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Небесная энциклопедия

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

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Мониторинг СМИ

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

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 8260. Отображено 100.
05-01-2012 дата публикации

Inhibitors of the 11-beta-hydroxysteroid dehydrogenase type 1 enzyme

Номер: US20120004206A1
Автор: Bryan K. Sorensen, Dariusz Wodka, James T. Link, Marina A. Pliushchev
Принадлежит: Dariusz Wodka, Link James T, Pliushchev Marina A, Sorensen Bryan K

The present invention relates to compounds which are inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme. The present invention further relates to the use of inhibitors of 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme for the treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, and other diseases and conditions that are mediated by excessive glucocorticoid action.

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Номер записи: 1
08-03-2012 дата публикации

Di-azetidinyl diamide as monoacylglycerol lipase inhibitors

Номер: US20120058986A1
Автор: Bin Zhu, Mark J. Macielag, Peter J. Connolly
Принадлежит: Janssen Pharmaceutica NV

Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein Q and Z are defined herein.

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Номер записи: 2
12-04-2012 дата публикации

Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same

Номер: US20120088746A1
Автор: Hirotaka Tanaka, John Kincaid, Kazunari Nakao, Kiran Sahasrabudhe, Maria de los Ángeles ESTIARTE-MARTÍNEZ, Matthew Alexander James Duncton, Matthew Cox, Satoshi Nagayama, Yuji Shishido
Принадлежит: PFIZER INC

Compounds are disclosed that have a formula represented by the following: Formula (I). The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, traumatic injury, and others.

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Номер записи: 3
07-06-2012 дата публикации

Synthesis of ttx intermediates

Номер: US20120142911A1
Автор: David Herrero, Luis Miguel Lozano Gordillo, Nuria Tabares Cantero, Pedro Noheda Marín, Raul Benito Arenas
Принадлежит: Consejo Superior de Investigaciones Cientificas CSIC

The present invention relates to the synthesis of intermediates which are useful in TTX synthesis and to the preparation thereof.

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Номер записи: 4
23-08-2012 дата публикации

New compounds, pharmaceutical compositions and uses thereof

Номер: US20120214785A1
Автор: Bernd Nosse, Gerald Juergen Roth, Heike Neubauer, Joerg Kley, Martin Fleck, Niklas Heine, Thorsten Lehmann-Lintz
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The invention relates to new compounds of the formula I to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

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Номер записи: 5
30-08-2012 дата публикации

Selective calcium channel modulators

Номер: US20120220564A1
Автор: Eric Simonson, Hassan Pajouhesh, Michael E. Grimwood, Yongbao Zhu, Yuanxi Zhou
Принадлежит: Zalicus Pharmaceuticals Ltd

Methods and compounds effective in ameliorating conditions characterized by unwanted calcium channel activity, particularly unwanted T-type calcium channel activity are disclosed using a series of compounds containing N-acylated cyclic amines linked to an aπl ring as shown in formula (I).

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Номер записи: 6
01-11-2012 дата публикации

Novel heterocyclic acrylamides and their use as pharmaceuticals

Номер: US20120277207A1
Автор: Alexis Denis, Mayalen Oxoby, Sonia Escaich, Vincent Gerusz
Принадлежит: FAB PHARMA Sas

The invention relates to novel heterocyclic acrylamide compounds (I), to the preparation of the compounds and intermediates used therein, to the use of the compounds as antibacterial medicaments and pharmaceutical compositions containing the compounds.

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Номер записи: 7
03-01-2013 дата публикации

Cyclic amine bace-1 inhibitors having a benzamide substituent

Номер: US20130004518A1
Автор: Andrew Stamford, Corey Strickland, Douglas W. Hobbs, Jared N. Cumming, Jeffrey F. Lowrie, Johannes H. Voight, Kurt W. Saionz, Samuel Chackalamannil, Suresh D. Babu, Tao Guo, Thuy X.H. Le, Ulrich Iserloh, Yan Xia, Ying Huang, Yusheng Wu
Принадлежит: Merck Sharp and Dohme LLC

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is R is —C(O)—N(R 27 )(R 28 ) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

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Номер записи: 8
25-04-2013 дата публикации

AZETIDINYL DIAMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS

Номер: US20130102585A1
Автор: Bian Haiyan, Chevalier Kristen, Clemente Jose, Connolly Pete, Flores Chris, LIN Shu-Chen, Liu Li, Mabus John, Macielag Mark, McDonnell Mark, Pitis Philip, Zhang Sui-Po, Zhang Yue-Mei, ZHU Bin
Принадлежит: Janssen Pharmaceutica NV

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

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Номер записи: 9
02-05-2013 дата публикации

C7-Fluoro Substituted Tetracycline Compounds

Номер: US20130109657A1
Автор: Diana Katharine Hunt, Jingye Zhou, Louis Plamondon, Robert B. Zahler, Roger B. Clark, Xiao-Yi Xiao
Принадлежит: Tetraphase Pharmaceuticals Inc

The present invention is directed to a compound represented by Structural Formula (A): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

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Номер записи: 10
09-05-2013 дата публикации

BIARYL AMIDE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF

Номер: US20130116227A1
Автор: Hasegawa Futoshi, Hori Seiji, Katayama Seiji, Suzuki Kuniko
Принадлежит: DAINIPPON SUMITOMO PHARMA CO., LTD.

Disclosed is a novel biaryl amide derivative represented by formula (1) and having an affinity for the aldosterone receptor; also disclosed is a pharmaceutically acceptable salt thereof. (In the formula, A is any of the groups represented by formula (a); L is —CONH—, etc.; Ris a substitutable aminosulfonyl group, etc.; Ris a hydrogen atom, etc.; Ris a hydrogen atom, etc.; Ris a hydrogen atom, a halogen atom, hydroxy group, a substitutable amino group, a substitutable Calkoxy group, a substitutable 4- to 7-membered cyclic amino group, etc.; R, Rand Rare each independently hydrogen atoms, etc.; Ris a halogen atom, a cyano group, etc.; Rand Rare each independently a hydrogen atom, etc.; and m is an integer such as 0.) 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein A is a group of formula (a).3. The compound of either claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is —NHCO—.4. The compound of either claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein L is —CONH—.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris [{'sub': '1-6', 'claim-text': [{'sub': '1-6', '(i) amino (in which the amino may be optionally substituted with the same or different 1 to 2 Calkyl),'}, {'sub': '1-6', '(ii) Calkoxy, or'}, '(iii) 4- to 7-membered cyclic amino),, '(a) Calkyl (in which the group may be optionally substituted with'}, {'sub': '1-6', '(b) Calkylcarbonyl,'}, '(c) aminocarbonyl, and', {'sub': '2', '(d) —C(═NH)—NH),'}], '1: aminosulfonyl group (in which the amino may be optionally substituted with the same or different 1 to 2 groups selected from the group consisting of'}{'sub': '1-6', '2: Calkylsulfonyl group, or'}{'sub': '1-6', '3: Calkylsulfonylamino group, or a pharmaceutically acceptable salt thereof.'}6. The compound of claim 5 , wherein Ris aminosulfonyl group claim 5 , or a pharmaceutically acceptable salt thereof.7. The compound of claim ...

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Номер записи: 11
16-05-2013 дата публикации

CYCLIC NITRO COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THEREOF AND USES THEREOF

Номер: US20130123216A1
Автор: Bednarski Mark D., Cannizzo Louis, Knox Susan, Ning Shoucheng, Velarde Stephen, Wardle Robert, Warner Kirstin
Принадлежит:

The present invention provides cyclic nitro compound, pharmaceutical compositions of cyclic nitro compounds and methods of using cyclic nitro compounds and/or pharmaceutical compositions thereof to treat or prevent diseases or disorders characterized by abnormal cell proliferation, such as cancer, inflammation, cardiovascular disease and autoimmune disease. 124-. (canceled)26. The compound of claim 25 , wherein two of R claim 25 , R claim 25 , R claim 25 , R claim 25 , Rand Rare nitro.27. The compound of claim 25 , wherein R claim 25 , R claim 25 , and Rare each independently hydrogen claim 25 , alkyl claim 25 , aryl claim 25 , or nitro; and Rand Reach represent independently for each occurrence hydrogen claim 25 , alkyl claim 25 , aryl claim 25 , or nitro.28. The compound of claim 26 , wherein R claim 26 , R claim 26 , and Rare each independently hydrogen claim 26 , alkyl claim 26 , aryl claim 26 , or nitro; and Rand Reach represent independently for each occurrence hydrogen claim 26 , alkyl claim 26 , aryl claim 26 , or nitro.29. The compound of claim 25 , wherein Ris nitro; and R claim 25 , R claim 25 , R claim 25 , R claim 25 , and Reach represent independently for each occurrence hydrogen claim 25 , alkyl claim 25 , aryl claim 25 , or nitro.30. The compound of claim 26 , wherein Ris nitro; and R claim 26 , R claim 26 , R claim 26 , R claim 26 , and Reach represent independently for each occurrence hydrogen claim 26 , alkyl claim 26 , aryl claim 26 , or nitro.31. The compound of claim 25 , wherein Rand Rare nitro; and R claim 25 , R claim 25 , R claim 25 , and Reach represent independently for each occurrence hydrogen claim 25 , alkyl claim 25 , or aryl.32. The compound of claim 26 , wherein Rand Rare nitro; and R claim 26 , R claim 26 , R claim 26 , and Reach represent independently for each occurrence hydrogen or alkyl.33. The compound of claim 25 , wherein Ris —C(O)-cycloalkyl claim 25 , —C(O)-arylalkyl claim 25 , —C(O)-heteroarylalkyl claim 25 , or —C(O)- ...

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Номер записи: 12
16-05-2013 дата публикации

AZETIDINYL DIAMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS

Номер: US20130123233A1
Автор: Bian Haiyan, Chevalier Kristen, Clemente Jose, Connolly Pete, Flores Chris, LIN Shu-Chen, Liu Li, Mabus John, Macielag Mark, McDonnell Mark, Pitis Philip, Zhang Sui-Po, Zhang Yue-Mei, ZHU Bin
Принадлежит: Janssen Pharmaceutica NV

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

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Номер записи: 13
16-05-2013 дата публикации

Adhesive Compositions for Bonding Composites

Номер: US20130123513A1
Автор: Rammon Richard M., Williamson Bobby Lee
Принадлежит: GEORGIA-PACIFIC CHEMICALS LLC

The present invention relates to a non-thermosetting composition made by reacting epichlorohydrin and a primary amine, to the use of that composition for making thermosetting (curable) adhesives suitable for bonding composites, to a method of preparing composites using the thermosetting (curable) adhesives, and to the related composites bonded with the thermosetting (curable) adhesives. 1. A non-thermosetting, reaction product of (a) epichlorohydrin and (b) an amine selected from the group consisting of ammonia, a primary amine and mixtures thereof, wherein the reaction product is produced by reacting the epichlorohydrin and the amine in a ratio of 0.40 to 0.92 moles of epichlorohydrin per atom equivalent of amine hydrogen and wherein the epi-amine reaction product is produced by reacting in a serial fashion separate portions of the epichlorohydrin and separate portions of the amine at a temperature of not greater than 60° C. This application is a divisional of co-pending U.S. patent application Ser. No. 12/718,391, filed on Mar. 5, 2010, which claims the benefit of U.S. Provisional Application No. 61/158,013 filed Mar. 6, 2009, each of which is hereby incorporated by reference in its entirety.The present invention is directed to a non-thermosetting composition made by reacting epichlorohydrin and an amine, to the use of that composition for making thermosetting (curable) adhesives, particularly adhesives suitable for bonding composites, to a method of preparing composites, particularly wood composites using the thermosetting (curable) adhesives, and to the related composites bonded with the cured thermosetting (curable) adhesives.A variety of composite materials are made by bonding into a unitary product a primary constituent, often a structural or reinforcement component, using a bonding agent or matrix material, such as an adhesive resin. Composites include engineered wood products (wood-adhesive composite products), insulation products and the like.Wood-adhesive ...

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Номер записи: 14
23-05-2013 дата публикации

DERIVATIVES OF AMINOINDANES, THEIR PREPARATION AND THEIR APPLICATION IN THERAPEUTICS

Номер: US20130131034A1
Автор: FOLLMANN Markus, Goberville Pascale, HACHTEL Stephanie, Hessler Gerhard, Kleemann Heinz-Werner, Maier Thomas, MC Cort Gary, Struebing Carsten, Thiers Bérangère, Wang Li-Hsing
Принадлежит: SANOFI

The instant invention relates to derivatives of formula (I) 5. A pharmaceutical composition comprising compound of claim 1 , or an addition salt of said compound to a pharmaceutically acceptable salt claim 1 , or an hydrate or solvate of said compound.6. The pharmaceutical composition according to further comprising at least one pharmaceutically acceptable excipient.7. A method of treating or preventing fibrotic disorders claim 5 , skeletal muscle dysfunction claim 5 , renal failure claim 5 , atherosclerosis claim 5 , heart failure claim 5 , cancer chronic obstructive pulmonary disease claim 5 , pain claim 5 , pulmonary hypertension claim 5 , ischemic stroke claim 5 , myocardial infarction claim 5 , inflammation or peripheral arterial occlusive disease in a patient in need thereof comprising administering to said patient a therapeutically effective amount of the pharmaceutical composition of .8. The method according to claim 7 , wherein said fibrotic disorder is focal segmental glomerulosclerosis.9. The method according to wherein said cancer is oesophageal cancer or breast cancer. The instant invention relates to derivatives of aminoindanes, to their preparation and to their application in therapeutics.Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 has been associated with fibrotic disorders, such as focal segmental glomerulosclerosis (a) Winn et al, 2005, 308, 1801-1804. b) Hsu et al., 2007, 1772, 928-936. c) Kriz, 2005, 11, 527-530. d) Winn et al, 2005, 17, 378-387), skeletal muscle dysfunction (Millay et al., 2009, 106, 19023-19028), renal failure, atherosclerosis, heart failure (Kuwahara et al., 2006, 116, 3114-26), cancer (e.g. oesophageal cancer, breast cancer) (a) Aydar et al., 2009, 9, 23. b) Cai et al., 2009, 125, 2281-2287. c) Shi et al., 2009, 58, 1443-1450), chronic obstructive pulmonary disease (Sel et al., 2008, 38, 1548-1558), pain (Alessandri-Haber ...

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Номер записи: 15
06-06-2013 дата публикации

COMPOUNDS AND THEIR USE AS IKACH BLOCKERS

Номер: US20130143858A1
Автор: Bostrom Jonas, Emtenas Hans, Granberg Kenneth, Llinas Antonio, Mogemark Mickael
Принадлежит: AstraZeneca AB

The invention relates to compounds according to Formula I: 111-. (canceled)1516-. (canceled) The present invention relates to a novel class of compounds which are pharmacologically effective as potassium channel inhibitors, in particular inhibitors of the acetylcholine operated inward rectifying potassium channel current, i.e. IKACh blockers.The invention also relates to processes for preparing such compounds, to pharmaceutical compositions containing them, to the use of such compounds and to methods for their therapeutic use, particularly in the treatment of cardiac arrhythmias.The normal electrophysiologic behaviour of the heart is determined by ordered propagation of excitatory stimuli that result in rapid depolarization of the cardiac cell, followed by a slower repolarization. The sum of these events creates the cardiac action potential in individual myocytes. Cardiac rhythm disturbances can be caused by abnormalities of impulse generation, propagation or the duration and configuration of such individual cardiac action potentials. The action potentials are generated by the integrated activity of specific ion currents through various transmembrane spanning ion channels with specific selectivity for individual ions (e.g. potassium, sodium, calcium, see Grant AO. Circ. Arrhythmia Electrophysiol. 2009; 2:185-194). The majority of these ion channels have been cloned and thus, their molecular components are known. This knowledge has enabled a more effective search for selective ion channel blockers, as specific ion channel targets can be recombinantly over-expressed in mammalian cells and be used for high capacity screening.Electrophysiological studies in the early 1950s showed the importance of the movement of K out of the cell to produce repolarization after the rapid depolarizing spike. Over the last 60 years, the introduction of single channel recording techniques and molecular cloning has resulted in a deeper understanding of cardiac repolarization and of the ...

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Номер записи: 16
06-06-2013 дата публикации

Guanidine compound

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

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

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Номер записи: 17
20-06-2013 дата публикации

Azetidine Derivatives

Номер: US20130158004A1
Автор: FLECK Martin, HEINE Niklas, NOSSE Bernd, ROTH Gerald Juergen
Принадлежит:

Azetidine derivatives of which the following is exemplary 2. A compound according to whereinX is O, and{'sub': '3', 'R is H or CH.'}3. A compound according to wherein Aris selected from a group consisting of: [{'sup': '1', 'wherein the above-mentioned phenyl, pyridinyl and pyrimidinyl are each substituted with one to three groups independently selected from R, and/or'}, {'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '2', '2', '3', '2', '2, 'wherein two adjacent carbon atoms of a phenyl group may be linked to each other via a —O—CH—O—, —O—CF—O—, —O—CH—CH—O—, —O—CH—CH—CH—CH—, —O—CH—CH—CH—C(CH)—, —O—CH—CH—CH—O— or —O—CH—C(CH)—CH—O— bridge, and'}, {'sub': '3', 'wherein the above-mentioned benzoxazolyl, benzoisoxalyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl and oxazolopyrimidinyl groups are each optionally substituted with Cl, CHor phenyl.'}], 'phenyl, pyridinyl, pyrimidinyl, benzoxazolyl, benzoisoxalyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl and oxazolopyrimidinyl,'}4. A compound according to wherein Ris selected from the group consisting of:{'sub': 1-4', '2-4', '3-7', '3-7', '2', '1-4', '3-7', '3-7', '1-3', '1-4', '2', '1-4', '2, 'sup': N1', 'N2, 'claim-text': wherein each alkyl, cycloalkyl and heterocyclyl may be optionally substituted with one to three substituents independently selected from the group consisting of F and CN, and', {'sub': '3', 'wherein each phenyl and pyridinyl group may be optionally substituted with one F or —OCH.'}], 'H, F, Cl, Br, CN, OH, C-alkyl, C-alkenyl, C-cycloalkyl, C-cycloalkyl-CH—, C-alkyl-O—, C-cycloalkyl-O—, C-cycloalkyl-C-alkyl-O—, C-alkyl-S(═O), RRN—, HO—C(═O)—, C-alkyl-O—C(═O)—, phenyl, phenyl-O—, phenyl-CH—O—, pyridinyl,'}5. A compound according to wherein Aris selected from the group consisting of:{'sup': '2', 'claim-text': {'sup': '2', 'sub': 1-2', '1-2', '1-3', '2, 'wherein Ris F, Cl, C-alkyl-, C-alkyl-O—, C-alkyl-C(═O)—NH or HO—CH—C(═O)—NH—.'}, 'phenylene and ...

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Номер записи: 18
27-06-2013 дата публикации

HEXAFLUOROISOPROPYL CARBAMATE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION

Номер: US20130165422A1
Автор: BARTSCH Regine, CHEURET Dorothee, EVEN Luc, Hoornaert Christian, Jeunesse Jean, MARGEUT Frank
Принадлежит: SANOFI

The disclosure relates to hexafluoroisopropyl carbamate derivatives of general formula (I): 2. The compound of formula (I) according to claim 1 , wherein:{'sup': '1', 'Rrepresents a phenyl, naphthyl, indanyl, benzoxazole, benzisoxazole, benzimidazole, benzotriazole, oxadiazole, indazole, isoxazole, pyridine, pyrazine, pyrimidine, thienyl, thiazole, benzothiophene, indole, dihydrobenzodioxane, benzothiadiazole, pyrazole, dihydrobenzoxazine or indoline group;'}{'sup': '2', 'sub': 3', '3', '2', '2', '2', '2', '2, 'Rrepresents one or more groups chosen from a halogen atom or a methyl, trifluoromethyl, methoxy, trifluoromethoxy, cyano, oxo, CHNHCO, CHSO, NHCO, NHSOand pyrrolidine-SOgroup;'}{'sup': '3', 'Rrepresents a group chosen from a phenyl and an oxazole; and also the compound 2,2,2-trifluoro-1-(trifluoromethyl)ethyl 4-{[3-(2-methylpyrimidin-4-yl)benzenesulphonylamino]methyl}piperidine-1-carboxylate,'}in the form of the base or of an addition salt with an acid.3. The compound of formula (I) according to claim 1 , wherein:{'sub': 2', '2', '2', '2', '3', '2, 'Z represents a bond or a CH, (CH), CH═CH, C≡C, OCHor OC(CH)group,'}in the form of the base or of an addition salt with an acid.4. The compound of formula (I) according to claim 1 , wherein:{'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '3', '2, 'A represents a bond, an oxygen atom, a sulphur atom, an OCHgroup, an O—(CH)group, an NH, NHCHor NH(CH)group, an SOor CO group, a CONH group, a CONHCHor CONH(CH)group, an SONH group, an SONHCHor SONH(CH)group, an SONHCO, SONHCONH or SONHCONHCHgroup, an OCONH group, an NHCONH group, an NHCONHCHgroup, an N(CH)CONHCH, NHCONH(CH)or N(CH)CONH(CH)group or an SON(CH)CHgroup,'}in the form of the base or of an addition salt with an acid.5. The compound of formula (I) according claim 1 , wherein m and n represent 1 claim 1 , in the form of the base or of an addition salt with an ...

