-DEFICIENCY-RELATED CONDITIONS

Номер: US20140051672A1
Автор: "OBrien Gary", CHEUNG Atwood Kim, CHIN Donovan Noel, Dales Natalie, FAZAL Aleem, HURLEY Timothy Brian, KERRIGAN John, SHU Lei, Sun Robert, SUNG Moo Je
Принадлежит:

The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof; 2. A compound of claim 1 , or a salt thereof claim 1 , wherein{'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'A is 6 member heteroaryl having 1-3 ring nitrogen atoms, which 6 member heteroaryl is substituted by phenyl or a heteroaryl having 5 or 6 ring atoms, 1 or 2 ring heteroatoms independently selected from N, O and S and substituted with 0, 1, or 2 substituents independently selected from C-Calkyl, mono- and di-C-Calkylamino, hydroxyC-Calkylamino, hydroxyC-Calkyl, aminoC-Calkyl and mono- and di-C-CalkylaminoC-Calkyl; or'}{'sub': 1', '4', '2', '4', '2', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'A is bicyclic heteroaryl having 9 to 10 ring atoms and 1, 2, or 3 ring heteroatoms independently selected from N, O or S, which heteroaryl is substituted with 0, 1, or 2 substituents independently selected from cyano, halogen, hydroxy, C-Calkyl, C-Calkenyl, C-Calkynyl, C-Calkoxy and C-Calkoxy substituted with hydroxy, C-Calkoxy, amino and mono- and di-C-Calkylamino.'}3. A compound of claim 1 , or a salt thereof claim 1 , wherein A is 2-hydroxy-phenyl which is substituted with 0 claim 1 , 1 claim 1 , 2 claim 1 , or 3 substituents independently selected from C-Calkyl claim 1 , haloC-Calkyl C-Calkoxy claim 1 , hydroxy claim 1 , cyano claim 1 , halogen claim 1 , amino claim 1 , mono- and di-C-Calkylamino claim 1 , heteroaryl and C-Calkyl substituted with hydroxy or amino claim 1 , which heteroaryl has 5 or 6 ring atoms claim 1 , 1 or 2 ring heteroatoms selected from N claim 1 , O and S and substituted with 0 claim 1 , 1 claim 1 , or 2 substituents independently selected from C-Calkyl claim 1 , mono- and di-C-Calkylamino claim 1 , hydroxyC-Calkylamino claim 1 , hydroxyC-Calkyl claim 1 , 4-7member heterocycleC-Calkyl claim 1 , aminoC-Calkyl and mono- and di-C-CalkylaminoC-Calkyl.4. A compound of claim 1 , or a salt thereof claim 1 , wherein A is 2 ...

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Номер записи: 20
13-03-2014 дата публикации

HETEROCYCLIC MODULATORS OF HIF ACTIVITY FOR TREATMENT OF DISEASE

Номер: US20140073634A1
Автор: Carroll Chris, Czakó Barbara, DiFrancesco Maria Emilia, Jones Philip, KANG Zhijun, Liu Gang, Marszalek Joe, MCAFOOS Timothy, Petrocchi Alessia
Принадлежит: Institute For Applied Cancer Science/The University of Texas MD Anderson Cancer Center

The present invention relates to compounds and methods which may be useful as inhibitors of HIF pathway activity for the treatment or prevention of cancer and other hypoxia-mediated diseases. 7. The compound as recited in wherein:n is 1;p is 1; and{'sub': 7', '8', '9', '10, 'R, R, R, and Rare each independently selected from the group consisting of alkyl, haloalkyl, perhaloalkyl, hydroxy, and cyclopropyl.'}9. The compound as recited in wherein:{'sub': 2', '4', '5', '2', '4', '5, 'two of X, X, and Xare N, and one of X, X, and Xare O; or'}{'sub': 2', '4', '5', '2', '4', '5', '2', '4', '5, 'one of X, X, and Xis N; one of X, X, and Xis O; and one of X, X, and Xis CH.'}13. The compound as recited in wherein Ris selected from the group consisting of hydrogen and C-Calkyl.14. The compound as recited in wherein two of X claim 13 , X claim 13 , and Xare N claim 13 , and one of X claim 13 , X claim 13 , and Xare O.15. The compound as recited in wherein one of X claim 13 , X claim 13 , and Xis N; one of X claim 13 , X claim 13 , is Xare O; and one of X claim 13 , X claim 13 , and Xis CH.17. The compound as recited in wherein:{'sub': 4', '5, 'Zand Zare CH; and'}{'sub': 39', '40, 'Rand Rare hydrogen.'}25. The compound as recited in wherein:{'sub': 4', '5, 'Zand Zare CH; and'}{'sub': 13', '16, 'Rand Rare hydrogen.'}35. A compound selected from the group consisting of Examples 1 to 23 claim 24 , 25 claim 24 , 27 to 106 claim 24 , 108 claim 24 , 111 to 113 claim 24 , 116 to 132 claim 24 , 135 to 152 claim 24 , and 154 to 270 claim 24 , or a salt thereof.36. A pharmaceutical composition comprising a compound as recited in together with a pharmaceutically acceptable carrier.37. A method of treatment of a HIF pathway-mediated disease comprising the administration of a therapeutically effective amount of a compound as recited in to a patient in need thereof.38. The method as recited in wherein said disease is cancer.39. The method as recited in wherein said cancer is selected from the ...

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Номер записи: 21
13-03-2014 дата публикации

Benzamide derivatives as p2x7 receptor antagonists

Номер: US20140073651A1
Автор: Dorte Renneberg, Francis Hubler, Kurt Hilpert, Mark Murphy
Принадлежит: ACTELION PHARMACEUTICALS LTD

The invention relates to benzamide derivatives of formula (I), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , n and Y are as defined in the description, their preparation and their use as pharmaceutically active compounds.

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Номер записи: 22
03-04-2014 дата публикации

Compounds as S-Nitrosoglutathione Reductase Inhibitors

Номер: US20140094465A1
Автор: Qiu Jian, Stout Adam, Sun Xicheng
Принадлежит:

The present invention is directed to compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same. 1. What is claimed is: {'br': None, 'sub': 1', '2, 'HO-Cy-linker-Cy-acidic moiety\u2003\u2003Formula 1'}, 'A method of inhibiting GSNOR in a patient in need thereof by administering an effective amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereofwherein{'sub': '1', 'Cyis selected from the group consisting of substituted and unsubstituted monocyclic aryl, substituted and unsubstituted bicyclic aryl, substituted and unsubstituted monocyclic heterocycle, substituted and unsubstituted bicyclic heterocycle, substituted and unsubstituted monocyclic heteroaryl, substituted and unsubstituted bicyclic heteroaryl, substituted and unsubstituted monocyclic cycloalkyl, and substituted and unsubstituted bicyclic cycloalkyl;'}{'sub': 2', '5', '6', '7', '2', '3', '2', '3', '2', '3', '5', '6', '1', '6', '1', '6', '1', '6', '7', '1', '6', '1', '6', '1', '6', '2', '3', '2', '3', '2', '3', '1', '3', '1', '3', '1', '3', '1', '8', '1', '8', '1', '8, 'linker is selected from the group consisting of a direct bond, O, S, SO, SO, C═O, CRR, NR, substituted and unsubstituted (C-C) alkyl, substituted and unsubstituted (C-C) heteroalkyl, substituted and unsubstituted (C-C) alkene, substituted and unsubstituted 5 or 6 membered aryl, substituted and unsubstituted 5 or 6 membered heteroaryl, substituted and unsubstituted 3-6 membered cycloalkyl, and substituted and unsubstituted 3-6 membered saturated heterocyclyl; wherein Rand Rare independently selected from the group consisting of hydrogen, (C-C) alkyl, (C-C) heteroalkyl, halogen, (C-C) haloalkyl, cyano, and hydroxyl; Ris selected from the group consisting of hydrogen, (C-C)alkyl, (C-C) haloalkyl, and (C-C) heteroalkyl; substitutions for the (C-C) alkyl, (C-C) heteroalkyl, and (C-C) alkene are selected from the group ...

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Номер записи: 23
10-04-2014 дата публикации

Guanidine compound

Номер: US20140100210A1
Автор: Daisuke Suzuki, Hiroyoshi Yamada, Hisashi Mihara, Kousei Yoshihara, Norio Seki, Susumu Yamaki
Принадлежит: Astellas Pharma Inc

[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that the compound or a salt thereof of the present invention exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. In addition, the present invention relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound or a salt thereof of the present invention, and an excipient.

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Номер записи: 24
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: 25
04-01-2018 дата публикации

SUBSTITUTED MONO- AND POLYAZANAPHTHALENE DERIVATIVES AND THEIR USE

Номер: US20180002321A1
Автор: Lane Heidi, Pohlmann Jens, Reinelt Stefan, Stieger Martin
Принадлежит:

Disclosed are compounds of formula (I) wherein A is CH or N, B is CR or N; and D is CR; R represents hydrogen, OH or NH; R1 and R2, independently of each other, represent hydrogen, N(R3), halogen, cyano, nitro, R4-C1-C4alkyl, R4-C1-C4halogenoalkyl, OH, R4-C1-C4alkoxy, R4-C1-C4halogenoalkoxy, SH, R4-C1-C4alkythio, R4-C1-C4halogenoalkylthio; R3 represents, independently at each occurrence, hydrogen, R4-C1-C4alkyl or R4-C1-C4halogenoalkyl; R3a represents, independently at each occurrence, hydrogen or C1-C4 alkyl; R4 represents, independently at each occurrence, hydrogen, halogen, cyano, OH, SH, NH, NH(CH) or N(CH); X represents a group of formula -E- or -E-F—, wherein E and F are different from each other and represent a group selected from —C(R3a)2-, —(C═O)—, —NR3a- and —O— and F is linked to Y, with the proviso that if X represents -E-F— one of E or F represents —C(R3a)- or —(C═O)—; Y represents a group selected from C1-C6alkyl, mono- or bicyclic C3-C11cycloalkyl, which may be partially unsaturated, mono- or bicyclic 3 to 11-membered heterocycloalkyl, which may be partially unsaturated, a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, wherein said heterocycloalkyl group and said group comprising at least one heteroaryl cycle comprise one or more heteroatoms selected from nitrogen, oxygen and sulfur and said group Y is either unsubstituted or substituted by one or more substituents and comprises including its substituents one or more than one nitrogen atom having a lone electron pair; and Z represents a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, said heteroaryl cycle comprising one or more heteroatoms selected from nitrogen, oxygen and sulfur, which aryl or heteroaryl group is unsubstituted or substituted by one or more substituents; including tautomers of said compounds, mixtures of two tautomeric forms of said compounds, and pharmaceutically acceptable salts of said compounds, tautomers thereof or mixtures of ...

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Номер записи: 26
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: 27
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: 28
14-01-2016 дата публикации

Pyridazine derivatives, compositions and methods for treating cognitive impairment

Номер: US20160008357A1
Автор: John A. Lowe, III
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 GABA A receptor, 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.

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Номер записи: 29
08-01-2015 дата публикации

Pyridazine derivatives and use thereof as medicaments for treating microrna viral infection

Номер: US20150011558A1
Автор: Guoming Zhao, Hongliang Wang, Junhai Xiao, Lili Wang, Song Li, Wu Zhong, Xian Zhang, Xiaokui Wang, Xinbo Zhou, Xingzhou Li, Yunde Xie, Zhibing Zheng
Принадлежит: Institute of Pharmacology and Toxicology of AMMS

Disclosed are pyridazine derivatives represented by Formula I or pharmaceutically acceptable salts or hydrates thereof, pharmaceutical compositions comprising the compounds, methods of treating and/or preventing diseases or disorders associated with viral infections in patients using the compounds, and the use of the compounds in preparing the medicaments for treating and/or preventing diseases or disorders associated with viral infections. The compounds represented by Formula I have antiviral activity, especially anti-microRNA viral activity. Symbols in the compounds represented are described in the specification.

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Номер записи: 30
14-01-2021 дата публикации

HISTONE DEMETHYLASE INHIBITORS

Номер: US20210009520A1
Автор: Chen Young K., Kanouni Toufike, Nie Zhe, Stafford Jeffrey Alan, Veal James Marvin, Wallace Michael Brennan
Принадлежит: CELGENE QUANTICEL RESEARCH, INC.

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted amidopyridine or amidopyridazine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like. 2. The compound or pharmaceutically acceptable salt of claim 1 , wherein each Ris hydrogen.3. The compound or pharmaceutically acceptable salt of claim 1 , wherein each Ris fluoro.4. The compound or pharmaceutically acceptable salt of claim 1 , wherein each Ris methyl.5. The compound or pharmaceutically acceptable salt of claim 1 , wherein one Ris hydrogen.6. The compound or pharmaceutically acceptable salt of claim 1 , wherein one Ris fluoro.7. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris hydrogen.8. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris hydrogen.9. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris hydrogen.10. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris hydrogen.11. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris hydrogen.12. The compound or pharmaceutically acceptable salt of claim 1 , wherein Rand Rare hydrogen.13. The compound or pharmaceutically acceptable salt of claim 1 , wherein Rand Rare hydrogen.14. The compound or pharmaceutically acceptable salt of claim 1 , wherein Rand Rare hydrogen.15. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris not hydrogen.16. The compound or pharmaceutically acceptable salt of claim 1 , wherein Ris chosen from optionally substituted C-Calkyl claim 1 , optionally substituted C-Calkoxy claim 1 , optionally substituted C-Ccarbocyclyl claim ...

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Номер записи: 31
10-01-2019 дата публикации

SULFONAMIDE COMPOUNDS AND USES AS TNAP INHIBITORS

Номер: US20190010126A1
Автор: COSFORD Nicholas D.P., Dahl Russell, Millan Jose Luis, Pinkerton Anthony B.
Принадлежит:

Described herein are compounds that modulate the activity of TNAP. In some embodiments, the compounds described herein inhibit TNAP. In certain embodiments, the compounds described herein are useful in the treatment of conditions associated with hyper-mineralization. 2. (canceled)3. (canceled)4. (canceled)5. (canceled)7. (canceled)8. The method of claim 1 , wherein Xis ═C(R)—.9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. The method of claim 1 , wherein Ris optionally substituted phenyl or optionally substituted 5- or 6-membered heteroaryl.14. (canceled)15. The method of claim 1 , wherein Rand Rare independently selected from the group consisting of —F claim 1 , —Cl claim 1 , —Br claim 1 , —CN claim 1 , —OMe claim 1 , and —OCF.16. (canceled)17. (canceled)18. (canceled)21. (canceled)22. The method of claim 20 , wherein: A is —C(O)—O—R claim 20 , wherein Ris selected from hydrogen claim 20 , optionally substituted alkyl claim 20 , optionally substituted cycloalkyl claim 20 , and optionally substituted phenyl.23. (canceled)24. (canceled)25. The method of claim 20 , wherein: A is —C(O)—N(R)—(R) claim 20 , wherein Rand Rtogether with the nitrogen atom to which they are attached form an optionally substituted heterocycloamino.26. The method of claim 25 , wherein the optionally substituted heterocycloamino is an optionally substituted pyrrolidine claim 25 , an optionally substituted piperidine claim 25 , an optionally substituted morpholine claim 25 , or an optionally substituted piperazine.27. The method of claim 20 , wherein: A is —C(O)—N(R)—(R) claim 20 , wherein Ris hydrogen and Ris optionally substituted alkyl claim 20 , optionally substituted cycloalkyl claim 20 , or optionally substituted phenyl.28. (canceled)29. The method of claim 20 , wherein: A is —C(O)—N(R)—(R) claim 20 , wherein Rand Rare hydrogen.30. (canceled)31. (canceled)32. (canceled)33. The method of claim 1 , wherein the vascular calcification is an arterial calcification.34. The method of ...

