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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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Применить Всего найдено 3434. Отображено 100.
26-01-2012 дата публикации

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

Номер: US20120022076A1
Автор: Andreas Maderna, Dinesh Barawkar, Hassan El Abdellaoul, Jean-Michel Vernier, Varaprasad Chamakura, Zhi Hong
Принадлежит: Individual

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

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Номер записи: 1
23-02-2012 дата публикации

Small molecule inhibitors of kynurenine-3-monooxygenase

Номер: US20120046324A1
Автор: Joseph M. Muchowski, Paolo Guidetti, Paul J. Muchowski, Robert Schwarcz
Принадлежит: University of Maryland at Baltimore

The present invention relates to compounds of Formula I below and their tautomers or pharmaceutically acceptable salts, compositions and methods of uses thereof.

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Номер записи: 2
17-05-2012 дата публикации

Compounds, Compositions and Methods for Modulating Uric Acid Levels

Номер: US20120122780A1
Автор: Jean-Luc Girardet, Martha De La Rosa
Принадлежит: Ardea Biociences Inc

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

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Номер записи: 3
31-05-2012 дата публикации

Substituted Esters as Cannabinoid-1 Receptor Modulators

Номер: US20120135975A1
Автор: Irene E. Whitney, Jeffrey J. Hale, Vincent J. Colandrea, William K. Hagmann
Принадлежит: Merck and Co Inc

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

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Номер записи: 4
07-06-2012 дата публикации

Microbiocidal heterocycles

Номер: US20120142700A1
Автор: Clemens Lamberth, Laura Quaranta, Mathias Stephan Respondex, Sarah SULZER-MOSSE
Принадлежит: SYNGENTA CROP PROTECTION LLC

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

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Номер записи: 5
19-07-2012 дата публикации

1,2,4-thiazoloidin-3-one derivatives and their use in the treatment of cancer

Номер: US20120183537A1
Автор: Allan Hallett, Jacob Westman, Jan Vagberg
Принадлежит: Betagenon Ab

According to the invention there is provided a compound of formula (I) wherein: A represents C(═N—W-D) or S; B represents S or C(—NH—W-D); when: A represents C(═N—W-D) and B represents S then the bond between B and the NH atom is a single bond; or A represents S and B represents C(—NH—W-D) then the bond between B and the NH atom is a double bond; X represents -Q-[CR x R y ] n —; W represents —[CR x R y ] m — or —C(O)—[CR x R y ] p —; Q represents a bond, —N(R a )—, —S—, or —O—; A 1 to A 5 respectively represent C(R 1 ), C(R 2 ), C(R 3 ), C(R 4 ) and C(R 5 ), or, alternatively, up to two of A 1 to A 5 may independently represent N; D represents phenyl, pyridyl or pyrimidinyl optionally substituted by one or more R 6 groups, which compounds are useful in the treatment of cancer.

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Номер записи: 6
30-08-2012 дата публикации

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

Номер: US20120220592A1
Автор: Alessandra Restivo, Carla Caccia, Cibele Sabido-David, Ermanno Moriggi, Florian Thaler, Laura Faravelli, Mauro Napoletano, Patricia Salvati
Принадлежит: Newron Pharmaceuticals SpA

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

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Номер записи: 7
21-03-2013 дата публикации

Inhibitors of Ion Channels

Номер: US20130072471A1
Автор: Fritch Paul Christopher, Markworth Christopher John, Marron Brian Edward, Maynard Andrew Thomas, Swain Nigel Alan
Принадлежит:

Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-gated sodium channels. More particularly, the invention provides substituted aryl sulfonamides, compositions comprising these compounds, as well as methods of using these compounds or compositions in the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrence of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a voltage-gated sodium channel. 2. The compound of claim 1 , with the proviso that the compound of formula (I) is not one of the following compounds:N-(5-methyl-3-isoxazolyl)-3-[[(5-methyl-3-isoxazolyl)amino]sulfonyl]-benzamide;3-[[(5-methyl-3-isoxazolyl)amino]sulfonyl]-N-1,3,4-thiadiazol-2-yl-benzamide;N-(5-ethyl-1,3,4-thiadiazol-2-yl)-3-(4-morpholinylcarbonyl)-benzenesulfonamide;1-[3-[[[5-(1,1-dimethylethyl)-4-methyl-2-thiazolyl]amino]sulfonyl]benzoyl]piperidine;N-(5-methyl-1,3,4-thiadiazol-2-yl)-3-(4-morpholinylcarbonyl)-benzenesulfonamide; andN-methyl-4-[[(1-methyl-1H-pyrazol-3-yl)amino]sulfonyl]-benzamide.3. The compound according to claim 2 , or a pharmaceutically acceptable salt claim 2 , wherein{'sup': '5', 'sub': 1', '10', '3', '8, 'Ris a member selected from (C-C)alkyl and (C-C)cycloalkyl,'}{'sub': 1', '4', '1', '4', '1', '4', '1', '4', '1', '4', '1', '4, 'wherein each is optionally substituted with one or more substituents selected from the group consisting of oxo, halogen, cyano, hydroxy, hydroxy(C-C)alkyl, hydroxy(C-C)alkoxy, (C-C)alkyl, halo(C-C)alkyl, (C-C)alkoxy, halo(C-C)alkoxy and phenyl.'}4. The compound according to claim 3 , or a pharmaceutically acceptable salt claim 3 , wherein Ris a member selected from (C-C)alkyl claim 3 , hydroxy(C-C ...

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Номер записи: 8
02-05-2013 дата публикации

Chemical Compounds

Номер: US20130109696A1
Автор: Greener Benjamin Scott, Marron Brian Edward, Millan David Simon, Rawson David James, Storer Robert Ian, Swain Nigel Alan
Принадлежит: PFIZER LIMITED

The invention relates to sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to new sulfonamide Nav1.7 inhibitors of formula (I) or pharmaceutically acceptable salts thereof, wherein X, Y, Y, Z, R, Rand Rare as defined in the description. Nav 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain. 2. A compound according to wherein X is S.3. A compound according to wherein X is CH.4. A compound according to wherein Z is either (a) a ‘C-linked’ 5-membered heteroaryl group containing two nitrogen atoms and one sulphur atom claim 1 , or (b) a ‘C-linked’ 6-membered heteroaryl group containing two nitrogen atoms.5. A compound according to wherein Z is ‘C-linked’ thiadiazolyl or ‘C-linked’ a pyrimidinyl.6. A compound according to wherein Yis Cl and Yis F.7. A compound according to wherein Yis CN and Yis H.8. A compound according to wherein Rand Rare independently H claim 1 , F claim 1 , Cl or R.9. A compound according to wherein Rand Rare independently H claim 1 , F claim 1 , CFor OCH.10. A compound according to wherein Ris H claim 1 , F claim 1 , Ror Het.11. A compound according to wherein Ris H; F; (C-C)alkyl claim 1 , optionally substituted by one to three halo atoms; (C-C)alkyloxy claim 1 , such as methoxy; or a ‘C-linked’ 6-membered heteroaryl group comprising one or two nitrogen atoms claim 1 , optionally substituted on a carbon atom by NH.12. A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof together claim 1 , as defined in claim 1 , with one or more pharmaceutically acceptable excipients.13. A pharmaceutical composition according to including one or more additional therapeutic agents.14. (canceled)15. (canceled)16. (canceled)17. (canceled)18. A method of treating a disorder in a human or animal for which a ...

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Номер записи: 9
11-07-2013 дата публикации

N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase

Номер: US20130177590A1
Автор: Amy Takvorian, Andrew P. Combs, Richard B. Sparks, Wenyu Zhu
Принадлежит: Incyte Corp

The present invention is directed to N-hydroxyamidino compounds which are modulators of indoleamine 2,3-dioxygenase (IDO), as well as pharmaceutical compositions thereof and methods of use thereof relating to the treatment of cancer and other diseases.

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Номер записи: 10
22-08-2013 дата публикации

Arylsulfonamide ccr3 antagonists

Номер: US20130217687A1
Автор: Jared Andrew Forrester, Tai Wei Ly
Принадлежит: Axikin Pharmaceuticals Inc

Provided herein are arylsulfonamides that are useful for modulating CCR3 activity, and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a CCR3-mediated disorder, disease, or condition.

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Номер записи: 11
29-08-2013 дата публикации

COMPOUND FOR INCREASING KINASE ACTIVE AND APPLICATION THEREOF

Номер: US20130225587A1
Автор: Hu Yunyan, Kang Xinshan, Long Wei, Ma Cunbo, Shen Xiaoyan, Tan Fenlai, Wang Yanping, Wang Yinxiang
Принадлежит:

The compound of Formula (I), pharmaceutically acceptable salts thereof, solvates thereof, chelates thereof, non-covalent complexes thereof or produgs of compounds mentioned above or the mixture of any form above mentioned are provided. The use of the compounds in manufacturing a medicament for the treatment and/or prevention of diabetes, obesity and related disorders. 2. The compound of claim 1 , wherein W is C.34-. (canceled)5. The compound of claim 2 , wherein Y is C claim 2 , X is O claim 2 , and wherein Z is C.6. The compound of claim 2 , wherein Y is N.7. The compound of claim 6 , wherein X is O.8. The compound of claim 7 , wherein Z is C.911-. (canceled)12. The compound of claim 1 , wherein W is N claim 1 , Y is C claim 1 , wherein X is O claim 1 , and wherein Z is C.1319-. (canceled)20. The compound of claim 1 , wherein Ris selected from the group consisting of —H claim 1 , lower alkanyl claim 1 , substituted lower alkanyl claim 1 , lower alkenyl claim 1 , substituted lower alkenyl claim 1 , lower alkynyl claim 1 , substituted lower alkynyl claim 1 , Calkoxy and substituted Calkoxy.21. The compound of claim 20 , wherein Ris —H; Ris selected from the group consisting of cycloalkyl claim 20 , substituted cycloalkyl claim 20 , heterocycloalkyl and substituted heterocycloalkyl; and wherein Ris 5 or 6 membered heteroaryl.2324-. (canceled)25. The compound of claim 1 , wherein Ris selected from the group consisting of C(═O)R claim 1 , SR claim 1 , SORand haloalkyl; and wherein Ris selected the group consisting of Calkanyl claim 1 , substituted Calkanyl claim 1 , NRR claim 1 , Calkoxy claim 1 , and substituted Calkoxy.26. The compound of claim 25 , wherein Ris —H; wherein Ris selected from the group consisting of cycloalkanyl claim 25 , substituted cycloalkanyl claim 25 , heterocycloalkyl and substituted heterocycloalkyl; and wherein Ris substituted 5- or 6-membered heteroaryl.28. The compound of claim 27 , wherein Ris C(═O)R; Ris NRR.29. The compound of claim 27 , ...

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Номер записи: 12
03-10-2013 дата публикации

Sulfonyl semicarbazides, semicarbazides and ureas, pharmaceutical compositions thereof, and methods for treating hemorrhagic fever viruses, including infections associated with arena viruses

Номер: US20130261087A1
Автор: Dennis E. Hruby, Dongcheng Dai, Thomas R. Bailey, Tove C. Bolken
Принадлежит: Siga Technologies Inc

Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain novel sulfonyl semicarbazides, carbonyl semicarbazides, semicarbazides, ureas and related compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by hemorrhagic fever viruses is disclosed, i.e., including but not limited to, Arenaviridae (Junin, Machupo, Guanarito, Sabia, Lassa, Tacaribe, Pinchinde, and VSV), Filoviridae (ebola and Marburg viruses), Flaviviridae (yellow fever, omsk hemorrhagic fever and Kyasanur Forest disease viruses), and Bunyaviridae (Rift Valley fever).

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Номер записи: 13
03-10-2013 дата публикации

FUNGICIDAL N-(2-PHENOXYETHYL)CARBOXAMIDE DERIVATIVES AND THEIR AZA, THIA AND SILA ANALOGUES

Номер: US20130261158A1
Автор: BENNABI Samir, Benting Jurgen, BRUNET Stephane, Dahmen Peter, Desbordes Philippe, Gary Stephanie, Grosjean-Cournoyer Marie-Claire, Rama Rachel, Rinolfi Philippe, TOQUIN Valérie, VOERSTE Arnd, Wachendorff-Neumann Ulrike
Принадлежит:

The present invention relates to fungicide N-(2-phenoxyethyl)carboxamide derivatives of formula (I), their aza, thia and sila analogues, their process of preparation, their use as fungicides, particularly in the form of fungicidal compositions and methods for the control of phytopathogenic fungi of plants using these compounds or their compositions. Formula (1) wherein A, T, W, X, n and Zto Zrepresent various substituents. 3. A compound according to wherein A is selected in the list consisting of A; A; Aand A.4. A compound according to wherein A represents Aand wherein Rrepresents a C-C-alkyl claim 3 , C-C-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; or C-C-alkoxy; Rrepresents a hydrogen atom or a halogen atom; Rrepresents a C-C-alkyl.5. A compound according to wherein W represents O or S.6. A compound according to wherein n represents 0 claim 1 , 1 or 2.7. A compound according to wherein X independently represents a halogen atom; C-C-alkyl; C-C-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; tri(C-C-alkyl)silyl; C-Calkoxy or C-C-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different or wherein two consecutive substituents X together with the phenyl ring form a substituted or non substituted 1 claim 1 ,3-benzodioxolyl; 1 claim 1 ,2 claim 1 ,3 claim 1 ,4-tetrahydro-quinoxalinyl; 3 claim 1 ,4-dihydro-2H-1 claim 1 ,4-benzoxazinyl; 1 claim 1 ,4-benzodioxanyl; indanyl; 2 claim 1 ,3-dihydrobenzofuranyl; or indolinyl.8. A compound according to wherein Zand Zindependently represent a C-C-alkyl.9. A compound according to wherein Zand Zindependently represent a hydrogen atom or a C-C-alkyl.10. A compound according to wherein Zand Zindependently represent a hydrogen atom or a C-C-alkyl.11. A compound according to wherein Zrepresents a C-Ccycloalkyl substituted by up to 10 groups or atoms that can be the same or different and that can be selected in the list consisting of halogen ...

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Номер записи: 14
19-12-2013 дата публикации

Compounds for the treatment of neurodegenerative diseases

Номер: US20130338202A1
Автор: Alan D. Snow, F. Michael Hudson, Franz F. Hefti, Geoffrey Golding, Joel Cummings, Judy Cam, Luke A. Esposito, Marisa C. YADON, Qubai Hu, Seok-Rye Choi, Thomas Lake, Ximin Li
Принадлежит: Proteo Tech Inc

Compounds and their pharmaceutically acceptable salts for treatment of synucleinopathies, such as Parkinson's disease and tauopathies.

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Номер записи: 15
13-02-2014 дата публикации

Cycloalkane Derivatives

Номер: US20140045862A1
Автор: Domon Yuki, Kimoto Hiroko, Kobayashi Hiroyuki, SHINOZUKA Tsuyoshi, Suzuki Sayaka, Tanaka Kyosuke
Принадлежит: Daiichi Sankyo Company, Limited

Disclosed herein are therapeutic agents and/or preventive agents for pain or therapeutic agents and/or preventive agents for a sodium channel associated disease. The present invention provides compounds represented by the following formula (I) or pharmacologically acceptable salts thereof: 2. The compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein in formula (I) claim 1 ,{'sup': 1', '2, 'Arand Arare each independently a heteroaryl group;'}{'sup': 1', '2', '3, 'R, Rand Rare each independently a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halogenated C1-C6 alkyl group or a C3-C7 cycloalkyl group;'}{'sup': 4', '5, 'Rand Rare each independently a hydrogen atom, a halogen atom, a C1-C6 alkyl group or a halogenated C1-C6 alkyl group; and'}the heteroaryl group is optionally substituted with one or two groups selected from the group consisting of a halogen atom, a C1-C6 alkyl group, a halogenated C1-C6 alkyl group, a hydroxyl group, a hydroxy C1-C6 alkyl group, a C3-C7 cycloalkyl group, an amino group, a C1-C3 alkylamino group and a di-C1-C3 alkylamino group.3. The compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein the heteroaryl group is a 5- or 6-membered nitrogen-containing aromatic heterocyclic group.4. The compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein Aris a pyridyl group claim 1 , a pyridazinyl group claim 1 , a pyrimidinyl group claim 1 , a pyrazolyl group or an imidazolyl group claim 1 , and wherein Aris optionally substituted.5. The compound or a pharmacologically acceptable salt thereof according to claim 4 , wherein Aris optionally substituted with one or two groups selected from the group consisting of a chlorine atom claim 4 , a fluorine atom claim 4 , a methyl group claim 4 , an ethyl group claim 4 , a trifluoromethyl group claim 4 , an amino group claim 4 , a methylamino group and a dimethylamino group.6. The compound or a ...

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Номер записи: 16
20-02-2014 дата публикации

5-membered ring heteroaromatic derivatives having npy y5 receptor antagonistic activity

Номер: US20140051862A1
Автор: Kyohei Hayashi, Naoki Omori, Yuusuke Tamura
Принадлежит: Shionogi and Co Ltd

This invention provides new compounds having NPY Y5 antagonistic activity. The present inventors found that a compound of the formula (I): wherein R 1 is substituted or unsubstituted alkyl or the like; p, q and r are each independently 0 or 1; ring A is oxadiazole; and R 2 is substituted or unsubstituted alkyl or the like, has NPY Y5 antagonistic activity.

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Номер записи: 17
20-03-2014 дата публикации

METHODS FOR INHIBITING FASCIN

Номер: US20140080843A1
Автор: Huang Xin-Yun, SHUE Christy Young
Принадлежит:

Provided are compositions and methods for treating a condition or disorder mediated by fascin activity in a subject in need thereof which method comprises administering to the subject a therapeutically effective amount of at least one compound of any one of Formula I-a to I-n, II, II-a, II-b or III or a pharmaceutically acceptable salt thereof. 6. The method of claim 1 , wherein Ris phenyl optionally substituted with one claim 1 , two claim 1 , or three groups chosen from halo and lower alkyl.7. The method of claim 1 , wherein Ris triazole.8. The method of claim 2 , wherein m is 0.9. The method of claim 1 , wherein Lis —N(R)S(O)—.10. The method of claim 1 , wherein Lis —S—.11. The method of claim 1 , wherein Xis OH and Xis O.12. The method of claim 1 , wherein Ris independently selected from the group consisting of OH claim 1 , halo claim 1 , lower alkyl claim 1 , and —OR.13. The method of claim 1 , wherein the compound is selected from5-(3,4-dichlorobenzyl)-1-(S,S,-dioxo-tetrahydrothiophen-3-yl)-1H-pyrazolo-[3,4-d]pyrimidin-4(5H)-one;N-(1-(4-(trifluoromethyl)benzyl)-1H-indazol-3-yl)furan-2-carboxamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-2,5-dimethylbenzenesulfonamide;N-(3(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-ethoxybenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-methoxybenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-ethylbenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-trimethylbenzenesulfonamide;(Z)—N-(3-(1H-1,2,4-triazol-3-ylthio)-4-oxonaphthalen-1(4H)-ylidene)benzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-4-bromobenzenesulfonamide;N-(3-(1H-1,2,4-triazol-3-ylthio)-4-hydroxynaphthalen-1-yl)-2,4-dimethylbenzenesulfonamide;5-(3-chlorobenzyl)-1-(2-hydroxyethyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one;2-(4-oxo-1-(S,S,-dioxo-tetrahydrothiophen-3-yl)-1H-pyrazolo[3,4-d]-pyrimidin-5(4H)-yl)-N-(3-( ...

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Номер записи: 18
03-01-2019 дата публикации

Compounds for the Detection, Capture and/or Separation of Polluting Gases

Номер: US20190001252A1
Автор: Jean-Manuel Raimundo, Julien Rodriguez, Olivier Yves Claude Siri, Philip Leslie Llewellyn, Vinicius Demétrio da Silva
Принадлежит: Aix Marseille Universite, CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

A subject of the present invention is the use of a compound having the general formula (I): (I) wherein V, W, X 4 , X 5 , X 6 , X 7 , X′ 4 , X′ 5 , X′ 6 , X′ 7 , Y, Y′, R 3 , R′ 3 , R 4 and R′ 4 are as defined in any one of claims 1 to 11 , for the detection, capture and/or separation of polluting gases, in particular those selected from the group comprising carbon dioxide, methane, sulfur dioxide, nitrogen oxides, carbon monoxide, linear hydrocarbons, linear mono-olefins and their mixtures, and preferably carbon dioxide. Another subject of the invention is a compound of formula (I) wherein V, W, X 4 , X 5 , X 6 , X 7 , X′ 4 , X′ 5 , X′ 6 , X′ 7 , Y, Y′, R 3 , R′ 3 , R 4 and R′ 4 are as defined in any one of claims 12 to 21 .

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Номер записи: 19
04-01-2018 дата публикации

COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES

Номер: US20180002298A1
Автор: CAM JUDY, CUMMINGS JOEL, ESPOSITO LUKE A., HU QUBAI, HUDSON F. MICHAEL, Lake Thomas, Snow Alan D., YADON MARISA C.
Принадлежит:

Compounds and their pharmaceutically acceptable salts for treatment of tauopathies, such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia/Parkinsonism linked to chromosome 17, amyotrophic lateral sclerosis/Parkinsonism-dementia complex, argyrophilic grain dementia, dementia pugilistic, diffuse neurofibrillary tangles with calcification, progressive subcortical gliosis and tangle only dementia. 2. A method of disrupting or inhibiting the formation claim 1 , deposition claim 1 , accumulation claim 1 , or persistence of tau fibrils and/or aggregates claim 1 , comprising administering a therapeutically effective amount of the compounds of .3. The method of claim 2 , where the compound administered is in an amount between 0.1 mg/Kg/day and 1000 mg/Kg/day.4. The method of claim 2 , where the compound is administered in an amount between 1 mg/Kg/day and 100 mg/Kg/day.5. The method of claim 2 , where amount of compound administered is in an amount between 10 mg/Kg/day and 100 mg/Kg/day.6. A method resulting in neuroprotection from a tauopathy in a mammal comprising the step of administrating a therapeutically effective amount of a compound of .7. The method of where the tauopathy is one selected from; Alzheimer's disease claim 6 , Pick's disease claim 6 , progressive supranuclear palsy claim 6 , corticobasal degeneration claim 6 , familial frontotemporal dementia/Parkinsonism linked to chromosome 17 claim 6 , amyotrophic lateral sclerosis/Parkinsonism-dementia complex claim 6 , argyrophilic grain dementia claim 6 , dementia pugilistic claim 6 , diffuse neurofibrillary tangles with calcification claim 6 , progressive subcortical gliosis and tangle only dementia.8. An article of manufacture claim 1 , comprising packaging material claim 1 , the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , contained within packaging material claim 1 , which is used for treating ...