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Номер записи: 19
27-06-2013 дата публикации

PROCESS FOR THE PREPARATION OF IODIDES

Номер: US20130165658A1
Автор: Gandelman Mark, Kulbitski Kseniya, Nisnevich Gennady
Принадлежит:

This invention is directed to a process for the preparation of high yield alkyl or aryl iodide from its corresponding carboxylic acid using N-iodo amides. 1. A process for the preparation of iodide , represented by scheme (1):{'br': None, 'R—COOH→R—I\u2003\u2003(1)'}comprising reacting R—COOH with N-iodo amide to yield R—I; wherein R is saturated, linear or branched, substituted or unsubstituted alkyl; substituted or unsubstituted aryl; saturated or unsaturated, substituted or unsubstituted mono- or poly-carbocyclic or heterocyclic ring.2. The process of claim 1 , wherein said amide is carboxamide or sulfonamide.3. The process of claim 1 , wherein said amide is lactame claim 1 , carbamate claim 1 , imide or ureide.4. The process of claim 1 , wherein said amide is 5 claim 1 ,5-dimethylhydantoin claim 1 , 3-benzyl-5 claim 1 ,5-dimethylhydantoin claim 1 , 5-methyl-5-phenylhydantoin claim 1 , 5 claim 1 ,5-diphenylhydantoin claim 1 , 5 claim 1 ,5-hexamethylenehydantoin claim 1 , 5 claim 1 ,5-pentamethylenehydantoin claim 1 , 5 claim 1 ,5-tetramethylenehydantoin claim 1 , succinimide claim 1 , phthalimide claim 1 , saccharine claim 1 , isocyanuric acid claim 1 , 5 claim 1 ,5-dimethylbarbituric acid claim 1 ,-glycoluril claim 1 , 3a claim 1 ,6a-diphenylglycoluril claim 1 , 3a claim 1 ,6a-dimethylglycoluril claim 1 , 4 claim 1 ,4 claim 1 ,5 claim 1 ,5-tetramethyl-2-imidazolidinone claim 1 , 4 claim 1 ,4-dimethyl-2-oxazolidinone or mixture thereof.5. The process of claim 1 , wherein said N-iodo amide is 1 claim 1 ,3-diiodo-5 claim 1 ,5-dimethylhydantoin (DIH) claim 1 , N-iodosuccinimide (NIS) claim 1 , triiodoisocyanuric acid (TICA) claim 1 , 2 claim 1 ,4 claim 1 ,6 claim 1 ,8-tetraiodoglycoluril (TIG) claim 1 , N-iodosaccharine (NISac) claim 1 , or mixture thereof.6. The process of claim 1 , which comprises subjecting the mixture of the R—COOH and N-iodoamide to heat claim 1 , ultrasound claim 1 , or electromagnetic radiation or combination thereof.7. The process of claim 1 ...

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Номер записи: 20
04-07-2013 дата публикации

Azetidine Derivatives

Номер: US20130172312A1
Автор: FLECK Martin, HEINE Niklas, NOSSE Bernd, ROTH Gerald Juergen
Принадлежит:

Azetidine derivatives of which the following is exemplary 2. A compound according to claim 1 , wherein{'sup': '2a', 'Ris H;'}{'sup': '2b', 'sub': '3', 'Ris CH; and'}{'sup': '3', 'Ris H.'}4. A compound according to claim 1 , wherein Aris selected from a group consisting of: {'sup': 'A', 'wherein each of the beforementioned groups may be substituted with one or two substituents R.'}, 'phenylene, pyridinylene, pyrimidinylene, benzofuranylene and benzo[1,3]dioxolylene,'}5. A compound according to claim 1 , wherein Ris F or Cl.6. A compound according to claim 1 , wherein Ris selected from a group consisting of:{'sub': 1-4', '3-6', '3-6', '3-6', '2', '1-4', '1-4', '2', '2, 'claim-text': [{'sub': '3', 'wherein each alkyl and cycloalkyl may be optionally substituted with one or more substituents selected from F, OH and —O—CH, and'}, {'sub': '3', 'wherein piperidinyl is optionally substituted with one or two CH.'}], 'H, C-alkyl, C-cycloalkyl, C-cycloalkyl-O—, tetrahydrofuranyl-O—, C-cycloalkyl-CH—O—, (C-alkyl)NH—, (C-alkyl)N—, phenyl, benzyl, phenyl-CH—O—, piperidinyl, morpholinyl, pyrrolidinyl and pyrrolyl,'}7. A compound according to claim 1 , wherein{'sup': '4', 'Ris selected from a group consisting of{'sub': 1-4', '3-6', '4-6', '3-6', '1-3', '2-6', '2-6', '1-6', '1-3', '1-3', '1-3, 'sup': N1', 'N2, 'claim-text': [{'sup': 'N1', 'sub': '1-3', 'wherein Ris selected from the group consisting of: H and O-alkyl; and'}, {'sup': 'N2', 'sub': 1-4', '3-7, 'wherein Ris selected from the group consisting of: H, C-alkyl, O-cycloalkyl and heteroaryl; and'}, {'sub': '2', 'wherein in each cycloalkyl and heterocyclyl a —CH— group may optionally be replaced by —C(═O)—, and'}, {'sub': 3', '1-3', '1-3', '1-3, 'wherein each alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl group may be optionally substituted with one to three substituents independently selected from the group consisting of: F, Cl, CN, OH, CF, C-alkyl, —O—(C-alkyl) and —NH—(C═O)—O-alkyl; and'}, 'wherein each heterocyclyl ...

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Номер записи: 21
04-07-2013 дата публикации

New azetidine derivatives, pharmaceutical compositions and uses thereof

Номер: US20130172316A1
Автор: FLECK Martin, NOSSE Bernd, ROTH Gerald Juergen
Принадлежит:

The invention relates to new azetidine derivatives of the formula I 2. A compound according to claim 1 , whereinR is H; and{'sup': '2', 'Aris phenylene.'}3. A compound according to claim 1 , wherein L is a straight chain C-alkylene group which is optionally substituted with one methyl group.4. A compound according to claim 1 , wherein{'sup': '1', 'Aris selected from the group consisting of {'sup': '1', 'wherein each of the beforementioned groups may be substituted with one or two substituents R.'}, 'phenyl, thiadiazolyl, pyridinyl, pyrimidinyl, pyridazinyl, quinolinyl, oxazolo[4,5-d]pyrimidinyl, 2,3-dihydro-benzo[1,4]dioxinyl and 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl,'}6. A compound according to claim 1 , wherein{'sup': '1', 'Ris selected from a group consisting of{'sub': 1-4', '3-5', '1-4', '3-6', '3-5', '2', '2, 'claim-text': wherein each alkyl and cycloalkyl group may be substituted by one to three F; and', {'sub': '2', 'wherein in the NH-group, one or both hydrogen atoms may independently be replaced by C1-4-alkyl or C3-5-cycloalkyl, wherein each alkyl and cycloalkyl group may be substituted by one or more F; and'}, {'sub': '3', 'wherein each phenyl group may be substituted by Cl or —OCH.'}], 'F, Cl, Br, C-alkyl, C-cycloalkyl, C-alkyl-O—, C-cycloalkyl-O—, C-cycloalkyl-CH—O—, HN—, thiophenyl and phenyl,'}7. A compound according to claim 1 , whereinT is selected from a group consisting of:{'sub': 1-3', '1-2', '1-2', '1-2', '2', '3-5', '3-5', '2-6', '2-6', '2, 'claim-text': wherein the heterocyclyl group is selected from the group consisting of: pyrrolidinyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl; and', 'and wherein each heteroaryl group is selected from the group consisting of: pyrrolyl, furanyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl and pyridyzinyl; and', {'sub': '2', 'wherein in each heterocyclyl a —CH-group may optionally be replaced by —C(═O)—; and'}, {'sub': 1-3', '1-3', ...

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Номер записи: 22
18-07-2013 дата публикации

AMINOTETRALINE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND THEIR USE IN THERAPY

Номер: US20130184238A1
Автор: Amberg Wilhelm, Behl Berthold, Hornberger Wilfried, Hutchins Charles W., Kling Andreas, Lange Udo, Mezler Mario, Ochse Michael
Принадлежит:

The present invention relates to aminotetraline derivatives of the formula (I) 4. Compound as claimed in claim 1 , wherein Ris hydrogen claim 1 , halogen or C-C-alkoxy.6. Compound as claimed in claim 1 , wherein Ris hydrogen or C-C-alkyl.8. Compound as claimed in claim 1 , wherein Ris hydrogen claim 1 , C-C-alkyl claim 1 , C-C-cycloalkyl-C-C-alkyl claim 1 , halogenated C-C-alkyl claim 1 , amino-C-C-alkyl claim 1 , CHCN claim 1 , —CHO claim 1 , C-C-alkylcarbonyl claim 1 , (halogenated C-C-alkyl)carbonyl claim 1 , C-C-arylcarbonyl claim 1 , C-C-alkoxycarbonyl claim 1 , C-C-aryloxycarbonyl claim 1 , —C(═NH)NH claim 1 , —C(═NH)NHCN claim 1 , C-C-alkylsulfonyl claim 1 , amino claim 1 , —NO or C-C-heterocyclyl.9. Compound as claimed in claim 1 , wherein Ris hydrogen or C-C-alkyl.10. Compound as claimed in claim 1 , wherein R claim 1 , Rtogether are optionally substituted C-C-alkylene claim 1 , wherein one —CH— of C-C-alkylene may be replaced by an oxygen atom.11. Compound as claimed in claim 1 , wherein Xis CRR.12. Compound as claimed in claim 11 , wherein Xis a bond.13. Compound as claimed in claim 1 , wherein Ris hydrogen or C-C-alkyl and Ris hydrogen or C-C-alkyl.14. Compound as claimed in claim 1 , wherein R claim 1 , Rtogether are optionally substituted C-C-alkylene.15. Compound as claimed in claim 1 , wherein Ris optionally substituted aryl or optionally substituted C-C-cycloalkyl.17. Compound as claimed in claim 1 , wherein n is 1.18. Compound as claimed in claim 1 , which is:7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile;7-Amino-8-(4-chlorobenzyl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile;Ethyl [7-cyano-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate;tert-Butyl [7-cyano-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate,or a physiologically tolerated salt thereof.19. A pharmaceutical composition comprising a carrier and a compound of .20. A method for treating a neurologic or psychiatric disorder ...

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Номер записи: 23
25-07-2013 дата публикации

Process for the preparation of ezetimibe and derivatives thereof

Номер: US20130190487A1
Автор: Alen Kljajic, Andrej Gartner, Anton Stimac, Barbara Mohar, Davor Kidemet, Gregor Sedmak, Matej Smrkolj, Michel Stephan, Miha Plevnik, Mojca Bevc, Primoz Benkic, Rok Zupet, Vesna Krošelj
Принадлежит: KRKA dd

The present invention relates to the method of preparing of ezetimibe and in particular to novel intermediates for its synthesis and an improved process for preparing such intermediates. Said intermediates may be obtained in high yields and purity in a fast and cost efficient manner. The present invention relates to a novel crystalline form of ezetimibe as well.

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Номер записи: 24
25-07-2013 дата публикации

APOPTOSIS PROMOTERS

Номер: US20130190488A1
Автор: Bruncko Milan, Ding Hong, Elmore Steven, Kunzer Aaron, Lynch Christopher L., McClellan William, Mitten Michael, Park Cheol-Min, Petros Andrew, Shoemaker Alexander, Song Xiaohong, Tu Noah, Wang Xilu, WENDT Michael
Принадлежит: ABBOTT LABORATORIES

Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member. 19-. (canceled)10. A compound , or a therapeutically acceptable salt thereof , wherein the compound is selected from the group consisting of:N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(5,6-dihydro-1(4H)-pyrimidin-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(2,4-dimenthyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-methyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(4,4-dimethyl-4,5-dihydro-1H-imidazol-1-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)-1-cyclohexen-1-yl)methyl)piperazin-1-yl(benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)oxy)-3-(trifluoromethyl)benzenesulfonamide;N-(4-(4-((2-(4-chlorophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-(trifluoromethyl)benzenesulfonamide;4-(((1R)-3-(bis(2-methoxyethyl)amino)-1 ...

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Номер записи: 25
08-08-2013 дата публикации

NAPHT-2-YLACETIC ACID DERIVATIVES TO TREAT AIDS

Номер: US20130203727A1
Автор: Babaoglu Kerim, Bacon Elizabeth, Bjornson Kyla, Guo Hongyan, Halcomb Randall L., Hrvatin Paul, Link John O., Liu Hongtao, McFadden Ryan, Mitchell Michael L., Roethle Paul, Taylor James, Trenkle James D., Vivian Randall W., Xu Lianhong
Принадлежит: Gilead Sciences, Inc.

The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula I and therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds of formula (I). 2. The compound of wherein Ris (C-C)alkyl claim 1 , (C-C)alkenyl or —O(C-C)alkyl wherein any (C-C)alkyl or (C-C)alkenyl of Ris optionally substituted with one or more groups selected from —O(C-C)alkyl claim 1 , halo claim 1 , oxo and —CN; and wherein Ris H.4. The compound of wherein Ris selected from:{'sub': 1', '6', '2', '6', '1', '6', '3', '7', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6, 'a) aryl, heterocycle and heteroaryl, wherein any aryl, heterocycle and heteroaryl is optionally substituted with one or more groups each independently selected from halo, (C-C)alkyl, (C-C)alkenyl, (C-C)haloalkyl, (C-C)cycloalkyl, —OH, —O(C-C)alkyl, —SH, —S(C-C)alkyl, —NH, —NH(C-C)alkyl and —N((C-C)alkyl), wherein (C-C)alkyl is optionally substituted with hydroxy, —O(C-C)alkyl, cyano or oxo;'}{'sub': 3', '14', '3', '14', '3', '7, 'sup': 1', '1, 'b) (C-C)carbocycle, wherein (C-C)carbocycle is optionally substituted with one or more Zgroups, wherein two Zgroups together with the atom or atoms to which they are attached optionally form a (C-C)carbocycle or heterocycle; and'}{'sup': 7', '1, 'c) aryl, heteroaryl and fused-heterocycle, wherein any aryl, heteroaryl and fused-heterocycle is substituted with one or more Zgroups and optionally substituted with one or more Zgroups.'}5. The compound of wherein Ris selected from:{'sub': 1', '6', '2', '6', '1', '6', '3', '7', '1', '6', '1', '6', '2', '1', '6', '1', '6', '2', '1', '6', '1', '6, 'a) aryl, heterocycle and heteroaryl, wherein any aryl, heterocycle and ...

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Номер записи: 26
08-08-2013 дата публикации

Nicotinic receptor non-competitive antagonists

Номер: US20130203860A1
Автор: Balwinder Singh Bhatti, Daniel Yohannes, Jason D. Speake, Matt S. Melvin, Ronald Joseph Heemstra, Srinivasa Rao Akireddy, Yunde Xiao
Принадлежит: Individual

The present invention relates to compounds that modulate nicotinic receptors as non-competitive antagonists, methods for their synthesis, methods for use, and their pharmaceutical compositions.

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Номер записи: 27
22-08-2013 дата публикации

NOVEL PROLYLCARBOXYPEPTIDASE INHIBITORS

Номер: US20130217660A1
Автор: Clements Matthew J., Debenham John S., Graham Thomas H., Shen Dong-Ming, Zhang Yong
Принадлежит:

Compounds of structural formula I are inhibitors of prolylcarboxypeptidase (PrCP). The compounds of the present invention are useful for the prevention and treatment of conditions related to the enzymatic activity of PrCP such as abnormal metabolism, including obesity; diabetes; metabolic syndrome; obesity related disorders; and diabetes related disorders. 2. The compound of wherein R claim 1 , R claim 1 , and Rare hydrogen; or a pharmaceutically acceptable salt thereof.4. The compound of wherein Ris phenyl claim 1 , wherein phenyl is unsubstituted or substituted with one to three substituents selected from R; or a pharmaceutically acceptable salt thereof.9. The compound of wherein Ris —C(O)—(CH)N(R)and Ris hydrogen; or Rand Rform a morpholine ring; or a pharmaceutically acceptable salt thereof.10. The compound of wherein q is 0 or 1; or a pharmaceutically acceptable salt thereof.12. The compound of wherein{'sup': '1', 'claim-text': (1) hydrogen,', {'sub': 2', '1-6, '(2) —COCalkyl,'}, {'sub': 2', 'p, '(3) —C(O)—(CH)-halogen,'}, {'sub': 2', 'p', '2, 'sup': 'f', '(4) —C(O)—(CH)N(R),'}, {'sub': 2', 'p', '2-6, '(5) —C(O)—(CH)—Ccycloheteroalkyl,'}, {'sub': 2', 'p, '(6) —C(O)—(CH)-heteroaryl, and'}, {'sub': 2', '2-3', '1-6, '(7) —(CH)—O—Calkyl,'}], 'Ris independently selected from the group consisting of{'sub': '2', 'sup': 'b', 'wherein each CH, alkyl, cycloheteroalkyl, and heteroaryl is unsubstituted or substituted with one to two groups independently selected from R;'}{'sup': '2', 'claim-text': (1) hydrogen,', {'sub': '1-6', '(2) —Calkyl, and'}, {'sub': '1-6', '(3) —Calkoxy,'}], 'Ris selected from the group consisting of{'sup': 'c', 'wherein each alkyl and alkoxy is unsubstituted or substituted with one to four substituents selected from R, or'}{'sup': 1', '2, 'sub': '1-3', 'Rand Rform a morpholine ring, wherein the morpholine ring is unsubstituted or substituted with —Calkyl and oxo;'}{'sup': 3', '4', '5, 'R, R, and Rare hydrogen;'}{'sup': '6', 'claim-text': [{'sub': 2 ...

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Номер записи: 28
22-08-2013 дата публикации

PHENOXY-AZETIDINE DERIVATIVES AS SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTOR MODULATORS

Номер: US20130217667A1
Автор: Chow Ken, CORPUZ EVELYN G., FANG WENKUI K., IM WHA-BIN, Wang Liming
Принадлежит: ALLERGAN, INC.

The present invention relates to novel phenoxy-azetidine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors. 2. A compound according to wherein Lis CH.3. A compound according to wherein Lis CH.4. A compound according to wherein a is 1 claim 1 , 2 or 3.9. A compound according to claim 1 , wherein:{'sup': '1', 'Ris H or halogen;'}{'sup': '2', 'Ris H or halogen;'}{'sup': '3', 'Ris H or halogen;'}{'sup': '4', 'Ris H or halogen;'}{'sup': '5', 'sub': '1-8', 'Ris H or Calkyl; and'}{'sup': '6', 'sub': '1-8', 'Ris H or Calkyl.'}10. A compound according to claim 1 , selected from:1-(4-{[5-(3-chlorophenyl)-6-(3,4-dimethylphenyl)hexyl]oxy}benzyl)azetidine-3-carboxylic acid;1-{4-[3-(3-chlorophenyl)-4-(3,4-dimethylphenyl)butoxy]benzyl}azetidine-3-carboxylic acid;1-(4-{[4-(3,5-difluorophenyl)-5-(3,4-dimethylphenyl)pentyl]oxy}benzyl)azetidine-3-carboxylic acid;1-(4-{[4-(3-chlorophenyl)-5-(3,4-dimethylphenyl)pentyl]oxy}benzyl)azetidine-3-carboxylic acid;1-(4-{[4-(3,4-difluorophenyl)-5-(3,4-dimethylphenyl)pentyl]oxy}benzyl)azetidine-3-carboxylic acid;1-(4-{[5-(3,4-dimethylphenyl)-4-(3-thienyl)pentyl]oxy}benzyl)azetidine-3-carboxylic acid; and1-(4-{[4-(2,3-difluorophenyl)-5-(3,4-dimethylphenyl)pentyl]oxy}benzyl)azetidine-3-carboxylic acid.11. A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound according to and a pharmaceutically acceptable adjuvant claim 1 , diluent or carrier.12. A pharmaceutical composition according to wherein the compound is selected from:1-(4-{[5-(3-chlorophenyl)-6-(3,4-dimethylphenyl)hexyl]oxy}benzyl)azetidine-3-carboxylic acid;1-{4-[3-(3-chlorophenyl)-4-(3,4-dimethylphenyl)butoxy]benzyl}azetidine-3-carboxylic acid;1-(4-{[4-(3,5-difluorophenyl)-5-(3,4-dimethylphenyl)pentyl]oxy}benzyl)azetidine-3-carboxylic acid;1-(4-{[4-(3-chlorophenyl)-5-(3,4-dimethylphenyl)pentyl]oxy}benzyl)azetidine-3 ...

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Номер записи: 29
22-08-2013 дата публикации

AZETIDINYL DIAMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS

Номер: US20130217669A1
Автор: Bian Haiyan, Chevalier Kristen, Clemente Jose, Connolly Pete, Flores Christopher, LIN Shu-Chen, Liu Li, Mabus John, Macielag Mark, McDonnell Mark, Pitis Philip, Zhang Sui-Po, Zhang Yue-Mei, ZHU Bin
Принадлежит: Janssen Pharmaceutica, NV

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

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Номер записи: 30
29-08-2013 дата публикации

SALTS

Номер: US20130225550A1
Автор: DE LA CRUZ Marilyn, Karpinski Piotr H., LIU Yugang
Принадлежит:

This invention relates to a hydrochloride, malate, oxalate and tartrate salt forms of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid (Compound I), to pharmaceutical compositions comprising this salt, to processes for forming this salt and to its use in medical treatment. In addition, the present invention also relates to new polymorphic forms of each of these salts, as well as to pharmaceutical compositions comprising these polymorphic forms, to processes for obtaining them, and their use in medical treatment. 1. A method of preventing or treating disorders or diseases mediated by lymphocytes , in a subject in need of such treatment , the method comprising administering to said subject a pharmaceutical composition comprising a therapeutically effective amount of a hydrochloride salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid , and a pharmaceutically acceptable adjuvant , diluent or carrier.2. A method according to claim 1 , wherein the hydrochloride salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid that is administered is greater than 60% crystalline.3. A method according to claim 2 , wherein the hydrochloride salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid that is administered is greater than 80% crystalline.4. A method according to claim 3 , wherein the hydrochloride salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid that is administered is greater than 90% crystalline.5. A method of preventing or treating organ or tissue transplant rejection claim 3 , graft versus host disease claim 3 , autoimmune diseases claim 3 , allergic diseases claim 3 , inflammatory diseases or conditions claim 3 , or muscle diseases in a subject in need ...

