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Небесная энциклопедия

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

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Мониторинг СМИ

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

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 5525. Отображено 100.
12-04-2012 дата публикации

Azole derivatives and fused bicyclic azole derivatives as therapeutic agents

Номер: US20120088778A1
Автор: Adnan M.M. Mjalli, Anitha Hari, David R. Jones, Ghassan Qabaja, Kwasi S. Avor, Ramesh Gopalaswamy, Robert C. Andrews, Suparna Gupta, Xiao-Chuan Guo, Xin Chen
Принадлежит: vTvx Holdings I LLC

This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, and their use in treating human or animal disorders. The compounds of the invention are useful as modulators of the interaction between the receptor for advanced glycated end products (RAGE) and its ligands, such as advanced glycated end products (AGEs), S100/calgranulin/EN-RAGE, β-amyloid and amphoterin, and for the management, treatment, control, or as an adjunct treatment for diseases in humans caused by RAGE. Such diseases or disease states include acute and chronic inflammation, the development of diabetic late complications such as increased vascular permeability, nephropathy, atherosclerosis, and retinopathy, the development of Alzheimer's disease, erectile dysfunction, and tumor invasion and metastasis.

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Номер записи: 1
26-04-2012 дата публикации

Carbonate derivatives for the treatment of cough

Номер: US20120101076A1
Автор: Pierangelo Geppetti, Riccardo Patacchini
Принадлежит: Chiesi Farmaceutici SpA

The invention relates to use of certain quinuclidine carbonate derivatives as cough suppressants, particularly for treating patients with upper respiratory tract infections or asthma.

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Номер записи: 2
21-06-2012 дата публикации

Muscarinic acetylcholine receptor antagonists

Номер: US20120157491A1
Автор: Brent W. McCleland, Christopher E. Neipp, Dramane I. Laine, Michael R. Palovich, Sonia M. Thomas
Принадлежит: Glaxo Group Ltd

Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided.

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Номер записи: 3
09-08-2012 дата публикации

Compounds for the treatment of hepatitis c

Номер: US20120201783A1
Автор: Andrew Nickel, Brett R. Beno, John A. Bender, John F. Kadow, Kap-Sun Yeung, Katharine A. Grant-Young, Kyle E. Parcella, Piyasena Hewawasam, Ying Han
Принадлежит: Bristol Myers Squibb Co

The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

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Номер записи: 4
09-08-2012 дата публикации

Therapeutic isoxazole compounds

Номер: US20120202786A1
Автор: Alan P. Kaplan, Andrew J. Mcriner, Terence P. Keenan
Принадлежит: Dart Neuroscience Cayman Ltd

The invention provides a compound of formula I: wherein A 1 , A 2 , A 3 , R 1 , X, Y, and B have any of the values described herein, as well as salts of such compounds, compositions comprising such compounds, and therapeutic methods that comprise the administration of such compounds. The compounds are inhibitors of monoamine oxidase B (MAO-B) enzyme function and are useful for improving cognitive function and for treating psychiatric disorders in animals.

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Номер записи: 5
23-08-2012 дата публикации

3,4-disubstituted 1h-pyrazole compounds and their use as cyclin dependent kinase and glycogen synthase kinase-3 modulators

Номер: US20120213791A1
Автор: Adrian Liam Gill, Alison Jo-Anne Woolford, Andrew James Woodhead, Gary Trewartha, Maria Grazia Carr, Michael Alistair O'brien, Paul Graham Wyatt, Theresa Rachel Early, Valerio Berdini
Принадлежит: ASTEX THERAPEUTICS LTD

The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof, and combinations thereof with other anti-cancer agents, for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3.

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Номер записи: 6
11-10-2012 дата публикации

Diazonium-free method to make an indazole intermediate in the synthesis of bicyclic 5-(trifluormethoxy)-1h-3-indazolecarboxylic acid amides

Номер: US20120259120A1
Автор: Thimma Rawalpally, Thomas Cleary, Yaohui Ji
Принадлежит: Thimma Rawalpally, Thomas Cleary, Yaohui Ji

The present invention provides novel methods for preparing 5-(trifluoromethoxy)-1H-3-indazolecarboxylic acid (3), which is a useful precursor for the preparation of bicyclic-5-trifluoromethoxy-1H-indazole-3-carboxylic acid amides of Formula (1). Compounds of Formula (1) are active as agonists and partial agonists of the nicotinic α-7 receptor and are being studied for their use in the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain, such as for the treatment of Alzheimer's disease and schizophrenia, as well as other psychiatric and neurological disorders. The present methods are useful for preparing compound (3) on scale up levels.

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Номер записи: 7
14-03-2013 дата публикации

Processes for preparing substituted pyrimidines

Номер: US20130066069A1
Автор: Andrew Miller, David Kay, Francesca Mazzei, Jean-Damien Charrier
Принадлежит: Vertex Pharmaceuticals Inc

The present invention provides a facile process for the preparation of tri- and tetra-substituted pyrimidines. The process is useful for preparing inhibitors of protein kinases, especially Aurora kinase. These inhibitors are useful for treating or lessening the severity of Aurora-mediated diseases or conditions.

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Номер записи: 8
28-03-2013 дата публикации

NOVEL PALONOSETRON SALTS AND PROCESSES FOR PREPARATION AND PURIFICATION THEREOF

Номер: US20130079521A1
Автор: Kaspi Joseph, Wang Yuan, Wensheng Tang, Xingzhong Zhang, Xungui He
Принадлежит: CHEMAGIS LTD.

Provided are novel salts of 2-(1-azabicyclo-[2.2.2]oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one, methods of using such salts, and processes for producing such salts. 1. (canceled)2. A method of preparing pure palonosetron or a salt thereof , the method comprising:(a) dissolving or partially dissolving impure palonosetron in an organic solvent;(b) optionally cooling the solution or partial solution of step (a) to a temperature below 20° C.;(c) admixing an acid and the solution of step (a) or step (b) to form crystals of a pure palonosetron salt, which is different from the HCl salt, and(d) optionally converting the pure palonosetron salt into the free base, wherein the impure palonosetron has a purity of up to 99.1% and an isomer ratio of up to 97:3 (3S),(3aS) isomer:(3S),(3aR) isomer, and the pure palonosetron or salt thereof has a purity of at least 99.5% and a (3S),(3aS):(3S),(3aR) isomer ratio of 99:1 or greater.3. The method of claim 2 , further comprising isolating the crystals.4. The method of claim 2 , wherein the organic solvent is selected from the group consisting of methanol claim 2 , ethanol claim 2 , n-propanol claim 2 , isopropanol claim 2 , and mixtures thereof.5. The method of claim 4 , wherein the organic solvent is ethanol.6. The method of claim 2 , wherein the acid of step (c) is selected from oxalic acid claim 2 , benzoic acid claim 2 , maleic acid claim 2 , malonic acid claim 2 , fumaric acid claim 2 , tartaric acid claim 2 , succinic acid claim 2 , citric acid claim 2 , methanesulfonic acid claim 2 , hydrobromic acid claim 2 , phosphoric acid claim 2 , and mixtures thereof.721-. (canceled) This patent application claims the benefit of U.S. Provisional Patent Application No. 60/932,139, filed May 29, 2007, which is incorporated herein by reference.The present invention relates to organic chemistry and more particularly to processes for preparation and purification of palonosetron and salts thereof.Palonosetron, 2-(1-azabicyclo-[ ...

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Номер записи: 9
18-04-2013 дата публикации

COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE

Номер: US20130095193A1
Автор: "ODonnell Michael Edward", Charrier Jean-Damien, Davis Christopher John, Durrant Steven John, KAY David, Knegtel Ronald Marcellus Alphonsus, MacCormick Somhairle, Pinder Joanne, Reaper Philip Michael, Storck Pierre-Henri, Twin Heather Clare, Young Stephen Clinton
Принадлежит: VERTEX PHARMACEUTICALS INCORPORATED

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. 2. The compound of claim 1 , wherein{'sub': 1-4', '1-4, 'J is halo, Calkyl, or Calkoxy;'}{'sup': '1', 'sub': 'q', 'Jis —(X)—Y;'}{'sub': 1-6', '1-6', '1-3, 'X is Calkyl wherein 0-2 methylene units of said Calkyl are replaced with NH, O, or S; X is optionally substituted with 1-2 occurrences of Calkyl or halo;'}{'sup': '1', 'sub': '1-3', 'or J and Jjoin together to form a 5-7 heterocyclyl having 1-2 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur; wherein the heterocyclyl is optionally substituted with 1 occurrence of halo or Calkyl;'}{'sup': '4', 'Jis CN or L-Z;'}{'sub': '2', 'L is C(O), S(O), or C(O)NR;'}{'sub': t—', '1-6', '1-6, 'Z is (U)Q or Calkyl wherein 0-2 methylene units of said Calkyl are replaced with O or NR;'}{'sub': '1-2', 'U is Calkyl;'}t is 0 or 1;{'sub': '3-6', 'Q is Ccycloalkyl or 4-6 membered saturated or partially saturated heterocyclyl having 1-2 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur; and'}{'sub': '1-4', 'R is H or Calkyl.'}3. The compound of claim 2 , wherein{'sup': '4', 'Jis CN or L-Z;'}{'sup': '5', 'Jis H;'}{'sup': '3', 'sub': '1-6', 'Jis Calkyl;'}{'sub': 1-4', '1-3, 'Y is hydrogen, Calkyl, or a 3-6 membered saturated or partially unsaturated heterocyclyl having 1-2 heteroatoms ...

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Номер записи: 10
25-04-2013 дата публикации

OXAZOLE TYROSINE KINASE INHIBITORS

Номер: US20130102592A1
Автор: BOFFEY Helen, CARR Andrew David, CHERRY Michael, ELLARD John Mark, OWOARE Richard Boakye, Reader John Charles, TAYLOR Susanne, WILSON Michelle
Принадлежит: SAREUM LIMITED

The invention provides a compound which is an amide of the formula (1), or a salt, solvate, N-oxide or tautomer thereof; wherein: a is 0 or 1; b is 0 or 1: provided that the sum of a and b is 0 or 1; T is O or NH Aris a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S, and being optionally substituted en by one or more substituents R; ArJs a monocyclic or bicyclic 5- to 10-membered aryl or heteroaryl group containing up to 4 heteroatoms selected from O, N and S and being optionally substituted by one or more substituents R; and Rand Rare as defined in the claims. The compounds are inhibitors of kinases and in particular FLT3, FLT4 and Aurora kinases. 176-. (canceled)85. A compound according to wherein Aris selected from substituted monocyclic 5- and 6-membered aryl and heteroaryl rings containing up to 2 heteroatoms selected from O claim 77 , N and S claim 77 , each of the aryl and heteroaryl rings being optionally substituted by one or more substituents R.86. A compound according to wherein Aris selected from optionally substituted phenyl claim 85 , thiophene claim 85 , furan claim 85 , pyridine and pyrazole rings.87. A compound according to wherein Aris phenyl optionally substituted by one or more substituent groups R.88. A compound according to wherein the aryl or heteroaryl group Aris substituted by 0 claim 77 , 1 or 2 substituents R.89. A compound according to wherein Ris selected from halogen; cyano; or a group R—R;{'sup': aa', 'cc', 'cc', 'cc', 'cc', 'cc', 'cc', 'cc, 'sub': 2', '2', '2, 'Ris a bond, O, CO, OC(O), C(O)O, NRC(O), C(O)NR, NR, OC(O)O, NRC(O)O, OC(O)NR, NRC(O)NR, S, SO, SO, SONR″ or NR″SOwherein'}{'sup': 'bb', 'claim-text': hydrogen; or', {'sup': '3a', 'a 3 to 8-membered non-aromatic carbocyclic or heterocyclic ring containing up to 2 heteroatoms selected from O, N and S and being optionally substituted by one or more substituents R; or'}, {'sup': '3a', 'a 5- or 6-membered ...

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Номер записи: 11
09-05-2013 дата публикации

Synthesis of mse-framework type molecular sieves

Номер: US20130115163A1
Автор: Hilda B. Vroman, Karl G. Strohmaier, Simon C. Weston
Принадлежит: ExxonMobil Research and Engineering Co

A method of synthesizing a crystalline molecular sieve having an MSE framework type comprises crystallizing a reaction mixture comprising a source of water, a source of an oxide of a tetravalent element, Y, selected from at least one of silicon, tin, titanium, vanadium, and germanium, optionally a source of a trivalent element, X, a source of an alkali or alkaline earth metal, M, and a source of organic dications, Q, such as 3-hydroxy-1-(4-(1-methylpiperidin-1-ium-1 yl)butyl)quinuclidin-1-ium, 3-hydroxy-1-(5-(1-methylpiperidin-1-ium-1-yl)pentyl)quinuclidin-1-ium, 1,1′-(butane-1,4-diyl)bis(1-methylpiperidin-1-ium), 1,1′-(pentane-1,5-diyl)bis(1-methylpiperidin-1-ium), 1,1′-(hexane-1,6-diyl)bis(1-methylpiperidin-1-ium), and 1,1′-((3as,6as)-octahydropentalene-2,5-diyl)bis(1-methylpiperidin-1-ium).

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Номер записи: 12
16-05-2013 дата публикации

NOVEL PROCESS FOR THE PREPARATION OF SOLIFENACIN SUCCINATE

Номер: US20130123502A1
Автор: Boddu Venkata Balalji, Ganala Naga Trinadhachari, Kamat Anand Gopalkrishna, Koilpillai Joseph Prabahar, Meenakshisunderam Sivakumaran, Upputuri Venkata Lakshmi
Принадлежит:

The present invention relates to a process for the preparation of Solifenacin succinate by condensing a compound of formula (IVb) with (RS)-3-quinuclidinol, wherein, R represents methyl, ethyl, isopropyl; to produce a diastereomeric mixture of (1S)-3,4-dihydro-1-phenyl-2(1H)-isoquinolinecarboxylic acid (3RS)-1-azabicyclo[2.2.2]oct-3-yl ester, which is treated with succinic acid in a solvent or mixture of solvents to produce optically pure Solifenacin succinate, Formula (X). 2. The process according to claim 1 , wherein the process of step-(i) is carried out in the presence of a base in a solvent.3. The process according to claim 2 , wherein the base used in step-(i) is selected from inorganic base such as sodium hydride claim 2 , potassium hydride claim 2 , sodium hydroxide claim 2 , potassium hydroxide claim 2 , lithium hydroxide claim 2 , sodium carbonate claim 2 , potassium carbonate and the organic base such as an amine claim 2 , for example diethylamine claim 2 , triethylamine claim 2 , diisopropylethylamine claim 2 , tert-butylamine claim 2 , pyridine.4. The process according to claim 2 , wherein the solvent used in step-(i) is selected from acetonitrile claim 2 , cyclic or acyclic alkanes such as hexane claim 2 , heptane claim 2 , methylcyclohexane claim 2 , aromatic solvents such as toluene claim 2 , halogenated solvents such as dichloromethane (MDC) claim 2 , dichloroethane claim 2 , chloroform claim 2 , esters such as ethyl acetate claim 2 , butyl acetate claim 2 , isopropyl acetate or ethers such as diethyl ether claim 2 , tetrahydrofuran or tert-butyl methyl ether and/or mixtures thereof.5. The process according to claim 1 , wherein the solvent used in step-(ii) is selected from methanol claim 1 , ethanol claim 1 , isopropanol claim 1 , ethyl acetate or mixtures there of.6. The process according to claim 1 , wherein the process is carried out in a single step without isolating diastereomeric mixture of Solifenacin.8. The process according to claim 7 , ...