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Номер записи: 20
01-01-2015 дата публикации

COMPOUNDS FOR INFLAMMATION AND IMMUNE-RELATED USES

Номер: US20150005320A9
Автор: Chen Shoujun, Chimmanamada Dinesh, Holmqvist Mats, Jiang Jun, Mahiou Jerome, Ono Mitsunori, Sun Lijun, Xie Yu, Yu Chih-Yi, Zhang Shijie
Принадлежит: Synta Pharmaceuticals Corp.

The invention relates to compounds of formula (I): 187-. (canceled)89. The compound of claim 88 , wherein Ais CH.90. (canceled)91. The compound of claim 88 , wherein Yis a substituted phenyl claim 88 , an optionally substituted pyridyl claim 88 , or an optionally substituted [1 claim 88 ,2 claim 88 ,3]-thiadiazolyl.92. The compound of claim 88 , wherein Yis a substituted phenyl.94. (canceled)95. A compound selected from the group consisting of:3-Fluoro-N-(2′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(2′-methyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(3′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-nicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-isonicotinamide;4-Trifluoromethyl-N-(2′-trifluoromethyl-biphenyl-4-yl)-nicotinamide;Pyridine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;Pyrazine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;2-methyl-pyridine-3-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;1-methyl-1H-imidazole-5-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethoxy-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-dimethoxybiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-methylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethylbiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid (2′-methoxy-5′-acetylbiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-difluoromethoxy-5′-chlorobiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid {2′-(N,N-dimethylamino)-5′-trifluoromethoxybiphenyl-4- ...

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Номер записи: 21
15-01-2015 дата публикации

CYCLOALKANE DERIVATIVES

Номер: US20150018551A1
Автор: Domon Yuki, Kimoto Hiroko, Kobayashi Hiroyuki, SHINOZUKA Tsuyoshi, Suzuki Sayaka, Tanaka Kyosuke
Принадлежит:

Disclosed herein are therapeutic agents and/or preventive agents for pain or therapeutic agents and/or preventive agents for a sodium channel associated disease. The present invention provides compounds represented by the following formula (I) or pharmacologically acceptable salts thereof: 131-. (canceled)33. The method of claim 32 , wherein the removal of the protecting group is conducted by reacting an acid and the compound represented by formula (VI) in a solvent.34. The method of claim 33 , wherein the solvent is selected from the group consisting of an ethers claim 33 , a halogenated hydrocarbon claim 33 , tetrahydrofuran claim 33 , 1 claim 33 ,4-dioxane and dichloromethane.35. The method of claim 33 , further comprising a scavenger.36. The method of claim 35 , wherein the scavenger is selected from the group consisting of trialkylsilane claim 35 , aryl ether claim 35 , triethylsilane and anisole.37. The method of claim 33 , wherein the acid is selected from the group consisting of an organic acid claim 33 , an inorganic acid claim 33 , trichloroacetic acid claim 33 , trifluoroacetic acid claim 33 , acetic acid claim 33 , sulfuric acid and hydrochloric acid.38. The method of claim 32 , wherein the reaction temperature is 0° C. to 200° C.39. The method of claim 32 , wherein the reaction time is from 1 hour to 48 hours.40. The method of claim 32 , wherein the deprotecting of the compound of formula (VI) is in a solvent and in the presence of a palladium catalyst under hydrogen atmosphere.41. The method of claim 40 , wherein the solvent is selected from the group consisting of ethers claim 40 , alcohols claim 40 , tetrahydrofuran claim 40 , methanol and ethanol.42. The method of claim 40 , wherein the catalyst is selected from the group consisting of a zero-valent palladium catalyst claim 40 , a palladium-activated carbon and a palladium hydroxide-activated carbon.43. The method of claim 40 , wherein the reaction temperature is from −20° C. to 120° C.44. The ...

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Номер записи: 22
17-01-2019 дата публикации

METABOTROPIC GLUTAMATE RECEPTOR NEGATIVE ALLOSTERIC MODULATORS (NAMS) AND USES THEREOF

Номер: US20190016715A1
Автор: COSFORD Nicholas David Peter, Raveendra-Panickar DHANYA, SHEFFLER Douglas J.
Принадлежит:

Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor negative allosteric modulators (NAMs), compositions comprising the compounds, and methods of using the compounds and compositions. 162.-. (canceled)65. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein X is —O—.66. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein Ris substituted or unsubstituted heteroaryl.67. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein n is 1 and Ris halogen or —CH.68. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein Ris —CF.69. The compound of claim 63 , or a pharmaceutically acceptable salt thereof claim 63 , wherein m is 0.71. A pharmaceutical composition comprising a compound of claim 63 , or a pharmaceutically acceptable salt claim 63 , and at least one pharmaceutically acceptable excipient.72. A method of treating a central nervous disorder (CNS) claim 63 , the method comprising the step of administering to a subject in need thereof claim 63 , an effective amount of a compound of claim 63 , thereby treating the disorder.75. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein X is —O—.76. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein Ris substituted or unsubstituted heteroaryl.77. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein n is 1 and Ris halogen or —CH.78. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein Ris —CF.79. The compound of claim 73 , or a pharmaceutically acceptable salt thereof claim 73 , wherein m is 0.81. A pharmaceutical composition comprising a compound of claim 73 , or a pharmaceutically acceptable salt claim 73 , and at least one pharmaceutically acceptable excipient.82. A method of treating ...

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Номер записи: 23
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: 24
16-01-2020 дата публикации

METHODS FOR INHIBITING FASCIN

Номер: US20200017506A1
Автор: Huang Xin-Yun, SHUE Christy Young
Принадлежит:

Provided are compositions and methods for treating a condition or disorder mediated by fascin activity in a subject in need thereof which method comprises administering to the subject a therapeutically effective amount of at least one compound of any one of Formula I-a to I-n, II, II-a, II-b or III or a pharmaceutically acceptable salt thereof. 6. The method of claim 1 , wherein Ris phenyl optionally substituted with one claim 1 , two claim 1 , or three groups chosen from halo and lower alkyl.7. The method of claim 1 , wherein Ris triazole.8. The method of claim 2 , wherein m is 0.9. The method of claim 1 , wherein Lis —N(R)S(O)—.10. The method of claim 1 , wherein Lis —S—.11. The method of claim 1 , wherein Xis OH and Xis O.12. The method of claim 1 , wherein Ris independently selected from the group consisting of OH claim 1 , halo claim 1 , lower alkyl claim 1 , and —OR.13. (canceled)16. The method of claim 15 , wherein Wis S.17. The method of claim 14 , wherein Ris phenyl optionally substituted with halo or alkyl.18. The method of claim 14 , wherein Ris phenyl optionally substituted with halo or alkyl.19. The method of claim 14 , wherein Rand Rare phenyl.20. The method of claim 14 , wherein Ris methyl claim 14 , phenyl claim 14 , or benzyl.2122-. (canceled)2467-. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/972,649, filed on Aug. 21, 2013, which claims the benefit of U.S. Provisional Patent Application No. 61/692,177, filed on Aug. 22, 2012, and U.S. Provisional Patent Application No. 61/778,015, filed on Mar. 12, 2013. The entire contents of the foregoing applications are hereby incorporated herein by reference in their entireties.The technology described herein was developed with funds from National Institutes of Health Grant No. R01 CA136837. The United States Government has certain rights to the technology.The present technology relates generally to methods for treating or preventing cancer.In recent years, progress has ...

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Номер записи: 25
25-01-2018 дата публикации

Novel glp-1 receptor modulators

Номер: US20180021346A1
Автор: Adam R. Yeager, Andrew Novak, Daniel Glynn, Enugurthi Brahmachary, Esther Martinborough, Junko Tamiya, Liming Huang, Manisha Moorjani, Marcus F. Boehm, Mark Mills, Michael Knaggs, Premji Meghani, Thomas Fowler
Принадлежит: Celgene International II SARL

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “ ” represents either or both the R and S form of the compound): where A, B, C, Y 1 , Y 2 , Z, R 1 , R 2 , R 3 , R 4 , R 5 , W 1 , n, p and q are as defined herein.

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Номер записи: 26
26-01-2017 дата публикации

COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES

Номер: US20170022174A1
Автор: CAM JUDY, CUMMINGS JOEL, ESPOSITO LUKE A., HU QUBAI, HUDSON F. MICHAEL, Lake Thomas, Snow Alan D., YADON MARISA C.
Принадлежит:

Compounds and their pharmaceutically acceptable salts for treatment of tauopathies, such as Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia/Parkinsonism linked to chromosome 17, amyotrophic lateral sclerosis/Parkinsonism-dementia complex, argyrophilic grain dementia, dementia pugilistic, diffuse neurofibrillary tangles with calcification, progressive subcortical gliosis and tangle only dementia. 2. A method of disrupting or inhibiting the formation claim 1 , deposition claim 1 , accumulation claim 1 , or persistence of tau fibrils and/or aggregates claim 1 , comprising administering a therapeutically effective amount of the compounds of .3. The method of claim 2 , where the compound administered is in an amount between 0.1 mg/Kg/day and 1000 mg/Kg/day.4. The method of claim 2 , where the compound is administered in an amount between 1 mg/Kg/between 10 mg/Kg/day and 100 mg/Kg/day.5. The method of claim 2 , where amount of compound administered is in an amount between 10 mg/Kg/day and 100 mg/Kg/day.6. A method resulting in neuroprotection from a tauopathy in a mammal comprising the step of administrating a therapeutically effective amount of a compound of .7. The method of where the tauopathy is one selected from; Alzheimer's disease claim 6 , Pick's disease claim 6 , progressive supranuclear palsy claim 6 , corticobasal degeneration claim 6 , familial frontotemporal dementia/Parkinsonism linked to chromosome 17 claim 6 , amyotrophic lateral sclerosis/Parkinsonism-dementia complex claim 6 , argyrophilic grain dementia claim 6 , dementia pugilistic claim 6 , diffuse neurofibrillary tangles with calcification claim 6 , progressive subcortical gliosis and tangle only dementia.8. An article of manufacture claim 1 , comprising packaging material claim 1 , the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , contained within packaging material claim 1 , which is ...

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Номер записи: 27
17-04-2014 дата публикации

COMPOUNDS FOR INFLAMMATION AND IMMUNE-RELATED USES

Номер: US20140107134A1
Автор: Chen Shoujun, Chimmanamada Dinesh, Holmqvist Mats, Jiang Jun, Mahiou Jerome, Ono Mitsunori, Sun Lijun, Xie Yu, Yu Chih-Yi, Zhang Shijie
Принадлежит: Synta Pharmaceuticals Corp.

The invention relates to compounds of formula (I): 187-. (canceled)89. The compound of claim 88 , wherein Ais CH.90. (canceled)91. The compound of claim 88 , wherein Yis a substituted phenyl claim 88 , an optionally substituted pyridyl claim 88 , or an optionally substituted [1 claim 88 ,2 claim 88 ,3]-thiadiazolyl.92. The compound of claim 88 , wherein Yis a substituted phenyl.94. (canceled)95. A compound selected from the group consisting of:3-Fluoro-N-(2′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(2′-methyl-biphenyl-4-yl)-isonicotinamide;3-Fluoro-N-(3′-trifluoromethyl-biphenyl-4-yl)-isonicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-nicotinamide;N-(2′-Trifluoromethyl-biphenyl-4-yl)-isonicotinamide;4-Trifluoromethyl-N-(2′-trifluoromethyl-biphenyl-4-yl)-nicotinamide;Pyridine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;Pyrazine-2-carboxylic acid (2′-trifluoromethyl-biphenyl-4-yl)-amide;2-methyl-pyridine-3-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;1-methyl-1H-imidazole-5-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethoxy-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethyl-biphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-dimethoxybiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-methoxy-5′-chlorobiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′,5′-bis-trifluoromethylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′-methoxy-5′-methylbiphenyl-4-yl)-amide;3-methyl-pyridine-4-carboxylic acid (2′,5′-dimethylbiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid (2′-methoxy-5′-acetylbiphenyl-4-yl)-amide;3-fluoro-pyridine-4-carboxylic acid (2′-difluoromethoxy-5′-chlorobiphenyl-4-yl)-amide;4-methyl-[1,2,3]-thiadiazole-5-carboxylic acid {2′-(N,N-dimethylamino)-5′-trifluoromethoxybiphenyl-4- ...

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Номер записи: 28
28-01-2021 дата публикации

Simplified Structural Mimetics of AIPS as Quorum Sensing Inhibitors

Номер: US20210024476A1
Автор: Helen Blackwell, Joseph VASQUEZ, Yiftah Tal Gan
Принадлежит: WISCONSIN ALUMNI RESEARCH FOUNDATION

Compounds that regulate quorum sensing in Staphylococcal bacteria and in particular in Staphylococcus aureus are provided. Compounds are described in formulas I, II, III, IV, V and VI herein. One or more compounds herein can be employed to inhibit QS and to thus inhibit virulence in Staphylococcus bacteria and in particular in Staphylococcus aureus. Compounds herein and pharmaceutical compositions containing one or more of these compounds are useful, for example, in treating infections of Staphylococcus bacteria and in particular of Staphylococcus aureus. Methods for treating such bacterial infections are provided.

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Номер записи: 29
24-04-2014 дата публикации

EPOXYEICOSATRIENOIC ACID ANALOGS AND METHODS OF MAKING AND USING THE SAME

Номер: US20140113884A1
Автор: Campell William B., Falck John Russell, Imig John David
Принадлежит:

Compounds and compositions comprising epoxyeicosatrienoic acid (EET) analogs that act as EET agonists and are useful as medications in the treatment of drug-induced nephrotoxicity, hypertension and other related conditions. Methods of making and using the compounds and compositions are further described. 5. A composition comprising a compound of and a pharmaceutically acceptable carrier.6. A method of reducing hypertension in a subject claim 1 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 1 , wherein hypertension in said subject is reduced.7. (canceled)8. (canceled)9. A method of reducing nephrotoxicity in a subject claim 1 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 1 , wherein nephrotoxicity in said subject is reduced.10. The method of claim 9 , wherein the nephrotoxicity is drug-induced.11. The method of claim 10 , wherein the nephrotoxicity is cisplatin-induced.12. (canceled)13. (canceled)14. A method of reducing cisplatin nephrotoxicity in a subject claim 1 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 1 , wherein cisplatin nephrotoxicity in said subject is reduced.15. (canceled)16. (canceled)17. A composition comprising a compound of and a pharmaceutically acceptable carrier.18. A method of reducing hypertension in a subject claim 4 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 4 , wherein hypertension in said subject is reduced.19. A method of reducing nephrotoxicity in a subject claim 4 , comprising administering to a subject a therapeutically effective amount of a compound according to claim 4 , wherein nephrotoxicity in said subject is reduced.20. The method of claim 19 , wherein the nephrotoxicity is drug-induced.21. The method of claim 20 , wherein the nephrotoxicity is cisplatin-in-induced.22. A method of ...

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Номер записи: 30
04-02-2016 дата публикации

Arginine methyltransferase inhibitors and uses thereof

Номер: US20160031839A1
Автор: Gideon Shapiro, Lorna Helen Mitchell, Richard Chesworth
Принадлежит: Epizyme Inc

Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

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Номер записи: 31
01-02-2018 дата публикации

ALLOSTERIC MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS

Номер: US20180030007A1
Автор: Bell Ian M., CAMPBELL BRIAN T., Crowley Brendan M., Duffy Joseph L., Greshock Thomas J., Guiadeen Deodial G., Harvey Andrew John, HUFF BELINDA C., Leavitt Kenneth J., Rada Vanessa L., Sanders John M., Shipe William D., SUEN LINDA M.
Принадлежит: Merck Sharp & Dohme Corp.

The present disclosure relates to compounds of formula I that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation 116-. (canceled)19. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the compound of .20. A pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) the pharmaceutically acceptable salt of .21. A method of treating a patient with mild to moderate dementia of the Alzheimer's type claim 17 , the method comprising administering to the patient the compound of in an amount effective to treat the patient. The present disclosure relates to compounds that are useful as modulators of α7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia.The α7 nAChR is a fast desensitizing ligand-gated ion channel that has high permeability to Ca. In human brain, α7 nAChRs are highly expressed in the cortex and hippocampus, regions associated with cognition, see for example, Breese et al. (1997) 387: 385-398. In neurons, α7 nAChRs are localized in both pre-synaptic and post-synaptic structures, where activation of the receptor can modulate neurotransmitter release, neuronal excitability, and intracellular signalling, see for example, Frazier et al. (1998) 18: 1187-1195.Cognitive impairments are prevalent in many neurological and psychiatric diseases, including Alzheimer's disease (AD), schizophrenia, and Parkinson's disease, and dysfunction in cholinergic signalling contributes to ...

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Номер записи: 32
05-02-2015 дата публикации

NOVEL GLP-1 RECEPTOR MODULATORS

Номер: US20150038416A1
Автор: Boehm Marcus F., Brahmachary Enugurthi, Fowler Thomas, Huang Liming, Knaggs Michael, Martinborough Esther, Meghani Premji, Moorjani Manisha, Novak Andrew, Tamiya Junko, Yeager Adam R.
Принадлежит:

The invention relates to compounds that modulate the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds are act as modulators or potentiators of GLP-1 receptor on their own, or with receptor ligands including GLP-1 peptides GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “” represents either or both the R and S form of the compound): 124-. (canceled)28. The method of wherein the malcondition is type I diabetes claim 27 , type II diabetes claim 27 , gestational diabetes claim 27 , obesity claim 27 , excessive appetite claim 27 , insufficient satiety or metabolic disorder.29. The method of wherein the malcondition is type I diabetes or type II diabetes.3029. The method of any one of - wherein A is a 5- or 6-membered heteroaryl group.3229. The method of any one of - wherein C is aryl.3429. The method of any one of - wherein B is heterocyclyl.3629. The method of any one of - wherein the compound is administered in combination with a second medicament.37. The method of wherein the second medicament is an agonist or modulator for glucagon receptor claim 36 , GIP receptor claim 36 , GLP-2 receptor claim 36 , or PTH receptor claim 36 , or glucagon-like peptide 1 (GLP-1) receptor.38. The method of wherein the second medicament is exenatide claim 36 , liraglutide claim 36 , taspoglutide claim 36 , albiglutide claim 36 , or lixisenatide.39. The method of wherein the second medicament is a DPPIV inhibitor. The invention relates to compounds that bind the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, and methods of their therapeutic and/or prophylactic use. The present invention is directed to compounds adapted to act as modulators or potentiators of GLP-1 receptor, including peptides GLP-1(7-36) and GLP-1(9-36), as well as peptide-based therapies such as exenatide and ...

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Номер записи: 33
05-02-2015 дата публикации

THIADIAZOLIDINEDIONES AS GSK-3 INHIBITORS

Номер: US20150038538A1
Автор: DE CRISTOBAL BLANCO Javier, DOMÍNGUEZ CORREA Juan Manuel, Fuertes Huerta Ana, HERRERO SANTOS Susana, López Ogalla Javier, MARTÍNEZ MONTERO Olga, Medina Padilla Miguel, Palomo Nicolau Francisco, PÉREZ DE LA CRUZ MORENO María Ángeles, RODRÍGUEZ SALGUERO Beatriz, Sánchez-Quesada Jorge
Принадлежит: ASD THERAPEUTICS PARTNERS LLC

The present invention relates to new thiadiazolidinediones of formula (I), or any pharmaceutically acceptable salt, solvate or prodrug thereof, and its use in the treatment of a disease in which glycogen synthase kinase 3 (GSK-3) is involved, particularly neurodegenerative diseases, inflammatory and autoimmune diseases and cardiovascular disorders. Additionally, there is provided a process for preparing such compounds, as well as pharmaceutical compositions comprising them. 2. The compound according to claim 1 , wherein the aryl radical in the substituent Ris phenyl.3. The compound according to claim 1 , wherein m is 1.4. The compound according to claim 1 , wherein Rand Rare hydrogen.5. The compound according to claim 1 , wherein n is 0.6. The compound according to claim 1 , wherein n is 1 and Ris —CO(O)R″ claim 1 , wherein R″ is an alkyl group.7. The compound according to claim 1 , wherein Ris ethyl or methyl claim 1 , optionally substituted with hydroxyl claim 1 , heterocyclyl or —C(O)OR′ claim 1 , wherein R′ is an alkyl group.10. A process according to claim 9 , where the steps 1 and 2 are performed in the absence of any solvent.11. A pharmaceutical composition comprising a compound of Formula (I) as defined in claim 1 , or a salt claim 1 , solvate or prodrug thereof claim 1 , and at least one pharmaceutically acceptable carrier claim 1 , adjuvant claim 1 , and/or vehicle.12. (canceled)13. A method for the therapeutic treatment of a cognitive claim 1 , neurodegenerative or neurological disease or condition claim 1 , said method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of Formula (I) as defined in claim 1 , or a salt claim 1 , solvate or prodrug thereof.14. A method for the therapeutic treatment of a disease or condition selected from diabetes claim 1 , inflammatory and autoimmune diseases claim 1 , cardiovascular disorders claim 1 , and pathologies selected from metabolic syndrome X claim 1 , ...