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Номер записи: 32
09-01-2020 дата публикации

Pharmaceutically Active Compounds

Номер: US20200010421A1
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 ASA

The invention is directed to compounds of general formula (I) 2464.-. (canceled)466. The method according to claim 465 , wherein one or both of Rand Rrepresents a protecting group.467. The method according to claim 465 , which is carried out in the presence of a coupling agent.469481.-. (canceled)483. A method according claim 482 , wherein Rrepresents a six-membered aliphatic carbocyclic ring claim 482 , optionally substituted by —(C═O)NRR claim 482 , —OR claim 482 , —SOR or Calkyl.484. A method according to claim 483 , wherein Rrepresents a six-membered aliphatic carbocyclic ring claim 483 , optionally substituted by —(C═O)NRRor —OR.485. A method according to claim 483 , wherein Rrepresents a six-membered aliphatic carbocyclic ring claim 483 , optionally substituted by —(C═O)NRR.486. A method according to claim 482 , wherein Rand/or Rrepresent:{'sub': 1-6', '3, '(a) Calkyl optionally substituted by —OCH; or'}{'sub': '1-6', '(b) cyclopropyl or cyclobutyl, any of which is optionally substituted by Calkyl; or'}{'sub': '1-6', '(c) a 4-membered heterocycloalkyl ring, optionally substituted by Calkyl; or'}{'sup': 'd', '(d) —(C═O)R; or'}{'sub': '2', 'sup': 'e', '(e) —SOR.'}487. A method according to claim 482 , wherein Rand/or Rrepresent:{'sub': 3', '2', '3', '2', '3', '3', '3', '2', '3', '3', '3', '2', '2', '3', '2', '2', '3', '1-6, '(a) —CH, —CHF, —C(CH)CF, —C(CH), —CHC(CH), —CH(CH), —CHCHor —CHCHCH; or Calkyl optionally substituted by cycloalkyl, halo or alkoxy; or'}{'sub': '1-6', '(b) Calkyl optionally substituted by cyclopropyl or cyclobutyl; or'}{'sub': 3', '2', '3, '(c) —OCHor —OCHCH; or'}{'sub': 3-6', '1-6, '(d) Ccycloalkyl optionally substituted by Calkyl.'} This application is a divisional of U.S. patent application Ser. No. 15/533,048, filed Jun. 5, 2017, which is a national phase entry pursuant to 35 U.S.C. § 371 of International Application No. PCT/EP2015/081168, filed Dec. 23, 2015, which claims the benefit of priority of Application No. GB 1423087.4, filed ...

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Номер записи: 33
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: 34
21-01-2016 дата публикации

Neprilysin inhibitors

Номер: US20160016918A1
Автор: Adam D. Hughes, Melissa Fleury, Roland Gendron
Принадлежит: Theravance Biopharma R&D Ip Llc

In one aspect, the invention relates to compounds having the formula: where R 1 -R 6 , a, b, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

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Номер записи: 35
18-01-2018 дата публикации

SUBSTITUTED PYRIDAZINE CARBOXAMIDE COMPOUNDS

Номер: US20180016240A1
Автор: Liang Congxin
Принадлежит:

The new pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases especially against ALK and are useful in treating disorders related to abnormal protein kinase activities such as cancer, neurological and psychiatric diseases. 1. (canceled)2. (canceled)3. (canceled)5. (canceled)6. (canceled)7. The compound of claim 4 , wherein Ris hydrogen.8. (canceled)9. (canceled)10. The compound of claim 4 , wherein the compound is:{5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-aminopyridazin-3-yl}-N-{4-[(4-methyl(1,4-diazaperhydroepinyl))carbonyl] phenyl}carboxamide; 'or a salt thereof; or a prodrug, or a salt of a prodrug thereof; or a hydrate, solvate, or polymorph thereof.', '{5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-aminopyridazin-3-yl}-N-[4-(1,4-diazaperhydroepinylcarbonyl)phenyl]carboxamide;'}13. The method of claim 11 , wherein the disease is mediated by the c-met claim 11 , ron claim 11 , Axl claim 11 , or ALK or its fusion proteins such as EML4-ALK and NPM-ALK kinases claim 11 , or the alterations of one or more of the c-met claim 11 , ron claim 11 , Axl claim 11 , and ALK kinases.14. The method of claim 11 , wherein the disease is cancer or a proliferation disease.15. The method of claim 11 , wherein the disease is lung cancer claim 11 , colon cancer claim 11 , breast cancer claim 11 , prostate cancer claim 11 , liver cancer claim 11 , brain cancer claim 11 , kidney cancer claim 11 , stomach cancer claim 11 , skin cancer claim 11 , bone cancers claim 11 , gastric cancer claim 11 , pancreatic cancer claim 11 , glioma claim 11 , lymphoma claim 11 , neuroblastoma claim 11 , hepatocellular carcinoma claim 11 , papillary renal carcinoma claim 11 , or head and neck squamous cell carcinoma.16. The method of claim 11 , wherein the disease is non-small cell lung cancer (NSCLC) resistant to the treatment by PF-2341066.17. The method of claim 11 , wherein the disease is non-small cell lung cancer (NSCLC) with brain metastasis.18. The ...

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Номер записи: 36
15-01-2015 дата публикации

Substituted 5-aminothieno[2,3-c]pyridazine-6-carboxamide analogs as positive allosteric modulators of the muscarinic acetylcholine receptor m4

Номер: US20150018309A1
Автор: Bruce J. Melancon, Craig W Lindsley, James C. Tarr, James M. Salovich, Michael R. Wood, P. Jeffrey Conn
Принадлежит: VANDERBILT UNIVERSITY

In one aspect, the invention relates to substituted 5-aminothieno[2,3-c]pyridazine-6-carboxamide analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M 4 (mAChR M 4 ); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

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Номер записи: 37
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: 38
26-01-2017 дата публикации

AMIDE-SUBSTITUTED HETEROCYCLIC COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFN ALPHA RESPONSES

Номер: US20170022192A1
Автор: Batt Douglas G., Kumar Amit, Lin Shuqun, Liu Chunjian, Liu Qingjie, Moslin Ryan M., Spergel Steven H., Tokarski John S., Weinstein David S., Wrobleski Stephen T., Zhang Yanlei
Принадлежит:

Compounds having the following formula I: 2. A compound of claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein Ris —C(O)R; or Calkyl claim 1 , Ccycloalkyl claim 1 , phenyl claim 1 , pyrazolyl claim 1 , thiazolyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyridazinyl claim 1 , pyrazinyl claim 1 , quinolinyl or pyrrolopyridinyl claim 1 , each group substituted by 0-4 groups selected from R.3. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein both Rand Rare hydrogen.5. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein Ris pyrazolyl claim 1 , thiazolyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyridazinyl claim 1 , pyrazinyl or quinolinyl claim 1 , each group substituted with 0-3 R.6. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein Ris —C(O)R; or Calkyl claim 1 , Ccycloalkyl or phenyl substituted with 0-3 R.8. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein Ris phenyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , triazolyl claim 1 , oxadiazolyl claim 1 , pyrimidinyl claim 1 , tetrazolyl claim 1 , pyrazolyl claim 1 , thiazolyl claim 1 , furanyl claim 1 , or pyranyl claim 1 , each group substituted with 0-4 R. (Especially phenyl substituted with 0-4 R).9. A compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof claim 1 , wherein:{'sup': 3a', 'b', '11', '11', 'b', 'c', 'b', 'c', 'b', 'a', 'a, 'sub': 2', '3', '2', '11', '11', 'p', 'p', '1-6, 'Rat each occurrence independently is hydrogen, Ph, CN, NH, OCF, OR, halo, cycloalkyl, C(O)NRR, S(O)NRR, C(O)R, SOR, NRSOR, NRC(O)R, haloalkyl, CN, 5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, S or O substituted with 0-3 Rand Calkyl substituted ...

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Номер записи: 39
26-01-2017 дата публикации

Substituted 5-aminothieno[2,3-c]pyridazine-6-carboxamide analogs as positive allosteric modulators of the muscarinic acetylcholine receptor m4

Номер: US20170022216A1
Автор: Bruce J. Melancon, Craig W. Lindsley, James C. Tarr, James M. Salovich, Michael R. Wood, Michael S. Poslusney, P. Jeffrey Conn
Принадлежит: VANDERBILT UNIVERSITY

In one aspect, the invention relates to substituted 5-aminothieno[2,3-c]pyridazine-6-carboxamide analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M 4 (mAChR M 4 ); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

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Номер записи: 40
26-01-2017 дата публикации

NEPRILYSIN INHIBITORS

Номер: US20170022219A1
Автор: Fleury Melissa, Gendron Roland, Hughes Adam D.
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

In one aspect, the invention relates to compounds having the formula: 14-. (canceled)5. The compound of claim 24 , where Ris selected from —ORand —NRR claim 24 , Ris H claim 24 , Ris H or —OH claim 24 , and Ris H.8. The compound of claim 24 , where Ris —NRR claim 24 , where Ris H and Ris H.9. The compound of claim 24 , where Ris H.1015-. (canceled)16. The compound of claim 24 , where a is 0; or a is 1 and Ris 3-chloro.17. The compound of claim 24 , where b is 0; orb is 1 and Ris 3′-chloro claim 24 , 3′-methyl claim 24 , or 2′-methoxy; or b is 2 and Ris 2′-fluoro-5′-chloro claim 24 , 2′ claim 24 ,5′-dichloro claim 24 , 2′-methyl-5′-chloro claim 24 , or 3′-chloro-5′-hydroxy.18. The compound of claim 24 , where the methylene linker on the biphenyl is substituted with 2 methyl groups.20. The compound of claim 24 , where{'sup': 1', '7, 'Ris —OR;'}{'sup': '2', 'Ris H;'}X is selected from pyrazole, triazole, benzotriazole, isoxazole, pyridazine, pyrimidine, and pyridyltriazole;{'sup': 3', '20', '21', '22', '23', '24, 'sub': 0-5', '1-6', '3', '3-7', '0-2', '1-6', '0-1', '3', '3, 'Ris selected from H; halo; —Calkylene-OH; —Calkyl; —CF; —Ccycloalkyl; —Calkylene-O—Calkyl; —C(O)R; —Calkylene-COOR; —C(O)NRR; —NHC(O)R; ═O; —C(CH)═N(OH); phenyl optionally substituted with one or two groups independently selected from halo, —OH, and —OCH; pyridinyl; pyrazinyl; and thiophenyl substituted with methyl or halo;'}{'sup': 4', '35', '3', '4, 'sub': 1-6', '1-2', '2', '2', '2', '1-3, 'Ris selected from H; —OH; —Calkyl; —Calkylene-COOR; —CHCH(OH)CHOH; pyridinyl; and phenyl optionally substituted with one halo group; or Rand Rare taken together to form -phenylene-O—(CH)—;'}{'sup': '5', 'a is 0; or a is 1 and Ris 3-chloro;'}{'sup': 6', '6, 'b is 0; or b is 1 and Ris 3′-chloro, 3′-methyl, or 2′-methoxy; or b is 2 and Ris 2′-fluoro-5′-chloro, 2′,5′-dichloro, 2′-methyl-5′-chloro, or 3′-chloro-5′-hydroxy;'}{'sup': '20', 'sub': '1-6', 'Ris —Calkyl;'}{'sup': '21', 'Ris H;'}{'sup': 22', '23', '22', ' ...

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Номер записи: 41
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: 42
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: 43
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: 44
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: 45
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: 46
01-02-2018 дата публикации

Pyridazinone and pyridone compounds

Номер: US20180029995A1
Автор: Auni Juhakoski, David Smith, Ferenc FÜLÖP, Ferenc Miklos, Istvan Szatmari, Laszlo Lazar, Lorand Kiss, Marjo Pihlavisto, Marta Palko, Zsolt Szakonyi
Принадлежит: Biotie Therapies Corp

The invention relates to pyridazinone and pyridone compounds having formula (I) or (I′), and pharmaceutically acceptable salts, hydrates, and solvates thereof wherein R 1 /R 4 and X and X 3 are as defined in the claims. The invention further relates to their use as inhibitors of copper-containing amine oxidases. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds, pharmaceutically acceptable salts, hydrates, or solvates thereof.

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Номер записи: 47
30-01-2020 дата публикации

Substituted mono- and polyazanaphthalene derivatives and their use

Номер: US20200031811A1
Автор: Heidi Lane, Jens Pohlmann, Martin Stieger, Stefan Reinelt
Принадлежит: Basilea Pharmaceutica International AG

Disclosed are compounds of formula (I) wherein A is CH or N, B is CR or N; and D is CR; R represents hydrogen, OH or NH 2 ; R1 and R2, independently of each other, represent hydrogen, N(R3) 2 , halogen, cyano, nitro, R4-C1-C4alkyl, R4-C1-C4halogenoalkyl, OH, R4-C1-C4alkoxy, R4-C1-C4halogenoalkoxy, SH, R4-C1-C4alkythio, R4-C1-C4halogenoalkylthio; R3 represents, independently at each occurrence, hydrogen, R4-C1-C4alkyl or R4-C1-C4halogenoalkyl; R3a represents, independently at each occurrence, hydrogen or C1-C4 alkyl; R4 represents, independently at each occurrence, hydrogen, halogen, cyano, OH, SH, NH 2 , NH(CH 3 ) or N(CH 3 ) 2 ; X represents a group of formula -E- or -E-F—, wherein E and F are different from each other and represent a group selected from —C(R3a)2-, —(C═O)—, —NR3a- and —O— and F is linked to Y, with the proviso that if X represents -E-F— one of E or F represents —C(R3a) 2 — or —(C═O)—; Y represents a group selected from C1-C6alkyl, mono- or bicyclic C3-C11cycloalkyl, which may be partially unsaturated, mono- or bicyclic 3 to 11-membered heterocycloalkyl, which may be partially unsaturated, a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, wherein said heterocycloalkyl group and said group comprising at least one heteroaryl cycle comprise one or more heteroatoms selected from nitrogen, oxygen and sulfur and said group Y is either unsubstituted or substituted by one or more substituents and comprises including its substituents one or more than one nitrogen atom having a lone electron pair; and Z represents a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, said heteroaryl cycle comprising one or more heteroatoms selected from nitrogen, oxygen and sulfur, which aryl or heteroaryl group is unsubstituted or substituted by one or more substituents; including tautomers of said compounds, mixtures of two tautomeric forms of said compounds, and pharmaceutically acceptable salts of said compounds, tautomers ...