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Номер записи: 13
06-06-2013 дата публикации

HETEROARYL CARBOXAMIDES

Номер: US20130144062A1
Автор: Böss Frank-Gerhard, Erb Christina, Hendrix Martin, Krüger Joachim, Luithle Joachim, Methfessel Christoph, Schreiber Rudy, Wiese Welf-Burkhard
Принадлежит: Bayer Pharma AG

The invention relates to novel heteroaryl carboxamides, a process for their preparation, and pharmaceutical compositions containing them. These materials are useful for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning and/or memory. 5) A compound having the IUPAC name:N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-quinolinecarboxamide hydrochloride;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenazinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-7-quinolinecarboxamide hydrochloride;N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-6-quinolinecarboxamide hydrochloride;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-methyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-propyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-4-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-propyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-4-methyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-(tetrahydro-2H-pyran-2-yl)-6-quinoline-carboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-(tetrahydro-2H-pyran-2-yl)-7-quinoline-carboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenyl-7-quinolinecarboxamide;or a salt thereof. This application is a Continuation application of U.S. application Ser. No. 10/496,404 filed on May 13, 2004, which is a 371 of PCT/EP02/12375 filed Nov. 6, 2002, which claims priority to German Patent Application No. 101 56 719.7 filed Nov. 19, 2001, the contents of each of which are incorporated herein by reference.The invention relates to novel heteroaryl carboxamides, processes for their preparation, and their use for producing medicaments for the treatment and/or prophylaxis of diseases and for ...

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Номер записи: 14
04-07-2013 дата публикации

QUINUCLIDINE ESTERS OF 1-AZAHETEROCYCLYLACETIC ACID AS ANTIMUSCARINIC AGENTS, PROCESS FOR THEIR PREPARATION AND MEDICINAL COMPOSITIONS THEREOF

Номер: US20130172302A1
Автор: Amari Gabriele, BOSSOLO Stefano, Pesenti Cristina
Принадлежит: CHIESI FARMACEUTICI S.p.A.

Compounds of formula (I): 2. A compound according to wherein:{'sub': 3', '3', '4, 'A is O, S, N(R), or C(R)R,'}{'sub': 1', '6', '1', '10', '1', '10, 'R1 is aryl, aryl(C-C)alkyl, or heteroaryl, each of which may be optionally substituted by one or more substituents selected from the group consisting of a halogen atom, (C-C)alkyl, (C-C)alkoxyl, aryloxy, and heteroaryl.'}3. A compound according to claim 1 , wherein:{'sub': 3', '4, 'A is C(R)R,'}m and n are both 2,{'sub': 1', '10', '1', '10, 'R1 is aryl or heteroaryl, each of which may be optionally substituted by one or more substituents selected from the group consisting of a halogen atom, (C-C)alkyl, (C-C)alkoxyl, aryloxy, and heteroaryl;'} {'br': None, 'sub': 2', '2, 'i': p', 'q, '(CH)-P—(CH)-W\u2003\u2003(Y)'}, 'R3 is a group of formula (Y)whereinp is 0, 1, or 3,P is CO,Q is 0,{'sub': 1', '10', '1', '10', '1', '10', '1', '10, 'W is s (C-C)alkyl, aryl, or heteroaryl, each of which may be optionally substituted by one or more substituents selected from the group consisting of a halogen atom, (C-C)alkyl, (C-C)alkoxyl, OH, and (C-C)alkanoyl.'}4. A compound according to claim 1 , wherein:W is phenyl, benzothioxolyl, thiophenyl, or thiazolyl, each of which may be optionally substituted by one or more substituents selected from the group consisting of a halogen atom, OH, methyl, and acetyl.5. A compound according to claim 1 , wherein:{'sup': '−', 'X is chloride, bromide, iodide, trifluoroacetate, formate, sulfate, phosphate, methanesulfonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate, or p-toluenesulfonate.'}8. A pharmaceutical composition claim 1 , comprising a compound according to and one or more pharmaceutically acceptable carriers or excipients.9. A pharmaceutical composition according to claim 8 , which is in a form selected from the group of a powder for inhalation claim 8 , propellant-driven pressurised metered dose inhaler claim 8 , and propellant-free nebulised ...

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Номер записи: 15
04-07-2013 дата публикации

PYRIDAZINONES AS GPR119 AGONISTS

Номер: US20130172323A1
Автор: Bakker Remko, Breitfelder Steffen, Buettner Frank, EICKELMANN Peter, Fox Thomas, GRAUERT Matthias, GRUNDL Marc, LEHMANN-LINTZ Thorsten, RIST Wolfgang
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to pyridazinone derivatives of general formula I, wherein the groups A, G and Rare as defined in the application, the tautomers thereof, stereoisomers thereof, the mixtures thereof and the salts thereof, which have valuable pharmacological properties, and in particular bind to the GPR119 receptor and modulate its activity. 8. The physiologically acceptable salts of the compounds of formula I according to .9. A medicament comprising a compound of formula I according to or a physiologically acceptable salt and an inert carriers or diluents.10. A method of treating or preventing a metabolic disease in a patient in need thereof comprising administering to the patient a compound according to .11. The compound according to claim 1 , excluding each of the compounds:5-methyl-6-[2-(3-thienyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(2-pyridyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(2-furyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(2-thienyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(3-pyridyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(2-pyrazinyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(4-pyridyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(1-acetyl-piperidino)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(4-methyl-5-oxazolyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(5-pyrimidinyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(2-amino-5-pyridyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,6-[2-(2-pyridyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,6-[2-(2-furyl)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(4-thiomorpholino)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(1-piperidino)-benzoxazol-6-yl]-4,5-dihydro-3(2H)-pyridazinone,5-methyl-6-[2-(1-oxido-4-thiomorpholino)-benzoxazol-6-yl]-4,5-dihydro ...

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Номер записи: 16
18-07-2013 дата публикации

Crystalline Form of (R)-7-Chloro-N-(Quinuclidin-3-yl)benzo[B]thiophene-2-Carboxamide Hydrochloride Monohydrate

Номер: US20130183380A1
Автор: Chesworth Richard, Ishige Takayuki, Kishida Muneki, Oliver-Shaffer Patricia, Shapiro Gideon
Принадлежит: EnVivo Pharmaceuticals, Inc.

Crystalline Forms I and II of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate and compositions, methods of manufacture and therapeutic uses thereof are described. 1. A crystalline Form I of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate , characterized by an x-ray powder diffraction pattern having peaks expressed as 2⊖ at one or both of 17.48 and 20.58±0.20 degrees when measured against an internal silicon standard.2. The crystalline Form I of claim 1 , characterized by an x-ray powder diffraction pattern further having at least one peak expressed as 2⊖ at 4.50 claim 1 , 9.04 claim 1 , 14.60 claim 1 , 15.14 claim 1 , 15.80 claim 1 , 16.60 claim 1 , 18.16 claim 1 , 18.44 claim 1 , 19.48 claim 1 , 21.74 claim 1 , and 25.46±0.20 degrees when measured against an internal silicon standard.3. The crystalline Form I of claim 2 , characterized by an x-ray powder diffraction pattern further having at least two peaks expressed as 2⊖ at 4.50 claim 2 , 9.04 claim 2 , 14.60 claim 2 , 15.14 claim 2 , 15.80 claim 2 , 16.60 claim 2 , 18.16 claim 2 , 18.44 claim 2 , 19.48 claim 2 , 21.74 and 25.46±0.20 degrees when measured against an internal silicon standard.4. The crystalline Form I of claim 2 , characterized by an x-ray powder diffraction pattern further having at least four peaks expressed as 2⊖ at 4.50 claim 2 , 9.04 claim 2 , 14.60 claim 2 , 15.14 claim 2 , 15.80 claim 2 , 16.60 claim 2 , 18.16 claim 2 , 18.44 claim 2 , 19.48 claim 2 , 21.74 and 25.46±0.20 degrees when measured against an internal silicon standard.5. The crystalline Form I of claim 2 , characterized by an x-ray powder diffraction pattern further having at least six peaks expressed as 2⊖ at 4.50 claim 2 , 9.04 claim 2 , 14.60 claim 2 , 15.14 claim 2 , 15.80 claim 2 , 16.60 claim 2 , 18.16 claim 2 , 18.44 claim 2 , 19.48 claim 2 , 21.74 and 25.46±0.20 degrees when measured against an internal silicon standard.6. The ...

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Номер записи: 17
18-07-2013 дата публикации

PYRIDAZINONE DERIVATIVES

Номер: US20130184260A1
Автор: BLAUKAT Andree, Dorsch Dieter, SCHADT Oliver, STIEBER Frank
Принадлежит:

Compounds of the formula (I), in which R, R, R, R, R have the meanings indicated in Claim , are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours. 16. A pharmaceutical composition claim 1 , comprising at least one compound of formula I according to or a pharmaceutically acceptable solvate claim 1 , salt claim 1 , tautomer or stereoisomer thereof claim 1 , and one or more pharmaceutically acceptable excipients and/or adjuvants.1725-. (canceled)26. A pharmaceutical composition according to claim 16 , further comprising at least one further pharmaceutically active ingredient.27. A kit claim 16 , comprising separate packs of{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) a compound of formula I according to or a pharmaceutically acceptable solvate, salt, tautomer or stereoisomer thereof,'}and(b) a further pharmaceutically active ingredient.28. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof.29. A compound according to claim 14 , or a pharmaceutically acceptable salt thereof. The invention had the object of finding novel compounds having valuable properties, in particular those which can be used for the preparation of medicaments.The present invention relates to compounds and to the use of compounds in which the inhibition, regulation and/or modulation of signal transduction by kinases, in particular tyrosine kinases and/or serine/threonine kinases, plays a role, furthermore to pharmaceutical compositions which comprise these compounds, and to the use of the compounds for the treatment of kinase-induced diseases.In particular, the present invention relates to compounds and to the use of compounds in which the inhibition, regulation and/or modulation of signal transduction by Met kinase plays a role.One of the principal mechanisms by which cellular regulation is effected is through the transduction of extracellular signals across the membrane that in turn modulate ...

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Номер записи: 18
18-07-2013 дата публикации

PYRIDAZINONE DERIVATIVES

Номер: US20130184261A1
Автор: BLAUKAT Andree, Dorsch Dieter, SCHADT Oliver, STIEBER Frank
Принадлежит:

Compounds of the formula (I), in which R, R, R, R, R, have the meanings indicated in Claim , are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours. 2. A method according to claim 1 , wherein in the compound of formula I or in a pharmaceutically acceptable solvate claim 1 , salt claim 1 , tautomer or stereoisomer thereof{'sup': 2', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '+', '−', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3, 'sub': 2', 'n', '2', '2', 'n', '2', '2', 'n', '2', 'p', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', 'n', '2', 'n', '2', 'n', '2', '2', 'n', '2', 'n', '2', 'n', '2', '2', 'n', '2', 'n', '2', 'n', '2, 'Rdenotes an unsaturated, saturated or aromatic 6-membered heterocycle having 1 to 4 N and/or O atoms, which is unsubstituted or mono-, di- or trisubstituted by Hal, A, [C(R)]OR, N═CRN(R), CN, COOR, [C(R)]N(R), [C(R)]Het, O[C(R)]OR, O[C(R)]N(R), O[C(R)]C≡C[C(R)]N(R), O[C(R)]NO(R), O[C(R)]Het, NR[C(R)]N(R), NR[C(R)]Het, [C(R)]NHCO[C(R)]N(R), [C(R)]NHCO[C(R)]Het, CONR[C(R)]N(R), CONR[C(R)]NRCOOA, CONR[C(R)]OR, CONR[C(R)]Het, COHet, CH═CH—COOR, CH═CH—N(R)and/or ═O.'}3. A method according to claim 1 , wherein in the compound of formula I or in a pharmaceutically acceptable solvate claim 1 , salt claim 1 , tautomer or stereoisomer thereof{'sub': m', '2', '2', '1', '2', '2', 'n', '2', 'n', '2', '2', 'n, 'sup': 3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3, 'Ar denotes phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di- or trisubstituted by A, Hal, CN, S(O)A, NRCOA, CON(R), O[C(R)]N(R), [C(R)]OR, CONR[C(R)]N(R)and/or CONR[C(R)]Het.'}4. A method according to claim 1 , wherein in the compound of formula I or in a pharmaceutically acceptable solvate claim 1 , salt claim 1 , tautomer or stereoisomer thereof ...

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Номер записи: 19
18-07-2013 дата публикации

Diaminocyclohexane compounds and uses thereof

Номер: US20130184262A1
Автор: Chongqing Sun, Maheswaran Sivasamban KARATHOLUVHU, William R. Ewing, Yanting Huang, Yeheng Zhu
Принадлежит: Bristol Myers Squibb Co

The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are agonists, partial agonists and modulators of the NPY Y4 receptor and may be used for the treatment and prophylaxis of various diseases and conditions.

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Номер записи: 20
25-07-2013 дата публикации

Bicyclic amides for enhancing glutamatergic synaptic responses

Номер: US20130190351A1
Автор: Leslie Street, Rudolf Mueller
Принадлежит: Cortex Pharmaceuticals Inc

This invention relates to bicyclic amide compounds, pharmaceutical compositions and methods for use in the prevention and treatment of a variety of conditions and/or disease states including cerebral insufficiency, through the enhancement of receptor functioning in synapses in brain networks responsible for basic and higher order behaviors as defined herein. These brain networks, which are involved in regulation of breathing, and cognitive abilities related to memory impairment, such as is observed in a variety of dementias, in imbalances in neuronal activity between different brain regions, as is suggested in disorders such as Parkinson's disease, schizophrenia, respiratory depression, sleep apneas, attention deficit hyperactivity disorder and affective or mood disorders, and in other disorders wherein a deficiency in neurotrophic factors is implicated, as well as other disorders as described herein.

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Номер записи: 21
01-08-2013 дата публикации

Alkaloid aminoester derivatives and medicinal composition thereof

Номер: US20130196978A1
Автор: Antonio Caligiuri, Gabriele Amari, Mauro Riccaboni
Принадлежит: Chiesi Farmaceutici SpA

Alkaloid aminoester compounds which act as muscarinic receptor antagonists are useful for the prevention and/or treatment of a broncho-obstructive or inflammatory diseases.

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Номер записи: 22
08-08-2013 дата публикации

SOLIFENACIN SALTS

Номер: US20130203804A1
Автор: Bonde-Larsen Antonio Lorente, Fuentes Gerardo Gutiérrez, López-Bachiller Jaime del Campo, Rodríguez Celso Sandoval, Sainz Yolanda Fernández
Принадлежит: CRYSTAL PHARMA, S.A.U.

The invention concerns fumarate salts of solifenacin, as well as pharmaceutical compositions comprising fumarate salts of solifenacin. The invention furthermore concerns a process for preparing solifenacin and salts thereof. The fumarate salt provides improved properties over the known solifenacin salts, especially in terms of its stability. The novel process for its preparation is furthermore improved over known processes for preparing solifenacin in that it provides a higher yield and recovers a greater amount of starting material. 1. A fumarate salt of solifenacin.216-. (canceled)17. The fumarate salt according to claim 1 , wherein said fumarate salt is a hydrogenfumarate (1:1) salt.18. The fumarate salt according to claim 1 , wherein said fumarate salt is substantially crystalline.19. A pharmaceutical composition comprising the fumarate salt according to and one or more pharmaceutically acceptable carriers claim 1 , wherein said pharmaceutical composition is a solid formulation.20. The pharmaceutical composition according to claim 19 , wherein said pharmaceutical composition is formulated for oral administration.21. The pharmaceutical composition according to claim 19 , wherein said pharmaceutical composition is in the form of a tablet claim 19 , a capsule claim 19 , a gelcap claim 19 , a granule claim 19 , a sachet or a pill.22. The pharmaceutical composition according to claim 21 , wherein said pharmaceutical composition is in the form of a tablet.23. A process for preparing solifenacin or a pharmaceutically acceptable salt thereof comprising:a) reacting a solifenacin base with a fumaric acid to form a fumarate salt thereof; andb) optionally transforming the fumarate salt obtained in step a) to solifenacin base and/or a different pharmaceutically acceptable salt of solifenacin.24. The process according to claim 23 , wherein step a) is preceded by the steps:a′) reacting 1(S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline with a C1-6 alkyl chloroformate to form a ...