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Номер записи: 31
05-09-2013 дата публикации

Bridged Spiro[2.4]heptane Ester Derivatives

Номер: US20130231319A1
Автор: Bur Daniel, Corminboeup Olivier, Gren Sylvaine, Grisostomi Corinna, Leroy Xavier, Pozzi Davide, Richard-Bildstein Sylvia
Принадлежит: ACTELION PHARMACEUTICALS LTD.

The invention relates to a method for preparing linear polymers having an amide end or having a star architecture comprising an amide core, by means of a ring opening using lactide and glycolide monomers or a lactide monomer ring in the presence of a catalyst, wherein the method includes the steps of: (i) reacting the excess monomer(s) with an initiator in a solvent, said initiator being selected from among an amine and an amino alcohol, given that the initiator has at least one primary or secondary amine function; (ii) adding a catalyst, said catalyst being a non-nucleophilic base and including at least one neutral sp2 nitrogen atom; and (iii) neutralizing the reaction mixture. Said novel method is particularly advantageous in that it can be easily monitored and enables better modulation of the polymers, and thus of the properties thereof, than the methods of the prior art. The invention also relates to novel polymers that are obtainable by means of said method. 2. The compound according to claim 1 , whereinY represents a bond or a methandiyl group;{'sup': '1', 'sub': 1', '4', '1', '4', '1', '2, 'Rrepresents an aryl- or a heteroaryl-group, wherein the groups are independently unsubstituted, mono- or di-substituted, wherein the substituents are independently halogen, (C-C)alkyl, (C-C)alkoxy or (C-C)fluoroalkyl;'}{'sup': '2', 'claim-text': [{'sup': 3', '4, 'sub': '2', 'cyclopentyl or cyclohexyl, which are independently unsubstituted or mono-substituted with RRN—CH— or heterocyclyl-methyl;'}, {'sub': 2', '6', '1', '4, 'sup': 3', '4', '5', '6, '(C-C)alkyl, which is mono-substituted with —NRR, —C(O)NRR, or (C-C)alkoxy which is mono-substituted with heterocyclyl, wherein the heterocyclyl is unsubstituted or mono- or di-substituted at one of the carbon atoms with fluoro; or'}, {'sub': 1', '6, 'claim-text': [{'sub': 1', '4, 'with heterocyclyl, wherein the heterocyclyl is unsubstituted, or mono-substituted at a nitrogen atom with (C-C)alkyl and/or mono- or di-substituted at ...

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Номер записи: 32
05-09-2013 дата публикации

Ethynylbenzene derivatives

Номер: US20130231323A1
Автор: Eric J. Toone, Pei Zhou
Принадлежит: Duke University

Disclosed are compounds of formulae (I), (II), and (II)I: and pharmaceutically acceptable salts thereof, wherein the variables, R, R 1 , R 2 , R 3 , R 101 , L, D, Q, Y, X, and Z are defined herein. These compounds are useful for treating Gram-negative bacteria infections.

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Номер записи: 33
12-09-2013 дата публикации

AZETIDINE DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION IN THERAPY

Номер: US20130237513A1
Автор: SABUCO Jean-Francois
Принадлежит: SANOFI

The invention relates to azetidine derivatives having the formula (I): 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)1021.-. (canceled)22. A compound selected from the group consisting of:3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid methyl ester;3-({1-[bis(4-fluorophenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid methyl ester;3-({1-[bis(4-fluorophenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid3-({1-[bis(4-bromophenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid ethyl ester;3-({1-[bis(4-bromophenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid;3-({1-[bis(4-trifluoromethylphenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid ethyl ester;3-({1-[bis(4-trifluoromethylphenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid;3-({1-[bis(4-methoxyphenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid ethyl ester;3-({1-[bis(4-methoxyphenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid;3-({1-[bis(4-methylphenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid methyl ester;3-({1-[bis(4-methylphenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid;3-({1-[bis(4-cyanophenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid ethyl ester;3-({1-[bis(4-cyanophenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid;3-({1-[bis(4-trifluoromethoxyphenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid methyl ester;3-({1-[bis(4-trifluoromethoxyphenyl)methyl]azetidin-3-yl}methanesulphonylamino)-5-fluorobenzoic acid;3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}methanesulphonylamino)-2-fluorobenzoic acid methyl ester;3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}methanesulphonylamino)-2-fluorobenzoic acid;3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-yl} ...

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Номер записи: 34
19-09-2013 дата публикации

CARBAMATE AND UREA INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE 1

Номер: US20130244994A1
Автор: Claremon David A., Singh Suresh B., Tice Colin M., Ye Yuanjie, Zhuang Linghang
Принадлежит:

This invention relates to novel compounds of the Formula (I) 2. (canceled)3. (canceled)7. The compound of claim 4 , wherein{'sub': 7', '12', '9', '12', '1', '3', '1', '3', '1', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'sup': 4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4, 'Cy is (C-C)bicycloalkyl or (C-C)tricycloalkyl which is optionally substituted with 1-3 groups independently selected from halogen, cyano, (C-C)alkyl, halo(C-C)alkyl, hydroxy(C-C)alkyl, OR, N(R), COR, CHCOR; CON(R), CHCON(R), SON(R), SOR, NRCOR, NRCOR, NRSOR, NRCON(R)and OC(═O)N(R);'}{'sup': 1', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4, 'sub': 1', '8', '3', '8', '3', '8', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '1', '8', '3', '8', '3', '8', '1', '3', '1', '3, 'Ris (C-C)alkyl, (C-C)cycloalkyl, (C-C)cycloalkyl(C-C)alkyl or aryl, aryl(C-C)alkyl, each optionally substituted by 1-4 groups independently selected from halogen, cyano, (C-C)alkyl, halo(C-C)alkyl, hydroxy(C-C)alkyl, OR, N(R), COR, CHCOR; CON(R), CHCON(R), SON(R), SOR, NRCOR, NRCOR, NRSOR, NRCON(R)and OC(═O)N(R), wherein the (C-C)alkyl, (C-C)cycloalkyl, (C-C)cycloalkyl(C-C)alkyl and the alkyl portion of aryl(C-C)alkyl are further optionally substituted with oxo;'}{'sup': 2', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4', '4, 'sub': 1', '8', '2', '8', '1', '3', '1', '3', '1', '3', '1', '3', '1', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '1', '8', '2', '8', '1', '3', '1', '3, 'Ris (a) hydrogen; or (b) (C-C)alkyl, (C-C)alkenyl, aryl, aryl(C-C)alkyl, heteroaryl or heteroaryl(C-C)alkyl, each optionally substituted by 1-4 groups independently selected from halogen, cyano, (C-C)alkyl, halo(C-C)alkyl, hydroxy(C-C)alkyl, OR, N(R), COR, CHCOR; CON(R), CHCON(R), SON(R), SOR, NRCOR, NRCOR, NRSOR, NRCON( ...

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Номер записи: 35
19-09-2013 дата публикации

Calcium-sensing receptor-active compounds

Номер: US20130244995A1
Автор: Lars Kristian Albert Blæhr, Per VEDSØ
Принадлежит: Leo Pharma AS

Compounds of general formula (I), their use as calcium receptor-active compounds for the prophylaxis, treatment or amelioration of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism, pharmaceutical compositions comprising said compounds, and methods of treating diseases with said compounds.

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Номер записи: 36
19-09-2013 дата публикации

AZETIDINYL DIAMIDES AS MONOACYLGLYCEROL LIPASE INHIBITORS

Номер: US20130244997A1
Автор: Bian Haiyan, Chevalier Kristen, Clemente Jose, Connolly Peter J., Flores Christopher M., LIN Shu-Chen, Liu Li, Mabus John, Macielag Mark J., McDonnell Mark E., Pitis Philip M., Zhang Sui-Po, Zhang Yue-Mei, ZHU Bin
Принадлежит: Janssen Pharmaceutica NV

Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: 121.-. (canceled)23. A pharmaceutical composition comprising a compound of and at least one of a pharmaceutically acceptable carrier claim 22 , a pharmaceutically acceptable excipient claim 22 , and a pharmaceutically acceptable diluent.24. A pharmaceutical composition of claim 23 , wherein the composition is a solid oral dosage form.25. A pharmaceutical composition of claim 23 , wherein the composition is a syrup claim 23 , an elixir claim 23 , or a suspension.26. The compound of wherein Y is thiazol-2-yl claim 22 , Z is 1-(4-fluorophenyl)-indol-5-yl claim 22 , and s is 0.28. A pharmaceutical composition comprising the compound of and at least one of a pharmaceutically acceptable carrier claim 27 , a pharmaceutically acceptable excipient claim 27 , and a pharmaceutically acceptable diluent.29. A pharmaceutical composition of claim 28 , wherein the composition is a solid oral dosage form.30. A pharmaceutical composition of claim 28 , wherein the composition is a syrup claim 28 , an elixir claim 28 , or a suspension. This application claims priority to U.S. provisional patent application Nos. 61/171,658 and 61/171,649, each filed Apr. 22, 2009, which are hereby incorporated by reference in their entirety.The research and development of the invention described below was not federally sponsored.has been used for the treatment of pain for many years. Δ-tetrahydrocannabinol is a major active ingredient from and an agonist of cannabinoid receptors (Pertwee, 2008, 153, 199-215). Two cannabinoid G protein-coupled receptors have been cloned, cannabinoid receptor type 1 (CBMatsuda et al., 1990, 346, 561-4) and cannabinoid receptor type 2 (CBMunro et al., 1993, 365, 61-5). CBis expressed centrally in brain areas, such as the hypothalamus and nucleus accumbens as well as peripherally in ...

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Номер записи: 37
26-09-2013 дата публикации

HEPATITIS B ANTIVIRAL AGENTS

Номер: US20130251673A1
Автор: Flores Osvaldo A., Hartman George D.
Принадлежит: Novira Therapeutics, INC.

The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention. 3. The compound of claim 1 , wherein{'sup': '5', 'sub': 3', '1', '6', '2', '1', '6', '1', '6', '1', '6, 'each Ris independently selected at each occurrence from the group consisting of CH, C-Calkoxy, halo, —CN, —NO, —C-Chaloalkyl, —C-Cdihaloalkyl, —C-Cand trihaloalkyl;'}{'sup': 10', '2, 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '3', '10', '3', '10', '1', '4', '3', '10', '1', '4', '3', '10', '1', '4', '1', '4, 'Ris OH, halo, C-Calkyl, C-Calkyl-OH, —C-Cchloroalkyl, —C-Cdichloroalkyl, —C-Ctrichloroalkyl, —C-Cfluoroalkyl, —C-Cdifluoroalkyl, —C-Ctrifluoroalkyl, C-Cheteroalkyl, C-Ccycloalkyl, a C-Cheterocycloalkyl, aryl, heteroaryl, —C-Calkyl-(C-Ccycloalkyl), —C-Calkyl-(C-Cheterocycloalkyl), —C-Calkyl-(aryl), or —C-Calkyl-(heteroaryl), and wherein the alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl ring is optionally substituted with 1-5 substituents selected from R;'}{'sup': 11', '2, 'sub': 1', '3', '1', '3, 'Ris a bond or C-Calkylene, wherein the C-Calkylene is optionally substituted with 1-3 substituents selected from R;'}{'sup': '2', 'sub': 2', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6', '1', '6, 'Ris independently selected at each occurrence from the group consisting of halo, —CN, —NO, —C-Calkyl, —C-Calkoxy, —C-Cfluoroalkyl, —C-Cheteroalkyl, C(O)—C-Calkyl, and C(O)—C-Calkoxy.'}4. The compound of claim 1 , wherein each Ris independently selected at each occurrence from the group consisting of CH claim 1 , C-Calkoxy claim 1 , halo claim 1 , fluoromethyl claim 1 , difluoromethyl claim 1 , trifluoromethyl claim 1 , chloromethyl claim 1 , dichloromethyl claim 1 , and trichloromethyl;{'sup': 10', '2, 'sub': 1', '6', '1', '6', '1', '6', '1', '6', '1 ...

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Номер записи: 38
26-09-2013 дата публикации

Monobactams

Номер: US20130252935A1
Автор: Brown Matthew F., Han Seungil, Lall Manjinder, Mitton-Fry Mark J., Plummer Mark, RISLEY Hud Lawrence, Shanmugasundaram Veerabahu, Starr Jeremy
Принадлежит: PFIZER INC.

The present invention is directed to a new class of monobactam derivatives and their use for treating bacterial infections. 3. The compound according to or a pharmaceutically acceptable salt thereof claim 2 , wherein E is C(H).5. The compound according to or a pharmaceutically acceptable salt thereof claim 4 , wherein X is —NH—C(═O)—.6. The compound according to or a pharmaceutically acceptable salt thereof claim 5 , wherein L is —(CH)—NH—(CH)—; p is 0 and q is 1.7. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand R claim 1 , together with the carbon atom to which they are attached claim 1 , form a (C-C)cycloalkyl.8. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare each methyl.9. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein X is —O—C(═O)—.10. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein L is absent claim 1 , —(CH)—NH—C(═O)—(CH)— claim 1 , —(CH)—NH—(CH)— claim 1 , —(CH)—C(═O)—NH—(CH)— claim 1 , or —(CH)-T-(CH) claim 1 , wherein T is isoxazole claim 1 , oxazole claim 1 , thiazole claim 1 , or pyrimidine;11. The compound according to or a pharmaceutically acceptable salt thereof claim 1 , wherein L is absent claim 1 , —(CH)-T-(CH) claim 1 , —(CH)—NH—C(═O)—(CH)— claim 1 , —CH(CH)—NH—C(═O)—NH—(CH)— claim 1 , —CH(CH)—NH—C(═O)—(CH)— claim 1 , —(CH)—C(═O)—NH—(CH)— claim 1 , or —(CH)-T-C(═O)—NH—(CH)—.15. A pharmaceutical composition comprising a compound according to or a pharmaceutically acceptable salt thereof claim 1 , in admixture with at least one pharmaceutically acceptable carrier.16. A method for treating bacterial infections in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound according to or a pharmaceutically acceptable salt thereof.17. (canceled) This application is a U.S. utility patent application, which ...

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Номер записи: 39
03-10-2013 дата публикации

RADIOFLUORINATED COMPOUNDS AND THEIR PREPARATION

Номер: US20130259802A1
Автор: ARSTAD ERIK, GLASER MATTHIAS EBERHARD
Принадлежит: HAMMERSMITH IMANET LIMITED

The present invention provides a process for [F]-fluorination of biomolecules containing a primary amino group such as proteins and peptides and in particular of peptides. The invention further provides reagents for this process, in particular F-labelled prosthetic groups for use in the preparation as well as non-labelled intermediates useful in the preparation of the [F]-labelled prosthetic groups. [F]-labelled compounds useful as radiopharmaceuticals, specifically for use in Positron Emission Tomography (PET) are also provided. 126-. (canceled)29. A method of wherein the diagnostic device is a Positron Emission Tomography scanner.37. Radiofluorination kit of further comprising a compound of formula (8):{'br': None, 'sup': '2', 'sub': '2', 'RNH\u2003\u2003(8)'}{'sup': '2', 'wherein Rdenotes a bio-molecule residue having at least one free amino function.'} The present invention relates to processes and reagents for [F]-fluorination, particularly of peptides. The resultant [F]-labelled compounds are useful as radiopharmaceuticals, specifically for use in Positron Emission Tomography (PET).Compounds labelled with short-lived positron emitting radionuclides are used for in vivo studies of human and non-human physiology. In particular, radiolabelled bioactive compounds which selectively interact with specific cell types are useful for the delivery of radioactivity to target tissues. The applications of bioactive compounds such as peptides and proteins, including antibodies and fragments of peptides are useful for receptor imaging. For example, radiolabelled peptides have significant potential for the delivery of radionuclides to the receptors expressed on cells of tissues, e.g. in tumours, infarcts and infected tissues for diagnosis, radiotherapy and monitoring of treatment. PET is a high resolution, non-invasive, imaging technique which has gained increased importance in the recent years for the visualisation of human disease.In PET, F is one of the most widely used ...

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Номер записи: 40
03-10-2013 дата публикации

Fatty Acid Inhibitors

Номер: US20130261099A1
Автор: Branchaud Bruce
Принадлежит: LIFE TECHNOLOGIES CORPORATION

Fatty acid inhibitors, pharmaceutical compositions including fatty acid inhibitors, methods for using fatty acid inhibitors to treat a variety of diseases, and methods for preparing fatty acid inhibitors are provided herein. 2. The compound of claim 1 , wherein the unsaturated or polyunsaturated fatty acid comprises an aliphatic chain having 5 to 23 carbons.3. The compound of claim 1 , wherein the unsaturated or polyunsaturated fatty acid is selected from a glycolipid claim 1 , a glycerolipid claim 1 , a phospholipid and a cholesterol ester.4. The compound of claim 1 , wherein Ris nitro (—NO).5. The compound of claim 1 , wherein the one or more electron withdrawing group is positioned on an alpha carbon of a carbon-carbon double bond of the non-naturally occurring claim 1 , unsaturated or polyunsaturated fatty acid.6. The compound of claim 1 , wherein a carbon-carbon double bond associated with Ris in cis configuration.7. The compound of claim 1 , wherein a carbon-carbon double bond associated with Ris in trans configuration.8. The compound of claim 1 , wherein the unsaturated or polyunsaturated fatty acid comprises two or more conjugated carbon-carbon double bonds.9. The compound of claim 8 , wherein Ris at any carbon in the two or more conjugated carbon-carbon double bonds.10. The compound of claim 1 , wherein at least Ris positioned at C-9 claim 1 , C-10 claim 1 , C-12 claim 1 , C-13 or a combination thereof.11. The compound of claim 1 , further comprising one or more non-carbon-carbon linkage selected from an ester linkage claim 1 , an ether linkage claim 1 , and a vinyl ether linkage.12. The compound of claim 1 , further comprising one or more functional group other than an electron withdrawing group positioned at any carbon of the unsaturated or polyunsaturated fatty acid.13. The compound of claim 1 , further comprising a pharmaceutically acceptable carrier claim 1 , excipient claim 1 , or combination thereof.14. The compound of claim 13 , further comprising ...

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Номер записи: 41
17-10-2013 дата публикации

Securing Element, Particularly Suitable for Use with Tablet-Arm Chairs

Номер: US20130270873A1
Автор: Alberto Lievore Motta
Принадлежит: SELLEX SA

The invention can be used to secure writing tablets to different types of chairs with legs of different thicknesses and diameters, such that writing tablets can be installed on simple chairs with no armrests. The invention is essentially characterised in that it comprises: a main part having two through-holes therein, namely a first hole for receiving and housing the tubular support of the writing tablet and a second hole dimensioned to be coupled to one of the legs of the chair, and a vertical rod; and a pivoting part connected to the main part by means of the rod, aligned with the second hole and adapted to open and close such that the securing element can be released from the leg of the chair.

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Номер записи: 42
17-10-2013 дата публикации

IMMUNOSUPPRESSANT FORMULATIONS

Номер: US20130273161A1
Автор: Bouillot Philippe Michel Rene, Reynaud Emeric
Принадлежит:

The present invention relates to a solid phase pharmaceutical composition comprising one or more pharmaceutically acceptable excipients and an active pharmaceutical ingredient (“API”) which is a compound of formula A1 or A2 or a pharmacologically acceptable salt, solvate or hydrate thereof, wherein the API is not exposed to a basic compound. 2. A composition according to wherein A is COOH.3. A composition according to wherein the API is 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid or a pharmaceutically acceptable salt.4. A composition according to wherein the API is 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid or a hemifumarate salt thereof.5. A composition according to wherein the API is in a mixture of materials which is free of basic compounds.6. A solid phase pharmaceutical composition according to claim 3 , wherein the API is in the form of particles having an X90 diameter of at least 8 μm.7. A composition according to wherein the particles have an X90 diameter of from 10 μm to 300 μm.8. A composition which is in unit dosage form and complies with the US Pharmacopeia claim 6 , European Pharmacopeia and Japanese Pharmacopeia harmonised content uniformity requirements as in force on 1 Jan. 2011.9. A solid phase pharmaceutical composition according to claim 3 , wherein the API has a crystallinity of 80% or more.10. A tablet comprising a compressed mixture consisting of 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid or a pharmaceutically acceptable salt thereof and one or more non-basic excipients claim 3 , the 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid or pharmaceutically acceptable salt being in the form of particles having an X90 diameter of from 10 μm to 200 μm.11. A tablet according to claim 10 , wherein the ...