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Номер записи: 48
30-01-2020 дата публикации

NEPRILYSIN INHIBITORS

Номер: US20200031847A1
Автор: Gendron Roland, Hughes Adam D.
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

In one aspect, the invention relates to compounds having the formula: 128-. (canceled)29. (2R ,4R)-5-Biphenyl-4-yl-4-{[5-(3-carbamoylpyrrolidine-1-carbonyl)-2H-pyrazole-3-carbonyl]-amino}-2-hydroxy-pentanoic acid or a pharmaceutically acceptable salt thereof.30. (2R ,4R)-5-Biphenyl-4-yl-2-hydroxy-4-{[5-(4-hydroxypiperidine-1-carbonyl)-2H-pyrazole-3-carbonyl]-amino}-pentanoic acid or a pharmaceutically acceptable salt thereof.31. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.32. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier.33. The pharmaceutical composition of claim 31 , further comprising an ATreceptor antagonist.34. The pharmaceutical composition of claim 32 , further comprising an ATreceptor antagonist.35. The pharmaceutical composition of claim 33 , wherein the ATreceptor antagonist is selected from abitesartan claim 33 , azilsartan claim 33 , azilsartan medoxomil claim 33 , benzyllosartan claim 33 , candesartan claim 33 , candesartan cilexetil claim 33 , elisartan claim 33 , embusartan claim 33 , enoltasosartan claim 33 , eprosartan claim 33 , EXP3174 claim 33 , fonsartan claim 33 , forasartan claim 33 , glycyllosartan claim 33 , irbesartan claim 33 , isoteoline claim 33 , losartan claim 33 , milfasartan claim 33 , olmesartan claim 33 , olmesartan medoxomil claim 33 , opomisartan claim 33 , pratosartan claim 33 , ripisartan claim 33 , saprisartan claim 33 , saralasin claim 33 , sarmesin claim 33 , TAK-591 claim 33 , tasosartan claim 33 , telmisartan claim 33 , valsartan claim 33 , and zolasartan.36. The pharmaceutical composition of claim 34 , wherein the ATreceptor antagonist is selected from abitesartan claim 34 , azilsartan claim 34 , azilsartan medoxomil claim 34 , benzyllosartan claim 34 , candesartan claim 34 , candesartan cilexetil claim 34 , elisartan claim 34 , embusartan claim 34 , enoltasosartan claim 34 , eprosartan claim 34 , EXP3174 claim 34 , ...

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Номер записи: 49
04-02-2021 дата публикации

COMPOUND, PHOTORESIST COMPOSITION COMPRISING SAME, PHOTORESIST PATTERN COMPRISING SAME, AND METHOD FOR MANUFACTURING PHOTORESIST PATTERN

Номер: US20210032208A1
Автор: AN Junhyun, LIM Minyoung
Принадлежит: LG CHEM, LTD.

A compound represented by Chemical Formula 1, a photoresist composition comprising the same, a photoresist pattern comprising the same, and a method for preparing a photoresist pattern 2. The compound of claim 1 , wherein Rand Rare the same as or different from each other claim 1 , and each independently hydrogen; a halogen group; an ester group; a substituted or unsubstituted Cto Calkyl group; a substituted or unsubstituted Cto Caryl group; or a substituted or unsubstituted Cto Cheteroaryl group.3. The compound of claim 1 , wherein Rto Rare the same as or different from each other claim 1 , and each independently a substituted or unsubstituted Cto Caryl group.4. The compound of claim 1 , wherein Arand Arare the same as or different from each other claim 1 , and each independently hydrogen; or a halogen group claim 1 , and at least one of Arand Aris a halogen group.5. The compound of claim 1 , wherein Ris a substituted or unsubstituted Cto Calkyl group.7. A photoresist composition comprising:a resin;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the compound of ;'}a photoacid generator (PAG);an acid diffusion control agent; anda quencher.8. The photoresist composition of claim 7 , wherein the resin comprises at least one resin selected from a (meth)acrylate-based resin; a norbornene resin; a styrene-based resin; and an epoxy resin.9. The photoresist composition of claim 7 , comprising the compound in an amount of from 0.1 parts by weight to 20 parts by weight based on 100 parts by weight of the resin.10. The photoresist composition of claim 7 , comprising the photoacid generator in an amount of from 0.1 parts by weight to 20 parts by weight based on 100 parts by weight of the resin.11. The photoresist composition of claim 7 , comprising the acid diffusion control agent in an amount of from 0.1 parts by weight to 20 parts by weight based on 100 parts by weight of the resin.12. The photoresist composition of claim 7 , further comprising at least one material ...

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Номер записи: 50
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: 51
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: 52
11-02-2016 дата публикации

BIARYL AMIDE COMPOUNDS AS KINASE INHIBITORS

Номер: US20160038504A1
Автор: AVERSA Robert John, BARSANTI Paul Andrew, Burger Matthew T., Dillon Michael Patrick, DIPESA Alan, Hu Cheng, Lou Yan, NISHIGUCHI Gisele A., Pan Yue, POLYAKOV Valery Rostislavovich, RAMURTHY Savithri, RICO Alice C., SETTI Lina Quattrocchio, Smith Aaron, SUBRAMANIAN Sharadha, TAFT Benjamin R., TANNER Huw Roland, Wan Lifeng, YUSUFF Naeem
Принадлежит: NOVARTIS AG

The present invention provides compounds of Formula (I) as described herein, and salts thereof, and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent. 120-. (canceled)22. A pharmaceutical composition comprising a compound of or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers.23. A combination comprising a therapeutically effective amount of a compound according to or a pharmaceutically acceptable salt thereof and one or more therapeutically active co-agents.24. A method of treating a proliferative disorder selected from non-small cell lung cancer and ovarian cancer claim 31 , comprising administering to a subject in need thereof a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.2527-. (canceled) The invention provides compounds that inhibit Raf kinases, and are accordingly useful for treating certain disorders associated with excessive Raf kinase activity, including cell proliferation disorders such as cancers. The invention further provides pharmaceutical compositions containing these compounds and methods of using these compounds to treat conditions including cancer.Protein Kinases are involved in very complex signaling cascades that regulate most cellular functions, including cell survival and proliferation. These signaling pathways have been heavily studied, particularly in the context of disorders caused by dysregulated cellular function, such as cancer. The mitogen-activated protein kinase (MAPK) cascade has been studied extensively, for example, and kinases in this pathway (e.g., RAS, RAF, MEK, and ERK) have been exploited as target sites for drug discovery. Mutated B-Raf is found in a significant fraction of malignancies (over 30% of all tumors and 40% of ...

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Номер записи: 53
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: 54
08-02-2018 дата публикации

INHIBITORS OF TRYPTOPHAN-2,3-DIOXYGENASE OR INDOLEAMINE-2,3-DIOXYGENASE

Номер: US20180037553A1
Автор: Cowley Phillip M., Davis Susan, Huggett Margaret, Kiczun Michael, Wise Alan
Принадлежит: IOMet Pharma Ltd.

Provided is a compound for use in medicine for inhibiting tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO), which compound comprises formula (I) wherein X, X, and X, may be the same or different and each is independently selected from C and N; X, X, X, and Xmay be the same or different and each is independently selected from C, N, O and S wherein when Xis N it has a double bond and wherein when Xis N it has a double bond; the dotted line is a bond which may be present or absent; R, R, R, R, R, R, and Rmay be present or absent and may be the same or different and each is independently selected from H and a substituted or unsubstituted organic group, provided that at least one of R, R, Rand Rcomprises a group Y; and provided that the number of R, R, R, R, R, R, and Rgroups present is such that the respective valencies of X, X, X, X, X, X, and Xare maintained; and wherein Y is a group having a formula selected from (II), (III), (IV), (V) wherein L may be present or absent, and may be a substituted or unsubstituted organic linking group, and Rand Rmay be the same or different and are selected from H and a substituted or unsubstituted organic group, Xis selected from C and N, and each Rmay be the same or different and is selected from H and a substituted or unsubstituted organic group. 13-. (canceled)5. (canceled)6. The compound according to claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein{'sup': '312', 'claim-text': [{'sub': 1', '6', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'a substituted or unsubstituted linear or branched C-Calkyl-aryl group selected from —CHPh, —CH(2,3 or 4)F-Ph, —CH(2,3 or 4)Cl-Ph, —CH(2,3 or 4)Br-Ph, —CH(2,3 or 4)I-Ph, —CHCHPh, —CHCHCHPh, —CHCHCHCHPh, —CHCHCHCHCHPh, and —CHCHCHCHCHCHPh);'}, {'sub': 3', '8, 'a substituted or unsubstituted cyclic C-Calkyl group (such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ...

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Номер записи: 55
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: 56
07-02-2019 дата публикации

PYRIDAZINE DERIVATIVES AS EAAT2 ACTIVATORS

Номер: US20190040040A1
Автор: HODGETTS Kevin, LIN Chien-Liang Glenn
Принадлежит:

Pyridazine derivatives that activate the excitatory amino acid transporter 2 (EAAT2), and methods of use thereof for treating or preventing diseases, disorders, and conditions associated with glutamate excitotoxicity. 2. The compound of claim 1 , wherein Ris a 5-10 membered heteroaryl which is optionally substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 independently selected Rgroups.3. The compound of claim 1 , wherein Ris pyridyl which is optionally substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 independently selected Rgroups.4. The compound of any one of to claim 1 , wherein Ris a 5-10 membered heteroaryl which is optionally substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 independently selected Rgroups.5. The compound of any one of to claim 1 , wherein Ris selected from oxazolyl and pyridyl claim 1 , each of which is optionally substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 independently selected Rgroups.6. The compound of any one of to claim 1 , wherein Ris NRR claim 1 , wherein Rand Rindependently selected from H and Calkyl.7. The compound of any one of to claim 1 , wherein Rand Rare CH.8. The compound of any one of to claim 1 , wherein Ris C(O)NRR claim 1 , wherein Rand Rare independently selected from H claim 1 , Calkyl claim 1 , and 6-10 membered aryl optionally substituted with 1 claim 1 , 2 claim 1 , 3 claim 1 , or 4 independently selected Rgroups; or alternatively claim 1 , Rand Rattached to the same N atom claim 1 , together with the N atom to which they are attached claim 1 , form a 4-6 membered heterocycloalkyl group optionally substituted with 1 claim 1 , 2 claim 1 , or 3 independently selected Rgroups.9. The compound of any one of to and claim 1 , wherein Rand Rare independently selected from H and Calkyl.10. The compound of any one of to and claim 1 , wherein Rand Rare independently selected from H claim 1 , Calkyl claim 1 , and phenyl optionally substituted with Calkyl.11. The compound of any one of to and claim 1 , ...

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Номер записи: 57
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: 58
25-02-2016 дата публикации

Novel heterocyclic derivative and pharmaceutical composition comprising the same (as amended)

Номер: US20160052892A1
Автор: Hiroyuki Kai, Kentaro Asahi, Sae Jikihara, Takeshi Endoh, Tohru Horiguchi
Принадлежит: Shionogi and Co Ltd

The present invention provides novel compounds having a P2X 3 and/or P2X 2/3 receptor antagonistic effect. A pharmaceutical composition having a P2X 3 and/or P2X 2/3 receptor antagonistic effect comprising a compound of the formula (I): wherein ring A is substituted or unsubstituted 5 to 7-membered cycloalkane, substituted or unsubstituted 5 to 7-membered cycloalkene or the like; C is a carbon atom; —X— is —N(R 16 )— or the like; R 16 is hydrogen, substituted or unsubstituted alkyl or the like; R 7 is substituted or unsubstituted 5- or 6-membered heteroaryl, substituted or unsubstituted 6 to 10 membered aryl; Q 1 and Q 2 are each independently a carbon atom or a nitrogen atom; -L- is —O—, —S— or the like; R 6 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl or the like; R 2 is hydrogen, hydroxy or the like, or its pharmaceutically acceptable salt or a solvate thereof.

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Номер записи: 59
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: 60
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: 61
22-02-2018 дата публикации

PYRIDAZINE DERIVATIVES AS RORc MODULATORS

Номер: US20180051010A1
Автор: Cridland Andrew, FAUBER Benjamin, Hurley Christopher, Killen Jonathan, Van Niel Monique Bodil, Ward Stuart, Winship Paul
Принадлежит: Genentech, Inc.

Compounds of formula I: 2. The compound of claim 1 , wherein Rand Rare halo.3. The compound of claim 1 , wherein Rand Rare fluoro.4. The compound of claim 1 , wherein Ris hydrogen..5. The compound of claim 1 , wherein Ris -Calkylene-C(O)—NRRwherein the Calkylene- may be substituted once or twice with R.6. The compound of claim 1 , wherein Ris hetereoaryl selected from oxazolyl; isoxazolyl; oxadiazolyl; thiazolyl; isothiazolyl; thiadiazolyl; triazolyl; pyrrolyl; pyrazolyl; imidazolyl; tetrazolyl; pyridinyl; pyrimidinyl; pyrazinyl; and pyridazinyl claim 1 , each of which may be unsubstituted or substituted once or twice with R.7. The compound of claim 1 , wherein Ris heteroaryl-Calkyl wherein the heteroaryl is selected from oxazolyl; isoxazolyl; oxadiazolyl; thiazolyl; isothiazolyl; thiadiazolyl; triazolyl; pyrrolyl; pyrazolyl; imidazolyl; tetrazolyl; pyridinyl; pyrimidinyl; pyrazinyl; and pyridazinyl; wherein the heteroaryl portion of each may be unsubstituted or substituted once or twice with R.12. A composition comprising:(a) a pharmaceutically acceptable carrier; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(b) a compound of .'}13. A method for treating a disease selected from rheumatoid arthritis claim 1 , osteoarthritis claim 1 , psoriatic arthritis claim 1 , septic arthritis claim 1 , spondyloarthropathies claim 1 , gouty arthritis claim 1 , juvenile arthritis claim 1 , chronic obstructive pulmonary disease (COPD) claim 1 , asthma claim 1 , bronchospasm claim 1 , Irritable Bowel Syndrome (IBS) claim 1 , Inflammatory Bowel Disease (IBD) claim 1 , psoriasis claim 1 , biliary colic claim 1 , renal colic claim 1 , diarrhea-dominant IBS claim 1 , muscular sclerosis claim 1 , Sjogren's disease claim 1 , lupus claim 1 , and pulmonary fibrosis claim 1 , the method comprising administering to a subject in need thereof an effective amount of a compound of . This Application is a continuation of International Application No. PCT/EP2016/059859 filed on May 3 2016, ...