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Номер записи: 23
22-08-2013 дата публикации

QUINOLINE DERIVATIVES AND MELK INHIBITORS CONTAINING THE SAME

Номер: US20130217671A1
Автор: AHMED Feryan, Decomez Helene, HISADA Shoji, Huntley Raymond, Matsuo Yo, Nakamura Yusuke, Walker Joel R.
Принадлежит:

The present invention directs a compound represented by formula (I). 2. The compound or a pharmaceutically acceptable salt thereof of claim 1 , wherein Ris a hydrogen atom or a halogen and Ris a hydrogen atom.3. The compound or a pharmaceutically acceptable salt thereof of claim 2 , wherein Ris R[Rrepresents a cyano claim 2 , a C-Calkylsulfinyl claim 2 , a C-Calkylsulfonyl claim 2 , or —CO—R(wherein claim 2 , Rrepresents a C-Calkyl claim 2 , or a C-Ccycloalkyl)] claim 2 ,{'sup': 2', '2A', '2A', '6A', '7A', '6A', '7A', '10A', '10A', '6A', '7A, 'sub': 2', 'n', '3', '10', '1', '6, 'Ris R{Rrepresents an optionally substituted aryl which may have a substituent group selected from Substituent Group C, an optionally substituted aromatic heterocyclic group which may have a substituent group selected from Substituent Group H, or —NRR[wherein, Rrepresents a hydrogen atom, and Rrepresents —(CH)—R(wherein, n represents an integer of 0 to 6, and Rrepresents an optionally substituted C-Ccycloalkyl which may have a substituent group selected from Substituent Group D, an optionally substituted aryl which may have a substituent group selected from Substituent Group E, an aliphatic heterocyclic group which may be substituted with a C-Calkyl, an aromatic heterocyclic group which may have a substituent group selected from Substituent Group I), or Rand Rform with an adjacent nitrogen atom an optionally substituted heterocyclic group which may have a substituent group selected from Substituent Group F]},'}{'sup': 3', '3A', '3A, 'Ris R(Rrepresents an optionally substituted aryl which may have a substituent group selected from Substituent Group G, or an optionally substituted aromatic heterocyclic group which may have a substituent group selected from Substituent Group H), and'}{'sup': '4', 'Ris a hydrogen atom or a halogen, and'} [{'sub': 1', '6', '1', '6, 'Substituent Group C: a halogen, a hydroxy, a C-Calkoxy, and a di(C-Calkyl) amino;'}, {'sub': 1', '6', '1', '6', '1', '6', '1', '6', ' ...

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Номер записи: 24
22-08-2013 дата публикации

Compositions and Methods for Treatment of Neurodegenerative Disease

Номер: US20130217679A1
Автор: BANNISTER THOMAS, Berlinicke Cynthia, Vojkovsky Tomas, Yang Zhiyong, Zack Donald J.
Принадлежит:

Compounds, compositions, kits and methods for treating conditions related to neurodegeneration or ocular disease, are disclosed. 2. (canceled)3. The compound of claim 1 , wherein X is S(O).4. The compound of claim 1 , wherein Ris H or methyl.5. The compound of claim 1 , wherein Ris methyl or ethyl.6. The compound of claim 1 , wherein Ris methyl or ethyl.7. The compound of claim 1 , wherein the compound is a compound of formula (I) and n is one or two and each Ris methyl.8. The compound of claim 1 , wherein the compound is a compound of formula (I) and n is at least 3 claim 1 , and two occurrences of Rare gem-dimethyl groups and one occurrence of Ris oxo.9. The compound of claim 1 , wherein X is C(O) and Ris —N(RR).10. The compound of claim 9 , wherein Rand Rare each independently unsubstituted C-Calkyl.11. The compound of claim 9 , wherein Rand Rare taken together with the nitrogen atom to which they are attached to form a 4-10-membered heterocyclic ring.12. The compound of claim 1 , wherein the compound is a compound of formula (I) and Ris H and Ris —(CH)N(ethyl).14. A method of treating or preventing a neurodegenerative disease or disorder claim 1 , the method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to the subject claim 1 , thereby treating or preventing the neurodegenerative disease or disorder.15. The method of claim 14 , wherein the neurodegenerative disease or disorder is glaucoma.16. The method of claim 15 , wherein the neurodegenerative disease or disorder is glaucoma that is not neovascular glaucoma.17. The method of claim 14 , wherein the step of administering the compound includes administering the compound in a pharmaceutically acceptable composition.18. The method of claim 14 , wherein the subject is a mammal.19. The method of claim 14 , wherein the subject is a human.20. The method of claim 14 , further comprising the step of monitoring ...

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Номер записи: 25
22-08-2013 дата публикации

INDAZOLES, BENZOTHIAZOLES, BENZOISOTHIAZOLES, BENZISOXAZOLES, AND PREPARATION AND USE THEREOF

Номер: US20130217683A1
Автор: GAUSS Carla, HERBERT Brian, MA Jianguo, NGUYEN Truc, SCHUMACHER Richard, TEHIM Ashok, XIE Wenge
Принадлежит: MEMORY PHARMACEUTICALS CORPORATION

The present invention relates generally to the field of ligands for nicotinic acetylcholine receptors (nACh receptors), activation of nACh receptors, and the treatment of disease conditions associated with defective or malfunctioning nicotinic acetylcholine receptors, especially of the brain. Further, this invention relates to novel compounds (e.g., indazoles and benzothiazoles), which act as ligands for the α7 nACh receptor subtype, methods of preparing such compounds, compositions containing such compounds, and methods of use thereof. 147-. (canceled)49. A method according to claim 48 , wherein said patient is suffering from schizophrenia claim 48 , anxiety claim 48 , mania claim 48 , depression claim 48 , manic depression claim 48 , Tourette's syndrome claim 48 , Parkinson's disease claim 48 , Huntington's disease claim 48 , Alzheimer's disease claim 48 , Lewy Body Dementia claim 48 , Amyotrophic Lateral Sclerosis claim 48 , memory impairment claim 48 , memory loss claim 48 , cognition deficit claim 48 , attention deficit claim 48 , and/or Attention Deficit Hyperactivity Disorder.52. (canceled)53. (canceled)54. (canceled)55. (canceled)56. (canceled)57. (canceled)60. A method according to claim 59 , wherein said memory impairment is due to decreased nicotinic acetylcholine receptor activity.61. (canceled)62. (canceled)63. (canceled)64. (canceled)65. (canceled)66. (canceled)68. A method according to claim 67 , wherein said inflammatory disease is rheumatoid arthritis claim 67 , diabetes or sepsis.69. A method according to claim 48 , wherein said patient is a human.70. The method according to claim 48 , wherein R′ is H or CH.71. The method according to claim 48 , wherein Ris alkynyl having 2 to 6 carbon atoms claim 48 , fluorinated hydroxyalkyl having 1 to 4 carbon atoms claim 48 , or Ar-alkynyl.72. The method according to claim 48 , wherein said compound is of formula I.73. The method according to claim 72 , wherein Ris NH claim 72 , CF claim 72 , OCH claim 72 , ...

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Номер записи: 26
29-08-2013 дата публикации

PRODUCTION PROCESS OF OPTICALLY ACTIVE 3-QUINUCLIDINOL DERIVATIVE

Номер: US20130225824A1
Автор: AKASHI Masaya, ARAI Noriyoshi, INOUE Tsutomu, OHKUMA Takeshi, OOOKA Hirohito
Принадлежит: NIPPON SODA CO., LTD.

A process is provided for efficiently producing an optically active 3-quinuclidinol derivative of high optical purity using a readily available ruthenium compound as an asymmetric reduction catalyst. This process is a process for producing an optically active 3-quinuclidinol derivative represented by the following formula (III) comprising asymmetrically hydrogenating a 3-quinuclidinone derivative represented by the following formula (I) in the presence of a ruthenium compound (II) represented by formula (II): Ru(X)(Y)(P)[RRC*(NRR)-A-RRC*(NRR)] (in the formulas, R represents a hydrogen atom or C7 to C18 aralkyl group and the like, X and Y represent hydrogen atoms or halogen atoms and the like, Px represents a phosphine ligand, n represents 1 or 2, R1 to R8 represent hydrogen atoms or C1 to C20 alkyl groups and the like, * represents an optically active carbon atom and A represents an ethylene group and the like). 15-. (canceled) The present invention relates to a process for producing optically active 3-quinuclidinol derivatives that are useful as production raw materials of physiologically active substances, and particularly pharmaceuticals.The present application claims priority on Japanese Patent Application No. 2007-230973, filed on Sep. 6, 2007, and Japanese Patent Application No. 2008-032311, filed on Feb. 13, 2008, the contents of which are incorporated herein by reference.Many alkaloids, and particularly those compounds having an azabicyclo ring structure, are useful as physiologically active substances. In particular, optically active 3-quinuclidinol derivatives are important compounds as production raw materials of pharmaceuticals.A conventionally known process for industrial production of optically active 3-quinuclidinol consists of direct asymmetric hydrogenation of 3-quinuclidinone using inexpensive hydrogen gas for the hydrogen source in the presence of an asymmetric hydrogenation catalyst (Patent Documents 1 to 4).In this production process, an ...

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Номер записи: 27
03-10-2013 дата публикации

COMPOUNDS USEFUL AS INHIBITORS OF CHOLINE KINASE

Номер: US20130261114A1
Автор: Everitt Simon, Knegtel Ronald, Mortimore Michael, Rutherford Alistair
Принадлежит:

The present invention relates to compounds useful as inhibitors of choline kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions. 2. The compound of claim 1 , wherein Ris H.3. The compound according to any one of or claim 1 , wherein Ris R.4. The compound of claim 3 , wherein Ris phenyl claim 3 , a 5-6 membered monocyclic heteroaryl claim 3 , or an −8-12 membered bicyclic heteroaryl.5. The compound of claim 4 , wherein Ris phenyl claim 4 , benzothiazolyl claim 4 , pyridinyl claim 4 , indolyl claim 4 , or imidazolyl.7. The compound of claim 5 , wherein Ris phenyl or benzothiazolyl9. The compound of claim 7 , wherein Ris benzothiazolyl.11. The compound of claim 7 , wherein Ris phenyl.13. The compound according to claim 1 , wherein Jis —ORor R.14. The compound of claim 13 , wherein —Ris H.15. The compound of claim 13 , wherein —Ris R.16. The compound of claim 15 , wherein Ris —Caliphatic claim 15 , wherein up to four methylene groups may be replaced with C═O claim 15 , nitrogen claim 15 , sulfur claim 15 , or oxygen.17. The compound of claim 16 , wherein Ris substituted with at least one occurrence of W.18. The compound of claim 17 , wherein W is a −4-8 membered monocyclic heterocyclyl.19. The compound of claim 18 , wherein W is independently piperazinyl claim 18 , morpholinyl claim 18 , piperidinyl claim 18 , or pyrrolidinyl.21. The compound of claim 15 , wherein Ris independently a 5-6 membered monocyclic heteroaryl or −4-8 membered monocyclic heterocyclyl.22. The compound of claim 21 , wherein Ris a −4-8 membered monocyclic heterocyclyl.23. The compound of claim 22 , wherein Ris a pyranyl.25. The compound of claim 21 , wherein Ris a 5-6 membered monocyclic heteroaryl.26. The compound of claim 25 , wherein Ris an imidazolyl.28. The compound ...

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Номер записи: 28
24-10-2013 дата публикации

COMPOUNDS USEFUL AS INHIBITORS OF CHOLINE KINASE

Номер: US20130281445A1
Автор: Everitt Simon, Knegtel Ronald, Mortimore Michael, Rutherford Alistair
Принадлежит:

The present invention relates to compounds useful as inhibitors of choline kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions. 2. The compound of claim 1 , wherein n is 0.3. The compound according to any one of or claim 1 , wherein Qis independently selected from phenyl claim 1 , thiazolyl claim 1 , or pyridinyl.53. The compound according to any one of - claims 1 , wherein Qis phenyl.65. The compound according to any one of - claims 1 , wherein Jis NRR.7. The compound of claim 6 , wherein Ris Calkyl and Ris Calkyl.8. The compound according to any one of claim 6 , wherein Rand R claim 6 , taken together with the nitrogen to which they are bound claim 6 , form a 5 membered heterocyclic ring.9. The compound of claim 8 , wherein Jis pyrrolidinyl.106. The compound according to any one of - claims 1 , wherein Rand R claims 1 , taken together with the nitrogen to which they are bound claims 1 , form a 6 membered heterocyclic ring.11. The compound of claim 10 , wherein Jis piperidinyl.12. The compound according to any one of or claim 10 , wherein Jis ethyl or tert-butyl.1312. The compound according to any one of - claims 1 , wherein Qis absent.1412. The compound according to any one of - claims 1 , wherein Qis fused to Q.15. The compound of claim 14 , wherein Qis benzo.16. The compound of claim 15 , wherein Qis fused to Q1 to form naphthalene.17. The compound of claim 16 , wherein Jis Calkyl18. The compound of claim 17 , wherein Jis methyl.19. The compound of claim 14 , wherein Qis a 5 or 6 membered non-aromatic ring having 1-2 heteroatoms selected from nitrogen or oxygen.20. The compound of claim 19 , wherein Qis independently selected from pyrrolidinyl claim 19 , morpholinyl claim 19 , piperazinyl claim 19 , or dioxolyl.22. The compound of ...

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Номер записи: 29
07-11-2013 дата публикации

PHARMACEUTICAL COMPOSITION COMPRISING PYRIDONE DERIVATIVES

Номер: US20130296340A1
Автор: Cha Su Bong, Jang Young Koo, Joung Chan Mi, Maeng Cheol Young, Shin Hye Won, Yi Eun Jung
Принадлежит:

A pyridone derivative compound and a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof, and a preventive or therapeutic pharmaceutical composition for cognitive disorders that includes the pyridone derivative compound or a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof. 17-. (canceled)9. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein B is NH.10. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is thiazolyl claim 8 , benzothiazolyl claim 8 , pyridyl claim 8 , isoxazolyl claim 8 , isoquinolinyl claim 8 , quinolyl claim 8 , benzothiadiazolyl claim 8 , thiadiazolyl claim 8 , pyrazolyl or pyrazinyl claim 8 , which is optionally substituted by at least one selected from the group consisting of halo claim 8 , chlorophenyl claim 8 , C-Calkyl claim 8 , C-Ccycloalkyl claim 8 , C-Caralkyl claim 8 , C-Calkoxy claim 8 , and C-Caryl.11. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is thiazolyl or benzothiazolyl optionally substituted by at least one selected from the group consisting of halo claim 8 , chlorophenyl claim 8 , C-Calkyl claim 8 , C-Ccycloalkyl claim 8 , C-Caralkyl claim 8 , C-Calkoxy claim 8 , and C-Caryl.12. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is C-Cheteroaryl substituted by at least one selected from the group consisting of chloro claim 8 , methyl claim 8 , ethyl claim 8 , propyl claim 8 , iso-propyl claim 8 , tert-butyl claim 8 , cyclopentyl claim 8 , phenyl claim 8 , chlorophenyl claim 8 , benzyl claim 8 , cyclohexyl and methoxy.13. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is selected from thiazolyl claim 8 , methylthiazolyl claim 8 , ethylthiazolyl claim 8 , propylthiazolyl claim 8 , iso- ...