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Номер записи: 34
09-02-2017 дата публикации

Metabotropic Glutamate Receptor Positive Allosteric Modulators (PAMS) and Uses Thereof

Номер: US20170036987A1
Автор: COSFORD Nicholas D. P., DHANYA Raveendra Panickar, SHEFFLER Douglas J.
Принадлежит:

Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor positive allosteric modulators (PAMS), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds. 3. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': '1', 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'Lis absent, —CH—, —CHCH—, —CHCHCH—, or —CHCHCHCH—.'}4. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': '1', 'Lis absent.'}5. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sub': 1', '6, 'Z is halogen, or C-Calkyl.'}6. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sub': 3', '2', '3, 'Z is —CH, or —CHCH.'}9. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': 1', '4', '5, 'Ris —OH or —N(RR).'}10. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': '4', 'sub': 1', '6', '1', '6, 'X is —OH, —OR, C-Calkyl, or C-Cfluoroalkyl.'}11. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': 2', '4, 'sub': 1', '6', '1', '6, 'Ris hydrogen, halogen, —CN, —OH, —OR, substituted or unsubstituted C-Calkyl, or substituted or unsubstituted C-Cfluoroalkyl.'}12. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': '3', 'sub': 1', '6', '3', '6, 'Ris C-Calkyl, or C-Ccycloalkyl.'}13. The compound of any one of - , or a pharmaceutically acceptable salt thereof , wherein:{'sup': '3', 'sub': 3', '2', '3', '2', '2', '3', '3', '2', '2', '2', '2', '3', '3', '2', '3', '2', '3', '2', '3', '3, 'Ris —CH, —CHCH, —CHCHCH, —CH(CH), —CHCHCHCH, —CH(CH)CHCH, —CHCH(CH), —C(CH), cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.'}14. The compound of any one of - , or a pharmaceutically acceptable salt thereof , ...

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Номер записи: 35
08-02-2018 дата публикации

PARTICLES FOR ELECTROPHORETIC DISPLAYS

Номер: US20180037744A1
Автор: Farrand Louise Diane, Goulding Mark John, James Mark, Lutz Christopher, Smith Nathan, Wilson Jonathan Henry
Принадлежит:

This invention relates to polymer particles preferably with surface functionality for charge retention, a process for their preparation, the use of these particles for the preparation of an electrophoretic device, electrophoretic displays comprising such particle, and new polymerisable dyes. 118.-. (canceled)19. A coloured polymer particle for use in electrophoretic devices comprising at least one A-B diblock copolymer comprising a hydrophobic polymer block A and a hydrophilic polymer block B containing a charge or being chargeable , and monomer units of at least one monomer , of at least one polymerisable dye , optionally of at least one charged co-monomer , and optionally of at least one crosslinking co-monomer.20. The coloured polymer particle according to claim 19 , wherein block A is a polymethylmethacrylate block.21. The coloured polymer particle according to claim 19 , wherein block B comprises amino groups or carboxylic acid groups.22. The coloured polymer particle according to claim 19 , wherein block B is charged with 0.2% to 100% permanent charge based on partially or completely quaternised nitrogen groups or partially or completely neutralised acid groups.23. The coloured polymer particle according to claim 19 , wherein a polymerisable dye comprises a chromophore claim 19 , at least one polymerisable group claim 19 , optionally at least one linker group claim 19 , and optionally at least one charged group is used.24. The coloured polymer particle according to claim 19 , wherein the polymer particles have a diameter of 50-1000 nm.25. The coloured polymer particle according to claim 19 , wherein a water-soluble polymerisable dye is used.27. A process for the preparation of coloured polymer particles for use in electrophoretic devices claim 19 , comprisinga) the reaction of at least one monomer, at least one A-B diblock copolymer comprising a hydrophobic polymer block A and a hydrophilic polymer block B containing a charge or being chargeable, at least one ...

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Номер записи: 36
24-02-2022 дата публикации

SYNTHESIS OF 3-METHYL-1,2,4-THIADIAZOLE-5-CARBOHYDRAZIDE OR OF THE METHYL-d3 DEUTERATED FORM THEREOF

Номер: US20220056000A1
Автор: Dutheuil Guillaume, Hoveyda Hamid
Принадлежит:

The present invention relates to a method of synthesis of compound (I), wherein Rrepresents methyl or methyl-d3, thus corresponding to 3-methyl-1,2,4-thiadiazole-5-carbohydrazide or to the methyl-d3 deuterated form thereof. These compounds are useful as key intermediates in the synthesis of pharmaceutical compounds, especially fezolinetant and deuterated fezolinetant. 2. The process according to claim 1 , wherein X represents bromo or iodo.3. The process according to or claim 1 , wherein Rrepresents methyl or ethyl.4. The process according to any one of to claim 1 , wherein the alkoxycarbonylation reaction of step a) is performed in presence of carbon monoxide claim 1 , a palladium catalyst claim 1 , a base and an alcohol solvent claim 1 , and optionally in presence of an organophosphorus ligand.5. The process according to claim 4 , wherein the palladium catalyst is Pd(OAc) claim 4 , the organophosphorus ligand is 4 claim 4 ,5-bis(diphenylphosphino)-9 claim 4 ,9-dimethylxanthene (Xantphos) claim 4 , the base is sodium acetate and the solvent is selected from ethanol claim 4 , methanol and mixtures of methyl tert-butyl ether with ethanol or methanol.6. The process according to or claim 4 , wherein step a) is performed in ethanol as solvent or in a mixture of ethanol and methyl tert-butyl ether.7. The process according to any one of to claim 4 , wherein step a) is performed at a temperature ranging from 50° C. to 150° C.8. The process according to any one of to claim 4 , wherein step a) is performed in presence of Fe(CO).9. The process according to claim 4 , wherein the palladium catalyst is bis(triphenylphosphine)palladium chloride (Pd(PPh)Cl) claim 4 , the base is triethylamine and the solvent is ethanol.10. The process according to any one of to claim 4 , wherein the alkoxycarbonylation reaction of step a) is performed by lithium exchange by first contacting the compound of Formula (III) with an organolithium reagent; and then adding a chloroformate or a ...

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Номер записи: 37
07-02-2019 дата публикации

Modulators of indoleamine 2,3-dioxygenase

Номер: US20190040023A1
Автор: Hamilton D Dickson, Martha Alicia De La Rosa, Pek Yoke Chong, Vicente Samano, Vincent Wing-Fai TAI, Wieslaw Mieczyslaw Kazmierski
Принадлежит: GlaxoSmithKline Intellectual Property Development Ltd

Provided are compounds and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of HIV; including the prevention of the progression of AIDS and general immunosuppression.

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Номер записи: 38
18-02-2016 дата публикации

Methods of producing sulfilimine compounds

Номер: US20160046580A1
Автор: Timothy J. Adaway
Принадлежит: DOW AGROSCIENCES LLC

Methods of producing a sulfilimine compound, such as N-cyano-S-methyl-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]sulfilimine or other substituted sulfilimine compound. The method includes combining a sulfide compound, cyanamide, a hypochlorite compound, and a base, and oxidizing the sulfide compound to form the sulfilimine compound. The sulfide compound may include a 2-trifluoromethyl-5-(1-substituted)alkyl-thiopyridine compound. The base may include sodium hydroxide. A buffer, such as a phosphate buffer, may, optionally, be used in the reaction.

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Номер записи: 39
15-02-2018 дата публикации

MOLECULES HAVING CERTAIN PESTICIDAL UTILITIES, AND INTERMEDIATES, COMPOSITIONS, AND PROCESSES RELATED THERETO

Номер: US20180044332A1
Автор: Baum Erich W., Crouse Gary D., Fischer Lindsey G., Giampitro Natalie C., Petkus Jeff, Sparks Thomas C., Ward Andrew L.
Принадлежит:

This disclosure relates to the field of molecules having pesticidal utility against pests in phyla Nematoda, Arthropoda, and/or Mollusca, processes to produce such molecules and intermediates used in such processes, compositions containing such molecules, and processes of using such molecules against such pests. These molecules may be used, for example, as nematicides, acaricides, insecticides, miticides, and/or molluscicides. This document discloses molecules having the following formula (“Formula One”). 3. A molecule according to and having a structure listed in Table 4.4. A process comprising: applying a molecule according to to a locus to control a pest claim 1 , in an amount sufficient to control such pest. This Application is a continuation-in-part of U.S. patent application Ser. No. 14/959,377 filed on Dec. 4, 2015, which is a divisional of U.S. patent application Ser. No. 14/208,394 filed on Mar. 13, 2014, now U.S. Pat. No. 9,249,133, which claims the benefit and priority from U.S. provisional application Ser. No. 61/784,020 filed on Mar. 14, 2013, where the contents of which are incorporated by reference in their entireties.The U.S. patent application Ser. No. 14/959,377 filed on Dec. 4, 2015 is also a continuation of U.S. patent application Ser. No. 14/661,389 filed on Mar. 18, 2015, now U.S. Pat. No. 9,278,964, which is a continuation of U.S. patent application Ser. No. 14/208,430 filed on Mar. 13, 2014, now U.S. Pat. No. 9,029,560, which claims the benefit and priority from U.S. provisional application Ser. No. 61/784,020, which was filed on Mar. 14, 2013, where the contents of which are incorporated by reference in their entireties.This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Nematoda, Arthropoda, and Mollusca, processes to produce such molecules and intermediates used in such processes, compositions containing such molecules, and processes of using such molecules against such pests. These molecules ...

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Номер записи: 40
08-05-2014 дата публикации

HETEROCYCLIC INHIBITORS OF NECROPTOSIS

Номер: US20140128437A1
Автор: Cuny Gregory D., Degterrev Alexei, JR. John A., Proco, Teng Xin, Yuan Junying
Принадлежит:

The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I) and (Ia)-(Ie) and are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring the compounds of the invention. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role. 2. The compound of claim 1 , wherein{'sup': '1', 'Ris selected from methyl, ethyl, propyl, and butyl;'}{'sup': '2', 'Ris selected from hydrogen, halogen and cyano; and'}{'sup': '3', 'Ris selected from hydrogen, (S)-methyl, (S)-ethyl, (S)-propyl, and (S)-butyl;'}or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.3. The compound of claim 2 , wherein{'sup': '1', 'Ris selected from methyl and isopropyl;'}{'sup': '2', 'Ris selected from hydrogen, chlorine, bromine and cyano;'}{'sup': '3', 'Ris selected from hydrogen and (S)-methyl; and'}{'sup': 1', '2, 'each Xand Xis independently chlorine or fluorine;'}or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.4. The compound of claim 3 , wherein Ris methyl claim 3 , Ris cyano claim 3 , Ris (S)-methyl claim 3 , Xis chlorine claim 3 , and Xis fluorine;or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.8. The compound of claim 7 , wherein Ris F claim 7 , Ris H claim 7 , and Ris Cl claim 7 ,or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.9. The compound of claim 7 , wherein Ris F claim 7 , Ris a halogen claim 7 , and Ris Cl claim 7 ,or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.10. The compound of claim 7 , wherein Ris F claim 7 , Ris H claim 7 , and Ris F claim 7 ,or any pharmaceutically acceptable salt thereof, or stereoisomer thereof.11. The compound of claim 7 ...

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Номер записи: 41
13-02-2020 дата публикации

ACYL SULFONAMIDE NAV1.7 INHIBITORS

Номер: US20200048240A1
Автор: Guernon Jason M., Wu Yong-Jin
Принадлежит:

The present disclosure relates to compounds of formula I which inhibit NaV1.7, and include pharmaceutically acceptable salts, compositions comprising such compounds, and methods using and making such compounds and compositions. (I) 2. A compound of where Ris thiazolyl or thiadiazolyl.3. A compound of where Rand Rare halo.4. A compound of where Ris alkyl claim 1 , (cycloalkyl)alkyl claim 1 , or cycloalkyl claim 1 , and is substituted with 0-2 substituents selected from hydroxyalkyl claim 1 , alkoxyalkyl claim 1 , hydroxy claim 1 , alkoxy claim 1 , tetrahydrofuranyl claim 1 , tetrahydropyranyl claim 1 , and hexahydrofurofuranyl.5. A compound of where Ris (RRN)alkyl claim 1 , ((RRN)cycloalkyl)alkyl claim 1 , (((RRN)alkyl)cycloalkyl)alkyl claim 1 , (RRN)cycloalkyl claim 1 , or ((RRN)alkyl)cycloalkyl claim 1 , and is substituted with 0-3 halo or alkyl substituents.6. A compound of where Ris a [1-4.1-4.0-2]bridgedbicyclicamine with 0-3 halo or alkyl substituents.7. A compound of where A is N(R)(R).8. A compound of selected from the group consisting of5-Chloro-2-fluoro-4-((2-(piperidin-4-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;5-Chloro-2-fluoro-4-((2-(piperidin-3-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;5-Chloro-2-fluoro-4-((2-(piperidin-2-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;5-Chloro-2-fluoro-4-((2-(piperidin-2-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;5-Chloro-2-fluoro-4-((2-(1-methylpiperidin-4-yl)ethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;5-Chloro-2-fluoro-4-((morpholin-2-ylmethyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;4-(((1,4-Dioxan-2-yl)methyl)amino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;5-Chloro-2-fluoro-4-(((1-(morpholinomethyl)cyclopropyl)methyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;5-Chloro-2-fluoro-4-(((tetrahydro-2H-pyran-3-yl)methyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;5-Chloro-2-fluoro-4-(((tetrahydro-2H-pyran-2-yl)methyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;5-Chloro-2-fluoro-4 ...

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Номер записи: 42
15-05-2014 дата публикации

AROMATIC AMIDES AND USES THEREOF

Номер: US20140135332A1
Автор: COLLINS Ian, Czaplewski Lloyd George, Davies David, Haydon David John, MITCHELL Jeffrey Peter, Offermann Daniel, Palmer James T, Pitt Gary Robert William, Stokes Neil Robert
Принадлежит: BIOTA SCIENTIFIC MANAGEMENT PTY LTD

The present invention provides compounds of Formula (I): and salts, racemates, isomers, diastereoisomers, enantiomers, hydrates, solvates, N-oxides, pharmaceutically acceptable derivatives or prodrugs thereof. Also provided the use of these compounds as antibacterials, compositions comprising them and processes for their manufacture. 2. A compound according to wherein W is an optionally substituted 5-6-membered monocyclic heteroaryl or a 9-10-membered fused bicyclic heteroaryl group.4. A compound according to wherein A is an optionally substituted Caryl or an optionally substituted 5-6 membered heteoraryl containing one claim 1 , two claim 1 , three or four heteroatoms independently selected from O claim 1 , N and S.5. A compound according to wherein A Ris selected from Calkyl-R claim 1 , Calkyl and Calkenyl where each alkyl and alkenyl group may be optionally substituted with one or more Rgroups and t is an integer selected from 0 claim 1 , 1 claim 1 , 2 and 3.6. A compound according to wherein Ris Calkyl-Rand t is 1 claim 1 , 2 or 3.7. A compound according to wherein Ris selected from OR claim 1 , (C═O)R claim 1 , O(C═O)R claim 1 , C(═O)OR claim 1 , N(R) claim 1 , NRC(═O)R claim 1 , C(═O)N(R) claim 1 , NRC(═O)OR claim 1 , OC(═O)N(R) claim 1 , C(═O)N—NC(═O)R claim 1 , NHC(═O)NHCalkyl claim 1 , NHS(O)R claim 1 , S(O)R claim 1 , OS(O)R claim 1 , OP(═O)(OR)and P(═O)(OR)where Rand Rare as defined in .8. A compound according to in the form of a racemate claim 1 , a single enantiomer or mixtures thereof.11. A method of treating a bacterial infection in a subject comprising administering an effective amount of a compound as defined in or a pharmaceutically acceptable salt claim 1 , racemate claim 1 , isomer claim 1 , diastereoisomer claim 1 , enantiomer claim 1 , hydrate claim 1 , solvate claim 1 , N-oxide claim 1 , pharmaceutically acceptable derivative or prodrug thereof to the subject.12. A method according to wherein the compound is administered in combination with ...

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Номер записи: 43
21-02-2019 дата публикации

CATALYSTS

Номер: US20190055352A1
Автор: Chapman Andy, Chartoire Anthony, Hollis Emmalina, Kember Michael, Keyworth Colin, Williams Charlotte
Принадлежит:

The present invention relates to the field of polymerisation catalysts, and systems comprising these catalysts for polymerising carbon dioxide and an epoxide, a lactide and/or lactone, and/or an epoxide and an anhydride. The catalyst is of formula (I): 2. The catalyst of claim 1 , wherein at least one of Mor Mis Ni(II).3. The catalyst of claim 1 , wherein one of Mor Mis selected from Ni(II) and Ni(III)-X and the remaining occurrence of Mand Mis selected from Zn(II) claim 1 , Cr(III)-X claim 1 , Cr(II) claim 1 , Co(III)-X claim 1 , Co(II) claim 1 , Cu(II) claim 1 , Mn(III)-X claim 1 , Mn(II) claim 1 , Mg(II) claim 1 , Ni(II) claim 1 , Ni(III)-X claim 1 , Fe(II) claim 1 , Fe(III)-X claim 1 , Ti(II) claim 1 , Ti(III)-X claim 1 , V(II) claim 1 , V(III)-X claim 1 , Ge(IV)-(X)and Ti(IV)-(X).4. The catalyst of claim 3 , wherein the remaining occurrence of Mand Mis selected from Zn(II) claim 3 , Cr(III)-X claim 3 , Co(II) claim 3 , Cu(II) claim 3 , Mn(II) claim 3 , Mg(II) claim 3 , Ni(II) claim 3 , Ni(III)-X claim 3 , Fe(II) claim 3 , Fe(III)-X and V(II).5. The catalyst of claim 3 , wherein the remaining occurrence of Mand Mis selected from Zn(II) claim 3 , Cr(III)-X claim 3 , Co(II) claim 3 , Mn(II) claim 3 , Mg(II) claim 3 , Ni(II) claim 3 , Ni(III)-X claim 3 , Fe(II) claim 3 , and Fe(III)-X.6. The catalyst of claim 3 , wherein the remaining occurrence of Mand Mis selected from any of: Zn(II) claim 3 , Mg(II) claim 3 , Ni(II) claim 3 , Co(II) claim 3 , Co(III)-X and Ni(III)-X.7. The catalyst of claim 1 , wherein both Mand Mare Ni(II).8. The catalyst of claim 1 , wherein Ris selected from substituted or unsubstituted alkylene and substituted or unsubstituted arylene.9. The catalyst of claim 1 , wherein Ris selected from substituted or unsubstituted alkylene claim 1 , alkenylene claim 1 , alkynylene claim 1 , heteroalkylene claim 1 , heteroalkenylene claim 1 , heteroalkynylene claim 1 , arylene claim 1 , and cycloalkylene.10. The catalyst of claim 1 , wherein Ris selected ...

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Номер записи: 44
02-03-2017 дата публикации

N-ARYLAMIDINE-SUBSTITUTED TRIFLUOROETHYL SULFIDE DERIVATIVES AS ACARICIDES AND INSECTICIDES

Номер: US20170057914A1
Автор: ALIG Bernd, Becker Angela, CEREZO-GALVEZ SILVIA, FISCHER Reiner, Goergens Ulrich, Gomibuchi Takuya, HAHN Julia Johanna, ILG Kerstin, ITO Masahito, KOEHLER Adeline, Moradi Wahed Ahmed, Schwarz Hans-Georg, Shibuya Katsuhiko, Shimojo Eiichi, VOERSTE Arnd, Yamazaki Daiei
Принадлежит:

The present invention relates to novel N-arylamide-substituted trifluoroethyl sulfide derivatives of the formula (I) This application is a divisional application of U.S. application Ser. No. 14/366,715 (filed Jun. 19, 2014), which is a §371 National Stage Application of PCT/EP2012/075269 (filed Dec. 12, 2012), which claims priority to EP 11194855.0 (filed Dec. 21, 2011), the contents of each of which are incorporated herein by reference.Field of the InventionThe present invention relates to novel N-arylamidine-substituted trifluoroethyl sulfide derivatives, to their use as acaricides and insecticides for controlling animal pests and to processes and intermediates for their preparation.Description of Related ArtVarious substituted N-arylamidines and their insecticidal and acaricidal action have already been described in the literature in WO 2007/131680.On application, the active compounds already known from the publications mentioned above have disadvantages, be it that they may have no or else only insufficient insecticidal and/or acaricidal activity against animal pests, in particular at relatively low application rates.Accordingly, it is an object of the present invention to provide corresponding N-arylamidine-substituted trifluoroethyl sulfide derivatives which can be employed as insecticides and/or acaricides with satisfactory insecticidal and/or acaricidal activity against animal pests, in particular at relatively low application rates, with high selectivity and improved compatibility in crops of useful plants.The present invention now provides novel compounds of the formula (I)in whichIf appropriate, the compounds of the formula (I) may be present in various polymorphic forms or as mixtures of different polymorphic forms. Both the pure polymorphs and the polymorph mixtures are provided by the invention and can be used according to the invention.The compounds of the formula (I) optionally comprise diastereomers or enantiomers and also rotamers, tautomers and ...