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Номер записи: 62
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: 63
10-03-2022 дата публикации

CINNOLINE COMPOUNDS AND USES THEREOF

Номер: US20220073520A1
Автор: Cartwright Matthew W., Chan Bryan K., Favor David, Fong Kin Chiu, Gancia Emanuela, Gazzard Lewis J., Good Andrew, Heffron Timothy, Hu Yonghan, Lainchbury Michael, Madin Andrew, Malhotra Sushant, Seward Eileen Mary, Siu Michael, Wang Weiru, WEI Binqing, Zhou Aihe
Принадлежит: Genentech, Inc.

Cinnoline compounds of formula (I): 2. The compound of claim 1 , wherein Ris hydrogen claim 1 , fluoro claim 1 , chloro claim 1 , Calkyl.3. The compound of claim 1 , wherein Ris amino.4. The compound of claim 1 , wherein Ris hydrogen.5. The compound of claim 1 , wherein Ris hydrogen or halogen.6. The compound of claim 1 , wherein Ris Calkyl claim 1 , Ccycloalkyl claim 1 , or 5- to 14-membered heteroaryl; each optionally substituted with 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 substituents independently selected from R.7. The compound of claim 1 , wherein Ris Calkyl or Ccycloalkyl.8. The compound of claim 1 , wherein Ris 5- to 14-membered heteroaryl optionally substituted with 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 substituents independently selected from R.12. The compound of claim 1 , wherein Ris Calkyl claim 1 , 5- to 14-membered heteroaryl claim 1 , or 3- to 14-membered heterocyclyl; each optionally substituted with 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 substituents independently selected from R.13. The compound of claim 12 , wherein Ris Calkyl or 3- to 14-membered heterocyclyl optionally substituted with 1 claim 12 , 2 claim 12 , 3 claim 12 , 4 or 5 substituents independently selected from R.14. The compound of claim 12 , wherein Ris 5- to 14-membered heteroaryl optionally substituted with 1 claim 12 , 2 claim 12 , 3 claim 12 , 4 or 5 substituents independently selected from R.18. The compound of claim 1 , wherein Ris —C(O)R.19. The compound of claim 18 , wherein Ris —OR.20. The compound of claim 19 , wherein Ris Calkyl.21. The compound of claim 18 , wherein Ris —NRR.22. The compound of claim 21 , wherein Ris hydrogen.23. The compound of claim 21 , wherein Ris Calkyl or 3- to 14-membered heterocyclyl; each optionally substituted with 1 claim 21 , 2 claim 21 , 3 claim 21 , 4 or 5 substituents independently selected from R.24. The compound of claim 23 , wherein Ris selected from the group consisting of 2-propyl claim 23 , 2 claim 23 ,2 claim 23 ,2- ...

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Номер записи: 64
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: 65
20-02-2020 дата публикации

COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR

Номер: US20200055825A1
Автор: Berlin Michael, Chen Xin, CREW Andrew P., Crews Craig M., Dong Hanqing, Qian Yimin, Snyder Lawrence, Wang Jing, Zimmermann Kurt
Принадлежит:

The present disclosure relates to bifunctional compounds, which find utility to degrade (and inhibit) Androgen Receptor. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds Androgen Receptor such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of Androgen Receptor. 2. The compound of claim 1 , wherein Wis a 6-member aryl substituted with a CN and a Cl.3. The compound of claim 1 , wherein Q is a 4-member alicyclic group substituted with 4 methyl groups.4. The compound of claim 1 , wherein at least one of: Yis O claim 1 , Yis —NH— claim 1 , and Yis C═O.5. The compound of claim 1 , wherein Wis 6-member aryl or 6-member heteroaryl.6. The compound of claim 1 , wherein Rand Rare independently selected from H claim 1 , methyl or ethyl claim 1 , wherein the ethyl or methyl is optionally substituted by a hydroxyl.9. The compound of claim 1 , wherein Ris isopropyl and Ris an optionally substituted heteroaryl.10. The compound of claim 1 , wherein Ris a methyl group and Xa is S.12. A composition comprising an effective amount of a bifunctional compound of .13. The composition of claim 12 , wherein the composition further comprises a pharmaceutically acceptable carrier.14. A composition comprising an effective amount of a bifunctional compound of claim 11 , and a pharmaceutically acceptable carrier.15. A method of treating prostate cancer in a subject claim 1 , the method comprising administering a composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound as described in to a subject in need thereof claim 1 , wherein the compound is effective in treating ...

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Номер записи: 66
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: 67
22-05-2014 дата публикации

PYRIDAZINONE DERIVATIVES

Номер: US20140142088A1
Автор: Bacon Edward R., Bailey Thomas R., BECKNELL Nadine C., Chatterjee Sankar, Dunn Derek, Hostetler Greg A., HUDKINS Robert L., Josef Kurt A., Knutsen Lars J.S., Tao Ming, Zulli Alison L.
Принадлежит: CEPHALON, INC.

The present invention is directed to novel pyridazinone derivatives that mediate enzymatic activity. In particular, the compounds may be effective in the treatment of diseases or disease states related to the activity of the histamine H3 receptor, including, for example, neurodegenerative disorders, sleep/wake disorders, attention deficit hyperactivity disorder and cognition. 23-. (canceled)4. The compound according to claim 1 , or a stereoisomeric form claim 1 , mixture of stereoisomeric forms claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Y is O.5. (canceled)6. The compound according to claim 1 , or a stereoisomeric form claim 1 , mixture of stereoisomeric forms claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris a 4- to 9-membered heterocycloalkyl ring containing 1 nitrogen atom.7. The compound according to claim 6 , or a stereoisomeric form claim 6 , mixture of stereoisomeric forms claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein Ris a piperidinyl or pyrrolidinyl ring claim 6 , optionally substituted with 1 to 3 Rgroups.8. The compound according to claim 7 , or a stereoisomeric form claim 7 , mixture of stereoisomeric forms claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein the piperidinyl or pyrrolidinyl ring is attached to Y through a ring nitrogen atom.9. The compound according to claim 8 , or a stereoisomeric form claim 8 , mixture of stereoisomeric forms claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein the piperidinyl or pyrrolidinyl ring is substituted with one or two alkyl groups.10. The compound according to claim 7 , or a stereoisomeric form claim 7 , mixture of stereoisomeric forms claim 7 , or a pharmaceutically acceptable salt thereof claim 7 , wherein the piperidinyl ring is attached to Y through a ring carbon atom.11. The compound according to claim 10 , or a stereoisomeric form claim 10 , mixture of stereoisomeric forms ...

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Номер записи: 68
10-03-2016 дата публикации

Novel compounds as diacylglycerol acyltransferase inhibitors

Номер: US20160068487A1
Автор: Mui Cheung, Raghuram S. Tangirala
Принадлежит: GlaxoSmithKline LLC

This invention relates to novel compounds which are inhibitors of acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT-1), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination with weight management therapies or other triglyceride lowering therapy for the prevention or treatment of diseases related to DGAT-1 dysfunction or where modulation of DGAT-1 activity may have therapeutic benefit including but not limited to obesity, obesity related disorders, genetic (Type 1, Type 5 hyperlipidemia) and acquired forms of hypertriglyceridemia or hyperlipoproteinemia-related disorders, caused by but not limited to lipodystrophy, hypothyroidism, medications (beta blockers, thiazides, estrogen, glucocorticoids, transplant) and other factors (pregnancy, alcohol intake), hyperlipoproteinemia, chylomicronemia, dyslipidemia, non-alcoholic steatohepatitis, diabetes, insulin resistance, metabolic syndrome, cardiovascular outcomes, angina, excess hair growth (including syndromes associated with hirsutism), nephrotic syndrome, fibrosis such as mycocardial, renal and liver fibrosis, hepatitis C virus infection and acne or other skin disorders.

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Номер записи: 69
10-03-2016 дата публикации

SUBSTITUTED PYRIDAZINE CARBOXIMIDE COMPOUNDS

Номер: US20160068493A1
Автор: Liang Congxin
Принадлежит:

The new pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases especially against ALK and are useful in treating disorders related to abnormal protein kinase activities such as cancer, neurological and psychiatric diseases. 3. (canceled)5. The compound of formula I in wherein Rand Rtogether with nitrogen form a bi-cyclic heterocyclyl or heteroaryl optionally substituted by 1-3 groups of Z.6. (canceled)7. The compound of claim 4 , wherein Ris hydrogen.8. A compound selected from the following:{5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-aminopyridazin-3-yl}-N-{4-[(4-methylpiperazinyl)carbonyl]phenyl}carboxamide; and{5-[(1S)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-aminopyridazin-3-yl}-N-{4-[(4-methylpiperazinyl)carbonyl]phenyl}carboxamide.9. The compound of wherein the compound is selected from the following:{6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-[4-(morpholin-4-ylcarbonyl)phenyl]carboxamide;{6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-(4-{[4-(2-hydroxyethyl)piperazinyl]carbonyl}phenyl)carboxamide;{6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-{4-[(4-pyrrolidinylpiperidyl)carbonyl]phenyl}carboxamide;{6-Amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-{4-[(4-ethylpiperazinyl)carbonyl]phenyl}carboxamide;{6-Amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-{4-[(4-cyclopropylpiperazinyl)carbonyl]phenyl}carboxamide;N-(4-{[(2R)-2-(pyrrolidinylmethyl)pyrrolidinyl]carbonyl}phenyl) {6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}carboxamide; andN-{4-[((3S,5R)-3,5-dimethylpiperazinyl)carbonyl]phenyl}{6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}carboxamide.10. The compound of claim 2 , wherein the compound is selected from the following:{5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-aminopyridazin-3-yl}-N-{3-fluoro-4-[(4-methylpiperazinyl)carbonyl]phenyl}carboxamide;{5-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy ...

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Номер записи: 70
08-03-2018 дата публикации

THERAPEUTIC COMPOUNDS

Номер: US20180065936A1
Автор: JURUTKA Peter, MARSHALL Pamela, WAGNER Carl
Принадлежит: Arizona Board of Regents on behalf of Arizona State University

The invention provides compounds formula (I) and salts thereof: wherein R1-R4 have any of the values defined in the specification. The compounds are useful for treating conditions including Alzheimer's disease, Parkinson's disease, diabetes, cancer, inflammation, hyperresponsiveness, allergic conditions, asthma, and psychotic disorders such as schizophrenia. The compounds are also useful to lower IL-4, IL-5, or IL-15 levels in an animal. 2. The compound of wherein Ris (C-C)alkyl or (C-C)cycloalkyl-(C-C)alkyl-.3. (canceled)4. The compound of wherein Ris (C-C)alkoxy claim 1 , or (C-C)cycloalkyl-(C-C)alkoxy-.5. (canceled)6. The compound of wherein Ris (C-C)alkyl or (C-C)cycloalkyl-(C-C)alkyl-.7. (canceled)8. The compound of wherein Ris (C-C)alkoxy claim 1 , or (C-C)cycloalkyl-(C-C)alkoxy-.9. (canceled)10. The compound of wherein Ris isopropyl claim 1 , 2-methylpropoxy claim 1 , or cyclopropylmethoxy.11. The compound of wherein Ris isopropyl claim 1 , isopropoxy claim 1 , or 2-methylpropoxy.12. (canceled)13. The compound of wherein Ris ethyl.14. (canceled)18. A pharmaceutical composition comprising a compound as described in or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.19. A method for treating Alzheimer's disease claim 1 , Parkinson's disease claim 1 , diabetes claim 1 , cancer claim 1 , or a psychotic disorder in an animal comprising administering a compound as described in or a pharmaceutically acceptable salt thereof claim 1 , to the animal.2021-. (canceled)22. A method for treating cancer in an animal comprising administering a compound as described in or a pharmaceutically acceptable salt thereof claim 1 , to the animal.2324-. (canceled)25. A method to reduce inflammation or hyperresponsiveness in an animal comprising administering a compound as described in or a pharmaceutically acceptable salt thereof claim 1 , to the animal.26. A method to lower IL-4 claim 1 , IL-5 claim 1 , or IL-15 levels in an animal ...

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Номер записи: 71
11-03-2021 дата публикации

Pharmaceutically Active Compounds

Номер: US20210070708A1
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 ASA

The invention is directed to compounds of general formula (I) 25.-. (canceled)6. A compound according to claim 1 , wherein A represents an optionally substituted five- or six-membered heterocyclic ring.79.-. (canceled)10. A compound according to claim 1 , wherein A represents optionally substituted phenyl.1113.-. (canceled)14. A compound according to claim 1 , wherein Rrepresents a six-membered aliphatic carbocyclic or heterocyclic ring claim 1 , optionally substituted by —(C═O)NRR claim 1 , —SORor optionally substituted alkyl.1540.-. (canceled)41. A compound according to claim 14 , wherein Rand R claim 14 , together with the nitrogen atom to which they are attached claim 14 , form an optionally substituted 5- or 6-membered aromatic or aliphatic heterocyclic ring.42. A compound according to claim 41 , wherein the aromatic or aliphatic heterocyclic ring is optionally substituted by oxo or alkyl.4364.-. (canceled)65. A compound according to claim 1 , wherein Rrepresents an optionally substituted 5- or 6-membered aryl or heteroaryl ring.6679.-. (canceled)80. A compound according to claim 1 , wherein Rand R claim 1 , together with the carbon atom to which they are attached claim 1 , form an optionally substituted cycloalkyl ring claim 1 , optionally containing a heteroatom.81468.-. (canceled)470. A compound according to claim 469 , wherein A is optionally substituted phenyl.472. A compound according to claim 471 , wherein A is optionally substituted phenyl.473475.-. (canceled)478. The method according to claim 477 , wherein the Horner-Wadsworth reaction is carried out using triethyl phosphonoacetate.480. The method according to claim 479 , wherein the hydrogenation is palladium-catalysed hydrogenation. This application is a divisional of U.S. patent application Ser. No. 16/412,590, filed May 15, 2019, which is a divisional of U.S. patent application Ser. No. 15/533,048, filed Jun. 5, 2017, (now U.S. Pat. No. 10,336,702) which is a national phase entry pursuant to 35 U.S ...