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Номер записи: 30
07-11-2013 дата публикации

VINYL QUINUCLIDINE USEFUL AS A SYNTHESIS INTERMEDIATE IN THE PREPARATION OF (R)-MEQUITAZINE

Номер: US20130296553A1
Автор: Doris Eric, Larquetoux Laurent, Leroux Sébastien, Nicolas Marc
Принадлежит:

The present invention relates to the use of the vinyl quinuclidine enantiomer (R) of the following formula 2 as a synthesis intermediate in the preparation of (R)-mequitazine. 1. (canceled)4. The method according to claim 3 , wherein step (a) is carried out by ozonolysis.5. The method according to claim 3 , wherein step (a) is carried out from an acid addition salt of the (R) enantiomer of the vinyl quinuclidine of formula 2 as defined in .6. The method according to claim 3 , wherein step (b) is carried out in the presence of a hydride.7. The method according to claim 6 , wherein the hydride is NaBH.8. The method according to claim 3 , wherein R3 represents a mesylate (OMs).9. The method according to claim 8 , wherein step (c) is carried out in the presence of mesyl chloride (MsCl) and a base.10. The method according to claim 9 , wherein the base is pyridine.11. The method according to claim 3 , wherein step (d) is carried out in the presence of a base.12. The method according to claim 11 , wherein the base is potassium tert-butoxylate. The present invention relates to the optically pure vinyl quinuclidine of the following formula 2 as a synthesis intermediate in the preparation of the (R) enantiomer, dextrorotary, of the mequitazine of the following formula 1a:Mequitazine 1 is an active ingredient developed by the Pierre Fabre laboratories and commercialised in the racemic version thereof (mixture of 2 enantiomers 1a and 1b, Scheme 1) under the name of Primalan®. This medicine is used as an anti-histaminic for the treatment for example of urticaria, hay fever or certain allergies. Its preparation in the racemic form and in the levorotary form thereof 1b has been described in the patents FR 2 522 660 and EP 0 089 860. The drawback of the protocol for synthesising mequitazine in an optically active form (1a or 1b) is that it involves a step of resolution of the racemic, via the formation of a complex with tartaric acid. This resolution involves the loss of 50% at ...

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Номер записи: 31
21-11-2013 дата публикации

NOVEL QUINUCLIDINE DERIVATIVES AND MEDICINAL COMPOSITIONS CONTAINING THE SAME

Номер: US20130310353A1
Автор: BUIL ALBERO Maria Antonia, FERNANDEZ FORNER Maria Dolors, Prat Quinones Maria
Принадлежит:

Provided is a pharmaceutical composition comprising: (i) 3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo-[2.2.2]octane or an enantiomer, mixture of enantiomers, or a racemate thereof, wherein an anion X with a single negative charge is associated with the positive charge of the nitrogen atom; and (ii) a phosphodiesterase IV inhibitor and methods of using the same. 135-. (canceled)36. A pharmaceutical composition comprising:{'sup': '−', '(i) 3-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo-[2.2.2]octane or an enantiomer, mixture of enantiomers, or a racemate thereof, wherein an anion X with a single negative charge is associated with the positive charge of the nitrogen atom; and'}(ii) a phosphodiesterase IV inhibitor.37. The composition of further comprising a pharmaceutically acceptable carrier or diluent.38. The composition of wherein the anion X is chloride claim 36 , bromide claim 36 , iodide claim 36 , sulfate claim 36 , nitrate claim 36 , phosphate claim 36 , acetate claim 36 , maleate claim 36 , fumarate claim 36 , citrate claim 36 , oxalate claim 36 , succinate claim 36 , tartrate claim 36 , malate claim 36 , mandelate claim 36 , methanesulfonate claim 36 , p-toluenesulfonate claim 36 , or trifluoroacetate.39. The composition of which is suitable for inhalation.40. The composition of wherein the composition is a liquid inhalant claim 36 , powder inhalant claim 36 , or inhalation aerosol.41. The composition of further comprising a steroid.42. The composition of further comprising a βagonist.43. The composition of further comprising a βagonist.44. The composition of wherein the pharmaceutically acceptable carrier or diluent is lactose.45. A method for treating chronic obstructive pulmonary disease claim 36 , chronic bronchitis claim 36 , bronchial hyperreactivity claim 36 , asthma claim 36 , or rhinitis which method comprises administering to a human or animal patient in need of such treatment an effective ...

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Номер записи: 32
21-11-2013 дата публикации

Azolyl Urea Compounds and Methods of Use Thereof

Номер: US20130310357A1
Автор: Liu Gang
Принадлежит: AMBIT BIOSCIENCES CORPORATION

Provided herein are azolyl urea compounds for treatment of CSF-1R kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions. 3. The compound of claim 1 , wherein A is optionally substituted isoxazolyl or optionally substituted pyrazolyl claim 1 , wherein substituents when present are selected from one claim 1 , two or three Rgroups claim 1 , each independently selected from hydrogen claim 1 , halo claim 1 , alkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , alkoxy claim 1 , hydroxyl claim 1 , haloalkoxy claim 1 , cycloalkyl claim 1 , cycloalkylalkyl claim 1 , hydroxyalkyl claim 1 , haloalkyl claim 1 , aryl claim 1 , arylalkyl claim 1 , heterocyclyl claim 1 , heterocyclylalkyl claim 1 , heteroaryl claim 1 , and heteroarylalkyl claim 1 , where the alkyl claim 1 , alkenyl claim 1 , alkynyl claim 1 , alkoxy claim 1 , haloalkoxy claim 1 , cycloalkyl claim 1 , cycloalkylalkyl claim 1 , hydroxyalkyl claim 1 , haloalkyl claim 1 , aryl claim 1 , heterocyclyl claim 1 , and heteroaryl groups are optionally substituted with 1 to 5 groups selected from halo claim 1 , hydroxy claim 1 , alkoxy claim 1 , cycloalkyl claim 1 , cyano claim 1 , and —RN(R)(R) claim 1 , where Ris independently alkylene or a direct bond claim 1 , R claim 1 , and Rare each independently hydrogen or alkyl.9. The compound of claim 1 , where Ris hydrogen claim 1 , alkyl or alkoxy.10. The compound of claim 1 , where Ris hydrogen claim 1 , cycloalkyl claim 1 , heterocyclyl or heterocyclylalkyl claim 1 , where the cycloalkyl claim 1 , heterocyclyl and heterocyclylalkyl are optionally substituted with one or two alkyl groups.13. The compound of claim 1 , wherein each Qis independently selected from —CH claim 1 , —CH—CH claim 1 , —CHCF claim 1 , —CH—(CH) claim 1 , —C(O)O(CH) claim 1 , —(CH)S(O)CH claim 1 , —CHC(O)N(CH) claim 1 , —C(CH) claim 1 , cyclopropyl and oxetanyl.15. The compound of claim 1 , wherein the compound is ...

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Номер записи: 33
21-11-2013 дата публикации

5-HT3 RECEPTOR MODULATORS, METHODS OF MAKING, AND USE THEREOF

Номер: US20130310366A1
Автор: CIOFFI Christopher L., MANNING DAVID D.
Принадлежит: ALBANY MOLECULAR RESEARCH, INC.

Novel 5-HTreceptor modulators are disclosed. These compounds are used in the treatment of various disorders, including chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, and irritable bowel syndrome. Methods of making these compounds are also described in the present invention. 2. The compound according to in the (S) configuration.3. The compound according to in the (R) configuration.4. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to and a pharmaceutically acceptable carrier.5. A method of treating irritable bowel syndrome comprising:selecting a patient with irritable bowel syndrome; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to the patient a therapeutically effective amount of a compound according to or a pharmaceutically acceptable salt thereof.'}6. The method according to further comprising:{'sub': 3', '4, 'administering to the patient a therapeutically effective amount of a second serotonin 5-HTreceptor modulator or a serotonin 5-HTreceptor modulator.'}7. The method according to claim 6 , wherein the second serotonin 5HTreceptor modulator or serotonin 5HTreceptor modulator is selected from the group consisting of Alosetron claim 6 , renzapride claim 6 , cilansetron claim 6 , Tegaserod claim 6 , Prucalopride claim 6 , ondansetron claim 6 , somatostatin analogs claim 6 , muscarinic receptor antagonists claim 6 , laxatives claim 6 , antispasmodics claim 6 , antidepressants claim 6 , antidiarrheal agents claim 6 , prokinetic agents claim 6 , peripheral opiate narcotic antagonists claim 6 , and combinations thereof.8. A method of treating emesis comprising:selecting a patient with emesis; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to the patient a therapeutically effective amount of a compound according to or a pharmaceutically acceptable salt thereof.'}9. The method according to further comprising:administering to the patient a ...

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Номер записи: 34
28-11-2013 дата публикации

Tertiary amines, medicaments containing said amines, use thereof and processes for the preparation thereof

Номер: US20130316981A1
Автор: Armin Heckel, Dieter Hamprecht, Joerg Kley
Принадлежит: BOEHRINGER INGELHEIM INTERNATIONAL GMBH

The present invention relates to compounds of general formula (I) and the tautomers and the salts thereof, particularly the pharmaceutically acceptable salts thereof with inorganic or organic acids and bases, which have valuable pharmacological properties, particularly an inhibitory effect on epithelial sodium channels, the use thereof for the treatment of diseases, particularly diseases of the lungs and airways.

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Номер записи: 35
28-11-2013 дата публикации

PHARMACEUTICAL COMPOSITION COMPRISING PYRIDONE DERIVATIVES

Номер: US20130317059A1
Автор: Cha Hwa Ryun, Cha Su Bong, Jang Young Koo, Joung Chan Mi, Maeng Cheol Young, Shin Hye Won, Yi Eun Jung
Принадлежит: SK BIOPHARMACEUTICALS CO., LTD.

A pyridone derivative compound and a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof, and a preventive or therapeutic pharmaceutical composition for cognitive disorders that includes the pyridone derivative compound or a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof. 17-. (canceled)9. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein B is NH.10. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is phenyl or naphthyl optionally substituted by at least one selected from the group consisting of halo claim 8 , amino claim 8 , phenyl claim 8 , C-Calkyl claim 8 , C-Calkynyl claim 8 , C-Ccycloalkyl claim 8 , C-Calkoxy claim 8 , C-Caralkoxy claim 8 , C-Caryloxy claim 8 , C-Calkylthio claim 8 , C-Caralkylthio claim 8 , C-Carylthio claim 8 , C-Calkylsulfonyl and C-Cheteroaryl.11. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein A is phenyl optionally substituted by at least one selected from the group consisting of halo claim 8 , amino claim 8 , phenyl claim 8 , C-Calkyl claim 8 , C-Calkynyl claim 8 , C-Ccycloalkyl claim 8 , C-Calkoxy claim 8 , C-Caralkoxy claim 8 , C-Caryloxy claim 8 , C-Calkylthio claim 8 , C-Caralkylthio claim 8 , C-Carylthio claim 8 , C-Calkylsulfonyl and C-Cheteroaryl.12. The compound of or a pharmaceutically acceptable salt claim 8 , solvate or hydrate thereof claim 8 , wherein the compound is a compound of Formula I and A is phenyl optionally substituted by at least one selected from the group consisting of halo claim 8 , amino claim 8 , phenyl claim 8 , C-Calkyl claim 8 , C-Calkynyl claim 8 , C-Ccycloalkyl claim 8 , C-Calkoxy claim 8 , C-Caralkoxy claim 8 , C-Caryloxy claim 8 , C-Calkylthio claim 8 , C-Caralkylthio claim 8 , C-Carylthio claim 8 , C-Calkylsulfonyl and C-Cheteroaryl.13. The compound of or a pharmaceutically ...

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Номер записи: 36
19-12-2013 дата публикации

Amides of acetic and propionic acids

Номер: US20130338186A1
Автор: Christina Erb, Christoph Methfessel, Frank-Gerhard Bob, Joachim Luithle, Katrin Schnizler, Marja Van Kampen, Timo Flessner
Принадлежит: Bayer Healthcare AG

The invention relates to novel amides of acetic and propionic acids, methods for production and use thereof for the production of medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning ability and memory.

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Номер записи: 37
02-01-2014 дата публикации

2-Phenoxy- and 2-Phenylsulfonamide Derivatives with CCR3 Antagonistic Activity for the Treatment of Inflammatory or Immunological Disorders

Номер: US20140005176A1
Автор: Bacon Kevin, Fukushima Keiko, HASHIMOTO Kentaro, Li Yingfu, Marumo Makiko, MORIWAKI Toshiya, Nunami Noriko, SUGIMOTO Hiromi, Tsuno Naoki, Urbahns Klaus, Yoshida Nagahiro
Принадлежит: Axikin Pharmaceuticals, Inc.

Provided herein are 2-phenoxy- and 2-phenylsulfonamide derivatives with CCR3 antagonistic activity. These compounds are useful for the treatment of diseases associated with CCR3 activity, including but not limited to, atopic dermatitis, allergic rhinitis, rheumatoid arthritis, Grave's disease, HIV infection, Alzheimer's disease, atherosclerosis and other inflammatory and/or immunological disorders. 117.-. (canceled)22. The method of claim 18 , wherein the compound claim 18 , its tautomeric or stereoisomeric form claim 18 , or a physiologically acceptable salt thereof claim 18 , is selected from the group consisting of:(R)—N-(1-Aza-bicyclo[2.2.2]oct-3-yl)-5-cyano-2-(3,5-dichloro-phenoxy)-benzenesulfonamide;(S)—N-(1-Aza-bicyclo[2.2.2]oct-3-yl)-5-cyano-2-(3,5-dichloro-phenoxy)-benzenesulfonamide;N-(1-aza-bicyclo[2.2.2]oct-3-yl)-2-(3,5-dichloro-phenylsulfanyl)-5-nitro-benzenesulfonamide; and(R)-5-cyano-2-(3,5-dichlorophenoxy)-N-(2-(2,5-dioxopyrrolidin-1-yl)ethyl)-N-(1-aza-bicyclo[2.2.2]oct-3-yl)benzenesulfonamide.23. The method of claim 18 , wherein the compound claim 18 , its tautomeric or stereoisomeric form claim 18 , or a physiologically acceptable salt thereof is formulated with one or more pharmaceutically acceptable excipients.24. The method of claim 23 , wherein the excipient is an inert substance selected from the group consisting of a carrier claim 23 , a diluent claim 23 , a flavoring agent claim 23 , a sweetener claim 23 , a lubricant claim 23 , a solubilizer claim 23 , a suspending agent claim 23 , a binder claim 23 , a tablet disintegrating agent and an encapsulating agent. The present invention relates to a benzenesulfonamide derivative, which is useful as an active ingredient of pharmaceutical preparations. The benzenesulfonamide derivatives of the present invention have CCR3 (CC type chemokine receptor 3) antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with CCR3 activity, in particular for the treatment of ...