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Номер записи: 45
20-02-2020 дата публикации

HETEROCYCLIC P2X7 ANTAGONISTS

Номер: US20200055831A1
Автор: CUSANO Valentina, Pevarello Paolo, SEVERI Elda, SODANO Mariangela, Thomas Russell, VITALONE Rocco
Принадлежит:

Disclosed are compounds of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions containing them, and to a process for the preparation of the compounds: 2. A compound of Formula (I) or a pharmaceutically acceptable salt thereof according to wherein:{'sup': '1', 'Ris independently selected from hydrogen atom, mono or substituted ammines, or aliphatic, aromatic, heteroaliphatic or heteroaromatic ring selected from cyclopentyl, cyclohexyl, piperidine, morpholine, pyrrolidine, piperazine, phenyl, pyridine, oxazole, pyrazole or thiazole.'}3. A compound of Formula (I) or a pharmaceutically acceptable salt thereof according to wherein:{'sup': '2', 'sub': 3', '7', '1', '4', '1', '4', '3', '5, 'Ris independently selected from phenyl, pyridine, pyrimidine, pyrazole, imidazole, naphthalene, quinoline, thiazole, furan, oxazole, oxadiazole, C-Ccycloalkyl, pyran, tetrahydropyran, dioxane, C-Calkyloxy, aliphatic, aromatic or heteroaromatic bicyclic rings, C-Calkyl chain or C-Calkynyl chain.'}4. A compound of Formula (I) or a pharmaceutically acceptable salt thereof according to wherein:{'sup': '1', 'Ris independently selected from hydrogen atom or from the group consisting of cyclopentyl, cyclohexyl, piperidine, morpholine, pyrrolidine, piperazine, ammines, phenyl, pyridine, oxazole, pyrazole or thiazole; and each of the above reported aliphatic, aromatic or heteroaliphatic or heteroaromatic ring may be condensed with another aromatic or heteroaromatic ring;'}{'sup': '2', 'sub': 3', '7', '1', '3', '1', '4', '3', '5, 'Ris independently selected from phenyl, pyridine, pyrimidine, pyrazole, imidazole, naphthalene, quinoline, thiazole, furan, oxazole, oxadiazole, C-Ccycloalkyl, pyran, tetrahydropyran, dioxane, aliphatic bicyclic rings, C-Calkyloxy, C-Calkyl chain or C-Calkynyl chain;'}n is 1 or 2;m is 0, 1 or 2;{'sup': 3', '4, 'sub': 3', '2', '3, 'Rand Rare, independently, —H, F, CH, —OH or —OCHCH;'}X is O or S;{'sup': '5', 'sub': '3', 'Ris H or —CH.'} ...

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Номер записи: 46
12-03-2015 дата публикации

CYCLIC CARBODIIMIDE COMPOUND, POLYESTER FILM, BACK SHEET FOR SOLAR CELL MODULE, AND SOLAR CELL MODULE

Номер: US20150068602A1
Автор: FUKUDA Makoto, Sakurai Seiya
Принадлежит: FUJIFILM Corporation

A polyester film including a cyclic carbodiimide compound represented by the following Formula (O-1) has good film thickness uniformity without increase in viscosity. Rand Rrepresent an alkyl group, an aryl group, or an alkoxy group; Rto Rand Rto Rrepresent a hydrogen atom, an alkyl group, an aryl group, or an alkoxy group; Xand Xrepresent a single bond, —O—, —CO—, —S—, —SO—, —NH—, or —CH—; and Lrepresents a divalent linking group. 2. The cyclic carbodiimide compound according to claim 1 , wherein both Rand Rin Formula (O-1) are hydrogen atoms.3. The cyclic carbodiimide compound according to claim 1 , wherein each of R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rin Formulas (O-1) and (O-2) independently represents a secondary or tertiary alkyl group claim 1 , or an aryl group.5. The polyester film according to claim 4 , wherein both Rand Rin Formula (O-1) are hydrogen atoms.6. The polyester film according to claim 4 , wherein each of R claim 4 , R claim 4 , R claim 4 , R claim 4 , Rand Rin Formulas (O-1) and (O-2) independently represents a secondary or tertiary alkyl group claim 4 , or an aryl group.7. The polyester film according to claim 4 , comprising the cyclic carbodiimide compound in an amount of 0.05% by mass to 5% by mass relative to 100% by mass of the polyester.8. The polyester film according to claim 4 , wherein a component derived from carboxylic acid in the polyester is a component derived from an aromatic dibasic acid or its derivative for forming an ester.9. The polyester film according to which is biaxially oriented. This application is a continuation application of International Application No. PCT/JP2013/062184, filed Apr. 25, 2013, which in turn claims the benefit of priority from Japanese Application No. 2012-113227, filed on May 17, 2012, and Japanese Application No. 2012-180258, filed on Aug. 15, 2012, the disclosures of which Applications are incorporated by reference herein in their entirety.1. Field of the InventionThe present ...

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Номер записи: 47
17-03-2016 дата публикации

CETP Inhibitors

Номер: US20160075724A1
Автор: Ali Amjad, Chen Yi-Heng, Deng Qiaolin, Dowst Adrian A., Hallet Gayle E., Hunt Julianne A., LI HONG, LU Zhijian, Napolitano Joann M., Quraishi Nazia, Sinclair Peter J., Smith Cameron J., Thompson Christopher F.
Принадлежит:

Compounds having the structures of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis: 221-. (canceled) This invention relates to a class of chemical compounds that inhibit cholesterol ester transfer protein (CETP) and therefore may have utility in the treatment and prevention of atherosclerosis.Atherosclerosis and its clinical consequences, coronary heart disease (CHD), stroke and peripheral vascular disease, represent a truly enormous burden to the health care systems of the industrialized world. In the United States alone, approximately 13 million patients have been diagnosed with CHD, and greater than one half million deaths are attributed to CHD each year. Further, this toll is expected to grow over the next quarter century as an epidemic in obesity and diabetes continues to grow.It has long been recognized that in mammals, variations in circulating lipoprotein profiles correlate with the risk of atherosclerosis and CHD. The clinical success of HMG-CoA Reductase inhibitors, especially the statins, in reducing coronary events is based on the reduction of circulating Low Density Lipoprotein cholesterol (LDL-C), levels of which correlate directly with increased risk for atherosclerosis. More recently, epidemiologic studies have demonstrated an inverse relationship between High Density Lipoprotein cholesterol (HDL-C) levels and atherosclerosis, leading to the conclusion that low serum HDL-C levels are associated with an increased risk for CHD.Metabolic control of lipoprotein levels is a complex and dynamic process involving many factors. One important metabolic control in man is the cholesteryl ester transfer protein (CETP), a plasma glycoprotein that catalyzes the movement of cholesteryl esters from HDL to the apoB containing lipoproteins, especially VLDL (see Hesler, C. B., et. al. (1987) 262(5), 2275-2282 ...

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Номер записи: 48
15-03-2018 дата публикации

NOVEL OXADIAZOLE DERIVATIVE AND PHARMACEUTICAL CONTAINING SAME

Номер: US20180072708A1
Автор: Kawai Akiyoshi, Yanagisawa Katsuhiko
Принадлежит:

An amyloid fibril formation inhibitor comprising a compound represented by the following general formulae (I) to (III): 4. The amyloid fibril formation inhibitor according to claim 1 , whereinin the general formula (I),{'sub': 6-12', '1-12, 'Ring A1 and Ring A3 are each independently a substituted or unsubstituted Caryl group or a substituted or unsubstituted Cheteroaryl group;'}Ring A2 is 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, or 1,3,4-thiadiazolyl;Q is —C(═O)—;X is —C(═O)—;{'sub': 2', 'm, 'Y is —(CH)—, where m is 1 or 2;'}{'sub': 2', 'n, 'Z is —(CH)—, where n is 1 or 2; and'}{'sub': 1', '1-10', '1-10', '1-10', '1-10, 'Ris a hydrogen atom, a Calkyl group, a Calkoxy group, a Chydroxyalkyl group, or a Calkoxyalkyl group.'}5. The amyloid fibril formation inhibitor according to claim 2 , whereinin the general formula (II),{'sub': 6-12', '1-12, 'Ring A1 and Ring A3 are each independently a substituted or unsubstituted Caryl group or a substituted or unsubstituted Cheteroaryl group;'}Ring A2 is 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, or 1,3,4-thiadiazolyl;n is 1 or 2;{'sub': 1', '2', '1-10', '1-10', '1-10', '1-10', '1-10', '1-10', '1-10', '1-10', '1-10, 'Rand Rare each independently a hydrogen atom, a Calkyl group, a Calkoxy group, a Chydroxyalkyl group, a Calkoxyalkyl group, a carboxyl group, an aminocarbonyl group, a Calkylaminocarbonyl group, a Cdialkylaminocarbonyl group, a Calkylaminoalkyl group, a Cdialkylaminoalkyl group, or a Caminoalkyl group;'}{'sub': x', '2', '1', 'x', '2', 'x', '2', '1', 'x', '2', '1, 'X is —NR—C(═O)—(CH)—, —NR—SO—, —C(═O)—NR—(CH)—, or —NR—(CH)—;'}1 is an integer of 0 to 2; and{'sub': x', '1-10', '1-10', '1-10', '1-10', '1-10', '1-10', '1-10', '1-10', '1-10, 'Ris a hydrogen atom, a Calkyl group, a Calkoxy group, a Chydroxyalkyl group, a Calkoxyalkyl group, a carboxyl group, an aminocarbonyl group, a Calkylaminocarbonyl group, a Cdialkylaminocarbonyl group, a Calkylaminoalkyl group, a Cdialkylaminoalkyl ...

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Номер записи: 49
05-03-2020 дата публикации

INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE

Номер: US20200069646A1
Автор: Balog James Aaron, Nara Susheel Jethanand, Roy Saumya, Seitz Steven P., Sistla Ramesh Kumar, Thangathirupathy Srinivasan, Thangavel Soodamani
Принадлежит:

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the disclosure. 2. The compound of claim 1 , wherein X is CH.3. The compound of claim 1 , wherein X is N.4. The compound of claim 1 , wherein Ris H.5. The compound of claim 1 , wherein Ris Calkyl.6. The compound of claim 1 , wherein Ris H.7. The compound of claim 1 , wherein Ris Calkyl.8. The compound of claim 1 , wherein Ris Calk-OCalkyl.9. The compound of claim 1 , wherein Ris H.10. The compound of claim 1 , wherein Ris Calkyl.11. The compound of claim 1 , wherein Ris phenyl optionally substituted with one claim 1 , two or three substituents independently selected from halogen claim 1 , Calk-O—Calkyl claim 1 , or —CN.12. The compound of claim 11 , wherein Ris 4-chlorophenyl claim 11 , 4-chloro-2-fluorophenyl claim 11 , 4-chloro-3-fluorophenyl claim 11 , 3-fluoro-4-methoxyphenyl claim 11 , 2-fluoro-4-methoxyphenyl claim 11 , or 4-cyano-3-methoxyphenyl.13. The compound of claim 1 , wherein Ris heteroaryl optionally substituted with one claim 1 , two or three substituents independently selected from halogen claim 1 , optionally substituted phenyl claim 1 , optionally substituted benzyl claim 1 , optionally substituted Calkyl claim 1 , Chaloalkyl claim 1 , Calk-O—Calkyl claim 1 , heterocyclyl claim 1 , and —CN.14. The compound of claim 13 , wherein Ris 1H-pyrazol-4-yl claim 13 , thiazol-2-yl claim 13 , furan-3-yl claim 13 , benzo[d][1 claim 13 ,3]dioxol-5-yl claim 13 , 2 claim 13 ,3-dihydrobenzofuran-5-yl claim 13 , benzofuran-5-yl claim 13 , benzo[b]thiophen-5-yl claim 13 , pyrimidin-5-yl claim 13 , 1H-indazol-4-yl claim 13 , 1H-pyrrolo[2 claim 13 ,3-c]pyridin-3-yl claim 13 , benzo[d]thiazol-2-yl claim 13 , imidazo[1 claim 13 ,2-a]pyridin-2-yl claim 13 , benzo[c][ ...

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Номер записи: 50
05-03-2020 дата публикации

ARYLQUINAZOLINES

Номер: US20200069690A1
Автор: Buchstaller Hans-Peter, Emde Ulrich, Fuchss Thomas, Mederski Werner
Принадлежит:

The invention relates to novel compounds of the formula (I) which can be used for the inhibition of serine-threonine protein kinases and for the sensitisation of cancer cells to anticancer agents and/or ionising radiation. 114-. (canceled)1720-. (canceled)21. The method of claim 15 , wherein the cancer cells are sensitized to ionising radiation selected from photon irradiation claim 15 , proton irradiation claim 15 , heavy-ion irradiation and neutron irradiation.22. The method of claim 15 , wherein the cancer cells are sensitized to anticancer agents selected from alkylating agents claim 15 , platinum compounds claim 15 , topoisomerase inhibitors claim 15 , DNA-modifying agents claim 15 , anticancer antibiotics and alpha emitters.23. The method of claim 22 , whereinthe anticancer agents are alkylating agents selected from altretamine, bendamustine, busulfan, carmustine, chloroambucil, chloromethine, cyclophosphamide, dacarbazine, ifosfamide, improsulfan tosylate, lomustine, melphalan, mitobronitol, mitolactol, nimustine, ranimustine, temozolomide, thiotepa, treosulfan, mechloroetamine, carboquone, apaziquone, fotemustine, glufosfamide, palifosfamide, pipobroman, trofosfamide and uramustine; or whereinthe anticancer agents are platinum compounds selected from carboplatin, cisplatin, eptaplatin, miriplatin hydrate, oxaliplatin, lobaplatin, nedaplatin, picoplatin and satraplatin; or whereinthe anticancer agents are topoisomerase inhibitors selected from etoposide, irinotecan, razoxane and sobuzoxane; or whereinthe anticancer agents are DNA-modifying agents selected from amrubicin, bisantrene, decitabine, mitoxantrone, procarbazine, trabectedine, clofarabine, amsacrine, brostallicin, pixantrone and laromustine; or whereinthe anticancer agents are anticancer antibiotics selected from bleomycin, dactinomycin, doxorubicin, epirubicin, idarubicin, levamisol, miltefosine, mitomycin C, romidepsin, streptozocin, valrubicin, zinostatin, zorubicin, daunurobicin, plicamycin, ...

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Номер записи: 51
05-06-2014 дата публикации

AMIDINE COMPOUND OR SALT THEREOF

Номер: US20140155597A1
Автор: Fujino Noritomo, MORI Ayumu, Ono Naoya, Tanikawa Tetsuya, TSURUTA Risa, Tsutsui Yasuhiro, Ushiki Yasunobu, Ushiyama Fumihito, YAMAGUCHI Toru, Yamamoto Keiko
Принадлежит:

The purpose of the present invention is to provide a novel compound which has an anti-fungal activity on pathogenic fungi including fungi belonging to the genus , the genus and the genus and is useful as a medicinal agent. A compound represented by formula (I) (wherein Arepresents a nitrogen atom or a group represented by formula CR; Aand Aare the same as or different from each other and independently represent a nitrogen atom or a group represented by formula CH; Rrepresents an aryl group which may be substituted by 1 to 5 substituents independently selected from a substituent group (2) or the like; Rand Rare the same as or different from each other and independently represent a hydrogen atom, a halogen atom, a Calkyl group, a Chaloalkyl group or a Calkoxy group; and Rand Rare the same as or different from each other and independently represent a hydrogen atom, a Chaloalkyl group, a Calkyl group or the like) or a salt thereof is useful as an anti-fungal agent. 2. The compound or the salt thereof according to claim 1 , wherein Rand Rare the same or different and represent a hydrogen atom or a Calkyl group.3. The compound or the salt thereof according to claim 1 , wherein Rand Rare the same or different and represent a Calkyl group.5. The compound or the salt thereof according to claim 1 , wherein Rand Rare the same or different and represent a Calkyl group.6. The compound or the salt thereof according to claim 1 , wherein Ais a nitrogen atom or a group represented by a formula CH.7. The compound or the salt thereof according to claim 1 , wherein Ris a Ccycloalkyl group which may be substituted with 1 to 5 substituents selected from Substituent Group 1 claim 1 , a Calkyl group which may be substituted with 1 to 6 substituents selected from Substituent Group 1 claim 1 , an aryl group which may be substituted with 1 to 5 substituents selected from Substituent Group 2 claim 1 , a heterocyclic group which may be substituted with 1 to 5 substituents selected from ...

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Номер записи: 52
23-03-2017 дата публикации

THIADIAZOLE-SUBSTITUTED ARYLAMIDES AS P2X3 AND P2X2/3 ANTAGONISTS

Номер: US20170081320A1
Автор: Chen Li, Dillon Michael Patrick, Feng Lichun, Lai Yingjie, YANG Minmin
Принадлежит: Roche Palo Alto LLC

Compounds of the formula I: 177-. (canceled)79. The compound of claim 78 , wherein Ris phenyl substituted at the 4-position with methyl or halo and optionally substituted at the 2- and 6-positions with halo.80. The compound of claim 78 , wherein Ris 4-methyl-phenyl.81. The compound of claim 78 , wherein Ris pyridin 2-yl substituted with methyl or halo at the 5-position.82. The compound of claim 78 , wherein Ris 5-methyl-pyridin-2-yl.83. The compound of claim 78 , wherein R claim 78 , Rand Rare hydrogen.84. The compound of claim 78 , wherein Ris hydrogen.85. The compound of claim 78 , wherein Ris hydrogen.86. The compound of claim 78 , wherein Ris methyl.87. The compound of claim 78 , wherein Ris heteroaryl selected from pyridinyl claim 78 , pyrimidinyl claim 78 , and pyrazinyl claim 78 , each of which may be optionally substituted once or twice with methyl.88. The compound of claim 78 , wherein Ris: Calkoxy-Calkyl; hydroxy-Calkyl; or heteroaryl selected from pyridinyl claim 78 , pyrimidinyl claim 78 , and pyrazinyl claim 78 , each of which may be optionally substituted once or twice with methyl.89. The compound of claim 78 , wherein Ris hydroxymethyl claim 78 , methoxymethyl claim 78 , pyrazin-2-yl or 5-methyl-pyrazin-2-yl.90. The compound of claim 78 , wherein Ris hydroxymethyl claim 78 , methoxymethyl claim 78 , pyrazin-2-yl claim 78 , 5-methyl-pyrazin-2-yl claim 78 , or 6-methyl-pyridazin-3-yl.91. The compound of claim 78 , wherein Ris hydroxymethyl claim 78 , methoxymethyl claim 78 , 5-methyl-pyrazin-2-yl claim 78 , 2-methyl-pyrimidin-5-yl claim 78 , 5-methyl-pyrimidin-2-yl claim 78 , hydroxymethyl or methoxymethyl.92. The compound of claim 78 , wherein Ris methyl claim 78 , ethyl claim 78 , n-propyl claim 78 , n-butyl claim 78 , isopropyl claim 78 , isobutyl claim 78 , tert-butyl claim 78 , cyclopropyl claim 78 , cyclobutyl claim 78 , cyclopropylmethyl claim 78 , phenyl claim 78 , trifluoromethyl claim 78 , difluoromethyl claim 78 , fluoromethyl claim 78 , ...

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Номер записи: 53
21-03-2019 дата публикации

Amide-Sulfamide Derivatives, Compositions, and Uses Related to CXCR4 Inhibition

Номер: US20190084980A1
Автор: Bai Renren, Shi Qi, Shim Hyunsuk
Принадлежит: EMORY UNIVERSITY

This disclosure relates amide-sulfamide compounds disclosed herein and uses related to CXCR4 inhibition. In certain embodiments, the compounds have formula I, salts, derivatives, and prodrugs thereof wherein, A is a bridging aryl or heterocyclyl and Rand Rare further disclosed herein. In certain embodiments, the disclosure contemplates pharmaceutical compositions comprising compounds disclosed herein. In certain embodiments, the disclosure relates to methods of treating or preventing CXCR4 related diseases or conditions by administering an effective amount of a compound disclosed herein to a subject in need thereof. 2. The compound of claim 1 , wherein Ris pyrazolo[1 claim 1 ,5-a]pyridine.3. The compound of claim 1 , wherein Ris 2 claim 1 ,4-difluorophenyl or 3 claim 1 ,4-difluorophenyl.4. The compound of claim 1 , wherein Ris pyrimidine.5. The compound of claim 1 , wherein Ris 2 claim 1 ,3-dihydrobenzofuran.6. The compound of claim 1 , wherein Ris 1 claim 1 ,2 claim 1 ,3-thiadiazole.7. The compound of selected from:N-(4-((2,3-dihydrobenzofuran-5-sulfonamido)methyl)benzyl)pyrazolo[1,5-a]pyridine-2-carboxamide;N-(4-((2,4-difluorophenylsulfonamido)methyl)benzyl)pyrimidine-5-carboxamide;N-(4-((3,4-difluorophenylsulfonamido)methyl)benzyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide, andN-(4-(phenylsulfonamidomethyl)benzyl)-4-((pyrimidin-2-ylamino)methyl)benzamide.8. A pharmaceutical comprising a compound of or salt or derivative or prodrug thereof and a pharmaceutically acceptable excipient claim 1 , diluent claim 1 , or carrier.9. The pharmaceutical composition of further comprising another active ingredient.10. A method of treating or preventing cancer comprising administering pharmaceutical composition comprising a compound of to a subject in need thereof.11. A method of treating or preventing cancer comprising administering pharmaceutical composition comprising a compound of in combination with another active ingredient to a subject in need thereof12. A method of ...