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Номер записи: 72
29-05-2014 дата публикации

SPECIFIC CARBOXAMIDES AS KCNQ2/3 MODULATORS

Номер: US20140148468A1
Автор: Bahrenberg Gregor, Kühnert Sven, LUCAS Simon, Schröder Wolfgang
Принадлежит: Grünenthal GmbH

The invention relates to specific carboxamides, to processes for their preparation, to medicaments comprising these compounds and to the use of these compounds in the preparation of medicaments. 3. The compound according to claim 1 , wherein{'sup': '1', 'Arepresents S; and'}{'sup': 2', '12', '13, 'sub': '2', 'claim-text': {'sup': 12', '13, 'wherein Rand Rboth represent H or both represent F.'}, 'Arepresents S, S(═O)or CRR,'}4. The compound according to claim 1 ,wherein{'sup': 3', '7', '4', '7', '5', '7', '6', '7, 'n denotes 1 and Arepresents CR, Arepresents CR, Arepresents CRand Arepresents CR; or'}{'sup': 3', '4', '7', '5', '7', '6', '7, 'n denotes 1 and Arepresents N, Arepresents CR, Arepresents CRand Arepresents CR; or'}{'sup': 3', '7', '4', '5', '7', '6', '7, 'n denotes 1 and Arepresents CR, Arepresents N, Arepresents CRand Arepresents CR; or'}{'sup': 3', '7', '4', '7', '5', '6', '7, 'n denotes 1 and Arepresents CR, Arepresents CR, Arepresents N and Arepresents CR; or'}{'sup': 3', '4', '5', '7', '6', '7, 'n denotes 1 and Arepresents N, Arepresents N, Arepresents CRand Arepresents CR; or'}{'sup': 3', '4', '7', '5', '6', '7, 'n denotes 1 and Arepresents N, Arepresents CR, Arepresents N and Arepresents CR; or'}{'sup': 3', '4', '7', '5', '7', '6, 'n denotes 1 and Arepresents N, Arepresents CR, Arepresents CRand Arepresents N; or'}{'sup': 3', '7', '4', '5', '7', '6, 'n denotes 1 and Arepresents CR, Arepresents N, Arepresents CRand Arepresents N; or'}{'sup': 3', '7', '4', '5', '6', '7, 'n denotes 1 and Arepresents CR, Arepresents N, Arepresents N and Arepresents CR; or'}{'sup': 3', '7', '4', '7', '5', '6, 'n denotes 1 and Arepresents CR, Arepresents CR, Arepresents N and Arepresents N; or'}{'sup': 3', '4', '7', '5', '7, 'n denotes 0 and Arepresents S, Arepresents CRand Arepresents CR;'}or{'sup': 3', '4', '7', '5, 'n denotes 0 and Arepresents S, Arepresents CRand Arepresents N;'}or{'sup': 3', '4', '7', '5', '7, 'n denotes 0 and Arepresents O, Arepresents CRand ...

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Номер записи: 73
15-03-2018 дата публикации

PYRIDAZINE DERIVATIVES AS RORc MODULATORS

Номер: US20180072683A1
Автор: Bronner Sarah M., Crawford James J., Cridland Andrew, FAUBER Benjamin, Gancia Emanuela, Hurley Christopher, Killen Jonathan, Van Niel Monique Bodil, Ward Stuart
Принадлежит: Genentech, Inc.

Compounds of formula I: 2. The compound of claim 1 , wherein:a five or six membered hetereoaryl selected from: oxazolyl; isoxazolyl; oxadiazolyl; thiazolyl; isothiazolyl; thiadiazolyl; triazolyl; pyrrolyl; pyrazolyl; imidazolyl; tetrazolyl; pyridinyl; pyrimidinyl; pyrazinyl; pyridazinyl; and triazinyl; orphenyl.3. The compound of claim 1 , wherein A is a five or six membered hetereoaryl selected from: oxazolyl; isoxazolyl; oxadiazolyl; thiazolyl; triazolyl; pyrrolyl; pyrazolyl; imidazolyl; tetrazolyl; pyridinyl; pyrimidinyl; pyrazinyl; and pyridazinyl.4. The compound of claim 1 , wherein X is —C(O)—.5. The compound of claim 1 , wherein X is —SO—.6. The compound of claim 1 , wherein Y is a bond.7. The compound of claim 1 , wherein Y is Calkylene.8. The compound of claim 1 , wherein Y is methylene.9. The compound of claim 1 , wherein Z is a bond.10. The compound of claim 1 , wherein Z is Calkylene.11. The compound of claim 1 , wherein Z is methylene.12. The compound of claim 1 , wherein m is 0 or 1.13. The compound of claim 1 , wherein Rand Rare halo.14. The compound of claim 1 , wherein Rand Rare fluoro.15. The compound of claim 1 , wherein Ris hydrogen.16. The compound of claim 1 , wherein Ris Calkyl.19. A composition comprising:(a) a pharmaceutically acceptable carrier; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(b) a compound of .'}20. A method for treating a disease selected from rheumatoid arthritis claim 1 , osteoarthritis claim 1 , psoriatic arthritis claim 1 , septic arthritis claim 1 , spondyloarthropathies claim 1 , gouty arthritis claim 1 , juvenile arthritis claim 1 , chronic obstructive pulmonary disease (COPD) claim 1 , asthma claim 1 , bronchospasm claim 1 , Irritable Bowel Syndrome (IBS) claim 1 , Inflammatory Bowel Disease (IBD) claim 1 , psoriasis claim 1 , biliary colic claim 1 , renal colic claim 1 , diarrhea-dominant IBS claim 1 , muscular sclerosis claim 1 , Sjogren's disease claim 1 , lupus claim 1 , and pulmonary fibrosis claim 1 , ...

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Номер записи: 74
15-03-2018 дата публикации

TRANS-CYCLOHEPTENES AND HETERO-TRANS-CYCLOHEPTENES FOR BIOORTHOGONAL COUPLING

Номер: US20180072761A1
Автор: FANG Yinzhi, Fox Joseph, Zhang Han
Принадлежит: University of Delaware

A substituted trans-cycloheptene according to formula (I); wherein: a) Z and L are each selected from the group consisting of SiR, CH, CHOH, and CHR; Ris phenyl or CH; Ris phenyl, CH, (CH)CN, or (CH)OH, wherein n is an integer from 1 to 5; Rand Rare each individually selected from the group consisting of H, OH, and CH; and Z and L are not both SiRR; or b) Z is BocN, L is CH, Ris H, and Ris H; or c) Z is C=0, L is CH, Ris H, and Ris H. 2. The substituted trans-cycloheptene according to claim 1 , wherein Z claim 1 , L claim 1 , R claim 1 , and Rare according to any one of combinations a) through l):{'sub': '2', 'sup': a', 'b, 'a) Z is CHOH, L is CH, Ris H, and Ris H;'}{'sub': 2', '2, 'sup': a', 'b, 'b) Z is CHCHOH, L is CH, Ris H, and Ris H;'}{'sub': 2', '2, 'sup': a', 'b, 'c) Z is CH, L is CH, and Ris OH, and Ris H;'}{'sub': '2', 'sup': a', 'b, 'd) Z is CH, L, is CHOH, Ris OH, and Ris H;'}{'sub': '2', 'sup': a', 'b, 'e) Z is BocN, L, is CH, Ris H, and Ris H;'}{'sub': '2', 'sup': a', 'b, 'f) Z is C═O, L is CH, Ris H, and Ris H;'}{'sup': 1', '2', 'a', 'b', '1', '2, 'sub': 2', '3', '2', '3', '2', '4, 'g) Z is SiRR, L is CH, Ris H, Ris H, Ris CH, and Ris either (CH)CN or (CH)OH;'}{'sub': 3', '2', '3', '2', '3', '3, 'sup': a', 'b, 'h) Z is SiCH(CH)OH, L is CH, Ris CH, and Ris CH;'}{'sub': 2', '2, 'sup': a', 'b, 'i) Z is SiPh, L is CH, Ris H, and Ris H;'}{'sub': 3', '2', '2, 'sup': a', 'b, 'j) Z is Si(CH), L is CH, Ris OH, and Ris H;'}{'sub': 2', '2, 'sup': a', 'b, 'k) is CH, L is SiPh, Ris H, and Ris H;'}{'sub': 2', '3', '2', '4, 'sup': a', 'b, 'l) Z is CH, L is SiCH(CH)OH, Ris H, and Ris H.'}3. An adduct of the substituted trans-cycloheptene according to with a molecule selected from the group consisting of tetrazines claim 1 , ketenes claim 1 , conjugated dienes claim 1 , and 1 claim 1 ,3-dipoles.4. The adduct according to claim 3 , wherein the molecule is a tetrazine.5. The adduct according to claim 3 , wherein the molecule is a ketene.6. The adduct according to claim ...

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Номер записи: 75
05-03-2020 дата публикации

AMIDE-SUBSTITUTED HETEROCYCLIC COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFN ALPHA RESPONSES

Номер: US20200071315A1
Автор: Batt Douglas G., Kumar Amit, Lin Shuqun, Liu Chunjian, Liu Qingjie, Moslin Ryan M., Spergel Steven H., Tokarski John S., Weinstein David S., Wrobleski Stephen T., Yanlei Yanlei
Принадлежит:

Compounds having the following formula I: 2. The method according to claim 1 , wherein the composition is in the form of a tablet claim 1 , a capsule claim 1 , granules claim 1 , a powder claim 1 , or a liquid formulation.3. The method according to claim 2 , wherein the composition is in the form of a tablet.4. The method according to claim 2 , wherein the composition is in the form of a capsule.5. The method according to claim 2 , wherein the composition is in the form of granules.6. The method according to claim 2 , wherein the composition is in the form of a powder.7. The method according to claim 2 , wherein the composition is in the form of a liquid formulation.8. The method according to claim 7 , wherein the composition is in the form of a syrup.9. The method according to claim 1 , wherein the composition is orally administered to the subject 1 to 4 times per day.10. The method according to claim 9 , wherein the composition is in the form of a tablet.12. The method according to claim 11 , wherein 1 tablet per day is administered to the subject.13. The method according to claim 11 , wherein 2 tablets per day are administered to the subject.15. The method according to claim 14 , wherein 1 tablet per day is administered to the subject.16. The method according to claim 14 , wherein 2 tablets per day are administered to the subject. This invention relates to compounds useful in the modulation of IL-12, IL-23 and/or IFNα by acting on Tyk-2 to cause signal transduction inhibition. Provided herein are amide-substituted heterocyclic compounds, compositions comprising such compounds, and methods of their use. The invention further pertains to pharmaceutical compositions containing at least one compound according to the invention that are useful for the treatment of conditions related to the modulation of IL-12, IL-23 and/or IFNα in a mammal.The heterodimeric cytokines interleukin (IL)-12 and IL-23, which share a common p40 subunit, are produced by activated antigen- ...

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Номер записи: 76
18-03-2021 дата публикации

NEPRILYSIN INHIBITORS

Номер: US20210079017A1
Автор: Fleury Melissa, Gendron Roland, Hughes Adam D.
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

In one aspect, the invention relates to compounds having the formula: 128-. (canceled)30. The method of claim 29 , wherein the disease is selected from hypertension claim 29 , heart failure claim 29 , and renal disease.31. The method of claim 29 , further comprising administering a therapeutic agent selected from an ATreceptor antagonist claim 29 , an angiotensin-converting enzyme inhibitor claim 29 , a phosphodiesterase inhibitor claim 29 , a renin inhibitor claim 29 , and a diuretic claim 29 , or a combination thereof.32. The method of claim 29 , further comprising administering an ATreceptor antagonist claim 29 , wherein the ATreceptor antagonist is selected from abitesartan claim 29 , azilsartan claim 29 , azilsartan medoxomil claim 29 , benzyllosartan claim 29 , candesartan claim 29 , candesartan cilexetil claim 29 , elisartan claim 29 , embusartan claim 29 , enoltasosartan claim 29 , eprosartan claim 29 , EXP3174 claim 29 , fonsartan claim 29 , forasartan claim 29 , glycyllosartan claim 29 , irbesartan claim 29 , isoteoline claim 29 , losartan claim 29 , milfasartan claim 29 , olmesartan claim 29 , olmesartan medoxomil claim 29 , opomisartan claim 29 , pratosartan claim 29 , ripisartan claim 29 , saprisartan claim 29 , saralasin claim 29 , sarmesin claim 29 , TAK-591 claim 29 , tasosartan claim 29 , telmisartan claim 29 , valsartan claim 29 , and zolasartan.33. The method of claim 29 , wherein Ris —OR; and Ris selected from H and —Calkyl.34. The method of claim 29 , wherein Ris H.35. The method of claim 29 , wherein X is selected from oxazole and isoxazole.36. The method of claim 29 , wherein Ris selected from H claim 29 , —Calkylene-OH claim 29 , —Calkyl claim 29 , and —Calkylene-O—Calkyl; and Ris H.37. The method of claim 29 , wherein a is 0; b is 0 claim 29 , 1 or 2; and each Ris independently selected from halo.38. The method of claim 29 , wherein Ris —OR; Ris selected from H and —Calkyl; Ris H; X is selected from oxazole and isoxazole; Ris selected from H ...

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Номер записи: 77
24-03-2016 дата публикации

Herbicidally active 2-(substituted-phenyl)-cyclopentane-1,3-dione compounds and derivatives thereof

Номер: US20160081334A1
Автор: ASPINALL Ian Henry, Avery Alaric James, Black Janice, BRIGGS Emma, CLOUDSDALE Ian Stuart, Dickson, Hachisu Shuji, Hardy Simon, JR. John Kenneth, Taylor John Benjamin, Viner Russell Colin, Wailes Jeffery Steven
Принадлежит: SYNGENTA LIMITED

The present invention relates to a compound of formula (I): wherein the substituents are as defined herein, and wherein the compound of formula (I) is optionally present as an agrochemically acceptable salt thereof. These compounds are thought to be suitable for use as herbicides. The invention therefore also relates to a method of controlling weeds, especially grassy monocotyledonous weeds, in crops of useful plants, comprising applying a compound of formula (I), or a herbicidal composition comprising such a compound, to the plants or to the locus thereof. 4. The compound of , wherein G is hydrogen; an agriculturally acceptable metal , or an agriculturally acceptable sulfonium or ammonium group; or G is —C(X)—Ror —C(X)—X—R , wherein X , R , X , Xand Rare as defined in .5. The compound of claim 4 , wherein:{'sup': a', 'a', 'b', 'c', 'b, 'when G is —C(X)—Ror —C(X)—X—R, then'}{'sup': a', 'b, 'Xand Xare oxygen,'}{'sup': 'c', 'Xis oxygen or sulfur,'}{'sup': 'a', 'sub': 1', '10', '2', '6', '2', '6', '3', '6', '1', '4', '1', '4', '3', '6', '1', '2', '1', '3', '1', '2', '1', '3', '1', '2', '1', '3', '1', '2', '1', '3', '1', '2, 'Ris C-Calkyl, C-Calkenyl, C-Calkynyl, C-Ccycloalkyl, C-CalkoxyC-Calkyl, C-Ccycloalkyl(C-C)alkyl, or phenyl or phenyl substituted by 1, 2 or 3 of, independently, C-Calkyl, C-Cfluoroalkyl, C-Calkoxy, C-Cfluoroalkoxy, fluorine, chlorine, bromine, cyano or nitro, or a monocyclic 5- or 6-membered heteroaryl or a monocyclic 5- or 6-membered heteroaryl substituted by 1, 2 or 3 of, independently, C-Calkyl, C-Cfluoroalkyl, C-Calkoxy, C-Cfluoroalkoxy, fluorine, chlorine, bromine or cyano; and'}{'sup': 'b', 'sub': 1', '10', '2', '5', '2', '2', '4', '2', '5', '2', '2', '4', '3', '6', '1', '4', '1', '4', '3', '6', '1', '2', '1', '3', '1', '2', '1', '3', '1', '2', '1', '3', '1', '2', '1', '3', '1', '2, 'Ris C-Calkyl, C-Calkenyl-CH—, C-Calkenyl-CH(Me)-, C-Calkynyl-CH—, C-Calkynyl-CH(Me)-, C-Ccycloalkyl, C-CalkoxyC-Calkyl, C-Ccycloalkyl(C-C)alkyl, or phenyl or ...