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Номер записи: 38
23-01-2014 дата публикации

5-ht3 receptor antagonists

Номер: US20140024644A1
Автор: Holger Monenschein, Holly Reichard, Huikai Sun, Maria Hopkins, Shota Kikuchi, Stephen Hitchcock, Todd Macklin
Принадлежит: Takeda California Inc, Takeda Pharmaceutical Co Ltd

The present invention provides 5-HT3 receptor antagonists of Formula (I): which are useful for the treatment of diseases treatable by inhibition of 5-HT3 receptor such as emesis, pain, drug addiction, neurodegenerative and psychiatric disorders, and GI disorders. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

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Номер записи: 39
23-01-2014 дата публикации

(2S,3R)-N-(2-((3-PYRIDINYL)METHYL)-1-AZABICYCLO[2.2.2]OCT-3-YL)BENZYOFURN-2-CARBOXAMIDE, NOVEL SALT FORMS, AND METHODS OF USE THEREOF

Номер: US20140024673A1
Автор: Bencherif Merouane, Benson Lisa, Dull Gary Maurice, Federov Nikolai, Gatto Gregory J., Jordan Kristen G., Mazurov Anatoly A., Miao Lan, Munoz Julio A., Pfeiffer Inigo, Pfeiffer Sondra, Phillips Teresa
Принадлежит: Targacept,Inc.

The present invention relates to (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide, novel salt forms thereof, methods for its preparation, novel intermediates, and methods for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central and autonomic nervous systems. 1. A method for treating one or more of mild cognitive impairment , age-associated memory impairment , pre-senile dementia , early onset Alzheimer's disease , senile dementia , dementia of the Alzheimer's type , or Alzheimer's disease comprising administering a compound (2S ,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide or a pharmaceutically acceptable salt thereof , substantially free of (2S ,3S)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , (2R ,3S)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , (2R ,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , and pharmaceutically acceptable salts thereof.2. The method of claim 1 , wherein the treatment is for Alzheimer's disease.3. The method of claim 1 , wherein the treatment is for early onset Alzheimer's disease. The present invention is a continuation of U.S. patent application Ser. No. 13/116,080, filed May 26, 2011, which is a continuation of U.S. patent application Ser. No. 12/184,312, filed Aug. 1, 2008, now U.S. Pat. No. 7,981,906 issued Jul. 19, 2011, which claims benefit to U.S. Provisional Application Nos. 60/971,654, filed Sep. 12, 2007, 60/953,610, filed Aug. 2, 2007, 60/953,613, filed Aug. 2, 2007, and 60/953,614 filed Aug. 2, 2007, each of which is incorporated herein by reference in its entirety.The present invention relates to (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide, novel salt forms thereof, methods for its preparation, novel intermediates, and methods for treating ...

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Номер записи: 40
30-01-2014 дата публикации

1,4-disubstituted 1,2,3-triazoles, methods for preparing same, and diagnostic and therapeutic uses thereof

Номер: US20140030191A1
Автор: Denis Guilloteau, Franck Suzenet, Frederic Pin, Johnny VERCOUILLIE, Sylvain Routier, Sylvie CHALON
Принадлежит: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

A compound having the following general formula (I): wherein: X is a nitrogen atom and Y is a carbon atom; or X is a carbon atom and Y is a nitrogen atom; the Ar group is an aryl or heteroaryl group; and the RN and RN′ groups, together with the carbon atoms to which they are bound, form a monocyclic or bicyclic azacycloalkane group. The pharmaceutically acceptable salts thereof, the hydrates or polymorphic crystalline structures thereof, and to the racemates, diastereoisomers, or enantiomers thereof are also described.

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Номер записи: 41
13-02-2014 дата публикации

COMPOUNDS CONTAINING AN ALICYCLIE STRUCTURE AND ANTI-TUMOR APPLICATION

Номер: US20140045779A1
Автор: XU LIFENG
Принадлежит:

This invention relates with anti-tumor activities of new compounds containing an adamantyl group or analogs thereof. The invention also relates with the medication applications of anti-tumor and other diseases by this kind of compounds with the combination of S, P, T structures containing adamantyl group and the formation of stereoisomer, tautomers, prodrug, pharmaceutically acceptable salts, complex salts or solvates to their anticancer application and anticancer agents, which have the following general formula: 2. The compound according to the S formula of claim 1 , wherein:{'sub': 1', '2', '3', '4', '2', '1-10, 'The dotted lines are optionally substituted single bonds, optionally substituted double bond or a optionally substituted heterocyclic group containing carbon, oxygen, sulfur or nitrogen element; said X, X, X, Xare, independently at each occurrence, C═O, C═S, C═NH, C═Rb—Ra, CHOH, CHORb, CHRb or substituent, where Rb contains, independently at each occurrence, one or combination of C, N or P element; Ra is H, H, optionally substituted straight-alkyl, optionally substituted branched-alkyl, Coptionally substituted saturated alkyl, optionally substituted 1-4 double bond, optionally substituted 1-4 triple bond, optionally substituted unsaturated alkyl, optionally substituted saturated or unsaturated alicyclic, optionally substituted arylcyclic, optionally substituted aryl or optionally substituted heterocyclic, optionally substituted arylheterocyclic, fused heterocyclic group where contains hydroxyl, halogen, oxygen, nitrogen, sulfur, phosphorus element or selenium element;'}{'sub': 1', '2', '3', '4', '5', '6', '7', '8, 'said A, A, A, A, A, A, Aor Ais, independently at each occurrence, optionally substituted independently cyclic, alkyl, aryl, alicyclic, heterocyclic, aliphatic, aromatic heterocyclic, heterocyclic, glycosyl, multi-hydroxyl, amino acid, phosphate, acyloxyl, phosphoric, sulfonyloxyl, alkoxy, aryloxyl, heterocyclic oxyl, aryl cyclic, aliphatic ...

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Номер записи: 42
20-02-2014 дата публикации

Substituted indole compounds having nos inhibitory activity

Номер: US20140051687A1
Автор: Jailall Ramnauth, Joanne Patman, Paul Renton, Shawn Maddaford, Subhash C. Annedi, Suman Rakhit
Принадлежит: Neuraxon Inc

The present invention features inhibitors of nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing conditions such as, for example, stroke, reperfusion injury, neurodegeneration, head trauma, CABG, migraine headache with and without aura, migraine with allodynia, central post-stroke pain (CPSP), neuropathic pain, morphine/opioid induced tolerance and hyperalgesia.

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Номер записи: 43
20-02-2014 дата публикации

STABLE CRYSTALLINE SALT OF (R)-3-FLUOROPHENYL-3,4,5-TRIFLUOROBENZYLCARBAMIC ACID 1-AZABICYCLO [2.2.2]OCT-3-YL ESTER

Номер: US20140051721A1
Автор: CATENA RUIZ Juan Lorenzo, HILDALGO RODRÍGUEZ José, Masip Masip Isabel, SERRA COMAS María del Carmen
Принадлежит: LABORATORIOS SALVAT, S.A.

The present invention refers to a stable crystalline salt of (R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo [2.2.2]oct-3-yl ester and its use as medicament, in particular for the treatment of urinary incontinence or other diseases involving genitourinary disorders 2. The method of claim 1 , wherein the D-tartrate salt of compound I is a substantially anhydrous crystalline salt.3. The method of claim 1 , wherein the disease involving genitourinary disorders is urinary incontinence.4. The method of claim 1 , wherein the disease involving genitourinary disorders is overactive bladder.6. The method of claim 5 , wherein the D-tartrate salt of compound I is a substantially anhydrous crystalline salt.7. A method of claim 5 , wherein the disease or condition involving genitourinary disorders is urinary incontinence.8. A method of claim 5 , wherein the disease or condition involving genitourinary disorders is overactive bladder. The present invention relates to a stable crystalline salt of (R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo [2.2.2]oct-3-yl ester and to pharmaceutical formulations of this salt, in particular for medical use including treatment of urinary incontinence urge or other diseases involving genitourinary disorders.WO0200652 discloses compound I ((R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo [2.2.2]oct-3-yl ester) which has the following formula (I)Compound I is also disclosed in WO2004000840. On the other hand, compound I is exemplified as hydrochloride salt in WO2003053966 as an intermediate in the synthesis of other compounds. However, this acid addition salt known from the prior art had the disadvantage that its physicochemical stability was poor. Upon storage or formulation of said known salt, progressive decomposition and concomitantly an increase in the amount and number of impurities was observed. Obviously, this problem is further aggravated under demanding environmental conditions such ...

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Номер записи: 44
27-02-2014 дата публикации

3-(HETEROARYL-OXY)-2-ALKYL-1-AZA-BICYCLOALKYL DERIVATIVES AS ALPHA. 7-NACHR LIGANDS FOR THE TREATMENT OF CNS DISEASES

Номер: US20140057921A1
Автор: Feuerbach Dominik, Frederiksen Mathias, Hurth Konstanze, ROY Bernard Lucien
Принадлежит: NOVARTIS AG

The present invention relates to 1-aza-bicycloalkyl derivatives of formula (I) wherein the substituents are as defined in the specification, to processes for their production, their use as pharmaceuticals in the prevention and treatment of psychotic and neurodegenerative disorders. The claimed compounds act as nicotinic acetylcholine receptors (NACHR) ligands. 115-. (canceled)171. A method for treating or preventing a disease or condition in which α7 nAChR activation plays a role or is implicated , in a subject in need of such treatment , which comprises administering to such subject a therapeutically effective amount of a compound of claim in free base or pharmaceutically acceptable acid addition salt form.20. A method according to claim 17 , wherein the compound of formula I is selected from the group consisting of(2SR,3RS)-3-[5-(1H-Indol-5-yl)-pyridin-2-yloxy-]2-methyl-1-aza-bicyclo[2.2.2]octane;(+)-3-[5-(1H-Indol-5-yl)-pyridin-2-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;(−)-3-[5-(1H-Indol-5-yl)-pyridin-2-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;(2SR,3RS)-3-[6-(1H-Indol-5-yl)-pyridazin-3-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;(2S,3R)-3-[6-(1H-Indol-5-yl)-pyridazin-3-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;(2R,3S)-3-[6-(1H-Indol-5-yl)-pyridazin-3-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;(2SR,3RS)-3-[5-(1H-Indol-5-yl)-pyrimidin-2-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;{'b': '3-', '(2S,3R)--[5-(1H-Indol-5-yl)-pyrimidin-2-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane;'}{'b': '3-', '(2R,3S)--[5-(1H-Indol-5-yl)-pyrimidin-2-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane; and'}(2SR,3RS)-3-[6-(1H-Indol-5-yl)-pyridin-3-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane.21. A method according to claim 17 , wherein the compound of formula I is (2SR claim 17 ,3RS)-3-[6-(1H-Indol-5-yl)-pyridazin-3-yloxy]-2-methyl-1-aza-bicyclo[2.2.2]octane.22. A method according to claim 17 , wherein the compound of formula I is(2S,3R)-3-[6-(1H-Indol-5-yl)-pyridazin-3-yloxy]-2-methyl-1-aza- ...

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Номер записи: 45
27-02-2014 дата публикации

TETRAHYDROISOQUINOLIN-1-ONE DERIVATIVE OR SALT THEREOF

Номер: US20140058100A1
Автор: Hisamichi Hiroyuki, Ishihara Tsukasa, Ishikawa Noriko, Maeno Kyoichi, Seki Norio, Shimada Itsuro, Shimizu Takafumi, Takuwa Tomofumi
Принадлежит: Seldar Pharma Inc.

To provide a pharmaceutical, in particular a compound which can be used as a therapeutic agent for irritable bowel syndrome (IBS). It was found that a tetrahydroisoquinolin-1-one derivative having an amide group at the 4-position or a pharmaceutically acceptable salt thereof has an excellent bombesin 2 (BB2) receptor antagonistic action. It is also found that the tetrahydroisoquinolin-1-one derivative is highly effective on bowel movement disorders. From the above, the tetrahydroisoquinolin-1-one derivative of the present invention is useful as a therapeutic agent for diseases associated with a BB2 receptor, in particular IBS. 1. (canceled)4. The method as described in claim 3 , wherein Ris —H.5. The method as described in claim 4 , wherein Ris phenyl which may be substituted with halogen claim 4 , lower alkyl claim 4 , or —OR.6. The method as described in or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris —N(R)-lower alkylene-(aryl or heteroaryl claim 5 , which may each be substituted) claim 5 , or —N(R)—O-lower alkylene-(aryl or heteroaryl claim 5 , which may each be substituted).7. The method as described in claim 6 , wherein Ris (lower alkylene)-OH or substituted cycloalkyl {wherein said lower alkylene may be substituted with a member selected from the group consisting of —OH and phenyl (which may be substituted with halogen claim 6 , lower alkyl claim 6 , or —OR claim 6 , and said substituted cycloalkyl is substituted with a member selected from the group consisting of —OR claim 6 , —N(R) claim 6 , —N(R)C(O)R claim 6 , —N(R)-lower alkylene-OR claim 6 , —N(R)S(O)-lower alkyl and heterocyclic group}.8. The method according to claim 3 , wherein the compound is (4-{[({[(3R claim 3 ,4R)-3-(2 claim 3 ,4-dichlorophenyl)-2-{(1S claim 3 ,2S)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-1 claim 3 ,2 claim 3 ,3 claim 3 ,4-tetrahydroisoquinolin-4-yl]carbonyl}amino)oxy]methyl}phenyl)acetic acid claim 3 , or a pharmaceutically acceptable salt thereof.10. The ...

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Номер записи: 46
06-03-2014 дата публикации

Pyrimidine derivatives as protein kinase inhibitors

Номер: US20140066436A1
Автор: Claire June Flynn, Jonathan James Hollick, Michael George Thomas, Stuart Donald Jones
Принадлежит: Cyclacel Ltd

The present invention relates to a compound of formula (VII)I, or pharmaceutically acceptable salt or ester thereof, wherein: X is NR 7 ; Y is O or N—(CH 2 ) n R 19 ; n is 1, 2 or 3; m is 1 or 2; R 1 and R 2 are each independently H, alkyl or cycloalkyl; R 4 and R 4′ are each independently H or alkyl; or R 4 and R 4′ together form a spiro cycloalkyl group; R 19 is H, alkyl, aryl or a cycloalkyl group; R 6 is OR 8 or halogen; and R 7 and R 8 are each independently H or alkyl. Further aspects relate to pharmaceutical compositions comprising said compounds and use therefore in the treatment of proliferative disorders and the like.

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Номер записи: 47
20-03-2014 дата публикации

MUSCARINIC ACETYLCHOLINE RECEPTOR ANTAGONISTS

Номер: US20140080863A1
Автор: Laine Dramane Ibrahim, McCleland Brent W., Neipp Christopher E., Palovich Michael R., THOMAS Sonia M.
Принадлежит: Glaxo Group Limited

Muscarinic Acetylcholine Receptor Antagonists and methods of using them are provided. 2. The compound according to wherein X is a pharmaceutically acceptable anion selected from the group consisting of chloride claim 1 , bromide claim 1 , iodide claim 1 , hydroxide claim 1 , sulfate claim 1 , nitrate claim 1 , phosphate claim 1 , acetate claim 1 , trifluoroacetate claim 1 , fumarate claim 1 , citrate claim 1 , tartrate claim 1 , oxalate claim 1 , succinate claim 1 , mandelate claim 1 , methanesulfonate claim 1 , and p-toluenesulfonate.3. The compound according to wherein M is O.4. The compound according to wherein n is 2.5. The compound according to wherein l is 2.6. The compound according to wherein V is CH.7. The compound according to wherein V is O.8. The compound according to wherein M is CH.9. The compound according to wherein l is 1.10. The compound according to wherein l is 2.15. The compound according to which is:4-[hydroxy(diphenyl)methyl]-1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-1-azoniabicyclo[2.2.2]octane bromide.16. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier thereof.17. A pharmaceutical composition comprising a compound according to claim 15 , and a pharmaceutically acceptable carrier thereof.18. A pharmaceutical composition according to in a form suitable for administration by oral or nasal inhalation.19. A pharmaceutical composition according to wherein the form is suitable for administration by inhalation via a medicament dispenser selected from a reservoir dry powder inhaler claim 18 , a multi-dose dry powder inhaler claim 18 , or a metered dose inhaler.20. A pharmaceutical composition according to which is a dry powder composition. This invention relates to novel quinuclidines derivatives, pharmaceutical compositions, and use thereof in treating muscarinic acetylcholine receptor mediated diseases of the respiratory tract.Acetylcholine released from cholinergic neurons in the ...