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Номер записи: 43
17-10-2013 дата публикации

FLUORENE COMPOUND AND PHARMACEUTICAL USE THEREOF

Номер: US20130274240A1
Автор: Ito Hirotsugu, Kobayashi Satoru, Morita Toru, Motomura Takahisa, Nagamori Hironobu, Shinkai Hisashi, Suzawa Koichi
Принадлежит:

The present invention provides an agent for the prophylactic or treatment of diabetes, diabetic complications, insulin resistance syndrome, metabolic syndrome, hyperglycemia, dyslipidemia, atherosclerosis, cardiac failure, cardiomyopathy, myocardial ischemia, brain ischemia, cerebral apoplexy, pulmonary hypertension, hyperlactacidemia, mitochondrial disease, mitochondrial encephalomyopathy or cancer, namely, a PDHK inhibitor and the like. A compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof, or a solvate thereof: 217.-. (canceled)18. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof claim 1 , and a pharmaceutically acceptable carrier.1923.-. (canceled)24. A method of inhibiting PDHK in a mammal claim 1 , comprising administering a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof to the mammal.25. A method of inhibiting PDHK2 in a mammal claim 1 , comprising administering a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof to the mammal.26. A method of decreasing the blood glucose level in a mammal claim 1 , comprising administering a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof to the mammal.27. A method of decreasing lactate level in a mammal claim 1 , comprising administering a pharmaceutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a solvate thereof to the mammal.28. A method for the treatment or prophylaxis of diabetes claim 1 , diabetic complications claim 1 , insulin resistance syndrome claim 1 , metabolic syndrome claim 1 , hyperglycemia claim 1 , dyslipidemia claim 1 , atherosclerosis claim 1 , ...

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Номер записи: 44
31-10-2013 дата публикации

DIAZENIUMDIOLATE HETEROCYCLIC DERIVATIVES

Номер: US20130289003A1
Автор: Ali Amjad, Baker Robert K., Dellureficio James, Guo Zhiqiang, Henderson Timothy J., Lo Michael Man-Chu, Metzger Edward, Shah Shrenik K., Wang Jun, WHITEHEAD Brent, Yan Lin
Принадлежит:

A compound having the structure: useful for treating hypertension, Pulmonary Arterial Hypertension (PAH), congestive heart failure, conditions resulting from excessive water retention, cardiovascular disease, diabetes, oxidative stress, endothelial dysfunction, cirrhosis, pre-eclampsia, osteoporosis or nephropathy. 4. A compound of claim 1 , wherein Ris hydrogen claim 1 , —C(O)OH claim 1 , or —C(O)OCH claim 1 , or a pharmaceutically acceptable salt thereof.5. A compound of claim 1 , wherein Ris hydrogen claim 1 , or a pharmaceutically acceptable salt thereof.6. A compound of claim 1 , wherein Ris —CDCalkyl claim 1 , —C(CH) claim 1 , —CHCH claim 1 , or —CH(CH).8. A compound of claim 1 , wherein Ris hydrogen claim 1 , —CH claim 1 , C(O)OCH claim 1 , —C(O)OH claim 1 , phenyl claim 1 , or a pharmaceutically acceptable salt thereof.9. A compound of claim 1 , wherein Ris hydrogen or —CH claim 1 , or a pharmaceutically acceptable salt thereof.10. A compound of claim 1 , wherein Rand Rare attached to the same carbon atom and together form ═O claim 1 , or a pharmaceutically acceptable salt thereof.16. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CHor —CH.17. A compound of claim 1 , wherein Rand R claim 1 , together with the N atom to which they are attached claim 1 , form a 5- or 6-membered heterocyclic ring containing 1 N atom claim 1 , which ring is unsubstituted or substituted with —CHOH.18. A compound of claim 1 , wherein Rtogether with R claim 1 , forms ═O.19. A compound of claim 1 , which is{'sup': '2', 'O-[(3R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl]1-(N-tert-butyl-N-methylamino)diazen-1-ium-1,2-diolate,'}{'sup': '2', 'O-[(3S)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl]1-(N-tert-butyl-N-methylamino)diazen-1-ium-1,2-diolate,'}{'sup': '2', 'O-[(3R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl]1-(N-tert-butyl-N-ethylamino)diazen-1-ium-1,2-diolate,'}{'sup': '2', 'O-[(3R)-1-(tert-butoxycarbonyl)pyrrolidin-3-yl]1-(N-tert-butyl-N- ...

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Номер записи: 45
07-11-2013 дата публикации

PROLINAMIADE DERIVATIVES AS THROMBIN INHIBITOR, PREPRARATION METHOD AND APPLICATION THEREOF

Номер: US20130296245A1
Автор: Huang Yu, Li Min, Shan Hanbin, Yu Xiong, Yuan Zhedong
Принадлежит:

Provided are a compound of formula (I), pharmaceutically acceptable salts thereof, preparation methods and applications thereof for inhibiting thrombin, and applications in the treatment and prevention of thrombin-mediated and thrombin-related diseases. 6. The compound of formula (I) claim 1 , pharmaceutically acceptable salt and pharmaceutically acceptable prodrug thereof according to claim 1 , characterized in that the pharmaceutically acceptable salt is selected from the salts derived from pharmaceutically acceptable inorganic acid and organic acid.7. The compound of formula (I) claim 6 , pharmaceutically acceptable salt and pharmaceutically acceptable prodrug thereof according to claim 6 , characterized in that the inorganic acid and organic acid are selected from sulfuric acid claim 6 , sulfurous acid claim 6 , hydrochloric acid claim 6 , acetic acid claim 6 , hydrobromic acid claim 6 , nitric acid claim 6 , phosphoric acid claim 6 , metaphosphoric acid claim 6 , pyrophosphoric acid claim 6 , maleic acid claim 6 , fumaric acid claim 6 , succinic acid claim 6 , citric acid claim 6 , perchloric acid claim 6 , p-toluenesulfonic acid claim 6 , tartaric acid claim 6 , formic acid claim 6 , acetic acid claim 6 , propanoic acid claim 6 , heptylic acid claim 6 , oxalic acid claim 6 , benzoic acid claim 6 , propandioic acid claim 6 , succinic acid claim 6 , succinic acid claim 6 , cis-butenedioic acid claim 6 , hydroxybutanoic acid claim 6 , citric acid claim 6 , methanesulfonic acid claim 6 , benzenesulfonic acid claim 6 , lactic acid or mandelic acid.8. The compound of formula (I) claim 6 , pharmaceutically acceptable salt and pharmaceutically acceptable prodrug thereof according to claim 6 , characterized in that the inorganic acid and organic acid are selected from hydrochloric acid or acetic acid.9. The compound of formula (I) claim 1 , pharmaceutically acceptable salt and pharmaceutically acceptable prodrug thereof according to claim 1 , characterized in that the ...

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Номер записи: 46
07-11-2013 дата публикации

Substituted tetracyclines

Номер: US20130296279A1
Автор: Adam Morgan
Принадлежит: Concert Pharmaceuticals Inc

The invention in one embodiment is directed to a compound of formula (I) or a pharmaceutically acceptable salt thereof. The invention is also directed to a composition comprising the compound of formula I or a pharmaceutically acceptable salt, and methods of treating the indications listed herein.

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Номер записи: 47
14-11-2013 дата публикации

NOVEL COMPOUNDS USEFUL FOR THE TREATMENT OF METABOLIC AND INFLAMMATORY DISEASES

Номер: US20130303515A1
Автор: "Pourbaix-Lebraly Christelle Dominique Bénédicte", Brys Reginald Christophe Xavier, De Vos Steve Irma Joel, Pizzonero Mathieu Rafaël, SANIÈRE Laurent Raymond Maurice, Triballeau Nicolas, Vandeghinste Nick Ernest René
Принадлежит:

Compounds are disclosed that have a formula represented by the following: 3. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Y is Me claim 1 , Et claim 1 , Pr claim 1 , iPr claim 1 , or —CH-Ph.5. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Ris —(CH)—COOH claim 1 , —(CH)—COOH claim 1 , —(CH)—SONH claim 1 , or —(CH)—SONHMe.6. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Cyis phenyl claim 1 , or naphthalene.7. A compound or pharmaceutically acceptable salt thereof claim 1 , according to claim 1 , wherein Cyis thiophenyl claim 1 , benzothiophenyl claim 1 , benzofuranyl claim 1 , benzoisoxazolyl claim 1 , benzoxazolyl or indolyl.8. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein m is 1 or 2.9. A compound or pharmaceutically acceptable salt thereof according to claim 8 , wherein each Rgroup is independently selected from F claim 8 , Cl claim 8 , Br claim 8 , Me claim 8 , CF claim 8 , and OMe.10. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein m is 0.11. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Lis a single bond.12. A compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein Lis —CH—.13. A compound according to claim 1 , wherein the compound is 4-[[(R)-1-(Benzo[b]thiophene-3-carbonyl)-2-methyl-azetidine-2-carbonyl]-(3-chloro-benzyl)-amino]-butyric acid; or a pharmaceutically acceptable salt claim 1 , or a solvate claim 1 , or a solvate of the pharmaceutically acceptable salt.14. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof claim 1 , according to claim 1 , and a pharmaceutically acceptable carrier.15. The pharmaceutical composition according to comprising a further therapeutic agent.16. (canceled)17. A method for the treatment of inflammatory conditions claim 1 ...

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Номер записи: 48
21-11-2013 дата публикации

NOVEL AZETIDINE DERIVATIVES AS SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTOR MODULATORS

Номер: US20130310359A1
Автор: Bhat Smita S., Chow Ken, CORPUZ EVELYN G., FANG WENKUI K., IM WHA-BIN, Sinha Santosh C.
Принадлежит: ALLERGAN, INC.

The present invention relates to novel azetidine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors. 2. The method according to claim 1 , wherein said compound is represented by Formula I wherein:{'img': {'@id': 'CUSTOM-CHARACTER-00014', '@he': '2.46mm', '@wi': '4.57mm', '@file': 'US20130310359A1-20131121-P00001.TIF', '@alt': 'custom-character', '@img-content': 'character', '@img-format': 'tif'}, 'sup': 14', '15, '“” represents a double bond “—CR═CR—”.'}3. The method according to claim 1 , wherein said compound is represented by Formula I wherein:{'img': {'@id': 'CUSTOM-CHARACTER-00015', '@he': '2.46mm', '@wi': '4.57mm', '@file': 'US20130310359A1-20131121-P00001.TIF', '@alt': 'custom-character', '@img-content': 'character', '@img-format': 'tif'}, '“” represents a triple bond “—C≡C—”.'}4. The method according to claim 1 , wherein said compound is represented by Formula I wherein:{'sup': '1', 'sub': '2', 'Lis CH.'}5. The method according to claim 1 , wherein said compound is represented by Formula I wherein:{'sup': '1', 'Lis O, S or NH.'}9. The method according to claim 1 , wherein said compound is selected from:1-{4-[3-(3-chlorophenyl)-4-(3,4-dimethylphenyl)but-1-yn-1-yl]benzyl}azetidine-3-carboxylic acid;1-{4-[3-(3-Chloro-phenyl)-4-(3,4-dimethyl-phenyl)-but-1-ynyl]-3-methyl-benzyl}-azetidine-3-carboxylic acid;1-{4-[4-(3,4-dimethylphenyl)-3-(3-methoxyphenyl)but-1-yn-1-yl]benzyl}azetidine-3-carboxylic acid;1-{4-[3-(4-chlorophenyl)-4-(3,4-dimethylphenyl)but-1-yn-1-yl]benzyl}azetidine-3-carboxylic acid;1-{4-[4-(3,4-di methylphenyl)-3-(3-methylphenyl)but-1-yn-1-yl]benzyl}azetidine-3-carboxylic acid;1-{4-[4-(3,4-Dichloro-phenyl)-3-(3-fluoro-phenyl)-but-1-ynyl]-benzyl}-azetidine-3-carboxylic acid;1-[4-(3,4-diphenylbut-1-yn-1-yl)benzyl]azetidine-3-carboxylic acid; and1-{4-[(1E)-4-(3,4-dimethylphenyl)-3-(3-fluorophenyl)but-1-en-1-yl]benzyl}azetidine-3- ...

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Номер записи: 49
21-11-2013 дата публикации

NOVEL OXIME AZETIDINE DERIVATIVES AS SPHINGOSINE 1-PHOSPHATE (S1P) RECEPTOR MODULATORS

Номер: US20130310360A1
Автор: Chow Ken, CORPUZ EVELYN G., FANG WENKUI K., IM WHA-BIN, Wang Liming
Принадлежит: ALLERGAN, INC.

The present invention relates to novel oxime azetidine derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors. 2. A compound according to selected from:1-{4-[({[(1E)-2-(3,5-difluorophenyl)-3-(3,4-dimethylphenyl)-1-methylpropylidene]amino}oxy)methyl]benzyl}azetidine-3-carboxylic acid;1-{4-[({[(1E)-2-(3-chlorophenyl)-3-(3,4-dimethylphenyl)-1-methylpropylidene]amino}oxy)methyl]benzyl}azetidine-3-carboxylic acid;3-(4-{(1E)-N-[3-(3,4-dimethylphenyl)-2-(3-methylphenyl)propoxy]ethanimidoyl}benzyl)cyclobutanecarboxylic acid;3-(4-{(1E)-N-[2-(3-chlorophenyl)-3-(3,4-dimethylphenyl)propoxy]ethanimidoyl}benzyl)cyclobutanecarboxylic acid.3. A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound according to and a pharmaceutically acceptable adjuvant claim 1 , diluents or carrier.4. A pharmaceutical composition according to wherein the compound is selected from:1-{4-[({[(1E)-2-(3,5-difluorophenyl)-3-(3,4-dimethylphenyl)-1-methylpropylidene]amino}oxy)methyl]benzyl}azetidine-3-carboxylic acid;1-{4-[({[(1E)-2-(3-chlorophenyl)-3-(3,4-dimethylphenyl)-1-methylpropylidene]amino}oxy)methyl]benzyl}azetidine-3-carboxylic acid;3-(4-{(1E)-N-[3-(3,4-dimethylphenyl)-2-(3-methylphenyl)propoxy]ethanimidoyl}benzyl)cyclobutanecarboxylic acid;3-(4-{(1E)-N-[2-(3-chlorophenyl)-3-(3,4-dimethylphenyl)propoxy]ethanimidoyl}benzyl)cyclobutanecarboxylic acid.6. A method of claim 5 , wherein the pharmaceutical composition is administered to the mammal to treat ocular disease claim 5 , wet and dry age-related macular degeneration claim 5 , diabetic retinopathy claim 5 , retinopathy of prematurity claim 5 , retinal edema claim 5 , geographic atrophy claim 5 , glaucomatous optic neuropathy claim 5 , chorioretinopathy claim 5 , hypertensive retinopathy claim 5 , ocular ischemic syndrome claim 5 , prevention of inflammation-induced fibrosis in ...

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Номер записи: 50
28-11-2013 дата публикации

N-SUBSTITUTED BENZAMIDES AND METHODS OF USE THEREOF

Номер: US20130317000A1
Автор: Chowdhury Sultan, DEHNHARDT Christoph Martin, FOCKEN Thilo, GRIMWOOD Michael Edward, HEMEON Ivan William, Jia Qi, Ortwine Daniel, SAFINA Brian, Sun Shaoyi, Sutherlin Daniel P., ZENOVA Alla Yurevna
Принадлежит:

The invention provides novel compounds having the general formula: 2. The compound of wherein:{'sup': 1', '1A', '1B', '1A', '1B', 'R1', 'R1', '1A', '1B', 'R1', '1', 'R1', '1R', 'R1a', 'R1b', '1R', 'R1a', '1R', 'R1a', '1R', 'R1a', 'R1c', '1R', 'R1a', 'R1b', '1R', 'R1a', 'R1a', 'R1b', '1R', 'R1a', 'R1b', '1R', 'R1a', 'R1b', '1R', 'R1a', '1R', 'R1a', '1R', 'R1a', 'R1b', '1R', 'R1c', '1R', 'R1a', 'R1b', '1R', 'R1a', 'R1a', 'R1b', '1R', 'R1a', 'R1c', '1R', 'R1a', 'R1b', 'R1c, 'sub': 1-8', '1-8', '1-8', '3-12', '2-11', '1-8', '1-8', '0-1', '0-1', '1-4', '1-4', '2-4', '2-4', '1-8', '1-8', '2', '0-1', '0-1', '0-1', '0-1', '0-1', '0-1', '0-1', '0-1', '0-1', '0-1', '0-1', '0-1', '1-2', '0-1', '1-2', '0-1', '1-2', '0-1', '1-2', '1-4', '1-4', '2-4', '2-4', '1-8', '1-8', '3-8', '5-6', '2-7', '1-8', '1-8', '3-8', '5-6', '2-7, 'Ris Calkyl, Chaloalkyl, Calkoxy, Ccycloalkyl, C-linked Cheterocycloalkyl or —NRR, wherein Rand Rare each independently selected from the group consisting of hydrogen, Calkyl, Calkoxy, (6-10 membered aryl)-(X)—, (5-10 membered heteroaryl)-(X)—, and wherein Rand Rare optionally combined to form a 3 to 8 membered heterocyclic ring optionally comprising 1 additional heteroatoms selected from N, O and S as ring vertex and optionally fused thereto is a benzene or pyridine ring; Xis selected from the group consisting of Calkylene, Cheteroalkylene, Calkenylene, Calkynylene; and wherein the aliphatic and aromatic portions of Rare optionally substituted with from 1 to 5 Rsubstituents selected from the group consisting of Calkyl, Chaloalkyl, F, Cl, Br, I, —OH, —CN, —NO, ═O, —(X)NRR, —(X)OR, —(X)SR, —(X)N(R)C(═O)OR, —(X)OC(═O)N(R)(R), —(X)N(R)C(═O)N(R)(R), —(X)C(═O)N(R)(R), —(X)N(R)C(═O)R, —(X)C(═O)OR, —(X)OC(═O)R, —(X)—P(═O)(OR)(OR), —(X)S(O)R, —(X)S(O)N(R)(R), —(X)N(R)S(O)N(R)(R) and —(X)N(R)S(O)(R), wherein Xis selected from the group consisting of Calkylene, Cheteroalkylene, Calkenylene and Calkynylene; wherein Rand Rare independently selected from the group ...

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Номер записи: 51
28-11-2013 дата публикации

N-SUBSTITUTED BENZAMIDES AND METHODS OF USE THEREOF

Номер: US20130317001A1
Автор: ANDREZ Jean-Christophe, Chowdhury Sultan, DECKER Shannon Marie, DEHNHARDT Christoph Martin, FOCKEN Thilo, GRIMWOOD Michael Edward, HEMEON Ivan William, Jia Qi, LI JUN, Ortwine Daniel F., SAFINA Brian, SHENG Tao, Sun Shaoyi, Sutherlin Daniel P., WILSON Michael Scott, ZENOVA Alla Yurevna
Принадлежит:

The invention provides novel compounds having the general formula: 3. The compound of wherein B is N and Ris absent.4. The compound of wherein B is C.5. The compound of wherein R claim 1 , Rand Rare each independently selected from H claim 1 , F claim 1 , or Cl.6. The compound of wherein Ris H claim 1 , F or Cl; Rand Rare each H; and Ris an optionally substituted group selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , —CN claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Ccycloalkyl claim 1 , and Calkoxy.7. The compound of wherein Ris Calkyl claim 1 , Chaloalkyl claim 1 , Ccycloalkyl or —NRR.8. The compound of claim 7 , wherein Ris selected from the group consisting of methyl claim 7 , ethyl claim 7 , propyl claim 7 , trifluoromethyl claim 7 , difluoromethyl claim 7 , monofluoromethyl claim 7 , isopropyl and cyclopropyl.11. The compound of wherein Ris selected from the group consisting of: methyl claim 1 , ethyl claim 1 , tert-butyl claim 1 , dimethylamino claim 1 , methylamino claim 1 , amino claim 1 , morpholino claim 1 , azetidino claim 1 , imidazolyl claim 1 , 3-hydroxyazetidino claim 1 , 3-fluoroazetidino claim 1 , cyclopropyl claim 1 , pyrrolidinyl claim 1 , 3 claim 1 ,3-difluoroazetidino claim 1 , tert-butyl claim 1 , ethyl claim 1 , 2-methoxyethyl claim 1 , 3-methoxyazetidino claim 1 , 2-hydroxyethyl claim 1 , 3-hydroxypyrrolidinyl claim 1 , and N-methylimidazolyl.12. The compound of wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is an optionally substituted group selected from the group consisting of Calkylene claim 1 , Calkenylene or Calkynylene.13. The compound of claim 1 , wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)(CH)—CH— or —CHCHCHCH—.14. The compound of claim 13 , ...

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Номер записи: 52
05-12-2013 дата публикации

Indanyloxyphenylcyclopropanecarboxylic acids

Номер: US20130324514A1
Автор: Dieter Hamprecht, Iain Lingard, Sara Frattini, Stefan Peters
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to compounds of general formula I, wherein the groups R 1 , R 2 , R 3 , m and n are defined as in claim 1 , which have valuable pharmacological properties, in particular bind to the GPR40 receptor and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2. Furthermore, the invention relates to novel intermediates, useful for the synthesis of compounds of formula I.