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Номер записи: 54
30-03-2017 дата публикации

Arginine methyltransferase inhibitors and uses thereof

Номер: US20170088529A1
Автор: Gideon Shapiro, Lorna Helen Mitchell, Richard Chesworth
Принадлежит: Epizyme Inc

Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

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Номер записи: 55
07-04-2016 дата публикации

NOVEL HISTONE DEACETYLASE INHIBITORS

Номер: US20160096804A1
Автор: Cecil Alexander R., MacCormick Somhairle, Nodes William J., Shuttleworth Stephen J., Silva Franck A., Tomassi Cyrille D.
Принадлежит:

The present invention is a compound of the formula or a pharmaceutically acceptable salt thereof. The compounds are useful as HDAC inhibitors. 3. A compound according to claim 2 , wherein W is —CONHOH.4. A compound of claim 3 , wherein each L is independently selected from a 5 or 6-membered nitrogen-containing heteroaryl claim 3 , which is optionally fused to a benzene.5. A compound of claim 1 , wherein in both L groups claim 1 , the atom that is directly bonded to the N is a carbon claim 1 , and at least one nitrogen atom is directly bonded to said carbon.6. A compound of claim 1 , wherein L is independently selected from pyridinyl claim 1 , pyrimidinyl claim 1 , pyridazinyl claim 1 , oxadiazolyl claim 1 , pyrazolyl claim 1 , thiadiazolyl claim 1 , pyrazinyl claim 1 , benzofused thiazolyl claim 1 , benzofused oxazolyl or benzofused imidazolyl claim 1 , preferably claim 1 , L is independently selected from pyridyl and pyrazinyl.7. A compound of claim 1 , wherein at least one L group is pyridyl or pyrazinyl.8. A compound of claim 1 , wherein Ris phenylene or phenylene substituted with a halogen.9. A compound of claim 1 , wherein at least one claim 1 , preferably both Rare H.10. A compound of claim 1 , wherein R′ that is attached to L is independently selected from the group consisting of H claim 1 , C-Calkyl or O—(C-Calkyl) claim 1 , halogen claim 1 , C-Cheterocycloalkyl claim 1 , aryl claim 1 , trifluoromethyl or heteroaryl.11. A compound of claim 1 , wherein at least one R′ is selected from the group consisting of H claim 1 , halogen claim 1 , CF claim 1 , C-Calkyl claim 1 , aryl optionally substituted with halogen claim 1 , heteroaryl optionally substituted with halogen or heterocycloalkyl.12. A compound of claim 1 , wherein at least one of the R′ that is attached to L is heterocycloalkyl.13. A compound according to claim 12 , wherein R′ attached to Ris hydrogen or halogen.14. A compound according to claim 12 , wherein at least one R′ is C-Calkyl optionally ...

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Номер записи: 56
07-04-2016 дата публикации

MOLECULES HAVING CERTAIN PESTICIDAL UTILITIES, AND INTERMEDIATES, COMPOSITIONS, AND PROCESSES RELATED THERETO

Номер: US20160096831A1
Автор: Baum Erich W., Crouse Gary D., Deamicis Carl, Fischer Lindsey G., Giampietro Natalie C., HAO Yan, JR. Ronald, Petkus Jeff, Ross, Sparks Thomas C., Ward Andrew
Принадлежит: DOW AGROSCIENCES LLC

This disclosure relates to the field of molecules having pesticidal utility against pests in phyla Nematoda, Arthropoda, and/or Mollusca, processes to produce such molecules and intermediates used in such processes, compositions containing such molecules, and processes of using such molecules against such pests. These molecules may be used, for example, as nematicides, acaricides, insecticides, miticides, and/or molluscicides. This document discloses molecules having the following formula (“Formula One”). 12-. (canceled)6. A molecule having a structure from compounds listed in Table P-one.7. A process comprising applying a molecule according to to a locus to control a pest claim 6 , in an amount sufficient to control such pest.8. A molecule having a structure from compounds listed in Table P-two.9. A process comprising applying a molecule according to to a locus to control a pest claim 8 , in an amount sufficient to control such pest.10. A molecule having a structure from compounds listed in Table 2A.11. A process comprising applying a molecule according to to a locus to control a pest claim 10 , in an amount sufficient to control such pest.12. A molecule having a structure from compounds listed in Table 2B.13. A process comprising applying a molecule according to to a locus to control a pest claim 12 , in an amount sufficient to control such pest.14. A molecule having a structure from compounds listed in Table 2C.15. A process comprising applying a molecule according to to a locus to control a pest claim 14 , in an amount sufficient to control such pest. This application is a divisional of U.S. patent application Ser. No. 14/208,394 filed on Mar. 13, 2014, which claims the benefit and priority from U.S. provisional application Ser. No. 61/784,020 filed on Mar. 13, 2013, where the contents of which are incorporated by reference in their entireties.This application is also a continuation of U.S. patent application Ser. No. 14/661,389 filed on Mar. 18, 2015, which is ...

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Номер записи: 57
28-03-2019 дата публикации

N1-PHENYLPROPANE-1,2-DIAMINE COMPOUNDS WITH SELECTIVE ACTIVITY IN VOLTAGE-GATED SODIUM CHANNELS

Номер: US20190092738A1
Автор: Greshock Thomas J., III Michael J., Kelly, Layton Mark E., Pero Joseph E., Roecker Anthony J., Zhang Ting
Принадлежит: Merck Sharp & Dohme Corp.

Disclosed are compounds of Formula A-1, or a salt thereof: Formula A-1, where J, K, Q and R1 are as defined herein, which compounds have properties for inhibiting sodium ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A-1 or their salts, and methods of treating pain (e.g. chronic pain), or cough or itch disorders using the same. 2) A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein one K is selected to be a linear claim 1 , branched claim 1 , or cycloalkyl comprising up to 6 carbon atoms claim 1 , which alkyl is partially or fully deuterated.4) A compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Jis a branched alkyl of up to 5 carbon atoms or a cyclic alkyl of up to 5 carbon atoms which is substituted on a ring carbon thereof with a linear claim 3 , branched claim 3 , or cycloalkyl moiety comprising up to 6 carbon atoms.5) A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Q is —(C═CF)—.6) A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Q is —(C═CH)—.7) A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Q is —(C═N)—.8) A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris Cl.9) A compound which is:(S)-5-chloro-2-fluoro-4-((2-(methylamino)-3-phenylpropyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;(S)-5-chloro-2-fluoro-4-((2-(methylamino)-3-phenylpropyl)amino)-N-(1,2,4-thiadiazol-5-yl)-benzenesulfonamide;(S)-5-chloro-2-fluoro-N-(5-fluorothiazol-2-yl)-4-((2-(methylamino)-3-phenylpropyl)amino)-benzenesulfonamide;(S)-5-chloro-2-fluoro-4-((3-(4-fluorophenyl)-2-(methylamino)propyl)amino)-N-(thiazol-2-yl)benzenesulfonamide;(S)-5-chloro-4-((3-cyclohexyl-2-(methylamino)propyl)amino)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;(S)-5-chloro-2-fluoro-4-((2-( ...

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Номер записи: 58
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: 59
08-04-2021 дата публикации

Il-17a modulators and uses thereof

Номер: US20210101886A1
Автор: Claudio Aquino, John R. Jacobsen, Margot G. Paulick, Martin S. Linsell, Paul R. Fatheree, Timothy J. Church, Wouter A. VAN DER LINDEN
Принадлежит: Dice Alpha Inc

The disclosure herein provides compounds and pharmaceutical compositions for the modulation of IL-17A useful for the treatment of inflammatory conditions, such as psoriasis.

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Номер записи: 60
19-04-2018 дата публикации

Therapeutic compounds and methods of use thereof

Номер: US20180105504A1
Автор: Birong Zhang, Daniel Sutherlin, Kwong Wah LAI, Michael Scott Wilson, Philippe Bergeron, Steven MCKERRALL
Принадлежит: Genentech Inc, Xenon Pharmaceuticals Inc

The invention provides a compound of formula I: or a pharmaceutically acceptable salt thereof, wherein the variables X, Y 1 -Y 5 , R 1 , R 2 , R 3 , R 4 , and Het have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.

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Номер записи: 61
26-04-2018 дата публикации

MOLECULES HAVING CERTAIN PESTICIDAL UTILITIES, AND INTERMEDIATES, COMPOSITIONS, AND PROCESSES RELATED THERETO

Номер: US20180111924A1
Автор: Demeter David A., Giampietro Natalie C., Sparks Thomas C., Webster Jeffery D.
Принадлежит:

This disclosure relates to the field of molecules having pesticidal utility against pests in phyla Nematoda, Arthropoda, and/or Mollusca, processes to produce such molecules and intermediates used in such processes, compositions containing such molecules, and processes of using such molecules against such pests. These molecules may be used, for example, as nematicides, acaricides, insecticides, miticides, and/or molluscicides. This document discloses molecules having the following formula (“Formula One” and “Formula Two”). 4. A process comprising: applying a molecule according to to a locus to control a pest claim 1 , in an amount sufficient to control such pest.5. A molecule having a structure from compounds listed in Table 1.6. A process comprising applying a molecule according to to a locus to control a pest claim 5 , in an amount sufficient to control such pest.7. A molecule having a structure from compounds listed in Table 2.8. A process comprising applying a molecule according to to a locus to control a pest claim 7 , in an amount sufficient to control such pest.9. A process according to claim 4 , wherein said pest is beet armyworm (BAW) claim 4 , cabbage looper (CL) claim 4 , or yellow fever mosquito (YFM).10. A molecule according to wherein at least one H is H or at least one C is C.11. A composition comprising a molecule according to and at least one other compound having insecticidal claim 1 , herbicidal claim 1 , acaricidal claim 1 , nematicidal claim 1 , or fungicidal activity.12. A composition comprising a molecule according to and a seed.13. A process comprising applying a molecule according to to a genetically modified plant claim 1 , or genetically-modified seed claim 1 , which has been genetically modified to express one or more specialized traits.14. A process comprising: orally administering; or topically applying; a molecule according to claim 1 , to a non-human animal claim 1 , to control endoparasites claim 1 , ectoparasites claim 1 , or both. ...

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Номер записи: 62
13-05-2021 дата публикации

MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE

Номер: US20210139467A1
Автор: De La Rosa Martha Alicia, KAZMIERSKI Wieslaw Mieczyslaw
Принадлежит:

Provided are IDO inhibitor compounds of Formula I and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases. 2. A compound or salt according to wherein Rand Rare independently H or CH claim 1 , or Rand Rtogether with the carbon to which they are bonded form a cyclopropyl ring.3. A compound or salt according to wherein Ris COH claim 1 , —C(O)—NH—S(O)—CF claim 1 , or —C(O)—NH—S(O)—CH.4. A compound or salt according to wherein Ris a pyridine claim 1 , thiadiazole claim 1 , pyrimidine claim 1 , pyrazine claim 1 , pyridazine claim 1 , triazol claim 1 , or thiazol claim 1 , optionally substituted with 1 or 2 substituent selected from the group consisting of F claim 1 , Cl claim 1 , and cyclopropyl.5. A compound or salt according to wherein Ris Calkyl or a 6-membered heterocycle containing an O or a N.6. A compound or salt according to wherein Ris unsubstituted.7. A compound or salt according to wherein Rand Rare independently H or CH claim 1 , or Rand Rtogether with the carbon to which they are bonded form a cyclopropyl ring; Ris COH claim 1 , —C(O)—NH—S(O)—CF claim 1 , or —C(O)—NH—S(O)—CH; Ris a pyridine claim 1 , thiadiazole claim 1 , pyrimidine claim 1 , pyrazine claim 1 , pyridazine claim 1 , triazol claim 1 , or thiazol claim 1 , optionally substituted with 1 or 2 substituent selected from the group consisting of F claim 1 , Cl claim 1 , and cyclopropyl; and Ris Calkyl or a 6-membered heterocycle containing an O or a N.8. A pharmaceutical composition comprising a compound or salt according to .9. A method of treating a disease or condition that would benefit from inhibition of IDO1 comprising the step of administration of a composition according to .10. The method of wherein in said disease or condition claim 9 , biomarkers of IDO activity are elevated.11. The method of wherein said biomarkers are plasma kynurenine or the plasma kynurenine/ ...

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Номер записи: 63
04-05-2017 дата публикации

COMPOSITIONS AND METHODS FOR TREATING CANCERS

Номер: US20170121297A1
Автор: Edderkaoui Mouad, Murali Ramachandran, PANDOL Stephen
Принадлежит: CEDARS-SINAI MEDICAL CENTER

The invention describes compounds that inhibit both HDAC and GSK3β (i.e., HDAC/GSK3β dual inhibitors). The invention further describes compositions containing these HDAC/GSK3β dual inhibitors, as well as methods and kits using these HDAC/GSK3β dual inhibitors to treat various medical conditions. The invention also provides methods and kits using a HDAC inhibitor and a GSK3β to treat various medical conditions, and compositions containing a HDAC inhibitor and a GSK3β. Medical conditions treatable with various embodiments of the invention include but are not limited to caners and tumors. 14107-. (canceled)108. A composition comprising a dual inhibitor of HDAC and GSK3β , wherein the dual inhibitor is a compound of or .109. The composition of claim 108 , further comprising a pharmaceutically acceptable carrier or excipient.110. The composition of claim 108 , wherein the composition further comprises an anti-cancer therapeutic agent.111. The composition of claim 110 , wherein the anti-cancer therapeutic agent is a chemotherapeutic agent.112. A method of treating claim 110 , preventing claim 110 , reducing the likelihood of having claim 110 , reducing the severity of and/or slowing the progression of a condition in a subject claim 110 , comprising:administering a therapeutically effective amount of a dual inhibitor of HDAC and GSK3β to the subject,{'claim-ref': [{'@idref': 'CLM-00001', 'claim 1'}, {'@idref': 'CLM-00009', '9'}], 'wherein the dual inhibitor is a compound of or , and'}wherein the condition is cancer or tumor,thereby treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of the condition in the subject.113. The method of claim 112 , wherein the condition is pancreatic cancer.114. The method of claim 112 , wherein the subject is a human.115. The method of claim 112 , further comprising administering an additional anti-cancer therapy.116. A composition comprising a HDAC inhibitor and a GSK3β inhibitor. ...

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Номер записи: 64
25-08-2022 дата публикации

New formulations

Номер: US20220267287A1
Автор: Jacob Westman, Thomas Edlund
Принадлежит: Betagenon Ab

There is provided an alkali metal salt of 4-chloro-N-[2-[(4-chlorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide and formulations thereof. This salt finds particular utility in the treatment or prevention of a disorder or condition ameliorated by the activation of AMPK.

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Номер записи: 65
25-04-2019 дата публикации

MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE

Номер: US20190119223A1
Автор: De La Rosa Martha Alicia, JOHNS Brian Alvin, KAZMIERSKI Wieslaw Mieczyslaw, SAMANO Vicente
Принадлежит: GlaxoSmithKline Intellectual Property Development Limited

Provided are IDO inhibitor compounds of Formula I and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases. 2. A compound or salt according to wherein n is 0.3. A compound according to wherein when one X is N claim 1 , said N is positioned adjacent to the carbon atom to which the depicted S—Ris bonded.4. A compound or salt according to wherein Ris Calkyl.5. A compound or salt according to wherein Ris t-butyl.6. A compound or salt according to wherein A is a benzene or pyridine ring.7. A compound or salt according to wherein Ris ortho to the depicted X-containing ring in Formula I.8. A compound or salt according to wherein Ris a 5-membered heterocycle or heteroaryl containing 1 to 4 heteroatoms selected from N claim 1 , S claim 1 , and O claim 1 , wherein said heterocycle or heteroaryl may optionally be substituted by a substituent selected from the group consisting of halogen claim 1 , Ccycloalkyl claim 1 , CHOH claim 1 , CHOCalkyl claim 1 , CalkyleneOC(O)Calkyl claim 1 , Calkyl optionally substituted by 1-3 halogens claim 1 , and wherein said CHOH is optionally converted into a prodrug by converting the CHOH group to a CHOC(O)CH claim 1 , CHOC(O)C(Calkyl) claim 1 , or OP(O)(OH)group claim 1 , or OP(O)(OCalkyl)group.9. A compound or salt according to wherein Ris a tetrazole ring optionally substituted by CHOH and wherein said CHOH is optionally converted into a prodrug by converting the CHOH group to a CHOC(O)CH claim 8 , CHOC(O)C(Calkyl) claim 8 , or OP(O)(OH)group claim 8 , or OP(O)(OCalkyl)group.10. A compound or salt according to wherein L is NHC(O)Calkylene.11. A compound or salt according to wherein L is NHC(O)CH.12. A compound or salt according to wherein Ris phenyl claim 1 , or a 4 to 6-membered heterocycle or heteroaryl containing 1 to 4 heteroatoms selected from N claim 1 , S claim 1 , and O; and wherein said phenyl claim 1 , ...

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Номер записи: 66
16-04-2020 дата публикации

THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF

Номер: US20200115354A1
Автор: BERGERON Philippe, Beveridge Ramsay, LAI Kwong Wah, Leclerc Jean-Philippe, Lemire Alexandre, MCKERRALL Steven, STURINO Claudio, SUTHERLIN Daniel, WILSON Michael Scott, Zhang Birong, Zhao Liang
Принадлежит:

The invention provides a compound of formula I: 12-. (canceled)6. The compound of claim 3 , wherein one of Yand Yis —CH(R)— and the other of Yand Yis —CH—; Ris not H; Yand Yare each —CH—; and Yand Yare each —CH—; or a pharmaceutically acceptable salt thereof.711-. (canceled)12. The compound of claim 6 , wherein Ris trifluoromethyl or phenyl that is optionally substituted with one to three substituents each independently selected from C-Calkyl claim 6 , cyano claim 6 , halo claim 6 , and C-Chaloalkyl; or a pharmaceutically acceptable salt thereof.13. The compound of claim 6 , wherein Ris trifluoromethyl or 3-trifluoromethylphenyl; or a pharmaceutically acceptable salt thereof.14. The compound of claim 6 , wherein Ris phenyl that is optionally substituted with one to three substituents Reach independently selected from the group consisting of C-Calkyl claim 6 , C-Ccycloalkyl claim 6 , C-Calkoxy claim 6 , C-Chaloalkoxy claim 6 , cyano claim 6 , halo claim 6 , hydroxy claim 6 , C-Ccycloalkoxy claim 6 , C-Chalocycloalkyl claim 6 , —S(C-Calkyl) claim 6 , —S(O)(C-Calkyl) claim 6 , —S(O)(C-Calkyl) claim 6 , —NH—NH(C-Calkyl) claim 6 , —N(C-Calkyl) claim 6 , 4-6 membered heterocycle claim 6 , and C-Chaloalkyl; or a pharmaceutically acceptable salt thereof.15. The compound of claim 6 , wherein Ris phenyl that is optionally substituted with one to three substituents Reach independently selected from the group consisting of C-Calkyl claim 6 , C-Ccycloalkyl claim 6 , C-Calkoxy claim 6 , C-Chaloalkoxy claim 6 , cyano claim 6 , halo claim 6 , and C-Chaloalkyl; or a pharmaceutically acceptable salt thereof.16. The compound of claim 6 , wherein Ris phenyl that is optionally substituted with one to three substituents Reach independently selected from the group consisting of F claim 6 , Cl claim 6 , CN claim 6 , C-Calkyl claim 6 , C-Ccycloalkyl claim 6 , C-Calkoxy claim 6 , C-Chaloalkyl claim 6 , and C-Chaloalkoxy; or a pharmaceutically acceptable salt thereof.17. The compound of claim ...

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Номер записи: 67
16-04-2020 дата публикации

MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE

Номер: US20200115374A1
Автор: De La Rosa Martha Alicia, KAZMIERSKI Wieslaw Mieczyslaw, SAMANO Vicente
Принадлежит:

Provided are IDO inhibitor compounds of Formula I and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases such as chronic viral infection, chronic bacterial infections, cancer, sepsis or a neurological disorder. 2. A compound or salt according to wherein one of Rand Ris H and the other is CH.3. A compound or salt according to wherein Ris COH.4. A compound or salt according to wherein Ris a 5 or 6-membered heterocycle or heteroaryl containing 1 to 3 heteroatoms selected from N claim 1 , and S.5. A compound or salt according to wherein Ris a pyridine claim 4 , thiadiazole claim 4 , pyrimidine claim 4 , pyrazine claim 4 , pyridazine claim 4 , triazol claim 4 , or thiazol.6. A compound or salt according to wherein Ris unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F claim 5 , Cl claim 5 , CN claim 5 , OCH claim 5 , CF claim 5 , cyclopropyl claim 5 , CONH claim 5 , CHCHOCH claim 5 , and CHOCH.7. A compound or salt according to wherein Ris a 6-membered heterocycle containing an O or a N.8. A compound or salt according to wherein Ris unsubstituted or substituted on the heteroatom by a substituent selected from the group consisting of halogen claim 7 , OH claim 7 , Calkyl; OCalkyl claim 7 , C(O)Ccycloalkyl claim 7 , C(O)Calkyl-O—Calkyl; C(O)Calkyl; C(O)—O—Calkyl claim 7 , and a 4 to 6-membered heterocycle or heteroaryl containing 1 to 4 heteroatoms selected from N claim 7 , S claim 7 , and O claim 7 , wherein said heterocycle or heteroaryl may optionally be substituted by 1 substituent selected from the group consisting of halogen claim 7 , Ccycloalkyl claim 7 , CHOH claim 7 , C(O)NH claim 7 , CN claim 7 , CHOCalkyl claim 7 , Calkyl optionally substituted by 1-3 halogens.9. A compound or salt according to wherein Ris unsubstituted or substituted on the heteroatom with OH or OCH.11. A pharmaceutical ...

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Номер записи: 68
24-07-2014 дата публикации

PIPERAZINE THIAZOLE DERIVATIVES USEFUL IN THE TREATMENT OF TAUOPATHIES SUCH AS ALZHEIMER'S DISEASE

Номер: US20140206699A1
Автор: Cecere Giuseppe, Griffioen Gerard, Nettekoven Matthias, Princen Katrien, Ratni Hasane, Rogres-Evans Mark, Vifian Walter
Принадлежит: REMYND NV

The present invention relates to a compound of formula (IA), wherein Gis lower alkyl; lower alkyl substituted by one or more halogens; cycloalkyl; tetrahydropyran-4-yl; phenethyl; phenethyl substituted by one or more halogens; phenoxymethyl; phenoxymethyl substituted by one or more halogens; benzyloxyethyl; benzyloxy-ethyl substituted by one or more halogens; or is —NRR; Ris hydrogen or lower alkyl; Ris lower alkyl; tetrahydropyran-4-yl; —CH-cycloalkyl; or cycloalkyl optionally substituted by lower alkyl substituted by one or more halogens; or Rand Rform together with the N-atom to which they are attached a heterocycloalkyl group with 4 or 5 carbon atoms, which is optionally substituted by one or more substituents selected from halogen; or lower alkyl substituted by one or more halogens; X is —CH— or —(CH)—; Ar is phenyl or pyridinyl; Ris halogen; lower alkyl; lower alkyl substituted by one or more halogens; or lower alkoxy; n is 1 or 2; or to a pharmaceutically active salt thereof, to a stereoisomeric form, including an individual diastereoisomer or enantiomer of the compound of formula (IA) as well as to a racemic or non-racemic mixture thereof. The present invention also relates to the use of a compound of formula (IA) for treating certain neurodegenerative disorders characterized by cytotoxic TAU misfolding and/or aggregation. 2. A compound of formula IA according to claim 1 , wherein X is —(CH)—.3. A compound of formula IA according to claim 2 , which compounds are1-[3-(4,4-Difluoro-piperidin-1-yl)-[1,2,4]thiadiazol-5-yl]-4-[2-(4-methoxy-phenyl)-ethyl]-piperazine1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(4,4-difluoro-piperidin-1-yl)-[1,2,4]thiadiazol-5-yl]-piperazine1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,3-difluoro-pyrrolidin-1-yl)-[1,2,4]thiadiazol-5-yl]-piperazine1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(4-fluoro-piperidin-1-yl)-[1,2,4]thiadiazol-5-yl]-piperazine1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(4-trifluoromethyl-piperidin-1-yl)-[1,2,4]thiadiazol-5-yl]-piperazine1-[2-(4- ...