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Номер записи: 48
27-03-2014 дата публикации

Partially Saturated Tricyclic Compounds and Methods of Making and Using Same

Номер: US20140088078A1
Автор: Cramp Susan Mary, Dyke Hazel Joan, Pallin Thomas David, Zahler Robert
Принадлежит: Zafgen, Inc.

The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2. 2. The tricyclic compound of claim 1 , wherein X′ is selected from the group consisting of: —O—* claim 1 , —N(R)—* claim 1 , —C(RR)—C(RR)—* claim 1 , —C(R)═C(R)—* claim 1 , —O—C(RR)—* claim 1 , —N(R)—C(RR)—* claim 1 , —O—C(O)—* claim 1 , —N(R)—C(O)—* claim 1 , —N═C(R)—* and —O—C(RR)—C(RR)—*;{'sup': '+', 'wherein the and * indicate the attachment points of X′ as indicated in Formula I.'}3. The tricyclic compound of claim 1 , wherein Xis selected from the group consisting of: —NH—* claim 1 , —O—CH—* claim 1 , —NH—CH—* claim 1 , —N═CH—* and —CH═CH—*;{'sup': '+', 'wherein the and * indicate the attachment points of X′ as indicated in Formula I.'}4. The tricyclic compound of claim 1 , wherein Xis selected from the group consisting of: —O—* claim 1 , —N(R)—* claim 1 , —C(RR)—C(RR)—* claim 1 , —O—C(RR)—* claim 1 , —N(R)—C(RR)—* claim 1 , —O—C(O)—* claim 1 , —N(R)—C(O)—* claim 1 , and —O—C(RR)—C(RR)—*; wherein the and * indicate the attachment points of Xas indicated in Formula II.5. The tricyclic compound of claim 1 , wherein Xis selected from the group consisting of: —O—CH—* and —NH—CH—*; wherein the and * indicate the attachment points of Xas indicated in Formula II.6. The tricyclic compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , Rand Rare independently selected for each occurrence from the group consisting of hydrogen and methyl.7. The tricyclic compound of claim 5 , wherein R claim 5 , R claim 5 , R claim 5 , Rand Rare hydrogen.8. The tricyclic compound of claim 1 , wherein R claim 1 , R claim 1 , Rand Rare independently selected for each occurrence from the group consisting of hydrogen claim 1 , fluorine claim 1 , cyano and Calkyl.9. The tricyclic compound of claim 7 , ...

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Номер записи: 49
27-03-2014 дата публикации

IMIDAZOPYRIDINE COMPOUNDS

Номер: US20140088080A1
Автор: HANAZAWA Takeshi, IIDA Maiko, IMAMURA Kenichiro, Imamura Yoshimasa, Koga Yuji, Maeno Kyoichi, NOZAWA Eisuke, OHNE Kazuhiko, Sato Ippei, Shibata Hiroshi, WATANABE Tsubasa
Принадлежит: Astellas Pharma Inc.

[Problem] 2. The compound or a salt thereof according to claim 1 , wherein{'sup': '1', 'Ais cyclohexyl, or phenyl optionally substituted with one or more F atoms,'}{'sup': '1', 'Ris H,'}{'sup': 2', '0, 'Ris R,'}{'sup': '3', 'Ris H,'}{'sup': '5', 'Ris H,'}{'sup': 4', '2', '3, 'Ris —Y-Aor A,'}{'sub': '1-10', 'sup': '2', 'Y is Calkylene optionally substituted with at least one group selected from Group G,'}{'sup': '2', 'sub': '2', 'Group Gis —COH and —OH,'}{'sup': '2', 'sub': '2', 'Ais H, cycloalkyl, pyridyl, or phenyl optionally substituted with a group selected from the group consisting of lower alkyl and —COH,'}{'sup': 3', '1', '1, 'Ais cycloalkyl selected from the group consisting of cyclopentyl, indanyl, dihydrocyclopentathienyl, dihydrocyclopentafuranyl, and dihydrocyclopentapyrrolyl, the above cycloalkyl is optionally substituted with at least one group selected from Group G, or piperidyl or pyrrolidinyl each optionally substituted with at least one group selected from Group G, and'}{'sup': 1', '0', '0', '0, 'sub': 2', '2', '2', '2', '2', '3', '3, 'Group Gis R, halogen, —COH, —OH, —COR, —CN, —NO, phenyl, —SO—NH, —SOH, and —SOR.'}4. The compound or a salt thereof according to claim 3 , wherein Ais 2 claim 3 ,6-difluorophenyl claim 3 , Ris methyl claim 3 , Ris a group represented by the formula (A) or the formula (B) claim 3 , X is —HC═CH— claim 3 , n is 1 claim 3 , Ris F claim 3 , and Ris —COH.6. The compound or a salt thereof according to claim 3 , wherein Ris methyl and Ris a group represented by the formula (C) or (D).7. The compound or a salt thereof according to claim 3 , wherein Ais cyclohexyl or 2 claim 3 ,6-difluorophenyl claim 3 , Ris methyl claim 3 , Ris A claim 3 , Ais a group represented by the formula (A) or the formula (B) claim 3 , X is —HC═CH— claim 3 , n is 1 claim 3 , Ris each H claim 3 , Ris H claim 3 , and Ris —COH.8. The compound or a salt thereof according to claim 3 , wherein Ris methyl and Ris a group represented by the formula (E).9. The ...

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Номер записи: 50
02-01-2020 дата публикации

PHARMACEUTICAL COMPOSITION COMPRISING PYRIDONE DERIVATIVES

Номер: US20200000782A1
Автор: Cha Su Bong, Jang Young Koo, Joung Chan Mi, Maeng Cheol Young, Shin Hye Won, Yi Eun Jung
Принадлежит:

A pyridone derivative compound and a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof, and a preventive or therapeutic pharmaceutical composition for cognitive disorders that includes the pyridone derivative compound or a pharmaceutically acceptable salt, isomer, solvate or hydrate thereof. 17-. (canceled)9. The method of claim 8 , wherein B is NH.10. The method of claim 8 , wherein A is thiazolyl claim 8 , benzothiazolyl claim 8 , pyridyl claim 8 , isoxazolyl claim 8 , isoquinolinyl claim 8 , quinolyl claim 8 , benzothiadiazolyl claim 8 , thiadiazolyl claim 8 , pyrazolyl or pyrazinyl claim 8 , which is optionally substituted by at least one selected from the group consisting of halo claim 8 , chlorophenyl claim 8 , C-Calkyl claim 8 , C-Ccycloalkyl claim 8 , C-Caralkyl claim 8 , C-Calkoxy claim 8 , and C-Caryl.11. The method of claim 8 , wherein A is thiazolyl or benzothiazolyl optionally substituted by at least one selected from the group consisting of halo claim 8 , chlorophenyl claim 8 , C-Calkyl claim 8 , C-Ccycloalkyl claim 8 , C-Caralkyl claim 8 , C-Calkoxy claim 8 , and C-Caryl.12. The method of claim 8 , wherein A is C-Cheteroaryl substituted by at least one selected from the group consisting of chloro claim 8 , methyl claim 8 , ethyl claim 8 , propyl claim 8 , iso-propyl claim 8 , tert-butyl claim 8 , cyclopentyl claim 8 , phenyl claim 8 , chlorophenyl claim 8 , benzyl claim 8 , cyclohexyl and methoxy.13. The method of claim 8 , wherein A is selected from thiazolyl claim 8 , methylthiazolyl claim 8 , ethylthiazolyl claim 8 , propylthiazolyl claim 8 , iso-propylthiazolyl claim 8 , tert-butylthiazolyl claim 8 , cyclopentylthiazolyl claim 8 , cyclohexylthiazolyl claim 8 , phenylthiazolyl claim 8 , chlorophenylthiazolyl claim 8 , benzylthiazolyl claim 8 , chlorothiazolyl and dimethylthiazolyl.14. The method of claim 13 , wherein B is NH.15. The method of claim 8 , wherein the compound is selected from the group consisting of:N-(1-azabicyclo[ ...

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Номер записи: 51
03-01-2019 дата публикации

TETRAHYDROISOQUINOLIN-1-ONE DERIVATIVE OR SALT THEREOF

Номер: US20190000832A1
Автор: Hisamichi Hiroyuki, Ishihara Tsukasa, Ishikawa Noriko, Maeno Kyoichi, Seki Norio, Shimada Itsuro, Shimizu Takafumi, Takuwa Tomofumi
Принадлежит: Selder Pharma Inc.

To provide a pharmaceutical, in particular a compound which can be used as a therapeutic agent for irritable bowel syndrome (IBS). It was found that a tetrahydroisoquinolin-1-one derivative having an amide group at the 4-position or a pharmaceutically acceptable salt thereof has an excellent bombesin 2 (BB2) receptor antagonistic action. It is also found that the tetrahydroisoquinolin-1-one derivative is highly effective on bowel movement disorders. From the above, the tetrahydroisoquinolin-1-one derivative of the present invention is useful as a therapeutic agent for diseases associated with a BB2 receptor, in particular IBS. 17-. (canceled)9. The pharmaceutical composition of claim 8 , wherein Ris —N(R)-lower alkylene-(aryl or heteroaryl claim 8 , which may each be substituted) claim 8 , or —N(R)—O-lower alkylene-(aryl or heteroaryl claim 8 , which may each be substituted).10. The pharmaceutical composition of claim 9 , wherein Ris phenyl which may be substituted with halogen claim 9 , lower alkyl claim 9 , or —OR.11. The pharmaceutical composition of claim 9 , wherein Ris —H.12. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition is a solid composition.13. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition is a liquid composition.14. The pharmaceutical composition of claim 13 , wherein the liquid composition is for parenteral administration.15. The pharmaceutical composition of claim 13 , wherein the liquid composition is for oral administration.17. The compound of claim 16 , wherein Ris —N(R)-lower alkylene-(aryl or heteroaryl claim 16 , which may each be substituted) claim 16 , or —N(R)—O-lower alkylene-(aryl or heteroaryl claim 16 , which may each be substituted).18. The compound of claim 17 , wherein Ris (lower alkylene)-OH or substituted cycloalkyl claim 17 , wherein said lower alkylene may be substituted with a member selected from the group consisting of —OH and phenyl (which may be substituted ...

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Номер записи: 52
07-01-2016 дата публикации

MUSCARINIC ACETYLCHOLINE RECEPTOR ANTAGONISTS

Номер: US20160002220A1
Автор: Laine Dramane Ibrahim, McCleland Brent W., Neipp Christopher E., Palovich Michael R., THOMAS Sonia M.
Принадлежит:

Methods of using Muscarinic Acetylcholine Receptor Antagonists are provided. 3. A compound according to selected from the group of:1-(2-{[(3-fluorophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;1-(2-{[(4-bromophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;1-(2-{[(4-chlorophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[bis(4-fluorophenyl)(hydroxy)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;4-{hydroxy[bis(3-methylphenyl)]methyl}-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;1-(2-{[(4-fluorophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylcarbonyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;1-{3-[(3-fluorophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-{hydroxy[bis(4-methylphenyl)]methyl}-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;4-[hydroxy(diphenyl)methyl]-1-{3-[(methylsulfonyl)amino]propyl}-1-azoniabicyclo[2.2.2]octane bromide;4-[bis(3-fluorophenyl)(hydroxy)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide;1-{3-[(3-chlorophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[hydroxy(di-2-thienyl)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[hydroxy(diphenyl)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;1-(2-{[(4-cyanophenyl)methyl]oxy}ethyl)-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;1-{3-[(4-bromophenyl)oxy]propyl}-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane bromide;4-[bis(4-fluorophenyl)(hydroxy)methyl]-1-[3-(phenyloxy)propyl]-1-azoniabicyclo[2.2.2]octane bromide;1-{3-[(4-fluorophenyl)oxy]propyl}-4-[ ...

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Номер записи: 53
02-01-2020 дата публикации

CLASS OF BIFUNCTIONAL COMPOUNDS WITH QUANTERNARY AMMONIUM SALT STRUCTURE

Номер: US20200002329A1
Автор: Chen Xiaoping, GAO Zejun, WANG Junyi, Wen Shouming
Принадлежит: Beijing Showby Pharmaceutical Co., Ltd.

The invention provides a class of compounds represented by formula (I), having bifunctional active quaternary ammonium salt structure of a β-adrenoreceptor agonist and an M receptor antagonist, a pharmaceutically acceptable salt, solvate, and optical isomer thereof. A pharmaceutical composition comprising such a compound with quaternary ammonium salt structure, a method for preparing such a compound with quaternary ammonium salt structure and an intermediate thereof, and uses thereof in treating pulmonary disorders are also provided. The compounds of the invention have high selectivity to the M receptor subtype, and have less adverse reaction and lower toxic and side effects in the treatment of pulmonary diseases such as COPD and asthma. 2. The compound according to claim 1 , or the pharmaceutically acceptable salt claim 1 , solvate claim 1 , optical isomer thereof claim 1 , wherein L is an unsubstituted phenyl claim 1 , pyridyl claim 1 , furyl or thienyl.3. The compound according to claim 1 , or the pharmaceutically acceptable salt claim 1 , solvate claim 1 , optical isomer thereof claim 1 , wherein W is unsubstituted (3-7C)cycloalkyl.4. The compound according to claim 3 , or the pharmaceutically acceptable salt claim 3 , solvate claim 3 , optical isomer thereof claim 3 , wherein W is cyclobutyl claim 3 , cyclopentyl or cyclohexyl.5. The compound according to claim 1 , or the pharmaceutically acceptable salt claim 1 , solvate claim 1 , optical isomer thereof claim 1 , wherein Rand Rare each independently selected from (1-1° C.)alkylene claim 1 , -(1-4C)alkyleneoxy claim 1 , alkyleneamido; and Ais independently selected from (6-10° C.)arylene claim 1 , wherein the arylene may be unsubstituted or substituted with 1-2 substituents independently selected from halogen claim 1 , (1-6C)alkyl claim 1 , (1-6C)alkoxy claim 1 , carboxy claim 1 , nitro claim 1 , cyano claim 1 , amido claim 1 , and ester group.6. The compound according to claim 1 , or the pharmaceutically ...