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Номер записи: 53
12-12-2013 дата публикации

GLP-1 POTENTIATORS FROM HEDYCHIUM CORONARIUM AND THEIR APPLICATIONS

Номер: US20130331323A1
Автор: Chen Hui-Ling, HUANG Jiann-Jyh, King K-Lim, Lee Shoei-Sheng, WU REY-YUH, Wu Yu-Yuan
Принадлежит: DEVELOPMENT CENTER FOR BIOTECHNOLOGY

A compound for controlling blood glucose level has a structure shown in Formula I: 5. A method for controlling blood glucose level claim 1 , comprising administering to a subject in need thereof the compound of .6. The method of claim 5 , further comprising administering to the subject a glucagon-like peptide-1 (GLP-1) receptor ligand to the subject.7. The method of claim 6 , wherein the GLP-1 receptor ligand is GLP-1 or exendin-4.8. The method of claim 6 , wherein the compound and the GLP-1 receptor ligand are administered together.10. The method of claim 9 , wherein the compound has a structure of 1A.11. The method of claim 9 , wherein the compound has a structure of 1B. 1. Technical Field of the InventionThe present invention relates to new uses of compounds, particularly a diterpenoid Galanal B, in the regulation of blood glucose levels.2. BackgroundGlucagon-like peptide-1 (GLP-1) analogues are a new class of hypoglycemic agents. GLP-1 is a member of the incretin family, which comprises gastrointestinal hormones that help control blood glucose levels after meals. GLP-1 exerts its functions by specific binding to GLP-1 receptor. GLP-1 receptor (GLP-1R) is widely distributed. In addition to pancreatic tissue, GLP-1 receptor is also distributed in the brain, lung, heart, kidney, etc. The wide distribution of this receptor contributes to the wide range of its functions.GLP-1 bind specifically to the GLP-1 receptor on the pancreatic beta cells. Activation of GLP-1R leads to stimulation of the adenylyl cyclase pathway, which eventually leads to increased insulin synthesis and release. In addition to the increased insulin synthesis and release, GLP-1 binding to its receptor also inhibits the production of glucagon and maintains constant levels of blood glucose after meals. Furthermore, GLP-1 also has a neuron regulatory function, which can delay gastric emptying and reduce appetite. At the same time, the hypoglycemic effect of GLP-1 is self-limiting and will not result ...

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Номер записи: 54
12-12-2013 дата публикации

Azetidine Derivatives

Номер: US20130331371A1
Автор: Brough Paul, Graham Christopher, Hart Terance, Macias Alba, Parsons Rachel, Roughley Stephen, Walls Steven
Принадлежит: VERNALIS (R&D) LTD.

Compounds of formula (I) are inhibitors of fatty acid amide hydrolase, (FAAH), and which are useful in the treatment of diseases or medical conditions which benefit from inhibition of FAAH activity, such as anxiety, depression pain, inflammation, and eating, sleep, neurodegenerative and movement disorders: 2. A method as claimed in wherein Aris optionally substituted phenyl.3. A method as claimed in wherein Aris phenyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyrazinyl or pyridazinyl claim 1 , any of which being optionally substituted.4. A method as claimed in wherein Aris 3-pyridyl claim 1 , pyrimidin-4-yl claim 1 , pyrazin-2-yl or pyridazin-3-yl claim 1 , any of which being optionally substituted.5. A method as claimed in wherein Aris an optionally substituted divalent phenylene or pyridinylene radical.7. A method as claimed in wherein any optional substituents in Ar claim 1 , Arand Arare independently selected from chloro claim 1 , fluoro claim 1 , bromo claim 1 , cyclopropyl claim 1 , methyl claim 1 , mono- claim 1 , di- or tri-methyl claim 1 , trifluoromethyl claim 1 , difluoromethyl claim 1 , monofluoromethyl claim 1 , methoxy claim 1 , ethoxy claim 1 , propoxy claim 1 , butoxy claim 1 , pentoxy claim 1 , 2-methoxyethoxy claim 1 , 2-benzyloxy-ethoxy claim 1 , 2-hydroxy-ethoxy claim 1 , mono- claim 1 , di- or tri-fluoromethoxy claim 1 , cyano claim 1 , hydroxyl; —CORand —SORwherein Ris hydrogen claim 1 , methyl or ethyl; tetrazolyl; —NRR claim 1 , —CHNRRand —C(═O)NRRwherein Rand Rare independently hydrogen claim 1 , methyl or ethyl.9. A method as claimed in wherein Aris phenyl claim 8 , 2-fluorophenyl claim 8 , 3-(2-methoxy-ethoxy)-phenyl claim 8 , or 2-methoxy-5-(2-methoxy-ethoxy)-phenyl.10. A method as claimed in wherein Aris pyridazin-3-yl.11. A method as claimed in selected from the group consisting of:3-(biphenyl-4-yloxy)-azetidine-1-carboxylic acid phenylamide;3-(Biphenyl-4-yloxy)-azetidine-1-carboxylic acid (3-fluoro-phenyl)-amide;3-(Biphenyl-4- ...

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Номер записи: 55
02-01-2014 дата публикации

HEMIFUMARATE SALT OF 1-[4-[1-(4-CYCLOHEXYL-3-TRIFLUOROMETHYL-BENZYLOXYIMINO)-ETHYL]-2-ETHYL-BENZYL]-AZETIDINE-3-CARBOXYLIC ACID

Номер: US20140005162A1
Автор: Ciszewski Lech, DE LA CRUZ Marilyn, Karpinski Piotr H., Mutz Michael, RIEGERT Christian, Schneeberger Ricardo, Vogel Caspar
Принадлежит:

This invention relates to a hemifumarate salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzylyazetidine-3-carboxylic acid (Compound I), to pharmaceutical compositions comprising this salt, to processes for forming this salt and to its use in medical treatment. In addition, the present invention also relates to new polymorphic forms of the hemifumarate salt form of Compound I, as well as to pharmaceutical compositions comprising these polymorphic forms, to processes for obtaining them, and their use in medical treatment. 1. A hemifumarate salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid.2. A hemifumarate salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid according to claim 1 , wherein said salt is substantially crystalline.3. Crystalline Form A of the hemifumarate salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid.4. Crystalline Form A of the hemifumarate salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid according to claim 3 , characterised in that the crystalline form has an X-ray powder diffraction pattern having at least one specific peak at about 2-theta=20.7°.5. Crystalline Form A of the hemifumarate salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid according to claim 3 , characterised in that the crystalline form has an X-ray powder diffraction pattern with specific peaks at about 2-theta=6.9° claim 3 , 17.5° claim 3 , 18.1° claim 3 , 20.4° claim 3 , and 20.7°.6. Crystalline Form A of the hemifumarate salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethyl-benzyl)-azetidine-3-carboxylic acid according to claim 3 , characterised in that the crystalline form has ...

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Номер записи: 56
16-01-2014 дата публикации

METHOD OF INHIBITING TAU PHOSPHORYLATION

Номер: US20140018341A1
Автор: Burns Barbier Lindsay, Wang Hoau-Yan
Принадлежит:

A method of inhibiting phosphorylation of the tau protein and/or a TLR4-mediated immune response is disclosed. The method contemplates administering to cells in recognized need thereof such as cells of the central nervous system an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, and contains at least four of the six pharmacophores of FIGS. - 1. A method of inhibiting phosphorylation of the tau protein that comprises the steps of administering to cells of the central nervous system in recognized need an effective amount of a of a compound or a pharmaceutically acceptable salt thereof that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1 , inhibits at least about 60 percent of the FITC-labeled naloxone binding when present at a 10 μM concentration and using unlabeled naloxone as the control inhibitor at the same concentration , said administration being carried out in the absence of a mu opioid receptor- (MOR-) binding effective amount of a separate MOR agonist or antagonist.2. The method according to claim 1 , wherein said compound contains at least four of the six pharmacophores of .3. The method according to claim 1 , wherein said compound or a pharmaceutically acceptable salt thereof is present dissolved or dispersed in a pharmaceutically acceptable diluent as a pharmaceutical composition when administered.4. The method according to claim 1 , wherein said compound exhibits less than about 80 percent the MOR stimulation provided by DAMGO at the same concentration.13. The method according to claim 12 , wherein said anion claim 12 , X claim 12 , is selected from the group consisting of phosphate claim 12 , hydrogenphosphate claim 12 , dihydrogenphosphate claim 12 , sulfate claim 12 , bisulfate claim 12 , chloride claim 12 , bromide claim 12 , iodide claim 12 , acetate claim 12 , formate claim 12 , benzenesulfonate claim 12 , methanesulfonate claim 12 , and ...

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Номер записи: 57
23-01-2014 дата публикации

AMINOCARBOXYLIC ACID DERIVATIVE AND MEDICINAL USE THEREOF

Номер: US20140023636A1
Автор: HABASHITA Hiromu, KURATA Haruto, Nakade Shinji
Принадлежит: ONO PHARMACEUTICAL CO., LTD.

The present invention relates to a compound represented by the formula (I), a salt thereof, an N-oxide form thereof, a solvate thereof, or a prodrug thereof, and a medicament containing the same. The compound represented by the formula (I) has an ability to bind to an S1P receptor (particularly, EDG-1, EDG-6, and/or EDG-8) and is useful for preventing and/or treating for rejection to transplantation, graft-versus-host disease, autoimmune diseases, allergic diseases, neurodegenerating diseases, and the like. 2. The compound according to claim 1 , a salt thereof claim 1 , an N-oxide form thereof claim 1 , a solvate thereof claim 1 , or a prodrug thereof claim 1 , wherein Z represents (1) a carboxyl group which may be protected claim 1 , (2) a hydroxy group which may be protected claim 1 , (3) a hydroxamic acid group which may be protected claim 1 , (4) a sulfonic acid group which may be protected claim 1 , (5) a boronic acid group which may be protected claim 1 , (6) a carbamoyl group which may be protected claim 1 , (7) a sulfamoyl group which may be protected claim 1 , (8) a —P(═O)(OR) (OR) group claim 1 , wherein Rand Reach independently represent a hydrogen atom and a C1-8 alkyl group claim 1 , or Rand Rjoin together to represent a C2-4 alkylene group claim 1 , or (9) a tetrazolyl group.4. The compound according to claim 1 , a salt thereof claim 1 , an N-oxide form thereof claim 1 , a solvate thereof claim 1 , or a prodrug thereof claim 1 , wherein a ring B is a benzene ring which may have a substituent(s) claim 1 , or a dihydronaphthalene ring which may have a substituent(s).10. The compound according to claim 1 , a salt thereof claim 1 , an N-oxide form thereof claim 1 , a solvate thereof claim 1 , or a prodrug thereof claim 1 , wherein ring A is a benzene ring or a pyridine ring.11. The compound according to claim 1 , a salt thereof claim 1 , an N-oxide form thereof claim 1 , a solvate thereof claim 1 , or a prodrug thereof claim 1 , wherein Rrepresents a ...

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Номер записи: 58
30-01-2014 дата публикации

AMINOTETRALINE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND THEIR USE IN THERAPY

Номер: US20140031331A1
Автор: Amberg Wilhelm, Behl Berthold, Hornberger Wilfried, Hutchins Charles W., Kling Andreas, Lange Udo, Mezler Mario, Ochse Michael
Принадлежит:

The present invention relates to aminotetraline derivatives of the formula (I) 234.-. (canceled)35. A method for inhibiting the glycine transporter GlyT1 in a mammal in need thereof which comprises the administration of an effective amount of a compound of .36. (canceled)37. A method for treating a neurologic or psychiatric disorder or pain in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of a compound of .38. (canceled)39. The compound of for use in a method of treating a neurologic or psychiatric disorder or pain.40. The method as claimed in claim 37 , wherein the disorder is associated with glycinergic or glutamatergic neurotransmission dysfunction.41. The method as claimed in claim 37 , wherein the neurologic disorder is selected from the group consisting of dementia claim 37 , cognitive impairment claim 37 , and attention deficit disorder.42. The method as claimed in claim 41 , wherein the attention deficit disorder is an attention deficit disorder with hyperactivity.43. The method as claimed in claim 37 , wherein the psychiatric disorder is selected from the group consisting of anxiety disorder claim 37 , depression claim 37 , bipolar disorder claim 37 , schizophrenia claim 37 , and psychosis.44. (canceled) This claims the benefit of U.S. Provisional Application No. 61/152,825, which was filed on Feb. 16, 2009, the contents of which are incorporated herein by reference.The present invention relates to aminotetraline derivatives, pharmaceutical compositions comprising such aminotetraline derivatives, and the use of such aminotetraline derivatives for therapeutic purposes. The aminotetraline derivatives are GlyT1 inhibitors.Dysfunction of glutamatergic pathways has been implicated in a number of disease states in the human central nervous system (CNS) including but not limited to schizophrenia, cognitive deficits, dementia, Parkinson disease, Alzheimer disease and bipolar disorder. A large ...

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Номер записи: 59
06-02-2014 дата публикации

MODULATORS OF SEROTONIN RECEPTORS

Номер: US20140038934A1
Автор: Brock Shireman T., Carruthers Nicholas I., Jablonowski Jill A., Tran Vi T.
Принадлежит: Janssen Pharmaceutica NV

Certain biphenyl compounds are serotonin modulators useful in the treatment of serotonin-mediated diseases. 122.-. (canceled)24. A method according to claim 23 , wherein the disease claim 23 , disorder claim 23 , or condition is selected from the group consisting of: sleep disorders claim 23 , depression/anxiety claim 23 , generalized anxiety disorder claim 23 , schizophrenia claim 23 , bipolar disorders claim 23 , cognitive disorders claim 23 , mild cognitive impairment claim 23 , Alzheimer's disease claim 23 , Parkinson's disease claim 23 , psychotic disorders claim 23 , phobic disorders claim 23 , obsessive-compulsive disorder claim 23 , mood disorders claim 23 , post-traumatic stress claim 23 , migraine claim 23 , pain claim 23 , eating disorders claim 23 , obesity claim 23 , sexual dysfunction claim 23 , metabolic disturbances claim 23 , hormonal imbalance claim 23 , hot flushes associated with menopause claim 23 , alcohol abuse claim 23 , drug abuse claim 23 , drug addiction claim 23 , alcohol addiction claim 23 , nausea claim 23 , inflammation claim 23 , centrally mediated hypertension claim 23 , sleep/wake disturbances claim 23 , jetlag claim 23 , and circadian rhythm abnormalities.26. A method according to claim 25 , wherein the disease claim 25 , disorder claim 25 , or condition is selected from the group consisting of: sleep disorders claim 25 , depression/anxiety claim 25 , generalized anxiety disorder claim 25 , schizophrenia claim 25 , bipolar disorders claim 25 , cognitive disorders claim 25 , mild cognitive impairment claim 25 , Alzheimer's disease claim 25 , Parkinson's disease claim 25 , psychotic disorders claim 25 , phobic disorders claim 25 , obsessive-compulsive disorder claim 25 , mood disorders claim 25 , post-traumatic stress disorder claim 25 , pain claim 25 , alcohol abuse claim 25 , drug abuse claim 25 , drug addiction claim 25 , and alcohol addiction.27. A method according to claim 25 , wherein the disease claim 25 , disorder claim 25 , ...

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Номер записи: 60
06-02-2014 дата публикации

Serotonin receptor modulator

Номер: US20140038943A1
Автор: Brock T. Shireman, Chandravadan R. Shah, Devin M. Swanson, Jill A. Jablonowski, Nicholas I. Carruthers, Vi Tran, Victoria Wong, Wenying Chai
Принадлежит: Janssen Pharmaceutica NV

Certain biphenyic compounds are serotonin modulators useful in the treatment of serotonin-mediated diseases.

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Номер записи: 61
06-03-2014 дата публикации

HETEROCYCLIC COMPOUND

Номер: US20140066420A1
Автор: KAKU Tomohiro, KAMAURA Masahiro, KASAI Shizuo
Принадлежит: Takeda Pharmaceutical Company Limited

The present invention relates to 2. The compound according to claim 1 , wherein ring A is benzene optionally further substituted;{'sup': '1', 'sub': '3-6', 'Ris an optionally substituted branched Calkyl group;'}{'sup': '1', 'sub': '2', 'Xis O, S, SO, SOor NH;'}{'sup': '2', 'sub': '1-3', 'Xis a bond or a Calkylene group;'}ring B is piperidine;{'sup': '3', 'Xis CO; and'}{'sup': '2', 'Ris an acyl group or an optionally substituted hydrocarbon group.'}3. The compound according to claim 1 , wherein ring A is benzene optionally further substituted by 1 to 3 substituents selected from the group consisting of (1) a halogen atom claim 1 , (2) an optionally halogenated Calkyl group and (3) an optionally halogenated Calkoxy group.4. The compound according to claim 1 , wherein Ris an isopropyl group or a tert-butyl group.5. The compound according to claim 1 , wherein Xis O.6. The compound according to claim 1 , wherein Xis a bond or methylene.8. The compound according to claim 1 , wherein Xis CO.9. The compound according to claim 1 , wherein Ris an acyl group or an optionally substituted hydrocarbon group.1126-. (canceled)27. {4-[(2-tert-Butyl-4-chlorophenoxy)methyl]piperidin-1-yl}(oxo)acetic acid or a salt thereof.28. [4-(2-tert-butylphenoxy)piperidin-1-yl](oxo)acetic acid or a salt thereof.29. {4-[(2-tert-butylphenoxy)methyl]piperidin-1-yl}(oxo)acetic acid or a salt thereof.30. A pharmaceutical composition comprising the compound according to and a pharmacologically acceptable carrier. The present invention relates to a novel heterocyclic compound, which is useful as an agent for the prophylaxis or treatment of diabetes and the like; and the like.Retinol binding protein 4 (hereinafter sometimes to be abbreviated as “RBP4”) is known to be a sole blood retinol transport protein mainly produced in the liver. In recent years, moreover, RBP4 is suggested to be an insulin resistance-inducing factor from the following literatures and the like.(1) Since RBP4 expression increases in ...

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Номер записи: 62
06-03-2014 дата публикации

S1P Receptors Modulators and Their Use Thereof

Номер: US20140066427A1
Автор: Damian W. Grobelny, Gurmit S. Gill
Принадлежит: Akaal Pharma Pty Ltd

The invention relates to novel compounds that have SIP receptor modulating activity. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate SIP receptor modulating activity or expression, for example, autoimmune response. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate SIP receptor modulating activity or expression such as autoimmune response.

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Номер записи: 63
20-03-2014 дата публикации

Inhibitors of Histone Deacetylase

Номер: US20140080800A1
Автор: Haggarty Stephen, Holson Edward, Tsai Li-Huei, Wagner Florence Fevrier, Weiwer Michel, ZHANG YAN-LING
Принадлежит:

The present invention relates to compounds of formula (I): 5. The compound of or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , or prodrug thereof claim 4 , wherein Ris selected from phenyl claim 4 , 2-pyridinyl claim 4 , 3-pyridinyl claim 4 , 4-pyridinyl claim 4 , 2-pyrimidinyl claim 4 , 4-pyrimidinyl claim 4 , 5-pyrimidinyl claim 4 , 2-pyrazinyl claim 4 , oxazolyl claim 4 , thiazolyl claim 4 , and isoxazolyl.12. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.13. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition wherein said condition is associated with histone deacetylase activity in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.14. The method of claim 13 , wherein the condition is selected from a neurological disorder claim 13 , memory loss or impairment claim 13 , cognitive function disorder or impairment claim 13 , extinction learning disorder claim 13 , fungal disease or infection claim 13 , inflammatory disease claim 13 , hematological disease claim 13 , and neoplastic disease.15. The method of claim 14 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress ...

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Номер записи: 64
20-03-2014 дата публикации

Inhibitors of Histone Deacetylase

Номер: US20140080802A1
Автор: Haggarty Stephen, Holson Edward, Tsai Li-Huei, Wagner Florence Fevrier, Weiwer Michel, ZHANG YAN-LING
Принадлежит:

The present invention relates to compounds of formula (I): 10. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.11. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.12. The method of claim 11 , wherein the condition is selected from a neurological disorder claim 11 , memory loss or impairment claim 11 , cognitive function disorder or impairment claim 11 , extinction learning disorder claim 11 , fungal disease or infection claim 11 , inflammatory disease claim 11 , hematological disease claim 11 , and neoplastic disease.13. The method of claim 11 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, phobia, social anxiety disorder, substance dependence recovery or Age Associated Memory Impairment (AAMI), or Age Related Cognitive Decline (ARCD);a hematological disease selected from acute myeloid leukemia, acute promyelocytic leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, myelodysplastic syndromes, and sickle cell anemia;a cancer; andan extinction learning disorder selected from a fear extinction deficit and post-traumatic ...

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Номер записи: 65
27-03-2014 дата публикации

FLUORINATED ARYLALKYLAMINOCARBOXAMIDE DERIVATIVES

Номер: US20140088074A1
Автор: Pevarello Paolo
Принадлежит: NEWRON PHARMACEUTICALS S.P.A.

Fluorinated arylalkylaminocarboxamide derivatives of formula (I) are described wherein W, J, n, R, R, R, R, Rand Rhave the meanings as defined in the specification and pharmaceutically salts thereof, pharmaceutical compositions containing them as active ingredients and their use as sodium and/or calcium channel modulators useful in preventing, alleviating and curing a wide range of pathologies, including neurological, psychiatric, cardiovascular, inflammatory, ophthalmic, urological, and gastrointestinal diseases, where the above mechanisms have been described as playing a pathological role. 2. A compound of claim 1 , wherein:{'sub': 2', 'm', '1', '4', '3', '6, 'W is a group A-[(CH)—O]— wherein: m is zero, 1, 2 or 3; A is (C-C)alkyl optionally substituted by one to three fluorine atoms; (C-C)cycloalkyl; phenyl optionally substituted with a halo group; or thiazolyl'}{'sub': 1', '4, 'J independently is hydrogen; C-Calkyl; chloro; or fluoro;'} [{'sup': '1', 'sub': 1', '4', '1', '4', '3', '6, 'Ris hydrogen; (C-C)alkyl optionally substituted with a hydroxy group or a (C-C)alkoxy group; or (C-C)cycloalkyl;'}, {'sup': '2', 'sub': 1', '4, 'Ris hydrogen; or (C-C)alkyl;'}, {'sup': '2′', 'sub': 1', '4', '1', '4', '1', '4, 'R is hydrogen or (C-C)alkyl optionally substituted with a (C-C)alkoxy or a phenyl group, the phenyl group being optionally substituted with a (C-C)alkoxy group;'}, {'sup': '3', 'sub': 1', '4, 'Ris hydrogen; or (C-C)alkyl;'}, {'sup': '4', 'sub': 1', '4, 'Ris hydrogen; (C-C)alkyl; phenyl; or cyclohexyl; or'}], 'n is 1 or 2;'}{'sup': 3', '4, 'sub': 1', '2', '1', '4, 'claim-text': [{'sup': '5', 'Ris hydrogen or fluoro; and'}, {'sup': '6', 'Ris fluoro;'}], 'Rand R, taken together with the adjacent nitrogen atom, form an azetidinyl, pyrrolidinyl, morpholinyl, piperidinyl or piperazinyl, the piperydinyl ring being optionally substituted with one or two (C-C)alkyl group(s) and the piperazinyl ring being optionally substituted on the other N-atom with a (C-C)alkyl, ...