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Номер записи: 69
14-05-2015 дата публикации

Substituted Acyloxyamidines as HCV NS3/4A Inhibitors

Номер: US20150133495A1
Автор: Lamarre Daniel
Принадлежит:

Disclosed herein is a compound of Formula I 3. The compound claim 1 , according to claim 1 , in which A is{'sub': 1', '7, '1) C-Calkyl,'}{'sub': 3', '7, '2) C-Calkyl,'}{'sub': 1', '7', 'n, '3) C-Calkyl-(aryl),'}{'sup': 3', '4, '4) (R)(R)C,'}{'sup': 5', '6', '7, '5) (R)(R)(R)C,'}6) aryl,7) heteroaryl,8) heterocyclyl, or9) biphenyl,{'sup': 10', '10, 'wherein the aryl is substituted with one or more Rsubstituents and the biphenyl is optionally substituted with one or more Rsubstituents;'}{'sup': '20', 'wherein the heteroaryl is substituted with one or more Rsubstituents; and'}{'sub': 1', '7', '1', '7, 'sup': '10', 'wherein the heterocyclyl is optionally substituted with C-Calkyl, aryl C-Calkyl, the aryl moiety being optionally substituted with one or more Rsubstituents.'}4. The compound claim 1 , according to claim 1 , in which G is1) aryl,{'sub': 1', '7, '2) C-Calkyl-aryl,'}3) heteroaryl, or{'sub': 1', '7, '4) C-Calkyl-heteroaryl,'}{'sup': '40', 'wherein the aryl and the heteroaryl are substituted with one or more Rsubstituents.'}5. The compound claim 1 , according to claim 1 , in which Rand Rare each independently1) H,{'sub': 1', '7, '2) C-Calkyl,'}{'sub': 3', '7, '3) C-Ccycloalkyl,'}4) aryl,5) heteroaryl, or{'sub': '2', '6) CH-heteroaryl,'}{'sup': 11', '20, 'wherein the aryl is optionally substituted with one or more Rsubstituents, and wherein the heteroaryl is optionally substituted with one or more Rsubstituents; or'}{'sup': 1', '2, 'when Ris H, Ris covalently bonded to G to form a 3 to 7-membered heterocycle containing one or more heteroatoms selected from N, S or O.'}6. The compound claim 1 , according to claim 1 , in which claim 1 , R claim 1 , Rwhen covalently bonded together form C-Ccycloalkyl or a heterocycle containing N or O heteroatoms optionally substituted with one or more Rsubstituents.7. The compound claim 1 , according to claim 1 , in which RRand Rare each independently{'sub': 1', '7, '1) C-Calkyl,'}{'sub': 3', '7, '2) C-Ccycloalkyl, or'}{'sup': 'X', ...

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Номер записи: 70
14-05-2015 дата публикации

Pde10 inhibitors and related compositions and methods

Номер: US20150133675A1
Автор: Jennifer Lynn Gage, Neil S. Cutshall, Thomas L. Little, Thomas Neil Wheeler
Принадлежит: Omeros Medical Systems Inc

Compounds that inhibit PDE10 are disclosed that have utility in the treatment of a variety of conditions, including (but not limited to) psychotic, anxiety, movement disorders and/or neurological disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, encephalitis, phobias, epilepsy, aphasia, Bell's palsy, cerebral palsy, sleep disorders, pain, Tourette's syndrome, schizophrenia, delusional disorders, drug-induced psychosis and panic and obsessive-compulsive disorders. Pharmaceutically acceptable salts, stereoisomers, solvates and prodrugs of the compounds are also provided. Also disclosed are compositions containing a compound in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for inhibiting PDE10 in a warm-blooded animal in need of the same.

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Номер записи: 71
10-05-2018 дата публикации

ARYLCYCLOPROPYLAMINE BASED DEMETHYLASE INHIBITORS OF LSD1 AND THEIR MEDICAL USE

Номер: US20180127406A1
Автор: ESTIARTE MARTINEZ Maria de los Àngeles, FYEE Matthew Colin Thor, MARTINELL PEDEMONTE Marc, ORTEGA MUÑOZ Alberto, TIRAPU FERNANDEZ DE LA CUESTA Iñigo
Принадлежит:

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). 157-. (canceled)59. The method of wherein said cancer is selected from prostate cancer claim 58 , breast cancer claim 58 , lung cancer claim 58 , colorectal cancer claim 58 , brain cancer claim 58 , skin cancer claim 58 , blood cancer claim 58 , leukemia claim 58 , lymphoma claim 58 , or myeloma.6078-. (canceled)79. The method of wherein (D) is oxadiazolyl claim 58 , wherein said oxadiazolyl has one substituent (R1).80. The method of wherein (B) has 0 claim 58 , 1 or 2 substituents R2.81. The method of wherein the substituents on the cyclopropyl moiety are in trans-configuration. The invention relates to (hetero)aryl cyclopropylamine compounds, particularly the compounds of formula (I), (Ia), (Ib), (II) or (III) 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.Aberrant gene expression in affected tissue as compared to normal tissue is a common characteristic of many human diseases. This is true for cancer and many neurological diseases which are characterized by changes in gene expression patterns. Gene expression patterns are controlled at multiple levels in the cell. Control of gene expression can occur through modifications of DNA:DNA promoter methylation is associated with suppression of gene expression. Several inhibitors of DNA methylation are approved for clinical use including the blockbuster Vidaza™. Another class of modifications involve histones which form the protein scaffold that DNA is normally associated with (coiled around) ...

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Номер записи: 72
11-05-2017 дата публикации

REACTIONS OF THIADIAZOLYL-OXIMINOACETIC ACID DERIVATIVE COMPOUNDS

Номер: US20170129906A1
Автор: BENOTTI Michele, Jukauskas Valdas, Moshos Kristos Adrian, SCANU Manuel
Принадлежит: Merck Sharp & Dohme Corp.

This disclosure relates to an improved synthesis of cephalosporin antibiotic compounds such as ceftolozane, and compositions and methods of use thereof. Thiadiazolyl-oximinoacetic acid compounds such as TATD can be reacted to yield the activated thiadiazolyl-oximinoacetic acid methanesulfonate ester compounds useful in the manufacture of cephalosporin antibiotic compounds. 130-. (canceled)32. The process of claim 31 , wherein the alkali metal carbonate particles have at least about 70% of the particles by weight in a range of from about 70 to about 250 micrometers.33. The process of claim 31 , wherein the alkali metal carbonate particles have at least about 80% of the particles by weight in a range of from about 70 to about 250 micrometers.34. The process of claim 31 , wherein the alkali metal carbonate particles have at least about 90% of the particles by weight in a range of from about 70 to about 250 micrometers.35. The process of claim 31 , wherein the alkali metal carbonate is potassium carbonate.36. The process of claim 31 , wherein Wis tert-butyl.37. The process of claim 31 , wherein Ris CH.38. The process of claim 31 , wherein the molar equivalent ratio of the compound of formula (Z-I) to the alkali metal carbonate is in a range of from about 0.6 to about 1.4.39. The process of claim 31 , wherein the reaction temperature is in a range of from about −5 to about 20° C.40. The process of claim 31 , wherein Xis Cl.41. The process of claim 31 , wherein the molar equivalent ratio of the compound of formula RSOXto the compound of formula (Z-I) is in a range of from about 1.3 to about 3.0.46. The process of claim 45 , wherein a total of about 1.05 to 1.30 equivalents of potassium carbonate are combined with compound (I).47. The process of claim 45 , wherein the reaction of compound (I) occurs in a solution at a temperature of about 0-13 degrees C.48. The process of claim 45 , wherein:(a) a total of about 1.05 to 1.30 equivalents of potassium carbonate are combined ...

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Номер записи: 73
01-09-2022 дата публикации

5-[(1S)-1-(4-BROMOPHENOXY)ETHYL]-2H-TETRAZOLE DERIVATIVES AND RELATED COMPOUNDS AS CLC-1 ION CHANNEL INHIBITORS FOR TREATING NEUROMUSCULAR DISORDERS

Номер: US20220274938A1
Автор: Broch-Lips Martin, COOPER Martin E, Dudekula Dastagiri, Knutsen Lars J.S., Labelle Marc, Pedersen Thomas Holm, Saraswat Neerja, TAJ Rafiq A
Принадлежит: NMD PHARMA A/S

The present disclosure relates to compounds suitable for treating, ameliorating and/or preventing neuromuscular disorders, including the reversal of drug-induced neuromuscular blockade. The compounds as defined herein can inhibit the CIC-1 ion channel. 4. The compound according to claim 1 , wherein Ris Cl or Br.5. The compound according to claim 1 , wherein Ris H claim 1 , F claim 1 , Cl claim 1 , Br or I.6. The compound according to claim 1 , wherein Ris a 5-6 membered aromatic heterocycle optionally substituted with one or more claim 1 , identical or different claim 1 , substituents R.7. The compound according to claim 1 , wherein Ris C1-5 alkyl optionally substituted with one or more claim 1 , identical or different claim 1 , substituents R.8. The compound according to claim 2 , wherein X is N and Y is NH.9. The compound according to claim 3 , wherein R claim 3 , is H.10. The compound according to claim 1 , wherein the compound is selected from the group consisting of:(2S)-2-(4-bromo-2-fluorophenoxy)-/V-{1-[(cyclopropylmethoxy)imino]ethyl}propanamide;(2S)-2-(4-bromophenoxy)-/V-[1-(methoxyimino)ethyl]propanamide;(2S)-2-(4-bromo-2-fluorophenoxy)-/V-[(4-fluorophenyl)(hydroxyimino)methyl]-3-methylbutanamide;(2S)-2-(4-bromo-2-fluorophenoxy)-/V-[1-(hydroxyimino)ethyl]-3-methylbutanamide;(2S)-2-(4-bromo-2-fluorophenoxy)-/V-[1-(hydroxyimino)ethyl]propanamide;(2S)-2-(4-bromophenoxy)-/V-[1-(hydroxyimino)ethyl]propenamide;(2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]-/V-cyanopropanamide;(2S)-A/-cyano-2-(2,4-dibromophenoxy)prc>panamide;(2S)-2-(4-bromophenoxy)-/V-cyanopropanamide;(2S)-2-(4-chlorophenoxy)-/V-cyanopropanamide;(2S)-2-(4-bromophenoxy)-/V-cyano-3-methylbutanamide;(2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]-/V-cyclobutoxypropanamide;(2S)-2-[4-bromo-2-(1,2-oxazol-3-yl)phenoxy]-/V-methoxypropanamide;(2S)-/V-acetyl-/V-[(1-acetylazetidin-3-yl)oxy]-2-(4-chlorophenoxy)propanamide;(2S)-/V-[(1-acetylazetidin-3-yl)oxy]-2-(4-chlorophenoxy)propanamide;(2S)-/V-(azetidin-3-yloxy ...

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Номер записи: 74
23-04-2020 дата публикации

CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF

Номер: US20200123114A1
Автор: Adler Marc, Buckman Brad Owen, Emayan Kumaraswamy, Ma Jingyuan, Nicholas John Beamond, Yuan Shendong
Принадлежит: Blade Therapeutics, Inc.

Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof. 3. The compound of or , wherein:{'sub': 1', '3-10, 'Ais selected from the group consisting of optionally substituted 6-10 membered heterocyclyl provided the 6-10-membered heterocyclyl is not substituted with oxo; optionally substituted 5-, 8-, or 9-membered heteroaryl; and optionally substituted Ccarbocyclyl;'}{'sub': 2', '6-10', '3-10', '2', '2, 'Ais selected from the group consisting of optionally substituted 3-10 membered heterocyclyl, optionally substituted Caryl, optionally substituted 5-10 membered heteroaryl, optionally substituted Ccarbocyclyl, —CR—, —S—, —S(═O)—, —SO—, —O—, —C(═S)—, —C(═O)—, —NR—, —CH═CH—, —OC(O)NH—, —NHC(O)NH—, —NHC(O)O—, —NHC(O)—, —NHC(S)NH—NHC(S)O—, —NHC(S)—, and single bond;'}{'sub': 4', '6-10', '3-10', '1-4', '2, 'Ais selected from the group consisting of optionally substituted Caryl, optionally substituted 5-10 membered heteroaryl, optionally substituted 3-10 membered heterocyclyl, optionally substituted Ccarbocyclyl, optionally substituted Calkyl, —S—, S(═O)—, —SO—, —O—, —C(═S)—, —C(═O)—, —NR—, —CH═CH—, —OC(O)NH—, —NHC(O)NH—, —NHC(O)O—, —NHC(O)—, —NHC(S)NH—, —NHC(S)O—, —NHC(S)—, and single bond;'}{'sub': 3', '6-10', '3-10, 'Ais selected from the group consisting of optionally substituted Caryl, optionally substituted 5-10 membered heteroaryl, optionally substituted 3-10 membered heterocyclyl, and optionally substituted Ccarbocyclyl;'}{'sub': 6', '6-10', '3-10', '1-8', '1-6', '2-6, 'Ais selected from the group consisting of optionally substituted Caryl, optionally substituted 5-10 membered heteroaryl, optionally substituted 3-10 membered heterocyclyl, optionally substituted Ccarbocyclyl, optionally substituted Calkyl, optionally substituted —O—Calkyl, optionally substituted —OCalkenyl, and any natural or non-natural amino acid side chain; and'}{'sup': 2', '3, 'sub': 1-4', '3-7', '6-10, 'each R, R, and Rare ...

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Номер записи: 75
03-06-2021 дата публикации

MORPHOLINE DERIVATES AS INHIBITORS OF VPS34

Номер: US20210163467A1
Автор: Stocking Emily M., Wrasidlo Wolfgang J.
Принадлежит: Neuropore Therapies, Inc.

The present disclosure relates to thiazole- or diathiazole-substituted aryl and heteroaryl compounds (I), pharmaceutical compositions containing them, and methods of using them, including treatment of disorders or disease related to regulation of the Vps34/PI3K III signaling pathway. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris C-Caryl or 4- to 10-membered heterocycloalkyl.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris phenyl.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris 5- or 6-membered heterocycloalkyl.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris tetrahydrofuranyl claim 1 , tetrahydropyranyl claim 1 , pyrrolidinyl claim 1 , piperidinyl claim 1 , piperazinyl claim 1 , or morpholinyl.6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris tetrahydrofuran-3-yl.7. The compound of claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris tetrahydropyran-4-yl.8. The compound of any one of - claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein L is —S(O)—.9. The compound of any one of - claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein L is —O—.10. The compound of any one of - claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein L is —C(O)—.11. The compound of any one of - claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein L is —CH—.12. The compound of any one of - claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Yis CH.13. The compound of any one of - claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Yis N.14. The compound of any one of - claim 5 , or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris a 5-membered heteroaryl ring.15. The compound of any one of ...

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Номер записи: 76
30-04-2020 дата публикации

Diamino-alkylamino-linked arylsulfonamide compounds with selective activity in voltage-gated sodium channels

Номер: US20200131167A1
Автор: Anthony J. Roecker, Christopher S. Burgey, Deping Wang, Gang Zhou, James Mulhearn, John E. Stelmach, Liangqin Guo, Mark E. Layton, Philippe G. Nantermet, Rajan Anand, Ronald M. Kim, Thomas J. Greshock, Tianying Jian, Ting Zhang, Walter Won
Принадлежит: Merck Sharp and Dohme LLC

Disclosed are compounds of Formula A, or a salt thereof: Formula (A), wherein: Het, Q and R 1A to R 4A are defined herein, which compounds have properties for blocking Na v 1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A or their salts, and methods of treating cough, itch, acute pain and neuropathic pain disorders using the same.

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Номер записи: 77
10-06-2021 дата публикации

COMPOUNDS

Номер: US20210171475A1
Автор: Atkinson Benjamin N, Bayle Elliott D, Fish Paul Vincent, Jones Edith Yvonne, Mahy William, Ruza Reinis Reinholds, Sipthorp James, Vecchia Luca, Willis Nicky John, Woodward Hannah, Zhao Yuguang
Принадлежит:

A compound for use in the treatment of a disease ameliorated by the inhibition of Notum of formula (I): (I) 2. A compound according to claim 1 , wherein Ar is Cheteroaryl claim 1 , with an optional substituent.5. A compound according to claim 2 , wherein there are three heteroatoms in the ring.6. A compound according to claim 1 , wherein the substituent is selected from OH claim 1 , OMe claim 1 , OEt and NHCN.7. A compound according to claim 6 , wherein the substituent is OH.8. A compound according to claim 1 , wherein the substituent is CHOH.9. A compound according to claim 1 , wherein there is no substituent on Ar.1020-. (canceled)21. A compound according to claim 1 , wherein Ris Cl claim 1 , Ris CFand Ris Cl.2224-. (canceled)25. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.26. (canceled)28. A compound according to claim 1 , wherein the compound is selected from:4-[2,4-dichloro-3-(trifluoromethyl)phenyl]-1H-triazole (306);2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-(methoxy-d3)-1,3,4-oxadiazole (241);2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-ethoxy-1,3,4-oxadiazole (242);4,5-dideuterio-1-[2,4-dichloro-3-(trifluoromethyl)phenyl]triazole (308);5-[2,4-dichloro-3-(trifluoromethyl)phenyl]-1,3,4-oxadiazol-2-ol (261);2-(2,4-dichloro-3-(trifluoromethyl)phenyl)-5-methoxy-1,3,4-oxadiazole (243);1-[2,4-dichloro-3-(trifluoromethyl)phenyl]triazole (295); andN-(5-(2,4-dichloro-3-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)cyanamide, ammonia salt (246).29. 1-[2 claim 1 ,4-dichloro-3-(trifluoromethyl)phenyl]triazole (295).30. A method of treatment of a disease or disorder ameliorated by the inhibition of Notum claim 1 , comprising administering to a patient in need of treatment claim 1 , a compound as defined in .31. A method according to claim 30 , wherein the disease or disorder is a neurodegenerative disorder or a central nervous system disorder.32. A method according to claim 30 , wherein the disease or ...

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Номер записи: 78
10-06-2021 дата публикации

GLYCOLATE OXIDASE INHIBITORS AND USE THEREOF

Номер: US20210171503A1
Автор: FERNANDES Miguel Xavier, Maag Hans
Принадлежит:

The present invention provides pyrazoles, isoxazoles, isothiazoles, thiadiazoles, and pyridazines according to Formula I as described herein, and pharmaceutically acceptable salts thereof. Pharmaceutical compositions and methods for treating primary hyperoxaluria, type I (PH) and kidney stones are also described. 3. (canceled)57-. (canceled)8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein W is —NR—.913-. (canceled)14. The compound of claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein:subscript n is 1;{'sup': 1', '1a, 'sub': '6-10', 'Ris selected from the group consisting of heteroaryl and -L-(Caryl), wherein aryl is substituted with R;'}{'sup': '1a', 'Ris selected from the group consisting of halo, cyano, and -M-heterocyclyl, heterocyclyl is optionally substituted with one or more amine protecting groups,'}{'sub': '1-6', 'L is selected from the group consisting of a bond, —O—, and Calkylene, and'}M is 2- to 6-membered heteroalkylene.1517-. (canceled)18. The compound of claim 8 , or a pharmaceutically acceptable salt thereof claim 8 , wherein:subscript n is 1{'sup': '1', 'Ris halo;'}{'sup': 3', '3a, 'sub': '7-16', 'Ris Carylalkyl substituted with R; and'}{'sup': '3a', 'Ris halo.'}1920-. (canceled)21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein each Y is independently selected from the group consisting of —O— and —CHR—.22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , Ris independently selected from the group consisting of halo claim 1 , cyano claim 1 , -M-(8- to 12-membered heterocyclyl) claim 1 , -M-(5- to 6-membered heteroaryl) claim 1 , -M-(Ccycloalkyl) claim 1 , and -M-(Caryl) claim 1 , wherein heterocyclyl claim 1 , heteroaryl claim 1 , cycloalkyl claim 1 , and aryl are optionally substituted with R.23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L claim 1 , M claim 1 , ...

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Номер записи: 79
10-06-2021 дата публикации

Benzenesulfonamide compounds and their use as therapeutic agents

Номер: US20210171537A1
Автор: Alla Yurevna Zenova, Charles Jay Cohen, Christoph Martin Dehnhardt, David Earl Bogucki, James Philip Johnson, JR., James Roy Empfield, Jean-Christophe ANDREZ, Kristen Nicole Burford, Michael Edward Grimwood, Michael Scott Wilson, QI Jia, Robert Joseph Devita, Shannon Marie Decker, Sultan Chowdhury, Syed Abid Hasan, Thilo FOCKEN
Принадлежит: Xenon Pharmaceuticals Inc

This invention is directed to benzenesulfonamide compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment of diseases or conditions associated with voltage-gated sodium channels, such as epilepsy and/or epileptic seizure disorders.