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Номер записи: 54
04-01-2018 дата публикации

PARTIALLY SATURATED TRICYCLIC COMPOUNDS AND METHODS OF MAKING AND USING SAME

Номер: US20180002307A1
Автор: Cramp Susan M., Dyke Hazel J., Pallin Thomas D., Zahler Robert
Принадлежит:

The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2. 144.-. (canceled)46. The tricyclic compound of claim 45 , wherein Ris selected from hydrogen or methyl.47. The tricyclic compound of claim 45 , wherein Ris selected from hydrogen or fluorine.48. The tricyclic compound of claim 45 , wherein Ris Calkenyl substituted by RRN—.49. The tricyclic compound of claim 45 , wherein Ris (Z)-3-(N claim 45 ,N-diethylamino)prop-1-enyl. This application is a continuation of U.S. patent application Ser. No. 15/014,524, filed Feb. 3, 2016; which is a continuation of U.S. patent application Ser. No. 14/116,023, filed Nov. 6, 2013; which is a national stage filing under U.S.C. §371 of PCT/US2012/036789, filed May 7, 2012; which claims priority to U.S. Provisional Patent Application 61/559,856, filed Nov. 15, 2011; and U.S. Provisional Patent Application 61/483,257, filed May 6, 2011; all of which are incorporated by reference in their entirety.Over 1.1 billion people worldwide are reported to be overweight. Obesity is estimated to affect over 90 million people in the United States alone. Twenty-five percent of the population in the United States over the age of twenty is considered clinically obese. While being overweight or obese presents problems (for example restriction of mobility, discomfort in tight spaces such as theater or airplane seats, social difficulties, etc.), these conditions, in particular clinical obesity, affect other aspects of health, i.e., diseases and other adverse health conditions associated with, exacerbated by, or precipitated by being overweight or obese. The estimated mortality from obesity-related conditions in the United States is over 300,000 annually (O'Brien et al. Amer J Surgery (2002) 184:4S-8S; and Hill et al. (1998) Science, ...

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Номер записи: 55
01-01-2015 дата публикации

PYRIDO[3,4-B] INDOLES AND METHODS OF USE

Номер: US20150005322A1
Автор: CHAKRAVARTY Sarvajit, JAIN Rajendra Parasmal
Принадлежит:

This disclosure relates to new heterocyclic compounds that may be used to modulate a histamine receptor in an individual. Pyrido[4,3-b]indoles are described, as are pharmaceutical compositions comprising the compounds and methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder. 17-. (canceled)9. (canceled) This application claims priority to U.S. Provisional Patent Application No. 61/245,140, filed Sep. 23, 2009, and U.S. Provisional Patent Application No. 61/245,259, filed Sep. 23, 2009, the disclosures of each of which are hereby incorporated herein by reference in their entireties.Not applicable.Neurotransmitters such as histamine, serotonin, dopamine and norepinephrine mediate a large number of processes in the central nervous system (CNS) as well as outside the CNS. Abnormal neurotransmitter levels are associated with a wide variety of diseases and conditions including, but not limited to, Alzheimer's disease, Parkinson's Disease, autism, Guillain-Barré syndrome, mild cognitive impairment, schizophrenia (such as cognitive impairment associated with schizophrenia (CIAS), positive symptoms, disorganized symptoms, and negative symptoms of schizophrenia), anxiety, multiple sclerosis, stroke, traumatic brain injury, spinal cord injury, diabetic neuropathy, fibromyalgia, bipolar disorders, psychosis, depression, attention-deficit disorder (ADD), attention-deficit hyperactivity disorder (ADHD), depression and a variety of allergic diseases. Compounds that modulate these neurotransmitters may be useful therapeutics.Histamine receptors belong to the superfamily of G protein-coupled seven transmembrane proteins. G protein-coupled receptors constitute one of the major signal transduction systems in eukaryotic cells. Coding sequences for these receptors, in those regions believed to contribute to the agonist-antagonist binding ...

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Номер записи: 56
12-01-2017 дата публикации

COT MODULATORS AND METHODS OF USE THEREOF

Номер: US20170008873A1
Автор: Bacon Elizabeth M., Balan Gayatri, Chou Chien-Hung, Clark Christopher T., Cottell Jeromy J., Kim Musong, Kirschberg Thorsten A., Link John O., Phillips Gary, Schroeder Scott D., Squires Neil H., Stevens Kirk L., Taylor James G., Watkins William J., Wright Nathan E., Zipfel Sheila M.
Принадлежит:

The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof. 2. The compound of claim 1 , wherein Ris hydrogen claim 1 , or a pharmaceutically acceptable salt thereof.3. The compound of claim 1 , wherein m is 0 claim 1 , or a pharmaceutically acceptable salt thereof.7. The compound according to claim 1 , wherein Ris hydrogen claim 1 , halo claim 1 , —CN claim 1 , —S(O)—R claim 1 , —S(O)R claim 1 , —SON(R)(R) claim 1 , —C(O)R claim 1 , —C(O)N(R)(R) claim 1 , Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , Ccycloalkyl claim 1 , aryl claim 1 , heterocyclyl claim 1 , or heteroaryl;{'sub': 1-9', '2-6', '2-6', '3-15, 'sup': '5', 'wherein each Calkyl, Calkenyl, Calkynyl, Ccycloalkyl, aryl, heterocyclyl, and heteroaryl may be optionally substituted with one to four Z, or a pharmaceutically acceptable salt thereof.'}8. The compound according to claim 1 , wherein Ris hydrogen claim 1 , halo claim 1 , —CN claim 1 , —C(O)R claim 1 , —S(O)R claim 1 , or heteroaryl claim 1 , or a pharmaceutically acceptable salt thereof.9. The compound according to claim 1 , wherein Ris hydrogen claim 1 , or a pharmaceutically acceptable salt thereof.10. The compound according to claim 1 , wherein Ris Calkyl claim 1 , Ccycloalkyl claim 1 , heterocyclyl claim 1 , aryl claim 1 , or heteroaryl; and said Calkyl claim 1 , Ccycloalkyl claim 1 , heterocyclyl claim 1 , aryl claim 1 , or heteroaryl may be optionally substituted with one to four substituents independently selected the group consisting of halo claim 1 , —CN claim 1 , —O—R claim 1 , —C(O)—R claim 1 , —C(O)O—R claim 1 , Calkyl claim 1 , and aryl claim 1 , or a pharmaceutically acceptable salt thereof.11. The compound according to claim 1 , wherein Ris Calkyl claim 1 , optionally substituted with one to four substituents independently selected the group consisting of halo claim 1 , —CN claim 1 , —O—R claim 1 , —C(O)O—R claim 1 , Calkyl claim 1 , and aryl claim 1 , or a ...

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Номер записи: 57
14-01-2016 дата публикации

QUINUCLIDINES FOR MODULATING ALPHA 7 ACTIVITY

Номер: US20160009706A1
Автор: Bilcer Geoffrey M., NG Raymond
Принадлежит:

Provided are substituted quinuclidine compounds, pharmaceutical compositions comprising such compounds, and methods of modulating α7 nicotinic acetylcholine receptors and treating neurological disorders using such compounds. 2. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris C-Calkyl or C-Ccycloalkyl claim 1 , wherein the C-Calkyl or C-Ccycloalkyl is unsubstituted or substituted with 1 to 5 halo substituents.3. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris unsubstituted C-Calkyl.4. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris —CH.5. The compound of claim 1 , or a salt thereof claim 1 , wherein R is C-Calkoxy claim 1 , which is unsubstituted or substituted with 1 to 5 halo substituents.6. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris —OCH.7. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris bromo.8. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris hydrogen.9. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris C-Calkyl or C-Ccycloalkyl.10. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris —CH.11. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris halo.12. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris fluoro or chloro.13. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris cyano.14. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris —OR claim 1 , and Ris hydrogen or unsubstituted C-Calkyl.15. The compound of claim 14 , or a salt thereof claim 14 , wherein Ris —CH.16. The compound of claim 1 , or a salt thereof claim 1 , wherein R is —OR claim 1 , and Ris C-Calkyl substituted with C-Calkoxy.17. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris hydrogen.18. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris C-Calkyl or C-Ccycloalkyl.19. The compound of claim 1 , or a salt thereof claim 1 , wherein Ris —CH.20. The compound of claim 1 , or ...

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Номер записи: 58
14-01-2016 дата публикации

CRYSTALLINE FORM OF (R)-7-CHLORO-N-(QUINUCLIDIN-3-YL)BENZO[B]THIOPHENE-2-CARBOXAMIDE HYDROCHLORIDE MONOHYDRATE

Номер: US20160009707A1
Автор: Chesworth Richard, Ishige Takayuki, Kishida Muneki, Oliver-Shaffer Patricia, Shapiro Gideon
Принадлежит:

Crystalline Forms I and II of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate and compositions, methods of manufacture and therapeutic uses thereof are described. 1. A crystalline Form II of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate , characterized by an x-ray powder diffraction pattern having peaks expressed as 2Θ at:i) one or both of 21.16 and 21.38±0.20 degrees when measured against an internal silicon standard; andii) at least four peaks selected from a group of peaks consisting of: 4.48, 9.00, 13.58, 15.62, 16.48, 19.02, 19.44, 22.46, and 25.00±0.20 degrees when measured against an internal silicon standard.2. The crystalline Form II of claim 1 , characterized by an x-ray powder diffraction pattern claim 1 , wherein at least six peaks are selected from the group of peaks.3. The crystalline Form II of claim 1 , characterized by an x-ray powder diffraction pattern claim 1 , wherein at least eight peaks are selected from the group of peaks.4. The crystalline Form II of claim 1 , characterized by an x-ray powder diffraction pattern claim 1 , wherein all of the peaks are selected from the group of peaks.5. A pharmaceutical composition comprising the crystalline Form II of .6. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Alzheimer's disease.7. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Schizophrenia.8. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Alzheimer's disease.9. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Schizophrenia.10. A pharmaceutical composition ...

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Номер записи: 59
09-01-2020 дата публикации

NOVEL IMAGING COMPOSITION AND USES THEREOF

Номер: US20200009090A1
Автор: DONNELLY Paul Stephen, Rudd Stacey Erin, Williams Spencer John
Принадлежит:

The invention discussed in this application relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. 2. The conjugate of claim 1 , wherein L is OR.3. The conjugate of claim 2 , wherein R is Cto Calkyl.4. The conjugate of claim 2 , wherein OR is selected from O-p-toluenesulfonate claim 2 , O-methanesulfonate claim 2 , O-trifluoromethanesulfonate claim 2 , O-benzenesulfonate claim 2 , and O-m-nitrobenzenesulfonate.5. The conjugate of claim 1 , wherein the target molecule is a polypeptide.6. The conjugate of claim 5 , wherein the polypeptide is an antibody.7. The conjugate of claim 6 , wherein the antibody is selected from trastuzumab claim 6 , rituximab and cetuximab.8. The conjugate of claim 1 , wherein the target molecule is a peptide.9. The conjugate of claim 8 , wherein the peptide is a targeting peptide.10. The conjugate of claim 9 , wherein the targeting peptide is selected from a cyclic RGD sequence claim 9 , bombesin and glu-N(CO)N-lys PSMA. This application is a Continuation of U.S. patent application Ser. No. 15/963,599, filed Apr. 26, 2018, which is a Continuation of U.S. patent application Ser. No. 15/518,333, filed Apr. 11, 2017, now U.S. Pat. No. 9,980,930, issued on May 29, 2018 and is a National Stage Application, filed under 35 U.S.C. 371, of International Application No. PCT/AU2015/050640, filed on Oct. 16, 2015, which claims priority to, and the benefit of, AU Application No. 2014904138, filed Oct. 16, 2014. The contents of each of these applications are incorporated by reference in their entirety.The present invention relates to hydroxamic acid-based compounds that are useful as imaging agents when bound to an appropriate metal centre, particularly for the imaging of tumours. The present invention also relates to compositions including the compounds, and to methods of imaging patients using the compounds.Zirconium-89 (Zr) is a positron-emitting ...

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Номер записи: 60
11-01-2018 дата публикации

TETRAHYDROISOQUINOLINES AS SELECTIVE NADPH OXIDASE 2 INHIBITORS

Номер: US20180009762A1
Автор: Cifuentes-Pagano Maria E., Pagano Patrick J., Skoda Erin M., Wipf Peter
Принадлежит: University of Pittsburgh - of the Commonwealth System of Higher Education

Embodiments of bridged tetrahydroisoquinolines and methods for their use in selectively inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 are disclosed. The disclosed compounds have a structure according to general formula I or a pharmaceutically acceptable salt thereof: 2. The method of claim 1 , wherein Ris Calkyl claim 1 , substituted or unsubstituted aryl claim 1 , or substituted or unsubstituted heteroaryl.3. The method of claim 2 , wherein:{'sup': '1', 'Ris hydrogen, halogen, or substituted or unsubstituted aryl;'}{'sup': '4', 'Ris lower alkyl, or substituted or unsubstituted aryl; and'}{'sup': '5', 'Ris hydrogen or halogen.'}4. The method of claim 3 , wherein Ris halogen.5. The method of claim 3 , wherein Ris bromo.6. The method of claim 1 , wherein Ris —CHRand Ris Calkyl claim 1 , substituted or unsubstituted Caryl claim 1 , or substituted or unsubstituted C-Cheteroaryl.9. The method of claim 1 , wherein the condition is a cardiovascular disease claim 1 , a neurodegenerative disease claim 1 , or cancer.10. The method of claim 9 , wherein the cardiovascular disease is atherosclerosis claim 9 , hypertension claim 9 , ischemia reperfusion claim 9 , cardiac hypertrophy claim 9 , cardiomyopathy claim 9 , stroke claim 9 , restenosis claim 9 , or any combination thereof.11. The method of claim 9 , wherein the cardiovascular disease is atherosclerosis.12. The method of claim 9 , wherein the neurodegenerative disease is Huntington's disease claim 9 , Alzheimer's disease claim 9 , Parkinson's disease claim 9 , or any combination thereof.13. The method of claim 1 , further comprising identifying the subject as having claim 1 , suspected of having claim 1 , or at risk of developing a condition mediated by Nox2 and/or reactive oxygen species produced by Nox2 activity by diagnosing the subject with a cardiovascular disease claim 1 , a neurodegenerative disease claim 1 , or cancer claim 1 , or determining that the subject has one or more risk factors ...

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Номер записи: 61
11-01-2018 дата публикации

SALTS OF AZA-BICYCLIC DI-ARYL ETHERS AND METHODS TO MAKE THEM OR THEIR PRECURSORS

Номер: US20180009801A1
Автор: Bianchi Jean-Claude, Buerger Eckart, Har Denis, Karpinski Piotr H., Marterer Wolfgang, Pignone Massimo, Prashad Mahavir, Stingelin Doris, Sutter Bertrand, Villhauer Edwin Bernard, Vivelo James Anthony, Waykole Liladhar Murlidhar, Wu Raeann
Принадлежит:

The present invention relates to salts of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane, to methods for making them or their precursors, to pharmaceutical compositions comprising them, and to their use as medicaments. 1. A salt of (R)-3-(6-(4-methylphenyI)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane wherein said salt is the fumarate , maleate , chloride , phosphate , succinate , or malonate salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane.2. The salt according to claim 1 , wherein the salt is the mono-fumarate salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in crystalline form.3. The salt according to claim 2 , wherein the salt is characterized by an XRPD pattern substantially the same as the XRPD pattern shown in .4. The salt according to claim 1 , wherein the salt is the mono-fumarate salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in crystalline form claim 1 , wherein the mean particle size of the crystals is at least 15 μm.5. The salt according to claim 2 , wherein the salt is the mono-fumarate salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in crystalline form claim 2 , and wherein the salt is in substantially pure form.6. The salt according to claim 2 , wherein the salt is the mono-fumarate salt of (R)-3-(6-(4-methylphenyl)-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in crystalline form claim 2 , and wherein the salt has a purity greater than 90 weight %.7. A method for the prevention claim 1 , treatment claim 1 , and/or delay of progression of a disease or condition claim 1 , in which nAChR α7 activation plays a role or is implicated claim 1 , in a subject in need of such treatment claim 1 , which comprises administering to such subject a therapeutically effective amount of a salt as defined in .8. A method for the prevention claim 1 , treatment claim 1 , and/or delay of progression of psychiatric or neurodegenerative ...