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Номер записи: 66
03-04-2014 дата публикации

Chemically Programmed Vaccination

Номер: US20140093518A1
Автор: Barbas, III Carlos F.
Принадлежит: The Scripps Research Institute

Provided herein is a method for chemically programmed vaccination. Methods include inducing a covalent-binding polyclonal antibody response in a subject and programming the polyclonal response with a targeting compound. 20. A method of extending the half life of a therapeutic drug in a patient in need thereof claim 1 , the method comprising the step of administering the compound of having formula I to the patient in need thereof.22. The method of claim 21 , wherein HIV-1 infection is inhibited by blocking the CCR5 and/or CXCR4 receptors.23. A method of generating covalent polyclonal antibodies claim 21 , the method comprising the steps of:preimmunizing a subject with an immunizing effective amount of a carrier protein-hapten complex; andadministering a targeting compound to the subject, thereby generating a covalent polyclonal antibody response to a target antigen.24. The method of claim 23 , wherein the target antigen is a tumor antigen claim 23 , a self antigen claim 23 , a toxin claim 23 , a cancer antigen claim 23 , a bacterial antigen claim 23 , a viral antigen claim 23 , or an integrin.25. The method of claim 24 , wherein the integrin is αvβ3 or αvβ5.26. The method of claim 24 , wherein the cancer is melanoma claim 24 , colon cancer claim 24 , glioma claim 24 , ovarian cancer claim 24 , cervical cancer claim 24 , breast cancer claim 24 , prostate cancer claim 24 , lung cancer claim 24 , a hematopoietic cancer claim 24 , or head and neck cancer.27. The method of claim 23 , wherein the carrier protein is selected from KLH claim 23 , BSA and ovalbumin.28. The method of claim 23 , wherein the subject is a human.29. The method of claim 24 , wherein the target antigen is CCR5.31. The method of claim 24 , wherein the targeting compound has formula I of .32. An enriched population of covalent polyclonal antibodies.33. A method of treating or preventing a disease or condition in a subject wherein the disease or condition involves cells claim 24 , tissue or fluid that ...

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Номер записи: 67
03-04-2014 дата публикации

SUBSTITUTED (E)-N'-(1-PHENYLETHYLIDENE)BENZOHYDRAZIDE ANALOGS AS HISTONE DEMETHYLASE INHIBITORS

Номер: US20140094445A1
Автор: Bearss David J., Sharma Sunil, Soma Venkataswamy, Stephens Bret, Vakayalapati Hariprasad, Warner Steven L.
Принадлежит: UNIVERSITY OF UTAH RESEARCH FOUNDATION

In one aspect, the invention relates to substituted (E)-N′-(1-phenylethylidene)benzohydrazide analogs, derivatives thereof, and related compounds, which are useful as inhibitors of lysine-specific histone demethylase, including LSD1; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions to treat disorders associated with dysfunction of the LSD1. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 3. A pharmaceutical composition comprising a therapeutically effective amount of a compound of and a pharmaceutically acceptable carrier.4. A method for the treatment of a disorder of uncontrolled cellular proliferation in a mammal claim 1 , the method comprising the step of administering to the mammal an effective amount of a compound of .5. A method for decreasing histone demethylase activity in a mammal claim 1 , the method comprising the step of administering to the mammal an effective amount of a compound of .7. A pharmaceutical composition comprising a therapeutically effective amount of a compound of and a pharmaceutically acceptable carrier.8. A method for the treatment of a disorder of uncontrolled cellular proliferation in a mammal claim 6 , the method comprising the step of administering to the mammal an effective amount of a compound of .10. A pharmaceutical composition comprising a therapeutically effective amount of a compound of and a pharmaceutically acceptable carrier.11. A method for the treatment of a disorder of uncontrolled cellular proliferation in a mammal claim 9 , the method comprising the step of administering to the mammal an effective amount of a compound of .13. A pharmaceutical composition comprising a therapeutically effective amount of a compound of and a pharmaceutically acceptable carrier.14. A method for the treatment of a disorder of ...

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Номер записи: 68
03-04-2014 дата публикации

Cyclic Amino Acids for the Treatment of Pain

Номер: US20140094446A1
Автор: MacLeod Bernard A., Puil Ernest, Wall Richard
Принадлежит: Therexcell Pharma Inc.

Compositions comprising cyclic amino acids or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier. Said compositions are for use in the treatment of pain. Pain includes both acute and chronic forms of pain. The preferred cyclic amino acid is 1-aminocyclobutane-1-carboxylic acid (ACBC). 110.-. (canceled)12. The method of wherein the pain is acute pain or chronic pain.13. The method of wherein the pain is neuropathic pain.1415-. (canceled)16. The method of wherein the composition is adapted for parenteral administration and the type of parenteral administration is selected from the group consisting of subcutaneous claim 11 , intramuscular claim 11 , intravenous and intrathecal administration.17. The method of wherein the patient is a human.1831-. (canceled)32. The method of claim 11 , wherein W and the attached carbon form an optionally substituted carbocycle.33. The method of claim 11 , wherein W and the attached carbon form an optionally substituted heterocycle.34. The method of claim 32 , wherein the carbocycle is cyclobutyl.36. The method of claim 35 , wherein X is oxygen.37. The method of claim 35 , wherein X is sulfur.38. The method of claim 35 , wherein X is NRand Ris hydrogen or alkyl.39. The method of claim 11 , wherein R is OH.40. The method of claim 11 , wherein the composition further comprises one or more pharmaceutically acceptable excipients claim 11 , or diluents claim 11 , or a combination thereof.41. The method of claim 16 , wherein the type of parenteral administration is intravenous.42. The method of claim 41 , wherein the compound is administered at a dose of from about 0.1 mg/kg to about 1000 mg/kg.43. The method of claim 41 , wherein the compound is administered at a dose of from about 1 mg/kg to about 500 mg/kg.44. The method of claim 11 , wherein the pain results from one or more causes selected from the group consisting of a peripheral neuropathy claim 11 , a central neuropathy claim 11 , a traumatic ...

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Номер записи: 69
10-04-2014 дата публикации

Guanidine compound

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

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

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Номер записи: 70
04-01-2018 дата публикации

Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

Номер: US20180000087A1
Автор: Baum Erich W., Benko Zoltan L., CHOY Nakyen, Crouse Gary D., Daeuble, DeKorver Kyle A., Demeter David A., Eckelbarger Joseph D., GRAY KAITLYN, Heemstra Ronald J., Hunter Ricky, JR. Ronald, Knueppel Daniel I., Li Fangzheng, Martin Timothy P., Nissen Jeffrey, Riener Michelle, Ross, Sparks Thomas C., SR. John F., Trullinger Tony K., Vednor Peter, Wessels Frank J., Yap Maurice C.
Принадлежит: DOW AGROSCIENCES LLC

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”). 2. A molecule according to claim 1 , wherein Ris selected from the group consisting of H and Cl.3. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , Cl claim 1 , Br claim 1 , CH claim 1 , and CF.4. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , CH claim 1 , CF claim 1 , and OCF.5. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , CH claim 1 , and CF.6. A molecule according to claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare H.7. A molecule according to claim 1 , wherein Ris Cl.8. A molecule according to claim 1 , wherein Ris Cl.9. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , Cl claim 1 , and CF.10. A molecule according to claim 1 , wherein Ris selected from the group consisting of H and CH.11. A molecule according to claim 1 , wherein Ris selected from the group consisting of cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , azetidinyl claim 1 , morpholinyl claim 1 , oxetanyl claim 1 , pyranyl claim 1 , tetrahydrothiophenyl claim 1 , thietanyl claim 1 , thietanyl-oxide claim 1 , and thietanyl-dioxide claim 1 ,{'sub': 3', '3', '3, 'wherein each cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ...

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Номер записи: 71
02-01-2020 дата публикации

Near-ir glucose sensors

Номер: US20200000383A1
Автор: Alex KUTYAVIN, Jacob William CLARY, Soya Gamsey, Sulolit Pradhan, Viachaslau Bernat
Принадлежит: Profusa Inc

Glucose-sensing luminescent dyes, polymers, and sensors are provided. Additionally, systems including the sensors and methods of using these sensors and systems are provided.

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Номер записи: 72
06-01-2022 дата публикации

SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF

Номер: US20220002242A1
Автор: Khan M. Amin
Принадлежит:

Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders. Orally delivered formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed. 2. The compound of claim 1 , wherein each occurrence of R claim 1 , R claim 1 , R claim 1 , and Ris H.3. (canceled)4. The compound of claim 1 , wherein each occurrence of Ris H.616.-. (canceled)17. The compound of claim 1 , wherein Ris selected from H and F.1820.-. (canceled)21. The compound of claim 1 , wherein Ris methyl.2226.-. (canceled)2830.-. (canceled)31. The compound of claim 27 , wherein Ris methyl; and{'sup': '5b', 'Ris H or halogen.'}3234.-. (canceled)3637.-. (canceled)38. The compound of claim 35 , wherein Ris H; and{'sup': '5a', 'Ris methyl.'}40. The compound of claim 35 , wherein Ris —NH.41. (canceled)43. A pharmaceutical composition comprising a compound of ; and a pharmaceutically acceptable excipient.44. (canceled)45. A method of treating of treating depression claim 1 , attention deficit disorder claim 1 , schizophrenia claim 1 , anxiety claim 1 , a migraine claim 1 , or neuropathic pain in a patient in need thereof claim 1 , the method comprising administering to the patient an effective amount of the compound of .4648.-. (canceled) This application claims priority to and the benefit of U.S. Provisional Patent Application No. 62/523,413, filed on Jun. 22, 2017, and U.S. Provisional Patent Application No. 62/369,465, filed on Aug. 1, 2016; the contents of each of which are hereby incorporated by reference herein in their entirety.An N-methyl-d-aspartate (“NMDA”) receptor is a postsynaptic, ionotropic receptor that is responsive to, inter alia, the excitatory amino acids glutamate and glycine and the synthetic compound NMDA. The NMDA receptor controls the flow of both divalent and monovalent ions into the ...

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Номер записи: 73
02-01-2020 дата публикации

Azetidine Derivatives

Номер: US20200000805A1
Автор: Brough Paul, Graham Christopher, Hart Terance, Macias Alba, Parsons Rachel, Roughley Stephen, Walls Steven
Принадлежит:

Compounds of formula (I) are inhibitors of fatty acid amide hydrolase, (F AAH), and which are useful in the treatment of diseases or medical conditions which benefit from inhibition of FAAH activity, such as anxiety, depression pain, inflammation, and eating, sleep, neurodegenerative and movement disorders: 2. A compound as claimed in wherein Aris optionally substituted phenyl.3. A compound as claimed in wherein Aris phenyl claim 1 , pyridyl claim 1 , pyrimidinyl claim 1 , pyrazinyl or pyridazinyl claim 1 , any of which being optionally substituted.4. A compound as claimed in wherein Aris 3-pyridyl claim 1 , pyrimidin-4-yl claim 1 , pyrazin-2-yl or pyridazin-3-yl claim 1 , any of which being optionally substituted.5. A compound as claimed in wherein Aris an optionally substituted divalent phenylene or pyridinylene radical.7. A compound as claimed in wherein any optional substituents in Ar claim 1 , Arand Arare independently selected from chloro claim 1 , fluoro claim 1 , bromo claim 1 , cyclopropyl claim 1 , methyl claim 1 , mono- claim 1 , di- or tri-methyl claim 1 , trifluoromethyl claim 1 , difluoromethyl claim 1 , monofluoromethyl claim 1 , methoxy claim 1 , ethoxy claim 1 , propoxy claim 1 , butoxy claim 1 , pentoxy claim 1 , 2-methoxyethoxy claim 1 , 2-benzyloxy-ethoxy claim 1 , 2-hydroxy-ethoxy claim 1 , mono- claim 1 , di- or tri-fluoromethoxy claim 1 , cyano claim 1 , hydroxyl; —CORi and —SORi wherein Ris hydrogen claim 1 , methyl or ethyl; tetrazolyl; —NRR claim 1 , —CHNRRand —C(═O)NRRwherein Rand Rare independently hydrogen claim 1 , methyl or ethyl.9. A compound as claimed in wherein Aris phenyl claim 8 , 2-fluorophenyl claim 8 , 3-(2-methoxy-ethoxy)-phenyl claim 8 , or 2-methoxy-5-(2-methoxy-ethoxy)-phenyl.10. A compound as claimed in wherein Aris pyridazin-3-yl11. A pharmaceutical composition comprising a compound as claimed in claim 1 , together with one or more pharmaceutically acceptable carriers and/or excipients.12. A method of treatment of a ...

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Номер записи: 74
07-01-2016 дата публикации

SYNTHESIS OF ACYCLIC AND CYCLIC AMINES USING IRON-CATALYZED NITRENE GROUP TRANSFER

Номер: US20160002145A1
Автор: Betley Theodore Alexander, Hennessy Elisabeth Therese
Принадлежит: President and Fellows of Harvard

The present invention provides novel synthetic methods for making acyclic secondary amines by reacting an azide with a compound bearing one or more C—H groups, catalyzed by a Fe-dipyrromethene complex. The acyclic secondary amines are thought to be formed through an intermolecular nitrene transfer. Also provided herein are methods of synthesizing protected (e.g., Boc- or Fmoc-protected) cyclic secondary amines (e.g., 5-, 6-, and 7-membered cyclic secondary amines) by reacting an azide that bears one or more C—H groups, catalyzed by a Fe-dipyrromethene complex. The protected cyclic secondary amines are thought to be formed through an intramolecular nitrene transfer and may be subsequently deprotected to yield cyclic secondary amines. 2. The method of claim 1 , wherein Ris optionally substituted alkyl.3. The method of claim 1 , wherein Ris adamantyl.4. The method of claim 1 , wherein Ris optionally substituted aryl.5. (canceled)6. The method of claim 1 , wherein Ris hydrogen.7. The method of claim 1 , wherein Rand Rare each hydrogen.8. The method of claim 1 , wherein Ris hydrogen or optionally substituted alkyl.9. The method of claim 1 , wherein Ris hydrogen.10. The method of claim 1 , wherein Ris optionally substituted alkyl.11. The method of claim 1 , wherein Ris optionally substituted aryl.12. (canceled)13. The method of claim 1 , wherein Rand Rare joined to form an optionally substituted carbocyclyl ring.14. The method of claim 1 , wherein L is R—O—R; and each occurrence of Ris independently optionally substituted alkyl.15. The method of claim 1 , wherein L is optionally substituted heterocyclyl.16. The method of claim 1 , wherein L is optionally substituted tetrahydrofuran or optionally substituted tetrahydropyran.17. The method of claim 1 , wherein L is optionally substituted heteroaryl.18. The method of claim 1 , wherein L is optionally substituted pyridine.22. The method of claim 21 , wherein the deprotection step comprises reacting an acidic compound claim 21 ...

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Номер записи: 75
04-01-2018 дата публикации

(THIO, OXO, AND SELENO) SEMICARBAZONE COMPLEXES WITH ZINC AND THEIR USE FOR TREATING CANCER

Номер: US20180002279A1
Автор: Augeri David J., Bencivenga Anthony F., Blanden Adam, Carpizo Darren R., Gilleran John A., Kimball Spencer David, Loh Stewart N., Yu Xin
Принадлежит:

The invention provides organic complexes of Zn of formula (I) that are useful for treating cancer, as well as compositions and kits comprising such complexes, and intermediate monomer compounds that are useful for the preparation of such complexes. 4. The complex of any one of - wherein the ratio of the number of compounds of formula (I) or ions or poly-ions thereof to zinc Zn ions is about 2:1; or a solvate thereof.8. A pharmaceutical composition , comprising a complex of any one of - or a solvate thereof , and a pharmaceutically acceptable carrier.9. An injectable pharmaceutical formulation comprising , a complex of any one of - or a solvate thereof , and a pharmaceutically acceptable carrier.10. A method of inhibiting cancer cell growth in vivo or in vitro , comprising contacting a cancer cell with a complex of any one of - or a solvate thereof.11. A method of treating cancer in an animal comprising administering a complex of any one of - or a solvate thereof to the animal.12. The method of claim 11 , further comprising administering zinc to the animal.13. The method of any one of - claim 11 , wherein the cancer is caused by mutations affecting zinc binding proteins.14. The method of any one of - claim 11 , wherein the cancer is associated with a zinc binding p53 mutation.15. The method of any one of - claim 11 , wherein the cancer is associated with a zinc binding p53 mutation selected from R175 claim 11 , C176 claim 11 , H179 claim 11 , C238 claim 11 , C242 claim 11 , and G245.16. A complex of any one of - or a solvate thereof for use in medical treatment.17. A complex of any one of - or a solvate thereof for the prophylactic or therapeutic treatment of cancer.18. The complex or solvate of wherein the cancer is caused by mutations affecting zinc binding proteins.19. The complex or solvate of claim 17 , wherein the cancer is associated with a zinc binding p53 mutation.20. The complex or solvate of claim 17 , wherein the cancer is associated with a zinc binding ...

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Номер записи: 76
04-01-2018 дата публикации

(THIO, OXO, AND SELENO) SEMICARBAZONE DERIVATIVES AND THEIR USE FOR TREATING CANCER

Номер: US20180002280A1
Автор: Augeri David J., Bencivenga Anthony F., Blanden Adam, Carpizo Darren R., Gilleran John A., Kimball Spencer David, Loh Stewart N., Yu Xin
Принадлежит:

The invention provides compounds of formula I and II and salts thereof, wherein R, R, Y, R, and Rhave any of the meanings described in the specification, as well as compositions comprising such compounds and salts, and methods for treating cancer using such compounds and salts. 3. A pharmaceutical composition , comprising , a compound of or or a pharmaceutically acceptable salt thereof , and a pharmaceutically acceptable carrier.4. An injectable pharmaceutical formulation comprising , a compound of or or a pharmaceutically acceptable salt thereof , and a pharmaceutically acceptable carrier.5. A method of inhibiting cancer cell growth in vivo or in vitro , comprising contacting a cancer cell with a compound of any one of - or a pharmaceutically acceptable salt thereof.6. A method of treating cancer in an animal comprising administering a compound of any one of - or a pharmaceutically acceptable salt thereof to the animal.7. The method of claim 6 , further comprising administering zinc to the animal.8. The method of any one of - claim 6 , wherein the cancer is caused by mutations affecting zinc binding proteins.9. The method of any one of - claim 6 , wherein the cancer is associated with a zinc binding p53 mutation.10. The method of any one of - claim 6 , wherein the cancer is associated with a zinc binding p53 mutation selected from R175 claim 6 , C176 claim 6 , H179 claim 6 , C238 claim 6 , C242 claim 6 , and G245.11. A compound of any one of - or a pharmaceutically acceptable salt thereof claim 6 , for use in medical treatment.12. A compound of any one of - or a pharmaceutically acceptable salt thereof claim 6 , for the prophylactic or therapeutic treatment of cancer.13. The compound or pharmaceutically acceptable salt of wherein the cancer is caused by mutations affecting zinc binding proteins.14. The compound or pharmaceutically acceptable salt of claim 13 , wherein the cancer is associated with a zinc binding p53 mutation.15. The compound or pharmaceutically ...

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Номер записи: 77
02-01-2020 дата публикации

BIARYL COMPOUND, PREPARATION METHOD AND USE THEREOF

Номер: US20200002280A1
Автор: Huang Yafei, Qiu Ruomeng, Tang Ting, Wang Yonghui
Принадлежит:

The present invention belongs to the technical field of chemical pharmaceuticals, and relates to a compound represented by general formula (I) or formula (II) and a preparation method thereof. The compounds are biaryl derivatives with RORγt activation activity. The biaryl derivatives disclosed in this invention can effectively activate the RORγt protein receptor, and thereby promote the differentiation of Th17 cells and increasing the production of IL-17, which can be used as an immune modulator for the treatment of various cancers or viral infection-related diseases. 2. The compound of Formula (I) or (II) or the pharmaceutically acceptable salt thereof according to claim 1 , wherein:{'sub': 1', '2', '3', '3', '5', '3', '6', '3', '6', '9', '10', '1', '2', '3', '2', '6', '3', '7', '1', '2', '3', '2', '6, 'claim-text': {'sub': 9', '10', '1', '6', '3', '6', '3', '8', '9', '10, 'wherein, R, Rare each independently selected from a group consisting of hydrogen, C-Calkyl, C-Ccycloalkyl and C-Cheterocycloalkyl, or Rand Rform a cyclic group having four to seven ring members together with the nitrogen atom to which they attach; the cyclic group contains or does not contain a second heteroatom selected from oxygen as a ring member.'}, 'R, Rand Rare each independently selected from a group consisting of hydrogen, C-Calkyl, C-Ccycloalkyl, C-Cheterocycloalkyl containing one oxygen atom, and —NRR, or any two of R, Rand Rform C-Calkyl alkenyl or C-Ccycloalkyl alkenyl, or R, Rand Rform C-Calkyl alkynyl;'}3. The compound of Formula (I) or (II) or the pharmaceutically acceptable salt thereof according to claim 2 , wherein Ris selected from a group consisting of C-Calkyl claim 2 , C-Ccycloalkyl claim 2 , C-Coxoheterocycloalkyl claim 2 , phenyl substituted with one or more R; pyridyl substituted with one or more R; pyrimidinyl substituted with one or more R; pyridone substituted with one or more R claim 2 , pyrazolyl substituted with one or more R claim 2 , pyrrolyl substituted with one ...