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Номер записи: 80
25-05-2017 дата публикации

HETEROCYCLIC INHIBITORS OF THE SODIUM CHANNEL

Номер: US20170145003A1
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 (1)-(11 1) 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. 2. The compound of claim 1 , wherein Rand Rare both perfluoralkyl groups.3. The compound of claim 1 , wherein Rand Rare both CFgroups.4. The compound of claim 1 , wherein Rand Rare both a halogen.5. The compound of claim 4 , wherein Rand Rare both F.6. The compound of claim 1 , wherein at least one of Rand Ris H.7. The compound of claim 1 , wherein at least one of Rand Ris H.8. The compound of claim 1 , wherein at least one of Rand Ris a halogen.9. The compound of claim 1 , wherein only one of Rand Ris CF.10. The compound of claim 1 , wherein only one of Rand Ris a halogen.11. The compound of claim 9 , wherein said Y is —CONH— and Ris sulfonyl methyl.14. The compound of claim 13 , wherein Rand Rare both perfluoralkyl groups.15. The compound of claim 13 , wherein Rand Rare both CFgroups.16. The compound of claim 13 , wherein Rand Rare both halogen.17. The compound of claim 13 , wherein Rand Rare both F.18. The compound of claim 13 , wherein at least one of Rand Ris a halogen claim 13 , nitrile claim 13 , or H.19. The compound of claim 13 , wherein Y is —SOCH—.20. The compound of claim 13 , wherein only one of Rand Ris CF.21. The compound of claim 13 , wherein at least one of Rand Ris a halogen.22. The compound of claim 13 , wherein one of Ror Ris chosen from —COH claim 13 , nitrile claim 13 , halogen claim 13 , C1-C3 alkoxy ...

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Номер записи: 81
14-08-2014 дата публикации

Cyclopropaneamine compound

Номер: US20140228405A1
Автор: Daisuke Tomita, Douglas Robert CARY, Ken Tsuchida, Naoki Tomita, Ryujiro HARA, Satoru Matsuda, Shigeo KAJII, Shinichi Imamura
Принадлежит: Takeda Pharmaceutical Co Ltd

The present invention provides a compound having a lysine-specific demethylase 1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for cancer, and central nervous system diseases, and the like. The present invention relates to a compound represented by the formula wherein A is a hydrocarbon group or heterocyclic group optionally having substituent(s); R is H, a hydrocarbon group or heterocyclic group optionally having substituent(s); A and R are optionally bonded to each other to form a ring optionally having substituent(s); Q 1 , Q 2 , Q 3 and Q 4 are each a hydrogen atom or a substituent; Q 1 and Q 2 , and Q 3 and Q 4 , are each optionally bonded to each other to form a ring optionally having substituent(s); X is H, an acyclic hydrocarbon group or saturated cyclic group optionally having substituent(s); Y 1 , Y 2 and Y 3 are each H, a hydrocarbon group or heterocyclic group optionally having substituent(s); X and Y 1 , and Y 1 and Y 2 , are each optionally bonded to each other to form a ring optionally having substituent(s); and Z 1 , Z 2 and Z 3 are each H or a substituent, or a salt thereof.

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Номер записи: 82
02-06-2016 дата публикации

Aryl lactam kinase inhibitors

Номер: US20160152621A1
Автор: Carolyn Diane Dzierba, Joanne J. Bronson, John E. Macor, Ramkumar Rajamani, Richard A. Hartz, Susheel Jethanand NARA, Vijay T. Ahuja
Принадлежит: Bristol Myers Squibb Co

The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.

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Номер записи: 83
16-05-2019 дата публикации

ARYLQUINAZOLINES

Номер: US20190142833A1
Автор: Buchstaller Hans-Peter, Emde Ulrich, Fuchss Thomas, Mederski Werner
Принадлежит:

The invention relates to novel compounds of the formula (I) which can be used for the inhibition of serine-threonine protein kinases and for the sensitisation of cancer cells to anticancer agents and/or ionising radiation. 120.-. (canceled)24. The compound according to claim 22 , in which {'sup': '1', 'Ris F; or'}, 'in the case of sub-formula (IIIa-B)'} {'sup': 1', '2, 'X, Xis CH; or'}, 'in the case of sub-formula (IIIa-C)'} [{'sup': '1', 'Xis CH, and'}, {'sup': '5', 'Ris H; or'}], 'in the case of sub-formula (IIIa-D)'} {'sup': '3', 'Ris OH; or'}, 'in the case of sub-formula (IIIa-E)'} [{'sup': '1', 'Xis CH, and'}, {'sup': '3', 'Ris OH; or'}], 'in the case of sub-formula (IIIa-F)'} [{'sup': '1', 'Xis CH, and'}, 'Y is CH; or, 'in the case of sub-formula (IIIa-G)'} [{'sup': '1', 'Xis CH, and'}, 'Cyc is pyridine, pyrazine or pyridazine, or pyrazolo[1,5-a]pyrimidinyl or imidazo[1,2-b]pyridazinyl; or, 'in the case of sub-formula (IIIa-H)'} {'sub': '2', 'Cyc is pyridine, pyrazine, pyridazine, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, furo[2,3-c]pyridinyl, furo[2,3-d}pyridazinyl, thieno[2,3-d}-pyridazinyl, thieno[2,3-d}pyrimidinyl or imidazo[4,5-c]pyridinyl, each of which may be unsubstituted, or may be mono- or disubstituted by methoxy, methyl, oxo, Cl or CHFO; or'}, 'in the case of th sub-formula (IIIa-J)'} [{'sup': '1', 'Ris F or Cl,'}, {'sup': '3', 'Ris OH,'}, {'sup': '5', 'Ris H, and'}, {'sup': 1', '2, 'X, Xis CH; or'}], 'in the case of sub-formula (IIIa-K)'} [{'sup': '1', 'Ris F,'}, {'sup': '3', 'Ris OH, and'}, {'sup': '5', 'Ris H; or'}], 'in the case of sub-formula (IIIa-L)'} [{'sup': '1', 'Ris F or Cl,'}, {'sup': '3', 'Ris OH,'}, {'sup': '5', 'Ris H,'}, {'sup': 1', '2, 'X, Xis CH, and'}, 'Cyc is pyridine, pyrazine or pyridazine, or pyrazolo[1,5-a]pyrimidinyl or imidazo[1,2-b]pyridazinyl; or, 'in the case of sub-formula (IIIa-M)'} [{'sup': '1', 'Ris F,'}, {'sup': '3', 'Ris OH,'}, {'sup': '5', 'Ris H, and'}, {'sub': '2', 'Cyc is pyridine, pyrazine, ...

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Номер записи: 84
07-05-2020 дата публикации

CATALYSTS

Номер: US20200140610A1
Автор: Adriaenssens Louis, Chapman Andy, Chartoire Anthony, Kember Michael, LEELAND James
Принадлежит:

Polymerisation catalysts and systems comprising said catalysts for polymerising carbon dioxide and an epoxide, a lactide and/or lactone, and/or an epoxide and an anhydride. The catalyst is of formula (I): 2. The catalyst of claim 1 , wherein Ris different from R claim 1 , and each occurrence of E claim 1 , E claim 1 , Eand Eis the same.3. The catalyst of claim 1 , wherein Ris the same as Rand at least one occurrence of E claim 1 , E claim 1 , Eand Eis different to a remaining occurrence of E claim 1 , E claim 1 , Eand Ee.4. The catalyst of claim 1 , wherein Ris different from Rand at least one occurrence of E claim 1 , E claim 1 , Eand Eis different to a remaining occurrence of E claim 1 , E claim 1 , Eand E.5. The catalyst of claim 1 , wherein Eand Eare the same claim 1 , and Eand Eare the same claim 1 , and wherein Eand Eare different from Eand E.6. The catalyst of claim 1 , wherein Eand Eare the same claim 1 , and Eand Eare the same claim 1 , and wherein Eand Eare different from Eand E.7. The catalyst of claim 1 , wherein Ror Ris selected from substituted or unsubstituted alkylene claim 1 , substituted or unsubstituted cycloalkylene or optionally substituted arylene.8. The catalyst of claim 1 , wherein Ris different from R claim 1 , Ris substituted or unsubstituted alkylene.9. The catalyst of claim 1 , wherein Ris different from Rand wherein Ris 2 claim 1 ,2-dimethylpropylene and Ris phenylene claim 1 , or Ris a disubstituted cycloalkylene which acts as a bridging group between two nitrogen centers in the catalyst of formula (I) and Ris 2 claim 1 ,2-dimethylpropylene claim 1 , or Ris 2 claim 1 ,2-dimethylpropylene and Ris propylene or ethylene claim 1 , or Ris propylene claim 1 , and Ris 2 claim 1 ,2-dimethylpropylene.10. The catalyst of claim 1 , wherein each E claim 1 , E claim 1 , Eand Eis NR claim 1 , and one of the Rgroups is different.11. The catalyst of claim 1 , wherein each ES claim 1 , E claim 1 , Eand Eis NR claim 1 , and two of the Rgroups are ...

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Номер записи: 85
17-06-2021 дата публикации

CYCLOPROPANAMINE COMPOUND AND USE THEREOF

Номер: US20210179603A1
Автор: DAINI Masaki, Hattori Yasushi, Ito Mitsuhiro, KAKU Tomohiro, KOJIMA Takuto, MATSUMOTO Shigemitsu, Morimoto Shinji, TOYOFUKU Masashi
Принадлежит:

The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula 2. The compound according to claim 1 , wherein A is(1) an optionally substituted heterocyclic group, or{'sub': '3-10', '(2) an optionally substituted Ccycloalkyl group,'}or a salt thereof.3. The compound according to claim 1 , wherein B is a ring selected from(1) a 5- or 6-membered aromatic heterocycle, and(2) a benzene ring fused with an optionally substituted 5- or 6-membered ring,wherein the ring represented by B is optionally substituted, and binds, via two adjacent carbon atoms with one atom in between, to a group represented by the formula (II), and a group represented by the formula (III),or a salt thereof.5. The compound according to claim 1 , wherein R claim 1 , Rand Rare each independently a hydrogen atom or an optionally substituted Calkyl group claim 1 ,or a salt thereof.6. The compound according to claim 1 , wherein Ris(1) a hydrogen atom,{'sub': '1-6', '(2) an optionally substituted Calkyl group,'}{'sub': '3-10', '(3) an optionally substituted Ccycloalkyl group, or'}(4) an optionally substituted heterocyclic group,or a salt thereof.8. The compound according to claim 1 , wherein A is{'sub': '1-6', '(1) a piperidinyl group, an isoxazolyl group, a pyrazolyl group, a thiadiazolyl group, a thiazolyl group, a tetrahydropyranyl group ...

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Номер записи: 86
01-06-2017 дата публикации

VINYLOGOUS THIOESTER COMPOUNDS AND METHODS OF USE

Номер: US20170152262A1
Автор: Allaway Robert, Bouley Stephanie, Sanchez Yolanda, Wood Matthew
Принадлежит:

Provided herein are vinylogous thioester compounds and methods for using the compounds. 2. The compound of claim 1 , wherein B and C are both H.3. The compound of claim 1 , wherein represents a double bond having E stereochemistry.4. The compound of claim 1 , wherein A is unsubstituted or is substituted with 1-3 substituents selected from the group consisting of —Cl claim 1 , —F claim 1 , —CN claim 1 , —CH claim 1 , —CHF claim 1 , —CF claim 1 , —OCH claim 1 , —SCH claim 1 , —OCHF claim 1 , —OCF claim 1 , —SCHF claim 1 , and —SCF.5. The compound of claim 1 , wherein A is phenyl.6. The compound of claim 1 , provided that:i. when A is unsubstituted phenyl, D is not 3-methylthio-1,2,4-thiadiazol-5-yl, 1-methyl-tetrazol-5-yl, 1-phenyl-tetrazol-5-yl, 4-cyano-5-methyl-isothiazol-3-yl, or 4-phenyl-thiazol-2-yl, and D does not comprise a moiety selected from the group consisting of 1,2,4-triazolyl, pyridinyl, pyrimidinyl, benzimidazol-2-yl, benzoxazol-2-yl, benzothiazol-2-yl and purinyl;ii. when A is 4-fluorophenyl, D is not 1-methylimidazol-2-yl, 1-phenyl-tetrazol-5-yl, 4-phenyl-thiazol-2-yl, or 4-methyl-1,2,4-triazol-3-yl, and D does not comprise a moiety selected from pyridinyl, pyrimidinyl, benzimidazol-2-yl, benzoxazol-2-yl, benzothiazol-2-yl; andiii. when A is 4-chlorophenyl, D is not 1H-1,2,4-triazol-5-yl, 1-methylimidazol-2-yl, 1-methyl-tetrazol-5-yl, 1-phenyl-tetrazol-5-yl, 3-methylthio-1,2,4-thiadiazol-5-yl, 4-phenyl-thiazol-2-yl, and D does not comprise a moiety selected from pyridinyl, pyrimidinyl, benzimidazol-2-yl, benzoxazol-2-yl, benzothiazol-2-yl.15. The compound of claim 1 , selected from compounds 1-36 claim 1 , 38 claim 1 , 39 claim 1 , 41-54 and 58-66 claim 1 , 68-72 claim 1 , 74-87 of Table 2 claim 1 , and pharmaceutically acceptable salts thereof.16. A method for treating a disorder associated with Ras deregulation or dysregulation comprising administering to a subject in need of treatment an effective amount of a compound of claim 1 , or a compound ...

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Номер записи: 87
28-08-2014 дата публикации

ZWITTERIONIC AZO DYESTUFFS FOR COLOURING KERATIN-INCLUDING FIBRES

Номер: US20140237735A1
Автор: Gross Wibke, Moch Melanie, Nemitz Ralph
Принадлежит: Henkel AG & Co. KGaa

The invention relates to agents for coloring keratinic fibers, in particular human hair, including in a cosmetic carrier at least one compound of the formula (I). The structures the of the general formula (I) have a heterocycle A which bears a quaternary nitrogen atom and thus a positive charge. The invention furthermore relates to the use of these novel azo dyes in agents for coloring hair and to the dyes themselves. 2. The agent of claim 1 , wherein the agent comprises at least one compound of the formula (I) claim 1 , in which A denotes one of structures (II) claim 1 , (III) claim 1 , (IV) claim 1 , (VI) claim 1 , (VII) claim 1 , (IX) claim 1 , (X) claim 1 , (XII) or (XIII).3. The agent of claim 1 , further comprising at least one compound of the formula (I) claim 1 , in which X denotes N—R3 and Y denotes (CH)with n equal to 2 or 3.4. The agent of claim 1 , further comprising at least one compound of the formula (I) claim 1 , in which X denotes N—R3 and R3 denotes a C-Calkyl group claim 1 , a C-Calkenyl group claim 1 , a methyl claim 1 , or an ethyl group.5. The agent of claim 1 , further comprising at least one compound of the formula (I) claim 1 , in which R1 and R2 mutually independently denote hydrogen claim 1 , a C-Calkyl group claim 1 , a C-Calkoxy group claim 1 , a halogen claim 1 , or a hydrogen.6. The agent of claim 1 , further comprising at least one compound of the formula (I) selected from:2-(methyl{4-[(3-methyl-1,3-thiazol-3-ium-2-yl)diazenyl]phenyl}amino)ethyl sulfate;2-(ethyl{4-[(3-methyl-1,3-thiazol-3-ium-2-yl)diazenyl]phenyl}amino)ethyl sulfate;3-(methyl{4-[(3-methyl-1,3-thiazol-3-ium-2-yl)diazenyl]phenyl}amino)propyl sulfate;3-(ethyl{4-[(3-methyl-1,3-thiazol-3-ium-2-yl)diazenyl]phenyl}amino)propyl sulfate;2-(methyl{3-methyl-4-[(3-methyl-1,3-thiazol-3-ium-2-yl)diazenyl]phenyl}amino)-ethyl sulfate;3-(ethyl{3-methyl-4-[(3-methyl-1,3-thiazol-3-ium-2-yl)diazenyl]phenyl}amino)propyl sulfate;2-[{4-[(1,3-dimethyl-1H-imidazol-3-ium-2-yl)diazenyl]phenyl}( ...

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Номер записи: 88
14-05-2020 дата публикации

FTO Inhibitors

Номер: US20200148628A1
Автор: Huang Niu, Peng Shiming
Принадлежит: National Institute of Biological Sciences, Beijing

The invention provides compounds that inhibit FTO (fat mass and obesity), including pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof, particularly obesity, with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition. 4. The composition of wherein:R1 and R2 are independently H or Me;R3 is H, OH or NHR, wherein R is H or C1-C4 alkyl; andR4 is optionally substituted, heterocyclic C3-C18 hydrocarbyl comprising an n-membered ring wherein n=3-18, including 1 to n−1 heteroatoms independently selected from N, O, S and P.5. The composition of wherein the heterocyclic C3-C18 hydrocarbyl is:a 3 membered ring that is an optionally substituted aziridine, oxirane or oxaziridine;a 4 membered ring that is an optionally substituted azetidine, oxetane or oxazetidine;a 5 membered ring that is an optionally substituted pyrrole, 1,2-diazole (pyrazole), 1,3 diazole (imidazole), thiazole, isothiazole, oxazole, isoxazole, furan, dioxole or thiophene;a 6 membered ring that is an optionally substituted pyridine, diazine, triazine, oxazine, thiazine, dioxine, oxathiine or dithiine;a 9 membered ring that is an optionally substituted indole, benzothiazole, benzooxazole, benzofuran, benzodioxole, benzothiophene or benzodithiole; ora 10 membered ring that is an optionally substituted quinoline, quinoxaline, quinazoline, chromene, benzodioxine, thiochromene or benzodithiine.6. The composition of wherein the heterocyclic C3-C18 hydrocarbyl is:a 4 membered ring that is an optionally substituted azetidine, oxetane or oxazetidine.7. The composition of wherein the heterocyclic C3-C18 hydrocarbyl is:a 5 membered ring that is an optionally substituted pyrrole, 1,2-diazole (pyrazole), 1,3 diazole (imidazole), thiazole, isothiazole, oxazole, isoxazole, furan, dioxole or thiophene.8. ...

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Номер записи: 89
14-06-2018 дата публикации

CYCLOPROPANAMINE COMPOUND AND USE THEREOF

Номер: US20180162853A1
Автор: DAINI Masaki, Hattori Yasushi, Ito Mitsuhiro, KAKU Tomohiro, KOJIMA Takuto, MATSUMOTO Shigemitsu, Morimoto Shinji, TOYOFUKU Masashi
Принадлежит:

The present invention provides a compound having a lysine-specific demethylase-1 inhibitory action, and useful as a medicament such as a prophylactic or therapeutic agent for schizophrenia, developmental disorders, particularly diseases having intellectual disability (e.g., autistic spectrum disorders, Rett syndrome, Down's syndrome, Kabuki syndrome, fragile X syndrome, Kleefstra syndrome, neurofibromatosis type 1, Noonan syndrome, tuberous sclerosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, spinocerebellar degeneration (e.g., dentatorubural pallidoluysian atrophy) and Huntington's disease), epilepsy (e.g., Dravet syndrome) or drug dependence, and the like. A compound represented by the formula 2. The compound according to claim 1 , wherein A is(1) an optionally substituted heterocyclic group, or{'sub': '3-10', '(2) an optionally substituted Ccycloalkyl group,'}or a salt thereof.3. The compound according to claim 1 , wherein B is a ring selected from(1) a 5- or 6-membered aromatic heterocycle, and(2) a benzene ring fused with an optionally substituted 5- or 6-membered ring,wherein the ring represented by B is optionally substituted, and binds, via two adjacent carbon atoms with one atom in between, to a group represented by the formula (II), and a group represented by the formula (III),or a salt thereof.5. The compound according to claim 1 , wherein R claim 1 , Rand Rare each independently a hydrogen atom or an optionally substituted Calkyl group claim 1 ,or a salt thereof.6. The compound according to claim 1 , wherein Ris(1) a hydrogen atom,{'sub': '1-6', '(2) an optionally substituted Calkyl group,'}{'sub': '3-10', '(3) an optionally substituted Ccycloalkyl group, or'}(4) an optionally substituted heterocyclic group,or a salt thereof.8. The compound according to claim 1 , wherein A is{'sub': '1-6', '(1) a piperidinyl group, an isoxazolyl group, a pyrazolyl group, a thiadiazolyl group, a thiazolyl group, a tetrahydropyranyl group ...

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Номер записи: 90
14-06-2018 дата публикации

BENZENESULFONAMIDE COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS

Номер: US20180162868A1
Автор: ANDREZ Jean-Christophe, Bogucki David Earl, Burford Kristen Nicole, Chowdhury Sultan, Cohen Charles Jay, DECKER Shannon Marie, DEHNHARDT Christoph Martin, Devita Robert Joseph, Empfield James Roy, FOCKEN Thilo, GRIMWOOD Michael Edward, Hasan Syed Abid, Jia Qi, Johnson, JR. James Philip, WILSON Michael Scott, ZENOVA Alla Yurevna
Принадлежит:

This invention is directed to benzenesulfonamide compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment of diseases or conditions associated with voltage-gated sodium channels, such as epilepsy and/or epileptic seizure disorders. 4. The compound of which is 5-chloro-2-fluoro-N-(thiazol-4-yl)-4-(4-(trifluoromethyl)-2 claim 3 ,3-dihydro-1H-inden-1-yloxy)benzenesulfonamide.6. The compound of selected from:4-((2-(azetidin-1-ylmethyl)-3,6-difluorobenzyl)oxy)-5-chloro-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;(R)-3-chloro-4-(1-phenylethoxy)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;(S)-3-chloro-4-(1-phenylethoxy)-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;(S)-3-chloro-2-fluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-2-yl)benzenesulfonamide;5-chloro-2-fluoro-4-(isoquinolin-8-ylmethoxy)-N-(thiazol-2-yl)benzenesulfonamide;(S)-2,5-difluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-2-yl)benzenesulfonamide;(R)-5-chloro-2-fluoro-N-(thiazol-2-yl)-4-(2,2,2-trifluoro-1-phenylethoxy)benzenesulfonamide;(S)-5-chloro-4-(1-(5-chloro-2-fluorophenyl)ethoxy)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;(S)-5-chloro-2-fluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-4-yl)benzenesulfonamide;(S)-5-chloro-4-(1-(3,4-dichlorophenyl)ethoxy)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;(S)-5-chloro-2-fluoro-4-(1-(3-fluorophenyl)ethoxy)-N-(thiazol-2-yl)benzenesulfonamide;(S)-5-chloro-2-fluoro-4-(1-phenylethoxy)-N-(thiazol-2-yl)benzenesulfonamide;(S)-5-chloro-2-fluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-2-yl)benzenesulfonamide;(S)-5-chloro-4-(1-(2-chlorophenyl)ethoxy)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;(S)-5-chloro-2-fluoro-4-(1-(3-fluorophenyl)ethoxy)-N-(thiazol-4-yl)benzenesulfonamide;(S)-5-chloro-4-(1-(2,6-difluorophenyl)ethoxy)-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide;(S)-5-chloro-4-(1-(2,6-difluorophenyl)ethoxy)-2-fluoro-N-(thiazol-4-yl)benzenesulfonamide;(R)-5-chloro-2 ...