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Номер записи: 78
14-03-2019 дата публикации

HISTONE DEMETHYLASE INHIBITORS

Номер: US20190077758A1
Автор: Chen Young K., Kanouni Toufike, Nie Zhe, Stafford Jeffrey Alan, Veal James Marvin, Wallace Michael Brennan
Принадлежит: CELGENE QUANTICEL RESEARCH, INC.

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted amidopyridine or amidopyridazine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like. 2. The compound or pharmaceutically acceptable salt of claim 1 , wherein R is hydrogen.3. The compound or pharmaceutically acceptable salt of claim 1 , wherein R is optionally substituted alkyl.4. A pharmaceutical composition comprising a pharmaceutical acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.5. A method of treating a histone demethylase-associated cancer in a subject in need thereof comprising administering to the subject the pharmaceutical composition of .6. A method of inhibiting a histone demethylase enzyme comprising contacting the histone demethylase enzyme with the compound of or a pharmaceutically acceptable salt thereof.7. A compound claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , selected from the group consisting of:3-[(2-cyclopropylbenzyl)amino]pyridine-4-carboxylic acid;3-[(4-chloro-2-methoxybenzyl)amino]pyridine-4-carboxylic acid;3-[(4-chloro-2-hydroxybenzyl)amino]pyridine-4-carboxylic acid;3-[(2-aminobenzyl)amino]pyridine-4-carboxylic acid;3-[(4-bromobenzyl)amino]pyridine-4-carboxylic acid;3-[(4-methylbenzyl)amino]pyridine-4-carboxylic acid;3-[(4-cyclopropylbenzyl)amino]pyridine-4-carboxylic acid;3-[(4-chloro-2-cyclopropylbenzyl)amino]pyridine-4-carboxylic acid;3-{[2-cyclopropyl-4-(trifluoromethyl)benzyl]amino}pyridine-4-carboxylic acid;3-[(naphthalene-1-ylmethyl)amino]pyridine-4-carboxylic acid;3-[(1H-indol-7-ylmethyl)amino]pyridine-4-carboxylic acid;3-[(2- ...

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Номер записи: 79
31-03-2022 дата публикации

NOVEL CDK 8/19 INHIBITORS

Номер: US20220098160A1
Автор: "CHESTNOVA Anna Jurevna", ALAFINOV Andrei Ivanovich, GORBUNOVA Svetlana Leonidovna, KASATKINA Mariia Andreevna, KOZHEMYAKINA Natalia Vladimirovna, KUSHAKOVA Anna Sergeevna, MAKSIMENKO Elena Aleksandrovna, MIKHAYLOV Leonid Evgen`evich, MINDICH Aleksei Leonidovich, MISHINA Mariia Sergeevna, MOROZOV Dmitry Valentinovich, POPKOVA Aleksandra Vladimirovna, SHEKHAUTSOU Artsiom Evgenievich
Принадлежит:

The present invention relates to novel compounds of formula (1), which have the properties of a CDK8/19 inhibitor, and to a pharmaceutical composition containing said compounds, and to the use of said compounds and composition as pharmaceutical preparations for treating diseases or disorders. 2. The compound according to wherein if Xis CR claim 1 , Xis CR claim 1 , and Xis N claim 1 , then X claim 1 , X claim 1 , Xrepresent CH;{'sub': ['1', '1', '2', '3', '4', '5', '6'], '#text': 'if Xis CR, and X, Xare N, then X, X, Xrepresent CH;'}{'sub': ['2', '2', '1', '3', '4', '5', '6'], '#text': 'if Xis CR, and X, Xare N, then X, X, Xrepresent CH;'}{'sub': ['1', '1', '2', '4', '3', '5', '6'], '#text': 'if Xis CR, and X, Xare N, then X, X, Xrepresent CH;'}{'sub': ['1', '1', '2', '2', '3', '5', '4', '6'], '#text': 'if Xis CR, Xis CR, and X, Xare N, then X, Xrepresent CH;'}{'sub': ['1', '1', '2', '2', '3', '4', '5', '6'], '#text': 'if Xis CR, Xis CR, and X, Xare N, then X, Xrepresent CH;'}{'sub': ['1', '1', '2', '2', '3', '6', '4', '5'], '#text': 'if Xis CR, Xis CR, and X, Xare N, then X, Xrepresent CH.'}5. The compound according to claim 3 , wherein if Xis CRand Xis N claim 3 , then X claim 3 , X claim 3 , Xrepresent CH;{'sub': ['2', '3', '4', '5', '6'], '#text': 'if X, Xare N, then X, X, Xrepresent CH;'}{'sub': ['2', '4', '3', '5', '6'], '#text': 'if X, Xare N, then X, X, Xrepresent CH;'}{'sub': ['2', '2', '3', '5', '4', '6'], '#text': 'if Xis CR, and X, Xare N, then X, Xrepresent CH;'}{'sub': ['2', '2', '3', '4', '5', '6'], '#text': 'if Xis CR, and X, Xare N, then X, Xrepresent CH;'}{'sub': ['2', '2', '3', '6', '4', '5'], '#text': 'if Xis CR, and X, Xare N, then X, Xrepresent CH.'}6. The compound according to claim 1 , wherein Y is —NH— claim 1 , —O— claim 1 , or —S—; and Z is —CH—.7. The compound according to claim 1 , which represents:2-methoxy-4-((2-(6-(4-methylpiperazin-1-carbonyl)naphth-2-yl)ethyl)amino)quinazolin-6-carbonitrile (1)2-(dimethylamino)-4-((2-(6-(4- ...

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Номер записи: 80
12-03-2020 дата публикации

POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4

Номер: US20200079756A1
Автор: Conn P. Jeffrey, Engers Darren W., Engers Julie L., Lindsley Craig W., Long Madeline F.
Принадлежит:

Disclosed herein are 2,4-dimethylquinoline-6-carboxamide compounds and 3,4-dimethylcinnoline-6-carboxamide compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M(mAChR M). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , whereinX is N.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': '1', 'X is CR.'}4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein{'sup': '1', 'sub': 1', '4, 'Ris C-Calkyl.'}5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein{'sup': '1', 'Ris methyl.'}6. The compound of any one of - claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein{'sup': '2', 'Ris hydrogen.'}9. The compound of any one of - claim 4 , or a pharmaceutically acceptable salt thereof claim 4 , wherein{'sup': '3', 'Ris hydrogen; and'}{'sup': 4', 'b', 'c, 'sub': 'n', 'Ris selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heteroalkyl, heterocycle, and —(CRR)—Y, each of which may be optionally substituted.'}10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof claim 9 , wherein{'sup': 4', 'b', 'c, 'sub': 3', '6', 'n, 'Ris selected from the group consisting of a 3- to 6-membered heterocycle having one heteroatom selected from N and O, C-Ccycloalkyl, and —(CRR)—Y;'}n is 1 or 2;{'sup': b', 'c, 'Rand Rare each hydrogen; and'}Y is selected from the group consisting of aryl and a 5- to 6-membered heteroaryl having 1 or 2 heteroatoms independently selected from N, O and S;{'sub': 1', '4', '1', '4', '1', '4', '1', '4', '3', ...

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Номер записи: 81
29-03-2018 дата публикации

THERAPEUTIC COMPOUNDS AND USES THEREOF

Номер: US20180086720A1
Автор: Albrecht Brian K., CÔTÉ Alexandre, Crawford Terry, Duplessis Martin, Good Andrew Charles, LEBLANC Yves, Magnuson Steven R., Nasveschuk Christopher G., Romero Anthony F., Tang Yong, Taylor Alexander M.
Принадлежит:

The present invention relates to compounds of formula (I): 2. The compound of wherein Ris 2-hydroxy phenyl that is optionally substituted with one or more groups independently selected from the group consisting of halo.34-. (canceled)5. The compound of wherein Ris H claim 1 , methyl claim 1 , or acetyl; and Ris H.6. (canceled)7. The compound of wherein Ris a 3-15 membered heterocyclyl that is optionally substituted with one or more groups independently selected from the group consisting of R claim 1 , oxo claim 1 , halo claim 1 , —NO claim 1 , —N(R) claim 1 , —CN claim 1 , —C(O)—N(W) claim 1 , —S(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —S—R claim 1 , —O—C(O)—R claim 1 , —C(O)—R claim 1 , —C(O)—R claim 1 , —S(O)—R claim 1 , —S(O)—R claim 1 , —N(R)—C(O)—R claim 1 , —N(R)—S(O)—R claim 1 , —N(R)—C(O)—N(R) claim 1 , and —N(R)—S(O)—R.9. The compound of wherein Ris an N-linked 3-15 membered heterocyclyl that is optionally substituted with one or more groups independently selected from the group consisting of R claim 1 , oxo claim 1 , halo claim 1 , —NO claim 1 , —N(R) claim 1 , —CN claim 1 , —C(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —S(O)—N(R) claim 1 , —S—R claim 1 , —O—C(O)—R claim 1 , —C(O)—R claim 1 , —C(O)—OR claim 1 , —S(O)—R—S(O)—R claim 1 , —N(R)—C(O)—R claim 1 , —N(R)—S(O)—R claim 1 , —N(R)—C(O)—N(R) claim 1 , and —N(R)—S(O)—R.11. The compound of wherein Ris —O—R.13. The compound of wherein Ris —N(R).15. The compound of wherein Ris selected from the group consisting of —Rand —C(O)—N(R).21. (canceled)23. A composition comprising a compound of formula (I) as described in claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable adjuvant claim 1 , carrier claim 1 , or vehicle.2425-. (canceled)26. A method for treating a BRG1-mediated disorder claim 1 , a BRM-mediated disorder and/or a PB1-mediated disorder in an animal comprising administering a compound of formula (I) as described in claim 1 , or a pharmaceutically acceptable ...

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Номер записи: 82
05-05-2022 дата публикации

CINNOLINIUM COMPOUNDS FOR USE IN A METHOD OF CONTROLLING UNWANTED PLANT GROWTH

Номер: US20220132847A1
Автор: Scutt James Nicholas, WILLETTS Nigel James
Принадлежит: SYNGENTA CROP PROTECTION AG

The present invention relates to herbicidally active cinnolinium 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, in crops of useful plants.

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Номер записи: 83
09-04-2015 дата публикации

NOVEL TETRAZINES AND METHOD OF SYNTHEZISING THE SAME

Номер: US20150099277A1
Автор: Devaraj Neal K., Seckute Jolita, YANG Jun
Принадлежит:

Provided herein, inter alia, are compositions and methods of synthesis and detection of tetrazines and diazonorcaradienes. 3. The method of claim 2 , wherein said contacting is in a cell.4. The method of claim 3 , further comprising detecting said diazonorcaradiene.5. The method of claim 4 , wherein one of R claim 4 , Rand Ris a detectable moiety.6. The method of claim 5 , wherein said detectable moiety is a fluorophore claim 5 , a radionuclide claim 5 , or a magnetic contrast agent.7. The method of claim 4 , wherein one of R claim 4 , Rand Ris a biomolecule moiety.8. The method of claim 7 , wherein said biomolecule moiety is attached to a detectable moiety.9. The method of claim 8 , wherein said biomolecule moiety is a nucleotide moiety claim 8 , a polynucleotide moiety claim 8 , an amino acid moiety claim 8 , a polypeptide moiety claim 8 , a protein moiety claim 8 , a glycan moiety claim 8 , a lipid moiety claim 8 , a glycolipid moiety or a polysaccharide moiety.10. The method of claim 9 , wherein said biomolecule is RNA moiety or DNA moiety.1112-. (canceled)13. The method of claim 9 , wherein said biomolecule is a protein moiety or polypeptide moiety.1518-. (canceled)19. The method of claim 14 , wherein Ris methyl.20. The method of claim 14 , wherein Ris a detectable moiety.21. The method of claim 20 , wherein said detectable moiety is a fluorophore claim 20 , a radionucleotide claim 20 , or a magnetic contrast agent.22. The method of claim 14 , wherein Ris a biomolecule moiety.23. The method of claim 22 , wherein said biomolecule is a nucleotide moiety claim 22 , a polynucleotide moiety claim 22 , an amino acid moiety claim 22 , a polypeptide moiety claim 22 , a protein moiety claim 22 , a glycan moiety claim 22 , a lipid moiety claim 22 , a glycolipid moiety claim 22 , or a polysaccharide moiety.24. The method of claim 23 , wherein said biomolecule is RNA moiety or DNA moiety.2526-. (canceled)27. The method of claim 23 , wherein said biomolecule is a protein ...