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Номер записи: 78
03-01-2019 дата публикации

C7-FLUORO SUBSTITUTED TETRACYCLINE COMPOUNDS

Номер: US20190002398A1
Автор: Clark Roger B., Hunt Diana K., Plamondon Louis, Shanghai Jingye, Xiao Xiao-Yi, Zahler Robert
Принадлежит:

The present invention is directed to a compound represented by Structural Formula (A): 4. The compound of claim 3 , wherein Ris hydrogen or a (C-C)alkyl.5. The compound of claim 3 , wherein Ris selected from (C-C)alkyl claim 3 , (C-C)cycloalkyl(C-C)alkyl claim 3 , (C-C)alkoxy(C-C)alkyl claim 3 , phenyl claim 3 , phenyl(C-C)alkyl claim 3 , (C-C)cycloalkyl and halo(C-C)alkyl claim 3 , wherein each alkyl claim 3 , alkoxy and cycloalkyl moiety in the groups represented by Ris optionally substituted with one or more substituents independently selected from the group consisting of (C-C)alkyl and halo; and each phenyl moiety in the groups represented by Ris optionally substituted with one or more substituents independently selected from the group consisting of (C-C)alkyl claim 3 , halo claim 3 , (C-C)alkoxy claim 3 , (C-C)alkoxy(C-C)alkyl claim 3 , —CN claim 3 , halo(C-C)alkyl claim 3 , and halo(C-C)alkoxy.6. The compound of any one of claim 3 , wherein Ris selected from hydrogen claim 3 , methyl and ethyl.7. The compound of claim 6 , wherein Ris selected from the group consisting of cyclopropyl claim 6 , cyclobutyl claim 6 , cyclopentyl claim 6 , cyclopropylmethyl claim 6 , cyclobutylmethyl claim 6 , phenyl claim 6 , benzyl claim 6 , —(CH)—O—CH claim 6 , —(CH)—OCH claim 6 , —C(CH) claim 6 , —CH(CH) claim 6 , —CHC(CH) claim 6 , —CHCH(CH) claim 6 , —CH—CF claim 6 , —(CH)—CHF claim 6 , and —(CH)CH; n is 0 claim 6 , 1 claim 6 , 2 claim 6 , 3 claim 6 , 4 claim 6 , 5 or 6; and wherein the phenyl or benzyl group represented by Ris optionally substituted with one or two substituents independently selected from the group consisting of (C-C)alkyl claim 6 , halogen claim 6 , (C-C)alkoxy claim 6 , (C-C)alkoxy(C-C)alkyl claim 6 , —CN claim 6 , halo(C-C)alkyl claim 6 , and halo(C-C)alkoxy.8. The compound of claim 7 , wherein Ris selected from cyclopropyl claim 7 , cyclopropylmethyl claim 7 , cyclobutyl claim 7 , cyclopentyl claim 7 , cyclohexyl claim 7 , —(CH)—O—CH claim 7 , —C(CH) ...

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Номер записи: 79
05-01-2017 дата публикации

ADO-RESISTANT CYSTEAMINE ANALOGS AND USES THEREOF

Номер: US20170002004A1
Автор: Duffy Lorna, Gourdet Benoit, Phillips Timothy, Unitt John, Zankel Todd C.
Принадлежит: RAPTOR PHARMACEUTICALS INC.

The present disclosure is directed to methods for treating diseases for which cysteamine is indicated and compounds useful in such methods. 2. The method of claim 1 , wherein Rand Rare independently selected from the group consisting of H claim 1 , methyl claim 1 , and ethyl.3. The method of claim 1 , wherein Rand R claim 1 , taken together with the nitrogen atom to which they are attached claim 1 , form a 5-membered heterocyclic ring.4. The method of claim 1 , wherein Ris methyl claim 1 , optionally wherein Ris methyl.5. (canceled)6. The method of claim 1 , wherein Rand R claim 1 , taken together with the carbon atom to which they are attached claim 1 , form a 3-membered carbocyclic ring.7. The method of claim 1 , wherein Ris methyl claim 1 , optionally wherein Ris methyl.8. (canceled)9. The method of claim 1 , wherein Rand R claim 1 , taken together with the carbon atom to which they are attached claim 1 , form a 3-membered carbocyclic ring.10. The method of claim 1 , wherein G is —CRRNRR claim 1 , and Rand R claim 1 , taken together with the atoms to which they are attached claim 1 , form a 6-membered heterocyclic ring claim 1 , optionally wherein Ris methyl.11. (canceled)12. The method of claim 1 , wherein G is —NRR claim 1 , and Rand R claim 1 , taken together with the atoms to which they are attached claim 1 , form a 4- or 6-membered heterocyclic ring.13. (canceled)14. (canceled)17. (canceled)18. (canceled)20. The method of wherein L is a 3- claim 19 , 4- claim 19 , 5- claim 19 , 6- claim 19 , 7- claim 19 , or 8-membered cycloalkyl ring or a 6-membered aryl ring.21. The method of wherein L is Calkyl.22. (canceled)23. The method of wherein A is a 3- claim 19 , 4- claim 19 , 5- claim 19 , 6- claim 19 , 7- claim 19 , or 8-membered monocyclic heterocycloalkyl ring claim 19 , a 6- claim 19 , 7- claim 19 , or 8-membered bicyclic heterocycloalkyl ring claim 19 , or a 5- or 6-membered heteroaryl ring.25. (canceled)26. (canceled)27. (canceled)28. (canceled)29. The ...

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Номер записи: 80
05-01-2017 дата публикации

N-SUBSTITUTED BENZAMIDES AND METHODS OF USE THEREOF

Номер: US20170002017A1
Автор: ANDREZ Jean-Christophe, Chowdhury Sultan, DECKER Shannon Marie, DEHNHARDT Christoph Martin, FOCKEN Thilo, GRIMWOOD Michael Edward, HEMEON Ivan William, Jia Qi, LI JUN, Ortwine Daniel F., SAFINA Brian, SHENG Tao, Sun Shaoyi, Sutherlin Daniel P., WILSON Michael Scott, ZENOVA Alla Yurevna
Принадлежит:

The invention provides novel compounds having the general formula: 3. The compound of wherein B is N and Ris absent.4. The compound of wherein B is C.5. The compound of wherein R claim 1 , Rand Rare each independently selected from H claim 1 , F claim 1 , or Cl.6. The compound of wherein Ris H claim 1 , F or Cl; Rand Rare each H; and Ris an optionally substituted group selected from the group consisting of H claim 1 , F claim 1 , Cl claim 1 , Br claim 1 , I claim 1 , —CN claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Ccycloalkyl claim 1 , and Calkoxy.7. The compound of wherein Ris Calkyl claim 1 , Chaloalkyl claim 1 , Ccycloalkyl or —NRR.8. The compound of claim 7 , wherein Ris selected from the group consisting of methyl claim 7 , ethyl claim 7 , propyl claim 7 , trifluoromethyl claim 7 , difluoromethyl claim 7 , monofluoromethyl claim 7 , isopropyl and cyclopropyl.11. The compound of wherein Ris selected from the group consisting of: methyl claim 1 , ethyl claim 1 , tert-butyl claim 1 , dimethylamino claim 1 , methylamino claim 1 , amino claim 1 , morpholino claim 1 , azetidino claim 1 , imidazolyl claim 1 , 3-hydroxyazetidino claim 1 , 3-fluoroazetidino claim 1 , cyclopropyl claim 1 , pyrrolidinyl claim 1 , 3 claim 1 ,3-difluoroazetidino claim 1 , tert-butyl claim 1 , ethyl claim 1 , 2-methoxyethyl claim 1 , 3-methoxyazetidino claim 1 , 2-hydroxyethyl claim 1 , 3-hydroxypyrrolidinyl claim 1 , and N-methylimidazolyl.12. The compound of wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is an optionally substituted group selected from the group consisting of Calkylene claim 1 , Calkenylene or Calkynylene.13. The compound of claim 1 , wherein Xis —O— or —N(H)—; Xis absent; the subscript m is 1; and -(L)- is selected from the group consisting of —CH— claim 1 , —C(═O)— claim 1 , —C(H)(CH)— claim 1 , —CH—CH— claim 1 , —CH—C(H)(CH)— claim 1 , —C(H)(CH)—C(H)— claim 1 , —CHCHCH— claim 1 , —CH—C(H)(CH)—CH— or —CHCHCHCH—.14. The compound of claim 13 , ...

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Номер записи: 81
13-01-2022 дата публикации

1-PHENYL-2-PHENYLETHANE DERIVATIVE

Номер: US20220009869A1
Автор: INOUE Takayoshi, MISAWA Kensuke, TSUNODA Shotaro
Принадлежит: KAO CORPORATION

Provided is a novel compound having a selective activating effect on ERβ. The present invention provides a compound represented by the following formula (1) wherein Rrepresents a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 6 carbon atoms and optionally substituted with a halogen atom, a 5-membered nitrogen-containing heteroaryl group, a 4- to 6-membered cyclic amino group, an alkanoylamino group having 2 to 6 carbon atoms and optionally substituted with a halogen atom, a 1-trifluoromethyl-1-hydroxymethyl group, or a 1-methylpropyl group; Rto Rare the same or different and each represent a hydrogen atom or a fluorine atom; and Rrepresents a hydrogen atom or an alkanoyl group having 2 to 5 carbon atoms, or a salt thereof. 2: An ERβ activating agent comprising the compound represented by the formula (1) or the salt thereof according to as an active ingredient.3: A skin aging preventing or ameliorating agent comprising the compound represented by the formula (1) or the salt thereof according to as an active ingredient.4: A sebum secretion inhibiting agent comprising the compound represented by the formula (1) or the salt thereof according to as an active ingredient.5: An acne preventing or ameliorating agent comprising the compound represented by the formula (1) or the salt thereof according to as an active ingredient.6: A hot flash preventing or ameliorating agent comprising the compound represented by the formula (1) or the salt thereof according to as an active ingredient.7: A prostatic hyperplasia preventing or ameliorating agent comprising the compound represented by the formula (1) or the salt thereof according to as an active ingredient.8: An androgen activation inhibiting agent comprising the compound represented by the formula (1) or the salt thereof according to as an active ingredient.932-. (canceled) The present invention relates to a compound having high selectivity for estrogen receptor 0.Estrogen, also called follicle hormone ...

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Номер записи: 82
20-01-2022 дата публикации

CYCLIC NITRO COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THEREOF AND USES THEREOF

Номер: US20220016077A1
Автор: Bednarski Mark D., Cannizzo Louis, Knox Susan, Ning Shoucheng, Velarde Stephen, Wardle Robert, Warner Kirstin
Принадлежит:

The present invention provides cyclic nitro compound, pharmaceutical compositions of cyclic nitro compounds and methods of using cyclic nitro compounds and/or pharmaceutical compositions thereof to treat or prevent diseases or disorders characterized by abnormal cell proliferation, such as cancer, inflammation, cardiovascular disease and autoimmune disease. 216.-. (canceled)17. A method for treating or preventing cancer in a patient comprising administering to a patient in need of such treatment or prevention a therapeutically effective amount of the compound of .18. (canceled)19. A method for treating tumor cells with a reduced intracellular environment in a patient claim 1 , comprising administering to the patient in need of treatment a therapeutically effective amount of the compound of .20. A method for treating or preventing solid tumors in a patient claim 1 , comprising administering to the patient in need of treatment or prevention a therapeutically effective amount of the compound of .21. A method for treating or preventing leukemias and lymphomas in a patient claim 1 , comprising administering to the patient in need of treatment or prevention a therapeutically effective amount of the compound of .22. A method for treating or preventing inflammation in a patient claim 1 , comprising administering to the patient in need of treatment or prevention a therapeutically effective amount of the compound of .23. A method for treating or preventing autoimmune disease in a patient claim 1 , comprising administering to the patient in need of treatment or prevention a therapeutically effective amount of the compound of .24. A method for treating or preventing cardiovascular disease in a patient claim 1 , comprising administering to the patient in need of treatment or prevention a therapeutically effective amount of the compound of . The present application claims priority to U.S. Provisional Application No. 60/707,851 filed Aug. 12, 2005 which is hereby incorporated by ...

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Номер записи: 83
11-01-2018 дата публикации

Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto

Номер: US20180007911A1
Автор: Baum Erich W., Benko Zoltan L., CHOY Nakyen, Crouse Gary D., Daeuble, DeKorver Kyle A., Demeter David A., Eckelbarger Joseph D., Heemstra Ronald J., Hunter Ricky, JR. Ronald, Knueppel Daniel I., Li Fangzheng, Martin Timothy P., Nissen Jeffrey, Riener Michelle, Ross, Sparks Thomas C., SR. John F., Trullinger Tony K., Vednor Peter, Wessels Frank J., Yap Maurice C.
Принадлежит: DOW AGROSCIENCES LLC

This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”). 2. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , and Cl.3. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , F claim 1 , and Cl.4. A molecule according to claim 1 , wherein Ris F or Cl.5. A molecule according to claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare each independently H.6. A molecule according to claim 1 , wherein Ris selected from the group consisting of Cl and Br.7. A molecule according to claim 1 , wherein Ris selected from the group consisting of Cl and Br.8. A molecule according to claim 1 , wherein Ris selected from the group consisting of H claim 1 , Cl claim 1 , and CF.9. A molecule according to claim 1 , wherein Ris selected from the group consisting of H and CH.10. A molecule according to claim 1 , wherein Ris selected from the group consisting of CH claim 1 , CHCH claim 1 , CHCHCH claim 1 , CHCHCHCH claim 1 , CHCHCHOCHCH claim 1 , CH claim 1 , CHCH claim 1 , CHCHCH claim 1 , CHCHCHCH claim 1 , CHCHCHCHCH claim 1 , CHCHCHCHCHCH claim 1 , CHCH(CH) claim 1 , CHcyclopropyl claim 1 , CHCHcyclopropyl claim 1 , CHcyclobutyl claim 1 , CHphenyl claim 1 , CHCHphenyl claim 1 , CHC═CH claim 1 , CHC═CH claim 1 , CHCF claim 1 , CHCHF claim 1 , CHCHCF claim 1 , CHCFCF claim 1 , CHCHCHCF claim 1 , CHCHCFCF claim 1 , CHCFCFCF claim 1 , CHCHCHCHF claim 1 , CHCHSCH ...

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Номер записи: 84
12-01-2017 дата публикации

(HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS

Номер: US20170008844A1
Автор: CASTRO PALOMINO LARIA Julio Cesar, ESTIARTE MARTINEZ Maria de los Àngeles, Fyfe Matthew Colin Thor, KURZ Guido, MARTINELL PEDEMONTE Marc, ORTEGA MUÑOZ Alberto, VALLS VIDAL Nuria
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. 6. The compound of claim 2 , wherein D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N claim 2 , O and S claim 2 ,wherein D is linked to the remainder of the compound of Formula I through a ring C atom,wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups,{'sub': '2', 'wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SOgroups, and'}{'sup': '3', 'wherein ring D is optionally substituted with one or more R.'}7. The compound of claim 2 , wherein D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from O and S claim 2 ,wherein D is linked to the remainder of the compound of Formula I through a ring C atom,wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups,{'sub': '2', 'wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SOgroups, and'}{'sup': '3', 'wherein ring D is optionally substituted with one or more R.'}8. The compound of claim 2 , wherein D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 heteroatom selected from N claim 2 , O and S claim 2 ,wherein D is linked to the remainder of the compound of Formula I through a ring C atom,wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups,{'sub': '2', 'wherein one S atom in ring D, if present, is optionally oxidized to form an SO group or an SOgroup, and'}{'sup': '3', 'wherein ring D is optionally substituted with one or more R.'}9. The compound of claim 2 , ...

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Номер записи: 85
12-01-2017 дата публикации

PROCESS FOR THE PRODUCTION OF CANNABIDIOL AND DELTA-9-TETRAHYDROCANNABINOL

Номер: US20170008868A1
Автор: Dialer Lukas, Petrovic Denis, WEIGL ULRICH
Принадлежит:

The present disclosure relates to the preparation of a cannabidiol compound or a derivative thereof. The cannabidiol compound or derivatives thereof can be prepared by an acid-catalyzed reaction of a suitably selected and substituted di-halo-olivetol or derivative thereof with a suitably selected and substituted cyclic alkene to produce a dihalo-cannabidiol compound or derivative thereof. The dihalo-cannabidiol compound or derivative thereof can be produced in high yield, high stereospecificity, or both. It can then be converted under reducing conditions to a cannabidiol compound or derivatives thereof. 6. The process of wherein the compound of formula (I) is selected from the group consisting of ethyl cannabidiolate claim 1 , delta-9-tetrahydrocannabinol and delta-8-tetrahydrocannabinol.7. The process of wherein the protic or first Lewis acid catalyst is selected from the group consisting of p-toluene sulfonic acid claim 1 , trifluoromethanesulfonic acid claim 1 , trifluoroacetic acid claim 1 , acetic acid claim 1 , sulfuric acid claim 1 , iron(II) chloride claim 1 , scandium(III) triflate claim 1 , zinc chloride claim 1 , aluminum chloride and combinations thereof.8. The process of wherein the second Lewis acid catalyst is selected from the group consisting of p-toluene sulfonic acid claim 1 , BF claim 1 , diethyl etherate claim 1 , BF*AcOH claim 1 , tri-isobutyl aluminum claim 1 , and combinations thereof.9. The process of wherein the reducing agent is a sulfur-containing compound.10. The process of wherein the reduction occurs in a polar solvent.11. The process of wherein the reduction occurs in the presence of an organic or weak inorganic base.16. The process of wherein the protic or first Lewis acid catalyst is selected from the group consisting of p-toluene sulfonic acid claim 12 , trifluoromethanesulfonic acid claim 12 , trifluoroacetic acid claim 12 , acetic acid claim 12 , sulfuric acid claim 12 , iron(II) chloride claim 12 , scandium(III) triflate claim ...

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Номер записи: 86
12-01-2017 дата публикации

PROCESS FOR THE PRODUCTION OF CANNABIDIOL AND DELTA-9-TETRAHYDROCANNABINOL

Номер: US20170008869A1
Автор: Dialer Lukas, Petrovic Denis, WEIGL ULRICH
Принадлежит:

The present disclosure relates to the preparation of a cannabidiol compound or a derivative thereof. The cannabidiol compound or derivatives thereof can be prepared by an acid-catalyzed reaction of a suitably selected and substituted di-halo-olivetol or derivative thereof with a suitably selected and substituted cyclic alkene to produce a dihalo-cannabidiol compound or derivative thereof. The dihalo-cannabidiol compound or derivative thereof can be produced in high yield, high stereospecificity, or both. It can then be converted under reducing conditions to a cannabidiol compound or derivatives thereof. 6. The process of wherein the compound of formula (I) is selected from the group consisting of ethyl cannabidiolate claim 1 , delta-9-tetrahydrocannabidiol and delta-8-tetrahydrocannabidiol.7. The process of wherein the protic or first Lewis acid catalyst is selected from the group consisting of p-toluene sulfonic acid claim 1 , trifluoromethanesulfonic acid claim 1 , trifluoroacetic acid claim 1 , acetic acid claim 1 , sulfuric acid claim 1 , iron(II) chloride claim 1 , scandium(III) triflate claim 1 , zinc chloride claim 1 , aluminum chloride and combinations thereof.8. The process of wherein the second Lewis acid catalyst is selected from the group consisting of p-toluene sulfonic acid claim 1 , BF claim 1 , diethyl etherate claim 1 , BF*AcOH claim 1 , tri-isobutyl aluminum claim 1 , and combinations thereof.9. The process of wherein the reducing agent is a sulfur-containing compound.10. The process of wherein the reduction occurs in a polar solvent.11. The process of wherein the reduction occurs in the presence of an organic or weak inorganic base.16. The process of wherein the protic or first Lewis acid catalyst is selected from the group consisting of p-toluene sulfonic acid claim 12 , trifluoromethanesulfonic acid claim 12 , trifluoroacetic acid claim 12 , acetic acid claim 12 , sulfuric acid claim 12 , iron(II) chloride claim 12 , scandium(III) triflate claim ...