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Номер записи: 91
29-09-2022 дата публикации

AMINO ACID TRANSPORT INHIBITORS AND THE USES THEREOF

Номер: US20220304984A1
Автор: Manning H. Charles, Schulte Michael
Принадлежит:

These compounds are glutamine transporter inhibitors, e.g., alanine, serine, cysteine-preferring transporter 2 (ASCT2) inhibitors. Glutamine transporter inhibitors are useful to treat a variety of diseases, disorders, or conditions including cancer. 4. The compound of claim 1 , wherein Ris optionally substituted heteroaryl claim 1 , or a pharmaceutically acceptable salt or solvate thereof.5. The compound of claim 1 , wherein Ris optionally substituted aryl claim 1 , or a pharmaceutically acceptable salt or solvate thereof.7. The compound of claim 6 , wherein R claim 6 , R claim 6 , R claim 6 , R claim 6 , R claim 6 , and Rare each hydrogen claim 6 , or a pharmaceutically acceptable salt or solvate thereof.8. The compound of claim 1 , wherein Q is Q-1 claim 1 , or a pharmaceutically acceptable salt or solvate thereof.10. The compound of claim 1 , wherein Q is Q-2 claim 1 , or a pharmaceutically acceptable salt or solvate thereof.12. The compound of claim 1 , wherein Q is Q-3 claim 1 , or a pharmaceutically acceptable salt or solvate thereof.14. The compound of claim 1 , wherein Q is Q-4 claim 1 , or a pharmaceutically acceptable salt or solvate thereof.16. The compound of claim 1 , wherein Q is Q-5 claim 1 , or a pharmaceutically acceptable salt or solvate thereof.18. The compound of claim 1 , wherein R is hydrogen claim 1 , or a pharmaceutically acceptable salt or solvate thereof.19. The compound of selected from the group consisting of:5-([1,1′-biphenyl]-4-yl)-1H-indole-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)benzofuran-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)benzo[b]thiophene-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)-1H-benzo[d]imidazole-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)benzo[d]oxazole-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)benzo[d]thiazole-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)furo[3,2-b]pyridine-2-carboxylic acid;5-([1,1′-biphenyl]-4-yl)thieno[3,2-b]pyridine-2-carboxylic ...

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Номер записи: 92
04-09-2014 дата публикации

MALIGNANT AND NON-MALIGNANT DISEASE TREATMENT WITH RAS ANTAGONISTS

Номер: US20140249163A1
Автор: Brownstein Michael J., Wikel James H.
Принадлежит: PICES THERAPEUTICS LLC

The present disclosure describes new inhibitors or antagonists of Ras useful for the treatment of conditions resulting from Ras-induced or mediated cellular processes, including cellular proliferation, differentiation, apoptosis, senescence, and survival. These cellular processes may be associated with a non-malignant or malignant disease, disorder, or pathological condition. The present disclosure also describes a method for inhibiting such Ras-induced or mediated cellular processes. The method entails administering a Ras antagonist in an amount effective to inhibit such cellular processes. 1. A Ras antagonist represented by the Formula (I):{'br': None, 'sup': 1', '2', '3', '4, 'R-R-R-R\u2003\u2003(I)'} [{'sup': '3', 'sub': '2', 'Rrepresents S, O, N, SO, SO, or Se; and'}, {'sup': '4', 'Rrepresents farnesyl or geranyl-geranyl; and'}], 'wherein [{'sup': '2', 'Rrepresents a 5-membered heterocyclic ring with at least one heteroatom; and'}, {'sup': '1', 'Rrepresents a 5- or 6-membered heterocyclic ring with at least one heteroatom.'}], 'wherein at least one of2. The Ras antagonist of claim 1 , wherein the heteroatoms of Ror Rare selected from the group consisting of O claim 1 , N claim 1 , S claim 1 , SO claim 1 , and SO.3. The Ras antagonist of claim 1 , wherein claim 1 , when Rrepresents a 5-membered heterocyclic ring with one or two heteroatoms claim 1 , Rrepresents CN claim 1 , C(═O)R claim 1 , S(═O)(═O)R claim 1 , COM claim 1 , SOM claim 1 , or an N(R)-substituted tetrazole: [{'sup': 5', '6', '7, 'Rrepresents hydrogen, hydroxyl, C1-C4 alkyloxy, C2-C4 alkenyloxy, C1-C4 hydroxyalkyloxy, C1-C4 aminoalkyloxy, or NRR;'}, {'sup': 6', '7', '6', '7, 'Rrepresents hydrogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 aminoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkyloxy, or C1-C4 alkylamino, and Rrepresents hydrogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 aminoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkyloxy, or C1-C4 alkylamino, or wherein Rand Rtogether form a ring comprising morpholine, ...

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Номер записи: 93
01-07-2021 дата публикации

GAS5 BINDING COMPOUNDS, FORMULATIONS, AND USES THEREOF

Номер: US20210198221A1
Автор: Cai Jianfeng, Patel Niketa A.
Принадлежит:

Provided herein are compounds that can bind GAS5 long non-coding RNA, compositions thereof, and uses thereof. 2. The compound of claim 1 , wherein the compound is capable of binding GAS5 long non-coding RNA.3. The compound of claim 2 , wherein the GAS5 long non-coding RNA has a sequence that is about 90%-100% identical to SEQ ID NO: 1.17. The pharmaceutical formulation of claim 15 , wherein the compound is capable of binding a GAS5 long non-coding RNA and wherein the GAS5 long non-coding RNA has a sequence that is 90%-100% identical to SEQ ID NO: 1.18. (canceled)19. The pharmaceutical formulation of claim 15 , further comprising an agent selected from the group consisting of: antisense or RNA interference molecules claim 15 , chemotherapeutics claim 15 , antineoplasic agents claim 15 , hormones claim 15 , antibiotics claim 15 , antivirals claim 15 , immunomodulating agents claim 15 , antinausea claim 15 , pain modifying agents claim 15 , anti-inflammatory agents claim 15 , antipyretics claim 15 , antibiotics claim 15 , and/or antibodies or fragments thereof.2023.-. (canceled)25. The method of claim 24 , wherein the disease or disorder is diabetes claim 24 , a cancer claim 24 , obesity claim 24 , a neurodegenerative disease claim 24 , or a combination thereof.2628.-. (canceled) This invention was made with government support under Grant Number 821-MR-EN-20606 awarded by the U.S. Department of Veterans Affairs. The government has certain rights to the invention.This application claims the benefit of and priority to co-pending U.S. Provisional Patent Application No. 62/267,650, filed on Dec. 15, 2015, entitled “GAS5-BINDING SMALL MOLECULE FOR TREATMENT OF DIABETES AND CANCER,” the contents of which is incorporated by reference herein in its entirety.This application also claims the benefit of and priority to co-pending U.S. Provisional Patent Application No. 62/398,624, filed on Sep. 23, 2016, entitled “GAS5 BINDING COMPOUNDS, FORMULATIONS, AND USES THEREOF,” the ...

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Номер записи: 94
21-06-2018 дата публикации

NOVEL HISTONE DEACETYLASE INHIBITORS

Номер: US20180170876A1
Автор: Cecil Alexander R. L., MacCormick Somhairle, Nodes William J., Shuttleworth Stephen J., Silva Franck A., Tomassi Cyrille D.
Принадлежит:

The present invention is a compound of the formula or a pharmaceutically acceptable salt thereof. The compounds are useful as HDAC inhibitors. 125-. (canceled)271. The compound of claim , wherein at least one L is pyrazinyl.281. The compound of claim , wherein the R′ attached to Ris hydrogen.291. The compound of claim , wherein L for each occurrence is pyrazinyl.301. The compound of claim , wherein R′ attached to L is independently selected for each occurrence from the group consisting of H , Calkyl , O—(Calkyl) , and halogen.311. A pharmaceutical composition comprising a compound of claim and a pharmaceutically acceptable carrier.32. A compound selected from the group consisting of: N-hydroxy-4-((pyrazin-2-yl(pyridin-2-yl)amino)methyl)benzamide; 4-(((5-fluoropyridin-2-yl)(pyrazin-2-yl)amino)methyl)-N-hydroxybenzamide; N-hydroxy-4-{[(pyrazin-2-yl)(pyrimidin-4-yl)amino]methyl}benzamide; 3-fluoro-N-hydroxy-4-{[(pyrazin-2-yl)(pyrimidin-4-yl)amino]methyl}benzamide; 4-{[bis(pyrazin-2-yl)amino]methyl}-N-hydroxybenzamide; 4-{[bis(pyrazin-2-yl)amino]methyl}-3-fluoro-N-hydroxybenzamide; and pharmaceutically acceptable salts thereof.331. A method of treating breast , ovarian , or prostate cancer in a patient in need thereof , comprising administering a therapeutically effective amount of a compound of claim . The present invention relates to novel compounds which are inhibitors of histone deacetylase (HDAC) and therefore have therapeutic utility.HDACs are zinc metalloenzymes that catalyse the hydrolysis of acetylated lysine residues. In histones, this returns lysines to their protonated state and is a global mechanism of eukaryotic transcriptional control, resulting in tight packaging of DNA in the nucleosome. Additionally, reversible lysine acetylation is an important regulatory process for non-histone proteins. Thus, compounds which are able to modulate HDAC have important therapeutic potential.WO2010/086646 discloses compounds which act as inhibitors of HDAC. The ...

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Номер записи: 95
21-06-2018 дата публикации

Simplified Structural Mimetics of AIPS as Quorum Sensing Inhibitors

Номер: US20180170889A1
Автор: BLACKWELL Helen, TAL-GAN Yftah, VASQUEZ Joseph
Принадлежит:

Compounds that regulate quorum sensing in bacteria and in particular in are provided. Compounds are described in formulas I, II, III, IV, V and VI herein. One or more compounds herein can be employed to inhibit QS and to thus inhibit virulence in bacteria and in particular in Compounds herein and pharmaceutical compositions containing one or more of these compounds are useful, for example, in treating infections of bacteria and in particular of Methods for treating such bacterial infections are provided. 3. The compound of claim 2 , wherein:{'sub': 1', '2', 'n, 'Lis —(CH)—, where n is 2-9 or 3-8, and all R are H;'}{'sub': 1', '2', 'n', '3, "Lis —(CH)—, where n is 2-9 or 3-8, and at least one of the R's are CH;"}{'sub': 1', '2', 'n', '3', '1', '2, "Lis —(CH)—, where n is 2-9 or 3-8, at least one of the R's are CHand Xand Xare selected from sec-butyl, isobutyl, benzyl, p-OH-benzyl or 3-indolylmethyl;"}{'sub': '1', 'Lis an alkoxyalkylene having 2-8 carbons and 1-3 oxygens, and all R are H;'}{'sub': 1', '3, "Lis an alkoxyalkylene having 2-8 carbons and 1-3 oxygens, and at least one of the R's are CH; or"}{'sub': 1', '3', '1', '2, "Lis an alkoxyalkylene having 2-8 carbons and 1-3 oxygens, and at least one of the R's are CHand Xand Xare selected from sec-butyl, isobutyl, optionally-substituted benzyl, cycloalkylalkyl or 3-indolylmethyl."}4. The compound of claim 1 , wherein W is S.5. The compound of claim 1 , wherein W is NH.6. The compound of claim 1 , wherein W is NCH.7. The compound of claim 1 , where —W—CO— is a double bond.8. The compound of claim 1 , wherein Xand Xare selected from sec-butyl claim 1 , isobutyl claim 1 , benzyl claim 1 , p-OH-benzyl claim 1 , p-F-benzyl claim 1 , p-Cl-benzyl claim 1 , m-F-benzyl claim 1 , m-Cl-benzyl claim 1 , cyclohexyl claim 1 , cyclopentyl claim 1 , or 3-indolylmethyl.9. The compound of claim 1 , wherein Xis selected from optionally-substituted benzyl and Xis selected from cyclohexylmethyl or cyclopentylmethyl.10. The compound of ...

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Номер записи: 96
22-06-2017 дата публикации

HYDROXYALKYLAMINE- and HYDROXYCYCLOALKYLAMINE-SUBSTITUTED DIAMINE-ARYLSULFONAMIDE COMPOUNDS WITH SELECTIVE ACTIVITY IN VOLTAGE-GATED SODIUM CHANNELS

Номер: US20170174674A1
Автор: Anthony J. Roecker, Deping Wang, Gang Zhou, James Mulhearn, Junying Zheng, Liangqin Guo, Philippe Nantermet, Rajan Anand, Ronald M. Kim, Thomas J. Greshock, Ting Zhang, Walter Won
Принадлежит: Merck Sharp and Dohme LLC

Disclosed are compounds of Formula A, or a salt thereof: wherein R 1 , R 2 , and E are defined herein, which compounds have properties for inhibiting Na v 1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A or their salts, and methods of treating pain disorders, cough, and itch using the same.

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Номер записи: 97
06-06-2019 дата публикации

SULFONAMIDES AS GPR40- AND GPR120-AGONISTS

Номер: US20190169142A1
Автор: ARAMINI Andrea, BECCARI Andrea, BIANCHINI Gianluca, DE PIZZOL Maria, LIBERATI Chiara Rossana Maria, SIRICO Anna, ZIPPOLI Mara
Принадлежит:

The invention relates to compounds acting as agonists of G-protein coupled receptor 120 (GPR120) and/or 40 (GPR40), and having formula (I): 117-. (canceled)19. The compound according to claim 18 , wherein A is phenyl claim 18 , naphthyl claim 18 , biphenyl or a saturated or unsaturated five-membered ring heterocycle having five ring atoms wherein 1 claim 18 , 2 claim 18 , 3 or 4 ring atoms are independently selected from N claim 18 , O and S.20. The compound according to claim 18 , wherein the five-membered ring heterocycle is selected from the group consisting of thienyl claim 18 , furyl claim 18 , pyrrolyl claim 18 , imidazolyl claim 18 , thiazolyl claim 18 , oxazolyl claim 18 , pyrazolyl claim 18 , isothiazolyl claim 18 , isoxazolyl claim 18 , 1 claim 18 ,2 claim 18 ,3-triazolyl claim 18 , tetrazolyl claim 18 , 1 claim 18 ,2 claim 18 ,3-thiadiazolyl claim 18 , 1 claim 18 ,2 claim 18 ,3-oxadiazolyl claim 18 , 1 claim 18 ,2 claim 18 ,4-triazolyl claim 18 , 1 claim 18 ,2 claim 18 ,4-thiadiazolyl claim 18 , 1 claim 18 ,2 claim 18 ,4-oxadiazolyl claim 18 , 1 claim 18 ,3 claim 18 ,4-triazolyl claim 18 , 1 claim 18 ,3 claim 18 ,4-thiadiazolyl claim 18 , 1 claim 18 ,3 claim 18 ,4-oxadiazolyl claim 18 , and benzimidazole claim 18 , which rings may optionally be partially saturated.21. The compound according to claim 18 , wherein R claim 18 , R claim 18 , Rare independently selected from the group consisting of —H claim 18 , -halogen claim 18 , —CF claim 18 , —OMe claim 18 , —OH claim 18 , phenyl claim 18 , —OPh claim 18 , —OCHPh claim 18 , —OCHOMe claim 18 , —OCHCN—NO claim 18 , —NH claim 18 , —NMe claim 18 , linear or branched C-Calkyl and —O(CH)—S(O)Me.22. The compound according to claim 18 , wherein n is 0 or 1.23. The compound according to claim 18 , wherein Ris in position meta on the aromatic ring.24. The compound according to claim 18 , wherein Y is a straight chain C-Chydrocarbon which may be saturated or unsaturated.25. The compound according to claim 18 , which ...

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Номер записи: 98
18-09-2014 дата публикации

SULFONYL SEMICARBAZIDES, SEMICARBAZIDES AND UREAS, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS FOR TREATING HEMORRHAGIC FEVER VIRUSES, INCLUDING INFECTIONS ASSOCIATED WITH ARENAVIRUSES

Номер: US20140275037A1
Автор: Bailey Thomas R., DENG Yijun, Laquerre Sylvie, Nitz Theodore J., Zhang Yanming
Принадлежит: Siga Technologies, Inc.

Compounds, methods and pharmaceutical compositions for treating viral infections, by administering certain novel semicarbazides, sulfonyl carbazides, ureas and related compounds in therapeutically effective amounts are disclosed. Methods for preparing the compounds and methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by hemorrhagic fever viruses is disclosed, i.e., including but not limited to Arenaviridae (Junin, Machupo, Guanavito, Sabia and Lassa), Filoviridae (ebola and Marburg viruses), Flaviviridae (yellow fever, omsk hemorrhagic fever and Kyasanur Forest disease viruses), and Bunyaviridae (Rift Valley fever). 134-. (canceled)38. A pharmaceutical composition of claim 35 , wherein n is 0 or 1.39. A pharmaceutical composition of claim 35 , wherein n is 0.40. A pharmaceutical composition of claim 35 , wherein m is 1 and p is 1.41. A pharmaceutical composition of claim 35 , wherein m is 0 and p is 0.44. A pharmaceutical composition of claim 35 , wherein the compound of formula I is selected from the group consisting of:N-2-(1,1,1,3,3,3-Hexafluoro-2-methylpropyl)-2-[4-(phenyl)-phenylsulfonyl]hydrazine-1-carboxamide;N-2-(1,1,1,3,3,3-Hexafluoro-2-methylpropyl)-2-[4-(2-methyl-2-propyl)-phenylsulfonyl]hydrazine-1-carboxamide;N-2-(1,1,1,3,3,3-Hexafluoro-2-methylpropyl)-2-[7-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazinyl)sulfonyl]hydrazine-1-carboxamide;N-2-(1,1,1,3,3,3-Hexafluoro-2-methylpropyl)-2-[5-(1-dimethylamino-naphthyl) sulfonyl]hydrazine-1-carboxamide; N-2-(1,1,1,3,3,3-Hexafluoro-2-methylpropyl)-2-[(2,4,6-trimethylphenyl)sulfonyl]hydrazine-1-carboxamide;N-2-(1,1,1,3,3,3-Hexafluoro-2-methylpropyl)-2-[(3-chloro-6-methoxyphenyl) sulfonyl]hydrazine-1-carboxamide;N-2-(1,1,1,3,3,3-Hexafluoro-2-methylpropyl)-2-[(3,6-dimethoxyphenyl)sulfonyl]hydrazine-1-carboxamide;N-2-(1,1,1,3,3,3-Hexafluoro-2-methylpropyl)-2-[(4-(4-[1,2,3]thiadiazolyl) phenyl)sulfonyl ...

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Номер записи: 99
18-09-2014 дата публикации

CYTOSINE DEAMINASE MODULATORS FOR ENHANCEMENT OF DNA TRANSFECTION

Номер: US20140275224A1
Автор: Carpenter Michael A., Harki Daniel A., Harris Reuben S., Li Ming, Perkins-Harki Angela L.
Принадлежит: Regents of the University of Minnesota

Compounds and methods are provided for enhancing or boosting the transfection rate or efficiency of mammalian cells by foreign DNA, such as bacterial plasmid DNA. Compounds, including natural products and inventive synthetic compounds can increase the effectiveness of uptake and incorporation of foreign DNA by mammalian cells, such as human cells, by suppression of DNA cytosine deamination, which is believed to be a mechanism by which these cells eliminate foreign DNA. Inhibition of the cytosine deaminase enzymes by compounds as described herein serves to provide more effective transfection of eukaryotic cells by plasmids including engineered gene sequences. Transfection can be used to study cellular processes, or to cure genetic diseases in human patients. The inventive materials and methods increase the efficiency and effectiveness of such transfection techniques. 410.-. (canceled)12. (canceled)14. (canceled)17. (canceled)18. The method of wherein the cytosine deaminase is any or all of APOBEC3A (A3A) claim 16 , APOBEC3B (A3B) claim 16 , APOBEC3C (A3C) claim 16 , APOBEC3D (A3D; also known as A3DE) claim 16 , APOBEC3F (A3F) claim 16 , APOBEC3G (A3G) claim 16 , APOBEC3H (A3H) claim 16 , AID claim 16 , APOBEC1 claim 16 , APOBEC2 claim 16 , APOBEC4 claim 16 , or any of Z1 claim 16 , Z2 claim 16 , and/or Z3 type APOBEC3.20. (canceled)21. The method of wherein the foreign DNA comprises a single-stranded or double-stranded DNA fragment claim 19 , a plasmid claim 19 , a cosmid claim 19 , a synthetic chromosome claim 19 , or engineered viral DNA.22. The method of wherein the foreign DNA is contacted with the target cell in the presence of the compound and further in the presence of a transfection adjuvant claim 19 , or with electroporation claim 19 , or with nucleofection claim 19 , or any combination thereof.23. The method of wherein the transfection adjuvant comprises a cationic lipid claim 22 , a cationic polymer claim 22 , a cationic peptide claim 22 , a pegylated ...

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Номер записи: 100