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Номер записи: 84
09-04-2015 дата публикации

Alpha 7 Nicotinic Acetylcholine Receptor Allosteric Modulators, Their Derivatives and Uses Thereof

Номер: US20150099758A1
Автор: Dasse Olivier, Putnam David
Принадлежит: Anvyl LLC

The present application is related to compounds represented by Formula I, which are novel positive allosteric modulators of al nAChRs. The application also discloses the treatment of disorders that are responsive to enhancement of acetylcholine action on al nAChRs in a mammal by administering an effective amount of a compound of Formula I. 8. The compound of wherein:{'sup': 9', '12, 'Rand Rare hydrogen; and pharmaceutically acceptable salts and prodrugs thereof.'}9. The compound of wherein:{'sup': 17', '13, 'Xis CR;'}{'sup': 18', '14, 'Xis CR;'}{'sup': 19', '15, 'Xis CR;'}and pharmaceutically acceptable salts and prodrugs thereof.10. The compound of wherein:{'sup': 17', '13, 'Xis CR;'}{'sup': 18', '14, 'Xis CR;'}{'sup': '19', 'Xis N;'}and pharmaceutically acceptable salts and prodrugs thereof.11. The compound of wherein:{'sup': '17', 'Xis N;'}{'sup': 18', '14, 'Xis CR;'}{'sup': 19', '15, 'Xis CR;'}and pharmaceutically acceptable salts and prodrugs thereof.12. The compound of wherein:{'sup': 17', '13, 'Xis CR;'}{'sup': '18', 'Xis N;'}{'sup': 19', '15, 'Xis CR;'}and pharmaceutically acceptable salts and prodrugs thereof.14. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or prodrug thereof claim 1 , and a pharmaceutically acceptable carrier or diluent.15. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from:[2-(benzylamino)pyridin-3-yl](5-chloro-2,3-dihydro-1H-indol-1-yl)methanone (compound 1);(5-chloro-2,3-dihydro-1H-indol-1-yl)[2-(phenylamino)pyridin-3-yl]methanone (compound 2);(5-chloro-2,3-dihydro-1H-indol-1-yl)[2-[(pyridin-2-ylmethyl)amino]pyridin-3-yl]-methanone (compound 3);(5-chloro-2,3-dihydro-1H-indol-1-yl)[2-[(2-phenylethyl)amino]pyridin-3-yl]methanone (compound 4);(5-chloro-2,3-dihydro-1H-indol-1-yl)[2-[(pyridin-3-ylmethyl)amino]pyridin-3-yl]-methanone (compound 5);(5-chloro-2,3-dihydro-1H-indol-1-yl)[2-[[2-(pyridin-2-yl)ethyl]amino]-pyridin-3-yl]- ...

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Номер записи: 85
12-04-2018 дата публикации

Molecules haveing pesticidal utiliy and intermediates, compositions and processes related thereto

Номер: US20180098541A1
Автор: Alex Nolan, David A. Demeter, John F. Daeuble, SR., Joseph D. Eckelbarger, Kaitlyn Gray, Nicolaas Vermeulen, Ricky Hunter, Ronald J. Heemstra, Ronald Ross, Jr., Timothy P. Martin, Tony K. Trullinger
Принадлежит: DOW AGROSCIENCES LLC

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”).

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Номер записи: 86
16-04-2015 дата публикации

Cyclopentylacrylamide derivative

Номер: US20150105581A1
Автор: Masanori Takadoi, Masanori Yamamoto, Yasumichi Fukuda, Yoshikazu Asahina
Принадлежит: Kyorin Pharmaceutical Co Ltd, Teijin Pharma Ltd

A compound having a hypoglycemic effect is provided. The compound and a pharmaceutically acceptable salt thereof are useful for the treatment or prevention of diabetes, obesity, and the like. The compound is represented by the general formula (1): (wherein R 1 and R 2 are each independently a hydrogen atom, a halogen atom, an amino group, a hydroxyl group, a hydroxyamino group, a nitro group, a cyano group, a sulfamoyl group, a C 1 to C 6 alkyl group, a C 1 to C 6 alkoxy group, a C 1 to C 6 alkylsulfanyl group, a C 1 to C 6 alkylsulfinyl group, a C 1 to C 6 alkylsulfonyl group, or a C 1 to C 6 alkoxy-C 1 to C 6 alkylsulfonyl group, and A is a substituted or unsubstituted heteroaryl group).

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Номер записи: 87
13-04-2017 дата публикации

ANDROGEN RECEPTOR ANTAGONISTS

Номер: US20170101384A1
Автор: Cortez Felipe de Jesus, ENGLAND Pamela M., Fletterick Robert J., Kuchenbecker Kristopher
Принадлежит:

Disclosed herein are compositions and methods for modulating the androgen receptor. 3. The compound of claim 2 , wherein Ring A is a 6 membered heteroaryl.4. The compound of claim 2 , wherein Ring A is a 6 membered heteroaryl not comprising an ortho heteroatom.12. The compound of claim 2 , wherein Ring B is a phenyl.13. The compound of claim 2 , wherein Ring B is a heteroaryl.14. The compound of claim 2 , wherein Ring B is a 6 membered heteroaryl.15. The compound of claim 2 , wherein Ris independently a halogen claim 2 , —CX claim 2 , —C(O)NHCH claim 2 , substituted or unsubstituted C-Calkyl claim 2 , substituted or unsubstituted 2 to 5 membered heteroalkyl claim 2 , substituted or unsubstituted C-Ccycloalkyl claim 2 , substituted or unsubstituted 3 to 6 membered heterocycloalkyl claim 2 , substituted or unsubstituted phenyl claim 2 , or substituted or unsubstituted 5 to 6 membered heteroaryl.18. The compound of claim 1 , wherein said compound is an antagonist of a nuclear receptor.19. The compound of claim 1 , wherein said compound is an antagonist of an androgen receptor.20. A pharmaceutical composition comprising a compound of one of to or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable excipient.21. The pharmaceutical composition of claim 20 , comprising a therapeutically effective amount of said compound.22. An androgen receptor protein covalently bound to an androgen receptor inhibitor claim 20 , wherein said compound is covalently bound to a cysteine residue of said androgen receptor protein.23. An androgen receptor protein covalently bound to a compound of one of to claim 20 , wherein said compound is covalently bound to a cysteine residue of said androgen receptor protein.24. A human androgen receptor protein covalently bound to a compound of one of to claim 20 , wherein said compound is covalently bound to Cys784 of said human androgen receptor protein.25. A compound of one of to claim 20 , or a pharmaceutically ...

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Номер записи: 88
21-04-2016 дата публикации

Novel Substituted Bicyclic Aromatic Compounds as S-Nitrosoglutathione Reductase Inhibitors

Номер: US20160108011A1
Автор: Qiu Jian, Stout Adam, Sun Xicheng
Принадлежит:

The present invention is directed to novel substituted bicyclic aromatic compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same. 4. The compound of wherein Ris hydrogen.5. The compound of where Ris hydrogen.8. The compound of where A is COOH.11. The compound of wherein A is COOH.12. Use of a compound of the Formula 1 as defined in or a pharmaceutically acceptable salt thereof as a GSNOR inhibitor.13. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to together with a pharmaceutically accepted carrier or excipient.14. A method of treatment of a disease or condition which comprises administering a therapeutically effective amount of a compound of Formula 1 as defined in to a patient in need thereof wherein the disease or condition is a pulmonary disorder.15. The method of wherein the disease or condition is selected from the group consisting of asthma claim 14 , chronic obstructive pulmonary disorder (COPD) and cystic fibrosis.16. A method of treatment of a disease or condition which comprises administering a therapeutically effective amount of a compound of Formula 1 as defined in to a patient in need thereof wherein the disease or condition is an inflammatory disease.17. The method of wherein the disease or condition is inflammatory bowel disease (IBD).18. A method of making a pharmaceutical composition comprising combining a compound of Formula 1 as defined in with a pharmaceutically acceptable carrier or excipient. This application is a continuation of U.S. application Ser. No. 13/991,973, filed Jun. 6, 2013. U.S. application Ser. No. 13/991,973 is a 35 U.S.C. §371 national phase application of PCT/US2011/065502, filed Dec. 16, 2011 (WO 2012/083171). PCT/US2011/065502 claims priority to U.S. Provisional Application Ser. No. 61/423,799, filed Dec. 16, 2010. Each of these applications is incorporated hereby ...

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Номер записи: 89
28-04-2016 дата публикации

alpha-SUBSTITUTED GLYCINAMIDE DERIVATIVE

Номер: US20160115119A1
Автор: Hirasawa Hideaki, Kawamura Naohiro, KOBAYASHI Junichi
Принадлежит: KISSEI PHARMACEUTICAL CO., LTD.

The present invention is to provide a novel α-substituted glycinamide derivative, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the same, and a pharmaceutical use thereof. 2. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein X is CH; and n is 1.4. The compound according to or a pharmaceutically acceptable salt thereof claim 3 , wherein Y is —CRR—.7. The compound according to or a pharmaceutically acceptable salt thereof claim 6 , wherein Ais a group selected from the group consisting of the following d1) and e):{'sub': 1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '7-10, 'd1) phenyl, wherein the ring is unsubstituted or substituted with 1 to 2 substituents independently selected from the group consisting of the following: a halogen atom, hydroxy, Calkyl, Calkoxy, hydroxy-Calkoxy, halo-Calkyl, halo-Calkoxy, cyano, amino, nitro, carboxy, (Calkyl)carbonylamino, (Calkyl)carbonyloxy, (Calkyl)carbonyl and (Caralkyloxy)carbonyl, and'}{'sub': 1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '7-10', '1-6', '1-6', '2-6', '1-6, 'e) heterocycle, wherein the ring is unsubstituted or substituted with 1 to 2 substituents independently selected from the group consisting of the following: a halogen atom, hydroxy, Calkyl, Calkoxy, halo-Calkyl, halo-Calkoxy, cyano, mono(di)Calkylamino, Calkylsulfanyl, amino, (Caralkyloxy)carbonyl, hydroxy-Calkyl, hydroxy-Calkoxy, Calkenyl, morpholino and (Calkyl)carbonyl.'}8. The compound according to or a pharmaceutically acceptable salt thereof claim 7 , wherein Ais a group selected from the group consisting of the following a2) claim 7 , b1) and c1):{'sub': 1-6', '1-6', '1-6, 'a2) phenyl, wherein the ring is unsubstituted or substituted with 1 to 2 substituents independently selected from the group consisting of the following: a halogen atom, hydroxy, hydroxy-Calkyl, cyano, amino, mono(di)Calkylamino and Calkoxy,'}b1) thiazolyl, and{'sub': 1-6', '1-6, 'c1) a group ...

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Номер записи: 90
28-04-2016 дата публикации

N-(HETEROARYL)-SULFONAMIDE DERIVATIVES USEFUL AS S100-INHIBITORS

Номер: US20160115158A1
Автор: EAST Stephen, FRITZSON Ingela, LIBERG David, MACKINNON Colin, PREVOST Natacha
Принадлежит:

A compound of formula (I), or a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising the compound. The compound is an inhibitor of interactions between S100A9 and interaction partners such as RAGE, TLR4 and EMMPRIN and as such is useful in the treatment of disorders such as cancer, autoimmune disorders, inflammatory disorders and neurodegenerative disorders. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H or halogen and Ris halogen or cyano.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H or halogen claim 1 , and Ris H claim 1 , C1-C3 alkyl optionally substituted with one or more F; or C1-C3 alkoxy optionally substituted with one or more F.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare halogens.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Y is CR.9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein W is N.10. (canceled)11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein X is N.12. The compound of claim 9 , or a pharmaceutically acceptable salt thereof claim 9 , wherein W and X are N.13. (canceled)14. The compound of claim 11 , or a pharmaceutically acceptable salt thereof claim 11 , wherein Y is CH claim 11 , Z is CR claim 11 , and Ris halogen.15. The compound of claim 12 , or a pharmaceutically acceptable salt thereof claim 12 , wherein Y is CR claim 12 , Z is CH claim 12 , and Ris halogen or S(O)C1-C3 alkyl.16. (canceled)17. (canceled)18. (canceled)19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein m is 1 and Ris H.20. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein m is 0.22. (canceled)23. A pharmaceutical composition comprising a compound according to claim 1 , or a ...

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Номер записи: 91
30-04-2015 дата публикации

HISTONE DEMETHYLASE INHIBITORS

Номер: US20150119397A1
Автор: Chen Young K., Kanouni Toufike, Nie Zhe, Stafford Jeffrey Alan, Veal James Marvin, Wallace Michael Brennan
Принадлежит:

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted amidopyridine or amidopyridazine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like. 121.-. (canceled)2524. The method of any one of - claims 22 , wherein Q is —COR claims 22 , and R is hydrogen.2624. The method of any one of - claims 22 , wherein Q is —C(O)N(H)CN.2724. The method of any one of - claims 22 , wherein Q is —C(O)N(H)OH.2824. The method of any one of - claims 22 , wherein Q is tetrazolyl.2924. The method of any one of - claims 22 , wherein Q is —COR and R is optionally substituted alkyl.30. The method of claim 22 , wherein Y is optionally substituted tetralinyl.31. The method of claim 22 , wherein Y is optionally substituted tetrahydroquinolinyl.32. The method of claim 22 , wherein Y is substituted pyridyl.33. The method of claim 22 , wherein Y is optionally substituted naphthyl.34. The method of claim 22 , wherein Y is optionally substituted indolyl.35. The method of claim 22 , wherein Y is optionally substituted benzofuranyl.36. The method of claim 22 , wherein Y is optionally substituted adamantyl.37. The method of claim 22 , wherein Y is optionally substituted indanyl.4241. The method of any one of - claims 39 , wherein Q is —COR claims 39 , and R is hydrogen.4341. The method of any one of - claims 39 , wherein Q is —C(O)N(H)CN.4441. The method of any one of - claims 39 , wherein Q is —C(O)N(H)OH.4541. The method of any one of - claims 39 , wherein Q is tetrazolyl.4641. The method of any one of - claims 39 , wherein Q is —COR and R is optionally substituted alkyl.47. The method of claim 39 , wherein Y is ...

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Номер записи: 92
27-04-2017 дата публикации

INHIBITORS OF THE WNT SIGNALLING PATHWAYS

Номер: US20170114070A1
Автор: BASTING Daniel, Bender Eckhard, Geisler Jens, GIESE Anja, Golz Stefan, Hägebarth Andrea, Lienau Philip, Liu Ningshu, Mönning Ursula, MÖWES Manfred, Puehler Florian, Schneider Dirk, SCOTT William, SIEGEL Franziska, Thede Kai, Zorn Ludwig
Принадлежит:

The present invention relates to inhibitors of the Wnt signalling pathways of general formula (I) as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative disorder, as a sole agent or in combination with other active ingredients. 4. A compound according to , or , wherein Rrepresents a hydrogen atom.5. A compound according to , , or , wherein Rrepresents a hydrogen atom.6. A compound according to , , , or , wherein Rrepresents a group selected from: C-C-alkyl- , C-C-alkoxy- , C-C-cycloalkoxy- , halo- , hydroxy- , fluoro-C-C-alkyl- , fluoro-C-C-alkoxy- , phenyl- , 5- to 6-membered heteroaryl- , cyano- , —C(═O)—O—C-C-alkyl , —C(═O)—N(R)(R) , R—S— , R—S(═O)— , R—S(═O)—; said C-C-alkyl- or C-C-alkoxy- group being optionally substituted , one or more times , identically or differently , with a substituent selected from: C-C-alkyl- , C-C-alkoxy- , halo-C-C-alkoxy- , hydroxy-C-C-alkoxy- , C-C-alkoxy-C-C-alkoxy- , C-C-cycloalkyl- , 3- to 10-membered heterocycloalkyl- , aryl- , heteroaryl- , —C(═O)R , —C(═O)O—(C-C-alkyl) , —OC(═O)—R , —N(H)C(═O)R , —N(R)C(═O)R , —N(H)C(═O)NRR , —N(R)C(═O)NRR , —N(H)R , —NRR , —C(═O)N(H)R , —C(═O)NRR.7. A compound according to , , , , or , wherein Lrepresents *N(H)—C(═O)**;{'sup': '2', 'wherein “*” indicates the point of attachment to R, and “**” indicates the point of attachment to the phenyl group.'}9. A compound of general formula (I) , or a stereoisomer , a tautomer , an N oxide , a hydrate , a solvate , or a salt thereof , particularly a pharmaceutically acceptable salt thereof , or a mixture of same , according to any one of to , for use in the treatment or prophylaxis of a disease.10. A pharmaceutical composition comprising ...