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Номер записи: 87
11-01-2018 дата публикации

THERAPEUTIC COMPOUNDS AND USES THEREOF

Номер: US20180009735A1
Автор: Albrecht Brian K., Audia James Edmund, CÔTÉ Alexandre, Duplessis Martin, Gehling Victor S., Good Andrew Charles, Harmange Jean-Christophe, LEBLANC Yves, Nasveschuk Christopher G., Taylor Alexander M., Vaswani Rishi G.
Принадлежит:

Provided herein are compounds of formula I: 23-. (canceled)4. The compound of claim 1 , wherein X is —CH— claim 1 , —CHCH— or —CHCHCH—.79-. (canceled)11. The compound of claim 1 , wherein X is or —N(R)C(R)—.1214-. (canceled)15. The compound of claim 1 , wherein Ris hydrogen claim 1 , halo claim 1 , heteroaryl claim 1 , —OR claim 1 , CN claim 1 , —C(O)—N(R)or —C(O)—OR claim 1 , wherein any heteroaryl of Ris optionally substituted with one or more Rgroups.1618-. (canceled)2022-. (canceled)2425-. (canceled)27. (canceled)2933-. (canceled)36. (canceled)40. (canceled)42. (canceled)43. A method of treating cancer in an animal comprising administering to the animal in need thereof a compound of formula I or a pharmaceutically acceptable salt thereof as described in .44. A method of treating an LSD1-mediated disorder in an animal comprising administering to the animal in need thereof a compound of formula I or a pharmaceutically acceptable salt thereof as described in .4549-. (canceled)50. A method of increasing efficacy of a cancer treatment comprising a cytotoxic agent in an animal comprising administering to the animal an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof as described in .51. (canceled)52. A method of delaying or preventing development of cancer resistance to a cytotoxic agent in an animal claim 1 , comprising administering to the animal a compound of formula I or a pharmaceutically acceptable salt thereof as described in .53. A method of extending the duration of response to a cancer therapy in an animal claim 1 , comprising administering to the animal undergoing the cancer therapy a compound of formula I or a pharmaceutically acceptable salt thereof claim 1 , as described in claim 1 , wherein the duration of response to the cancer therapy when the compound of formula I is administered is extended over the duration of response to the cancer therapy in the absence of the administration of the compound of formula I or ...

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Номер записи: 88
14-01-2021 дата публикации

HISTONE DEACETYLASE INHIBITORS

Номер: US20210009519A1
Автор: Bhagwat Shripad, Bridges Alexander, Luedtke Gregory
Принадлежит:

Provided herein are compounds and methods for inhibiting histone deacetylase (“HDAC”) enzymes (e.g., HDAC1, HDAC2, and HDAC3). 2. The compound of claim 1 , wherein ring A is a 4-7 membered heterocycloalkyl ring containing one nitrogen ring atom or a 7-9 membered bicyclic heterocycloalkyl ring containing one nitrogen ring atom; Z is O claim 1 , NR claim 1 , S claim 1 , or SO; Ris Calkyl claim 1 , Chydroxyalkyl claim 1 , or Calkylene-Ccycloalkyl; Ris H claim 1 , F claim 1 , Cl claim 1 , or CH; Ris H claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Calkylene-Ccycloalkyl claim 1 , C(O)Calkyl claim 1 , or C(O)Calkylene-Ccycloalkyl; and Ris H or Calkyl.3. The compound of or claim 1 , wherein ring A is a 7-9 membered bicyclic heterocycloalkyl ring containing one nitrogen ring atom.4. The compound of or claim 1 , wherein ring A is a 4-7 membered heterocycloalkyl ring containing one nitrogen ring atom.5. The compound of any one of to claim 1 , wherein Z is O or NR.6. The compound of any one of to claim 1 , wherein Ris Calkyl claim 1 , Chydroxyalkyl claim 1 , C(O)Calkyl claim 1 , Calkylene-Ccycloalkyl claim 1 , or Calkylene-Cheterocycloalkyl having 1 or 2 heteroatoms selected from O claim 1 , S claim 1 , N claim 1 , and N(Calkyl).7. The compound of any one of to claim 1 , wherein Ris H claim 1 , Calkyl claim 1 , Chydroxyalkyl claim 1 , Calkylene-Ccycloalkyl claim 1 , or Calkylene-Cheterocycloalkyl having 1 or 2 heteroatoms selected from O claim 1 , S claim 1 , N claim 1 , and N(Calkyl).8. The compound of claim 7 , wherein Ris Calkyl claim 7 , Chydroxyalkyl claim 7 , Calkylene-Ccycloalkyl claim 7 , or Calkylene-Cheterocycloalkyl having 1 or 2 heteroatoms selected from O claim 7 , S claim 7 , N claim 7 , and N(Calkyl).9. The compound of claim 7 , wherein Ris Calkyl claim 7 , Chydroxyalkyl claim 7 , or Calkylene-Ccycloalkyl.10. The compound of claim 7 , wherein Ris H.11. The compound of claim 7 , wherein Ris a Calkyl.12. The compound of claim 7 , wherein Ris methyl claim 7 , ...

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Номер записи: 89
14-01-2021 дата публикации

COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR

Номер: US20210009528A1
Автор: Berlin Michael, CREW Andrew P., Crews Craig M., Dong Hanqing, Hornberger Keith R., Snyder Lawrence B., Wang Jing, Zimmermann Kurt
Принадлежит:

The present disclosure relates to bifunctional compounds, which find utility to degrade (and inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor. 134.-. (canceled) This application is a continuation of U.S. application Ser. No. 16/577,901, filed Sep. 20, 2019, now allowed, which is a divisional application of U.S. application Ser. No. 15/730,728, filed Oct. 11, 2017, now U.S. Pat. No. 10,584,101, which claims priority to, and the benefit of, U.S. Provisional Application No. 62/406,888, filed Oct. 11, 2016, and U.S. Provisional Application No. 62/528,385, filed Jul. 3, 2017, all of which are incorporated by reference in their entirety for all purposes.This invention was made with government support under grant number 1R44CA203199-01 by the National Cancer Institute. The government has certain rights in the invention.U.S. patent application Ser. No. 14/686,640, filed on Apr. 14, 2015, published as U.S. Patent Application Publication No. 2016/0058872; U.S. patent application Ser. No. 14/792,414, filed on Jul. 6, 2015, published as U.S. Patent Application Publication No. 2015/0291562; U.S. patent application Ser. No. 14/371,956, filed on Jul. 11, 2014, published as U.S. Patent Application Publication No. 2014/0356322; U.S. patent application Ser. No. 15/074,820, filed on Mar. 18, 2016, published as U.S. Patent Application Publication No. 2016/0272639, are incorporated herein in their entireties. Furthermore, all references cited herein are incorporated by ...

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Номер записи: 90
14-01-2021 дата публикации

Benzamide compounds

Номер: US20210009543A1
Автор: Ahmed Abdi Samatar, Joseph Robert Pinchman, Kevin Duane Bunker, Peter Qinhua HUANG, Rakesh Kumar Sit
Принадлежит: Recurium IP Holdings LLC, Zeno Management Inc

Compounds of Formula (I) are provided herein. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions, including conditions characterized by excessive cellular proliferation, such as cancer and tumors, as well as viral infections such as HIV.

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Номер записи: 91
09-01-2020 дата публикации

AMIDE COMPOUND

Номер: US20200010487A1
Автор: Fukase Yoshiyuki, Fukumoto Shoji, Ishii Naoki, Kono Mitsunori, Ochida Atsuko, Oda Tsuneo, Sasaki Yusuke, Sato Ayumu, SHIRAI Junya, Tokuhara Hidekazu, Tomata Yoshihide, YAMAMOTO Satoshi
Принадлежит:

The present invention relates to compound (I) or a salt thereof which has a RORγt inhibitory action. In the formula (I), each symbol is as defined in the specification. 116-. (canceled)18. The method of claim 17 , wherein the substituent that Ring A optionally further has is a fluorine atom or a chlorine atom.19. The method of claim 17 , wherein Ris a tert-butyl group claim 17 , a neopentyl group or a trimethylsilyl group.21. The method of claim 17 , wherein Ris a hydrogen atom or a methyl group.22. The method of claim 17 , wherein the compound is (3S)—N-((1R)-2-((4-tert-Butyl-3-fluorophenyl)amino)-1-(4 claim 17 ,4-difluorocyclohexyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide or a salt thereof.23. The method of claim 17 , wherein the compound is N-((1R)-2-((3 claim 17 ,5-Difluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methyl-1 claim 17 ,2-oxazole-5-carboxamide or a salt thereof.24. The method of claim 17 , wherein the compound is (2R)—N-(4-tert-Butyl-3 claim 17 ,5-difluorophenyl)-2-(((3-hydroxy-1 claim 17 ,2-oxazol-5-yl)acetyl)amino)-2-(1-methyl-1H-indazol-5-yl)acetamide or a salt thereof.25. The method of claim 17 , wherein the compound is (3R)—N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide or a salt thereof.26. The method of claim 17 , wherein the compound is selected from the group consisting of(3S)—N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide,N-((1R)-2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methyl-1,2-oxazole-5-carboxamide,N-(2-((3-fluoro-4-(trimethylsilyl)phenyl)amino)-1-(4-(methoxymethyl)phenyl)-2-oxoethyl)-5-oxopyrrolidine-3-carboxamide,(2R)-2-(((2,4-dioxo-3,4-dihydropyrimidin-1 (2H)-yl)acetyl)amino)-N-(3-fluoro-4-(trimethylsilyl)phenyl)-2-(4-(methoxymethyl)phenyl)acetamide,(2R)—N-(3-fluoro-4-(trimethylsilyl)phenyl)-2-(4 ...

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Номер записи: 92
03-02-2022 дата публикации

Compounds for Treating Cannabinoid Toxicity and Acute Cannabinoid Overdose

Номер: US20220033393A1
Автор: Makriyannis Alexandros, Vemuri Kiran
Принадлежит:

The present invention relates to novel compounds that can act as antidotes for treating “Acute Cannabinoid Overdose” produced by classical cannabinoids such as Δ-tetrahydrocannabinol (THC) and several synthetic psychoactive cannabinoids (SPCs). The constituent THC exerts its psychotropic effects via CB1 receptor activation and SPCs mimic the effects of THC with higher potency and severe neurotoxicity. Compounds disclosed in this invention, their enantiomers, diastereomers, geometric isomers, racemates, tautomers, rotamers, atropisomers, metabolites, N-oxides, salts, solvates, hydrates, isotopic variations and their polymorphic forms can be therapeutically useful in an emergency setting for counteracting the intoxicating effects of acute THC ingestion and SPC overdose. Also, aspects of the invention are concerned with pyrazoles, imidazoles, triazoles, thiazoles, oxazoles, dihydropyrazoles, pyrrolidinones, azetidines, oxyazetidines and azaspiro[3.3]heptanes with unique pharmacokinetic and pharmacodynamic properties for treating “Acute Cannabinoid Overdose”. 12. A compound of claim 1 , its enantiomers claim 1 , diastereomers claim 1 , geometric isomers claim 1 , racemates claim 1 , tautomers claim 1 , rotamers claim 1 , atropisomers claim 1 , isotopic variations claim 1 , salts claim 1 , N-oxides claim 1 , hydrates and polymorphic forms (crystalline or amorphous) whereinR is a heteroaromatic group selected from pyrazolyl, imidazolyl, thiazolyl, oxazolyl, and triazolyl; and{'sub': 2', 'm', '2', 'n, 'R1 is -T-(CH)-Q-(CH)—Z,'}T is an aromatic or a heteroaromatic ring having 5 to about 8 carbon atoms as ring members,Q is CH═CH or C≡C;m and n are independently an integer from 0 to about 7;{'sub': '3', 'Z is COOX, and'}{'sub': 3', '1', '2, 'Xis H or alkyl, or NXX, alkylamino, di-alkylamino, ammonium salt, quaternary ammonium salt, or a heterocyclic ring having about 4 to about 7 ring members and optionally one additional heteroatom selected from O, N or S'}R2 is an aromatic ...

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Номер записи: 93
21-01-2016 дата публикации

BICYCLO [2.2.1] ACID GPR120 MODULATORS

Номер: US20160016880A1
Автор: Cheng Peter T.W., Shi Yan, Wang Ying, Wu Shung C., ZHANG Hao
Принадлежит:

The present invention provides compounds of Formula (I): (I) or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are GPR120 G protein-coupled receptor modulators which may be used as medicaments.

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Номер записи: 94
21-01-2016 дата публикации

THROMBOXANE RECEPTOR ANTAGONISTS

Номер: US20160016900A1
Автор: "OConnor Barry", Guiry Patrick, Kinsella B. Therese, Reid Helen
Принадлежит:

The invention generally relates to compounds that function as TP antagonists for treating thrombosis and other cardiovascular, renal, or pulmonary diseases. In some embodiments, the invention provides a compound including a substituted nitro phenoxy phenyl, a sulfonylurea, and an alkyl group. In some embodiments, the invention provides a method of treating thrombosis by administering an antithrombotic compound that preferentially binds to a thromboxane receptor, has preferential binding for either TPalpha (TPα) or TPbeta (TPβ) receptor subtype.

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Номер записи: 95
18-01-2018 дата публикации

Process for the synthesis of difluoromethyl ether-based compounds

Номер: US20180016227A1
Автор: Abdelmalik Slassi, Peter Dove
Принадлежит: Trillium Therapeutics ULC

The present application relates to a novel process for the preparation of difluoromethyl ether-based derivatives from, for example, aliphatic and aromatic hydroxyl precursors, compositions comprising these compounds and their use, in particular as precursors for medicines for the treatment of diseases, disorders or conditions. In particular, the present application includes the process of preparing compounds of Formula (I), and compositions and uses thereof:

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Номер записи: 96
18-01-2018 дата публикации

SOLID SUPPORTS AND PHOSPHORAMIDITE BUILDING BLOCKS FOR OLIGONUCLEOTIDE CONJUGATES

Номер: US20180016232A1
Автор: Gogoi Khirud, GUZAEV Andrei Pavel, VVEDENSKIY Vladimir V.
Принадлежит: AM Chemicals LLC

Novel non-nucleoside solid supports and phosphoramidite building blocks for preparation of synthetic oligonucleotides containing at least one non-nucleosidic moiety conjugated to a ligand of practical interest and synthetic processes for making the same are disclosed. Furthermore, oligomeric compounds are prepared using said solid supports and phosphoramidite building blocks, preferably followed by removal of protecting groups to provide oligonucleotides conjugated to ligands of interest. 2. The compound of wherein one of R and Ris selected from tris-(4-methoxyphenyl)methyl protecting group claim 1 , bis-(4-methoxyphenyl)phenylmethyl protecting group claim 1 , 9-phenylxanthen-9-yl protecting group claim 1 , or 9-(4-methoxyphenyl)xanthen-9-yl protecting group and the other of R and Ris selected from a residue of succinic acid optionally further attached to a solid phase material W via the second carboxylic function or a residue of diglycolic acid optionally further attached to a solid phase material W via the second carboxylic function.3. The compound of wherein one of R and Ris selected from tris-(4-methoxyphenyl)methyl protecting group claim 1 , bis-(4-methoxyphenyl)phenylmethyl protecting group claim 1 , 9-phenylxanthen-9-yl protecting group claim 1 , or 9-(4-methoxyphenyl)xanthen-9-yl protecting group and the other of R and Ris a phosphoramidite moiety PA.4. The compound of wherein each Rand Ris isopropyl group or Rand Rtogether with the nitrogen they are attached to form a cycle so that R+R=—(CH)— claim 3 , R+R=—(CH)— claim 3 , or R+R=—(CH)—O—(CH)—.5. The compound of wherein each A and Ais independently selected from —CH— or —(CH)—.6. The compound of wherein each E and Eis independently selected from —CH— claim 1 , —OCH— claim 1 , —(CH)— claim 1 , or —O(CH)—.7. The compound of wherein G is selected from an atom of hydrogen claim 1 , an alkyl group claim 1 , a trifluoroacetyl group claim 1 , (9H-fluoren-9-yl)methoxycarbonyl (Fmoc) group claim 1 , 6-( ...

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Номер записи: 97
18-01-2018 дата публикации

KAPPA OPIOID AGONISTS AND USES THEREOF

Номер: US20180016266A1
Автор: Anand Neel K., Duarte Franco J., Ren Zhongxu, Zhang Wen
Принадлежит:

Provided are compounds of Formula I: 2. The compound of claim 1 , wherein Ris a phenyl substituted with 1 claim 1 , 2 claim 1 , or 3 halogen atoms.3. The compound of claim 1 , wherein Ris methyl.4. The compound of claim 1 , wherein Ris phenyl substituted with —X-POLY.5. The compound of claim 1 , wherein Rand Rare taken together to form an optionally substituted pyrrolidinyl.6. The compound of claim 1 , wherein X is:{'sub': 2', '2', '2', '2', '2', '2', '2', '2, 'a covalent bond; —C(O)NH—; —C(O)NHCH—; —C(O)NHCHCH—; —OC(O)NH—; —C(O)NH—; —O—; —NHC(O)—; —NHC(O)CH—; —NHC(O)CHO—; —NHC(O)CHCH—; —NH—; or —NHS(O)—.'}7. The compound of claim 1 , wherein POLY is a poly(alkylene oxide) oligomer.8. The compound claim 1 , wherein POLY is a poly(ethylene oxide) oligomer.9. The compound of claim 1 , wherein POLY is end-capped with a hydroxyl group claim 1 , a lower alkoxy group claim 1 , or a trifluoromethoxy group.15. A pharmaceutical composition comprising a compound of and at least one pharmaceutically acceptable excipient.16. A method of treating pain or inflammation comprising administering a compound of to a patient in need thereof. This application a Continuation of U.S. application Ser. No. 14/900,039, filed 18 Dec. 2015, which is a 35 U.S.C. §371 application of International Application No. PCT/US2014/044535, filed 27 Jun. 2014, designating the United States, which claims the benefit of priority under 35 U.S.C. §119(e) to both U.S. Provisional Patent Application Ser. No. 61/929,685, filed 21 Jan. 2014, and U.S. Provisional Patent Application Ser. No. 61/841,042, filed 28 Jun. 2013, the disclosures of which are incorporated herein by reference in their entireties.The present disclosure relates to novel compounds and to their use as agonists of the kappa opioid receptor. The disclosure also relates to methods for preparation of the compounds and to pharmaceutical compositions containing such compounds. The compounds described herein relate to and/or have application(s) in ( ...

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Номер записи: 98
18-01-2018 дата публикации

INHIBITORS OF HISTONE DEACETYLASE

Номер: US20180016282A9
Автор: Haggarty Stephen J., Holson Edward, Tsai Li-Huei, Wagner Florence Fevrier, Weiwer Michel, ZHANG YAN-LING
Принадлежит:

The present invention relates to compounds of formula (I): 5. The compound of or a pharmaceutically acceptable salt claim 4 , hydrate claim 4 , solvate claim 4 , or prodrug thereof claim 4 , wherein Ris selected from phenyl claim 4 , 2-pyridinyl claim 4 , 3-pyridinyl claim 4 , 4-pyridinyl claim 4 , 2-pyrimidinyl claim 4 , 4-pyrimidinyl claim 4 , 5-pyrimidinyl claim 4 , 2-pyrazinyl claim 4 , oxazolyl claim 4 , thiazolyl claim 4 , and isoxazolyl.12. A pharmaceutical composition comprising an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate claim 1 , or prodrug thereof and a pharmaceutical carrier claim 1 , diluent claim 1 , or excipient.13. A method of treating claim 1 , alleviating claim 1 , and/or preventing a condition wherein said condition is associated with histone deacetylase activity in a subject comprising administering to the subject in need thereof an effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or prodrug thereof.14. The method of claim 13 , wherein the condition is selected from a neurological disorder claim 13 , memory loss or impairment claim 13 , cognitive function disorder or impairment claim 13 , extinction learning disorder claim 13 , fungal disease or infection claim 13 , inflammatory disease claim 13 , hematological disease claim 13 , and neoplastic disease.15. The method of claim 14 , wherein the condition is selected from:a cognitive function disorder or impairment associated with Alzheimer's disease, Huntington's disease, seizure induced memory loss, schizophrenia, Rubinstein Taybi syndrome, Rett Syndrome, Fragile X, Lewy body dementia, vascular dementia, ADHD, dyslexia, bipolar disorder and social, cognitive and learning disorders associated with autism, traumatic head injury, or attention deficit disorder, anxiety disorder, conditioned fear response, panic disorder, obsessive compulsive disorder, posttraumatic stress ...

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Номер записи: 99
15-01-2015 дата публикации

CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME

Номер: US20150018335A1
Автор: Chang Jae Won, CISAR Justin S., CRAVATT Benjamin F., GRICE Cheryl A., Jones Todd K., LUM Kenneth M., NIPHAKIS Micah J.
Принадлежит:

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition. 2. The compound of claim 1 , wherein T is CX.3. The compound of claim 1 , wherein Ris selected from the group consisting of methyl claim 1 , ethyl claim 1 , iso-propyl claim 1 , tert-butyl claim 1 , benzyl and phenyl.43. The compound of anyone of - claims 1 , wherein at least four occurrences of X is halogen.54. The compound of any one of - claims 1 , wherein six occurrences of X is halogen.76. The compound of any one of - claims 1 , wherein Rand Rtaken together with the nitrogen to which they are attached form a 4-7 membered heterocyclic ring B having an additional nitrogen.9. The compound of claim 8 , wherein:{'sup': '3', 'sub': 1', '2', 'w', '1', '2', 'w', '1', '2', '1-6, 'Lis selected from the group consisting of a bond, C-Calkylene, —C(O)—, —CH—C(O)—NH, —S(O)—, and C-Calkylene-S(O)—, wherein w is 0, 1, or 2, and wherein C-Calkylene is optionally substituted by a substituent selected from the group consisting of: phenyl, biphenyl, phenyloxyphenyl (each optionally substituted by halogen, Calkyl (optionally substituted by one, two or three halogens, or hydroxyl)), mono or bicyclic heteroaryl having 1, 2 or 3 heteroatoms independently selected from O, S, or N and mono or bicyclic heterocycle having 1, 2 or 3 heteroatoms independently selected from O, S, or N; and'}{'sup': 7', '7', 'a', 'b', 'a', 'b', 'a', 'b', 'a', 'b', 'a, 'sub': 3', '1-6', '1-6', '2', 'w', '1-6', '1-6', '1-6, 'Ris selected from the group consisting of phenyl, biphenyl, phenyloxyphenyl, and mono or bicyclic ...

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Номер записи: 100