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Номер записи: 93
18-04-2019 дата публикации

SUBSTITUTED CARBONUCLEOSIDE DERIVATIVES USEFUL AS ANTICANCER AGENTS

Номер: US20190111060A1
Автор: Kumpf Robert Arnold, McAlpine Indrawan James, McTigue Michele Ann, Patman Ryan, Rui Eugene Yuanjin, Tatlock John Howard, Tran-Dube Michelle Bich, Wythes Martin James
Принадлежит: PFIZER INC.

Compounds of the general formula): 125-. (canceled)28. The method of claim 27 , wherein the cancer is lung cancer claim 27 , bone cancer claim 27 , pancreatic cancer claim 27 , skin cancer claim 27 , cancer of the head or neck claim 27 , cutaneous or intraocular melanoma claim 27 , uterine cancer claim 27 , ovarian cancer claim 27 , rectal cancer claim 27 , cancer of the anal region claim 27 , stomach cancer claim 27 , colon cancer claim 27 , breast cancer claim 27 , uterine cancer claim 27 , carcinoma of the fallopian tubes claim 27 , carcinoma of the endometrium claim 27 , carcinoma of the cervix claim 27 , carcinoma of the vagina claim 27 , carcinoma of the vulva claim 27 , Hodgkin's Disease claim 27 , cancer of the esophagus claim 27 , cancer of the small intestine claim 27 , cancer of the endocrine system claim 27 , cancer of the thyroid gland claim 27 , cancer of the parathyroid gland claim 27 , cancer of the adrenal gland claim 27 , sarcoma of soft tissue claim 27 , cancer of the urethra claim 27 , cancer of the penis claim 27 , prostate cancer claim 27 , chronic or acute leukemia claim 27 , lymphocytic lymphomas claim 27 , cancer of the bladder claim 27 , cancer of the kidney or ureter claim 27 , renal cell carcinoma claim 27 , carcinoma of the renal pelvis claim 27 , neoplasms of the central nervous system (CNS) claim 27 , primary CNS lymphoma claim 27 , spinal axis tumors claim 27 , brain stem glioma claim 27 , or pituitary adenoma.29. The method of claim 27 , wherein the cancer is lymphoma.30. The method of claim 27 , wherein the cancer is colon cancer.31. The method of claim 27 , wherein the cancer is esophageal cancer.32. The method of claim 27 , wherein the cancer is stomach cancer.33. The method of claim 27 , wherein the cancer is lung cancer.34. The method of claim 27 , wherein the cancer is breast cancer.35. The method of claim 27 , wherein the cancer is ovarian cancer.36. The method of claim 27 , wherein the cancer is bladder cancer.37. The method ...

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Номер записи: 94
09-04-2020 дата публикации

Process for the preparation of 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1h-1,2,4-triazol-3-yl)phenyl)amino)-n-(methyl-d3)pyridazine-3-carboxamide

Номер: US20200109134A1
Автор: Amanda J. ROGERS, Bahar INANKUR, Bin Zheng, Daniel S. Treitler, DONG Lin, Eric M. SIMMONS, Jianji Wang, Joerg Deerberg, Jun Li, Ke Chen, Maxime C.D. SOUMEILLANT, Michael DUMMELDINGER, Michael J. Smith, Neil A. Strotman, Sergei Kolotuchin, Steven Tymonko, Tamas Benkovics, Victor W. Rosso
Принадлежит: Individual

The invention relates to an improved process for synthesizing 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide of the formula: [INSERT CHEMICAL STRUCTURE HERE] Compound I is currently in clinical trials for the treatment of auto-immune and auto-inflammatory diseases such as psoriasis.

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Номер записи: 95
05-05-2016 дата публикации

COMPOSITIONS INCLUDING 6-AMINOHEXANOIC ACID DERIVATIVES AS HDAC INHIBITORS

Номер: US20160122290A1
Автор: Hopper Allen, Peet Norton P., Rusche James R.
Принадлежит:

This invention relates to compounds of Formula (I) wherein Cy, L, Y, R, L, and Ar2 are defined herein, for the treatment of cancers, inflammatory disorders, and neurological conditions. 2. The compound according to claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Cyis selected from Cheterocycloalkyl claim 1 , which is substituted with n independently selected Rgroups.3. The compound according to claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Cyis selected from Caryl claim 1 , which is substituted with n independently selected Rgroups.4. The compound according to claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Cyis selected from Cheteroaryl claim 1 , which is substituted with n independently selected Rgroups.5. The compound according to claim 4 , or pharmaceutically acceptable salt thereof claim 4 , wherein Cyis indolyl or indazolyl claim 4 , each of which is substituted with n independently selected Rgroups.6. The compound according to claim 4 , or pharmaceutically acceptable salt thereof claim 4 , wherein Cyis indazolyl claim 4 , which is substituted with n independently selected Rgroups.7. The compound or salt of claim 6 , wherein n is 0.8. The compound or salt of claim 6 , wherein n is an integer selected from 1 and 2 claim 6 , and each occurrence of Ris independently selected from Calkyl and Calkoxy claim 6 , wherein said Calkyl and Calkoxy are each optionally substituted by 1 claim 6 , 2 claim 6 , or 3 independently selected R groups.9. The compound according to claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Cyis selected from phenyl and Cheteroaryl claim 1 , each of which is optionally substituted with n independently selected Rgroups.10. The compound according to claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Cyis phenyl claim 1 , which is optionally substituted with n independently selected Rgroups.11. The compound according to claim 1 , ...

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Номер записи: 96
07-05-2015 дата публикации

HETEROCYCLIC COMPOUND AND USE THEREFOR

Номер: US20150126487A1
Автор: SAKAMOTO Hiroki, SUGIMOTO Takahiro
Принадлежит:

The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity, and useful as a prophylactic or therapeutic drug for Alzheimer's disease, schizophrenia, pain, a sleep disorder and the like. The present invention relates to a compound represented by the formula (I): 3. The compound according to claim 1 , wherein Ris(a) an amino group optionally substituted by 1 or 2 substituents selected from(1) an amino group,{'sub': '1-6', '(2) a Calkyl group optionally substituted by 1 to 3 substituents selected from'}{'sub': 1-3', '3-6, '(i) a hydroxyl group, (ii) a Calkoxy group, (iii) a Ccycloalkyl group substituted by 1 to 3 hydroxyl groups, (iv) a phenyl group, (v) a furyl group, (vi) a tetrahydrofuranyl group, (vii) a piperidino group and (viii) a morpholino group,'}{'sub': '3-6', '(3) a Ccycloalkyl group optionally substituted by 1 to 3 substituents selected from a halogen atom, a hydroxyl group and a hydroxymethyl group,'}(4) a 4- to 10-membered cyclic amino group,{'sub': '1-6', '(5) a phenyl group optionally substituted by 1 to 3 substituents selected from a halogen atom, a Calkyl group optionally substituted by 1 to 3 halogen atoms and a hydroxymethyl group,'}(6) a dihydroindenyl group substituted by 1 to 3 hydroxyl groups,(7) a pyrazolyl group,(8) a tetrahydrofuranyl group, and(9) a tetrahydropyranyl group substituted by 1 to 3 hydroxyl groups, or(b) a 4- to 10-membered cyclic amino group optionally substituted by 1 to 3 substituents selected from a hydroxyl group and a hydroxymethyl group,{'sup': 2', '3, 'Rand Rare the same and each is a hydrogen atom or a halogen atom, or'}{'sup': 2', '3, 'sub': '1-3', 'Ris a hydrogen atom, and Ris a halogen atom, or a Calkoxy group substituted by 1 to 3 halogen atoms,'}X is —CH═ or —N═, andring A is a phenyl group wherein the 4-position is substituted by a substituent selected from{'sub': 1-3', '1-3', '1-3', '1-3, '(i) a Calkyl group substituted by 1 to 3 halogen atoms, ( ...

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Номер записи: 97
07-05-2015 дата публикации

PYRIDAZINE DERIVATIVES AS RORc MODULATORS

Номер: US20150126491A1
Автор: Bodil van Niel Monique, Cridland Andrew, FAUBER Benjamin, Gobbi Alberto, Hurley Christopher, Hurst David, Killen Jonathan, Maxey Robert, Ward Stuart
Принадлежит: Genentech, Inc.

Compounds of the formula I: 2. The compound of claim 1 , wherein X is a bond.3. The compound of claim 1 , wherein Ris hydrogen.4. The compound of claim 1 , wherein Ris hydrogen.5. The compound of claim 1 , wherein Ris:{'sub': '1-6', 'halo-Calkyl;'}halo;hydroxy;{'sub': '1-6', 'Calkoxy;'}{'sub': '1-6', 'hydroxy-Calkyl;'}{'sub': 1-6', '1-6, 'Calkoxy-Calkyl;'}{'sub': 1-6', '1-6', '1-6, 'Calkoxy-Calkoxy-Calkyl;'}cyano;{'sub': '1-6', 'cyano-Calkyl;'}{'sup': f', 'g', 'h', 'i, 'sub': 'm', '—(CRR)—NRR;'}{'sup': f', 'g', 'j', 'k, 'sub': 'm', '—(CRR)—C(O)—NRR;'}{'sup': f', 'g', 'm, 'sub': 'm', '—(CRR)—C(O)—R;'}{'sup': f', 'g', 'p', 'n, 'sub': 'm', '—(CRR)—NR—C(O)—R;'}{'sup': f', 'g', 'n, 'sub': 'm', '—(CRR)—O—C(O)—R;'}a six membered heteroaryl selected from pyridazin-2-yl, 1-methylpyridin-2-one-6-yl, pyridin-2-yl, and pyridin-3-yl,{'sub': 1-6', '1-6', '1-6', '3-6', '1-6', '1-6', '1-6', '1-6, 'a five membered heteroaryl selected from oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, triazolyl and pyrazolyl, each of which may be unsubstituted or substituted one or more times with Calkyl, Calkoxy, hydroxy-Calkyl, oxo, Ccycloalkyl, halo Calkyl amino, N—Calkyl-amino, cyano-Calkyl, or Calkoxycarbonyl;'}{'sub': 1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6, 'heteroaryl-Calkyl, wherein the Calkyl moiety may be unsubstituted or substituted one or more times with hydroxy or Calkoxy, and wherein the heteroaryl moiety is selected from pyrazolyl, oxadiazolyl and pyridinyl, each of which may be unsubstituted or substituted one or more times with Calkyl, hydroxy-Calkyl, hydroxy, Calkoxy, Calkoxy-Calkyl, amino-Calkyl, or oxo;'}{'sub': 1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6, 'heteroaryloxy-Calkyl, wherein the heteroaryl moiety is selected from oxadiazolyl, pyridinyl, and pyrazinyl, each of which may be unsubstituted or substituted one or more times with Calkyl, hydroxy-Calkyl, hydroxy, Calkoxy, Calkoxy Calkyl amino-Calkyl, or oxo;'}{'sub': 1-6', '1-6', '1-6, 'phenyl-Calkoxy- ...

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Номер записи: 98
03-05-2018 дата публикации

Substituted quinazolines as inhibitors of kras g12c

Номер: US20180118757A1
Автор: Jun Feng, Liansheng Li, Pingda Ren, Tao Wu, Yi Liu, YUAN LIU, Yun Oliver Long
Принадлежит: ARAXES PHARMA LLC

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R 1 , R 2a , R 3a , R 3b , R 4a , R 4b , G 1 , G 2 , L 1 , L 2 , m 1 , m 2 , A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

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Номер записи: 99
16-04-2020 дата публикации

METHODS FOR TREATING HUNTINGTON'S DISEASE

Номер: US20200113904A1
Автор: Babu Suresh, Bhattacharyya Anuradha, Hwang Seongwoo, Jani Minakshi, Moon Young-Choon, Sydorenko Nadiya
Принадлежит:

The present description relates to compounds, forms, and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease. 13-. (canceled)5. The compound of wherein (when present):{'sub': '1a', 'Ris selected from fluoro, chloro, hydroxyl, methyl, difluoromethyl, amino, methoxy or 1H-pyrazolyl or 1H-imidazol-1-yl,'}{'sub': '3a', 'wherein 1H-pyrazolyl is optionally substituted with 1 or 2 substituents each selected from R;'}{'sub': '3a', 'Ris selected from nitro or methyl or amino; and,'}{'sub': '4a', 'Ris methyl or ethyl;'}{'sub': '5a', 'Ris hydrogen or methyl;'}wherein a form of the compound is selected from the group consisting of a salt, hydrate, solvate, isotopologue, racemate, enantiomer, diastereomer, stereoisomer, and tautomer form thereof.6. (canceled)7. The compound of claim 4 , wherein the compound is selected from the group consisting of:2-{6-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl(methyl)amino]pyridazin-3-yl}-5-(1H-pyrazol-4-yl)phenol2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-ylamino)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol5-(1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol5-(1-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol2-[6-((1R,5S)-8-azabicyclo[3.2.1]oct-3-yloxy)pyridazin-3-yl]-5-(1H-pyrazol-4-yl)phenol5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}phenol5-(1H-imidazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol5-(5-methyl-1H-pyrazol-4-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol2-{6-[methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyridazin-3-yl}-5-(4-nitro-1H-pyrazol-1-yl)phenol6-[2-methoxy-4-(4-nitro-1H-pyrazol-1-yl)phenyl]-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine5-(4-amino-1H-pyrazol-1-yl)-2-{6-[(2,2,6,6-tetramethylpiperidin-4-yl)oxy]pyridazin-3-yl}phenol2-[6-( ...

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Номер записи: 100