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Номер записи: 62
08-01-2015 дата публикации

PYRIDAZINONE DERIVATIVES

Номер: US20150011534A1
Автор: BLAUKAT Andree, Dorsch Dieter, SCHADT Oliver, STIEBER Frank
Принадлежит: Merck Patent GmBH

Compounds of the formula (I), in which R, R, R, R, Rhave the meanings indicated in Claim , are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours. 127-. (canceled)29. A pharmaceutical composition according to claim 28 , which comprises a compound of formula I or a pharmaceutically acceptable solvate claim 28 , salt claim 28 , tautomer or stereoisomer thereof in an amount of 1 mg to 700 mg per unit dosage.30. A pharmaceutical composition according to claim 28 , which is in the form of a single dosage unit.31. A pharmaceutical composition according to claim 28 , which comprises a compound of formula I or a pharmaceutically acceptable salt thereof.32. A pharmaceutical composition according to claim 28 , wherein in the compound of formula I{'sup': 2', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '+', '−', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3, 'sub': 2', 'n', '2', '2', 'n', '2', '2', 'n', '2', 'p', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', 'n', '2', 'n', '2', 'n-', '2', '2', 'n', '2', 'n', '2', 'n', '2', '2', 'n', '2', 'n', '2', 'n, 'claim-text': {'sup': '3', 'sub': '2', 'CH═CH—N(R)and/or ═O.'}, 'Rdenotes pyrimidinyl, which is monosubstituted by Hal, A, [C(R)]OR, N═CRN(R), CN, COOR, [C(R)]N(R), [C(R)]Het, O[C(R)]OR, O[C(R)]N(R), O[C(R)]C≡C[C(R)]N(R), O[C(R)]NO(R), O[C(R)]Het, NR[C(R)]N(R), NR[C(R)]Het, [C(R)]NHCO[C(R)]N(R), [C(R)]NHCO[C(R)]Het, CONR[C(R)]N(R), CONR[C(R)]NRCOOA, CONR[C(R)]OR, CONR[C(R)]Het, COHet, CH═CH—COOR,'}33. A pharmaceutical composition according to claim 28 , wherein in the compound of formula I{'sub': m', '2', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', 'n, 'sup': 3', '3', '3', '3', '3', '3', '3', '3', '3', '3', '3, 'Ar denotes phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di- or trisubstituted by ...

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Номер записи: 63
14-01-2021 дата публикации

NOVEL BENZYLAMINO SUBSTITUTED PYRIDOPYRIMIDINONES AND DERIVATIVES AS SOS1 INHIBITORS

Номер: US20210009588A1
Автор: BAUM Anke, Frank Markus, GILLE Annika, GMACHL Michael, GOEPPER Stefan, HOFMANN Marco Hans, Kofink Christiane, OSTERMEIER Markus, RAMHARTER Juergen, RUDOLPH Dorothea Ingrid, SANTAGOSTINO Marco, SAVARESE Fabio, Stadtmueller Heinz, WIPPICH Julian, WUNBERG Tobias
Принадлежит:

The present invention encompasses compounds of formula (1) 2. A compound or salt according to claim 1 , wherein{'sup': 1', 'a1, 'Ris R;'}{'sup': a1', 'b1', 'c1, 'sub': 1-6', '1-6', '3-10', '4-10', '6-10', '1-6', '1-6', '3-10', '4-10', '6-10, 'Ris selected from the group consisting of Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl, Caryl and 5-10 membered heteroaryl, wherein the Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl, Caryl and 5-10 membered heteroaryl are all optionally substituted by one or more, identical or different Rand/or R;'}{'sup': b1', 'c1', 'c1', 'c1', 'c1', 'c1', 'c1', 'c1, 'each Ris independently selected from the group consisting of —OR, —NRR, halogen, —CN, —C(O)R, —C(O)ORand —C(O)NRR;'}{'sup': c1', 'd1', 'e1, 'sub': 1-6', '1-6', '3-10', '4-10', '6-10', '1-6', '1-6', '3-10', '4-10', '6-10, 'each Ris independently selected from the group consisting of hydrogen, Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl, Caryl and 5-10 membered heteroaryl, wherein the Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl, Caryl and 5-10 membered heteroaryl are all optionally substituted by one or more, identical or different Rand/or R;'}{'sup': d1', 'e1', 'e', 'e1', 'e1', 'e1', 'e1', 'e1, 'each Ris independently selected from the group consisting of —OR, —NRR, halogen, —CN, —C(O)R, —C(O)ORand —C(O)NRR;'}{'sup': 'e1', 'sub': 1-6', '1-6', '3-10', '4-10', '6-10, 'each Ris independently selected from the group consisting of hydrogen, Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl, Caryl and 5-10 membered heteroaryl.'}3. A compound or salt according to claim 2 , wherein{'sup': 1', 'a1, 'Ris R;'}{'sup': a1', 'b1', 'c1, 'sub': 1-6', '1-6', '3-10', '4-10', '1-6', '1-6', '3-10', '4-10, 'Ris selected from the group consisting of Calkyl, Chaloalkyl, Ccycloalkyl, Ccycloalkenyl, 3-10 membered heterocyclyl and 5-10 membered heteroaryl, ...

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Номер записи: 64
10-01-2019 дата публикации

AMIDES OF ACETIC AND PROPIONIC ACIDS

Номер: US20190010150A1
Автор: Böss Frank-Gerhard, Erb Christina, Flessner Timo, Luithle Joachim, Methfessel Christoph, Schnizler Katrin, Van Kampen Marja
Принадлежит: Bayer Intellectual Property GmbH

The invention relates to novel amides of acetic and propionic acids, methods for production and use thereof for the production of medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning ability and memory. 110-. (canceled)11: A method of improving perception , concentration , learning or memory , after a cognitive impairment in a patient in need thereof , comprising administering to the patient a compound selected from the group consisting of:2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(7-bromo-1-benzothien-2-yl)acetamide hydrochloride;2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(6-bromo-1-benzothien-2-yl)acetamide hydrochloride;2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(7-quinolinyl)acetamide hydrochloride;2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(2-naphthyl)acetamide hydrochloride; and2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(8-nitro-2-naphthyl)acetamide hydrochloride.12: The method of claim 11 , wherein the cognitive impairment is mild cognitive impairment or Alzheimer's disease.13: The method of claim 11 , wherein the cognitive impairment is schizophrenia or schizophrenia with dementia.14: The method of claim 11 , wherein the compound is 2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(7-bromo-1-benzothien-2-yl)acetamide hydrochloride.15: The method of claim 11 , wherein the compound is 2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(6-bromo-1-benzothien-2-yl)acetamide hydrochloride.16: The method of claim 11 , wherein the compound is 2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(7-quinolinyl)acetamide hydrochloride.17: The method of claim 11 , wherein the compound is 2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(2-naphthyl)acetamide hydrochloride.18: The method of claim 11 , wherein the compound is 2-(1-azabicyclo[2.2.2]oct-3-yl)-N-(8-nitro-2-naphthyl)acetamide hydrochloride.20: The method of claim 19 , wherein the cognitive impairment is mild cognitive impairment or Alzheimer's disease.21: The method of claim 19 , wherein the cognitive impairment is schizophrenia or schizophrenia with ...

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Номер записи: 65
17-01-2019 дата публикации

Anti-Viral Compounds

Номер: US20190015402A1
Автор: Bellizzi Mary E., Betebenner David A., Califano Jean-Christophe C., Carroll William A., Caspi Daniel D., DeGoey David A., Donner Pamela L., FLENTGE Charles A., Gao Yi, Hutchins Charles W., Hutchinson Douglas K., JINKERSON Tammie K., Kati Warren M., KEDDY Ryan G., Krueger Allan C., LI Wenke, Liu Dachun, Maring Clarence J., MATULENKO Mark A., MOTTER Christopher E., NELSON Lissa T., Patel Sachin V., Pratt John K., Randolph John T., Rockway Todd W., Sarris Kathy, Tufano Michael D., Wagaw Seble H., Wagner Rolf, Woller Kevin R.
Принадлежит: AbbVie Inc.

Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection. 14-. (canceled)5. A process of making methyl {(2S ,3R)-1-[(2S)-2-{5-[(2R ,5R)-1-{3 ,5-difluoro-4-[4-(4-fluorophenyl)piperidin-1-yl]phenyl}-5-(6-fluoro-2-{(2S)-1-[N-(methoxycarbonyl)-O-methyl-L-threonyl]pyrrolidin-2-yl}-1H-benzimidazol-5-yl)pyrrolidin-2-yl]-6-fluoro-1H-benzimidazol-2-yl}pyrrolidin-1-yl]-3-methoxy-1-oxobutan-2-yl}carbamate , or a pharmaceutically acceptable salt thereof , the process comprising:reacting (S)-6,6′-((2R,5R)-1-(3,5-difluoro-4-(4-(4-fluorophenyl)piperidin-1-yl)phenyl)pyrrolidine-2,5-diyl)bis(5-fluoro-2((S)-pyrrolidin-2-yl)-1H-benzo[d]imidazole) with (2 S, 3R)-3-methoxy-2-(methoxycarbonylamino)butanoic acid.6. The process of claim 5 , wherein the reacting step is performed in the presence of a peptide coupling reagent.7. The process of claim 6 , wherein the peptide coupling reagent is selected from the group consisting of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride/1-hydroxybenzotriazole (EDAC/HOBT) claim 6 , (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP) claim 6 , O-(7-azabenzotriazol-1-yl)-N claim 6 ,N claim 6 ,N′ claim 6 ,N′-tetramethyluronium hexafluorophosphate (HATU) claim 6 , propane phosphonic acid anhydride (T3P) claim 6 , and 3-(diethoxyphosphoryloxy)-1 claim 6 ,2 claim 6 ,3-benzotriazin-4(3H)-one (DEPBT).8. (S)-6 claim 6 ,6′-((2R claim 6 ,5R)-1-(3 claim 6 ,5-difluoro-4-(4-(4-fluorophenyl)piperidin-1-yl)phenyl)pyrrolidine-2 claim 6 ,5-diyl)bis(5-fluoro-2((S)-pyrrolidin-2-yl)-1H-benzo[d]imidazole).9. A process of making methyl {(2S claim 6 ,3R)-1-[(2S)-2-{5-[(2R claim 6 ,5R)-1-{3 claim 6 ,5-difluoro-4-[4-(4-fluorophenyl)piperidin-1-yl]phenyl}-5-(6-fluoro-2-{(2S)-1-[N-(methoxycarbonyl)-O-methyl-L-threonyl]pyrrolidin-2-yl}-1H- ...

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Номер записи: 66
18-01-2018 дата публикации

Methods of Treating an Overweight or Obese Subject

Номер: US20180016249A1
Автор: Vath James E.
Принадлежит:

The disclosure herein generally relates to methods of treating an overweight or obese condition, and overweight- or obesity-related conditions. In one embodiment, the disclosure provides a method of treating an overweight or obese condition involving administering to the subject in need thereof, an amount of a pharmaceutical composition including a MetAP-2 inhibitory compound, or a salt, ester, or prodrug thereof, effective to result in weight loss in the subject. 3. The method of claim 1 , wherein the subject has a Body Mass Index measurement selected from the group consisting of: at least about 25 kg/m claim 1 , at least about 30 kg/m claim 1 , and at least about 40 kg/m.412.-. (canceled)14. (canceled) This application is a continuation of U.S. Ser. No. 14/802,473, filed Jul. 17, 2015, which is a continuation of U.S. Ser. No. 14/616,002, filed Feb. 6, 2015, which is a continuation of U.S. Ser. No. 13/133,062, filed Sep. 22, 2011, (now abandoned) which is a national phase filing under 35 U.S.C. §371 of PCT/US2009/066809, filed Dec. 4, 2009, which claims priority to U.S. provisional applications U.S. Ser. No. 61/119,875 filed Dec. 4, 2008, U.S. Ser. No. 61/119,881 filed Dec. 4, 2008, U.S. Ser. No. 61/119,884 filed Dec. 4, 2008, U.S. Ser. No. 61/119,886 filed Dec. 4, 2008, U.S. Ser. No. 61/275,688 filed Aug. 3, 2009, and U.S. Ser. No. 61/260,194 filed Nov. 11, 2009, each application of which is hereby incorporated by reference in its entirety.Obesity is a complex medical disorder of appetite regulation and metabolism resulting in excessive accumulation of adipose tissue mass. Typically defined as a body mass index (BMI) of 30 kg/mor more, obesity is a world-wide public health concern that is associated with cardiovascular disease, diabetes, certain cancers, respiratory complications, osteoarthritis, gallbladder disease, decreased life expectancy, and work disability. The primary goals of obesity therapy are to reduce excess body weight, improve or prevent obesity- ...

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Номер записи: 67
18-01-2018 дата публикации

Glutarimide Derivatives, Use Thereof, Pharmaceutical Composition Based Thereon and Methods for Producing Glutarimide Derivatives

Номер: US20180016253A1
Автор: Kromova Tatyana Alexandrovna, Nebolsin Vladimir Evgenievich
Принадлежит:

Biologically active glutarimide derivatives of the following formula: 1. A compound having the following formula:or a pharmaceutically acceptable salt thereof. This application is a continuation of U.S. application Ser. No. 14/783,911 filed Oct. 12, 2015, now allowed, which is a U.S. National Stage application under 35 U.S.C. §371 of International Application PCT/RU2014/000264 (published as WO 2014/168522 A1), filed Apr. 10, 2014, which claims priority to Application RU 2013116826, filed Apr. 12, 2013. Benefit of the filing date of each of these prior applications is hereby claimed. Each of these prior applications is hereby incorporated by reference in its entirety.The invention relates to novel biologically active compounds, in particular to glutarimide derivatives or pharmaceutically acceptable salt thereof, to use thereof as agents for the prevention and treatment of upper respiratory tract diseases, and to methods for preparing said compounds.Upper respiratory tract chronic diseases are the most common diseases in children and adults throughout the world. The upper respiratory tract chronic diseases include, in particular, rhinosinusitis.Rhinosinusitis is an inflammation of the mucous tunic of the nose and paranasal sinuses (PNS) and is the most actual problem in the otorhinoryngology (Fokkens W. J., Lund V. J., Mullol J. et al., European Position Paper on Rhinosinusitis and Nasal Polyps. Rhinology 2007; 45; 20:1-139). A cause of rhinosinusitis almost always is mucous congestion, blockage of natural ostia of the PNS, and a disturbance in their ventilation when the mechanism of mucociliary clearance suffers since said mechanism is an important primary innate mechanism protecting the respiratory tract from damaging action of inhaled pollutions, allergens and causal organisms.Acute rhinosinusitis is a frequent complication of an acute respiratory viral infection (ARVI).Today, the rhinosinusitis therapy starts with administration of corticosteroids since they have ...

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Номер записи: 68
18-01-2018 дата публикации

Glutarimide Derivatives, Use Thereof, Pharmaceutical Composition Based Thereon and Methods for Producing Glutarimide Derivatives

Номер: US20180016254A1
Автор: Kromova Tatyana Alexandrovna, Nebolsin Vladimir Evgenievich
Принадлежит:

A medicament or pharmaceutical composition for the treatment of a respiratory tract disease, which is a compound having the following formula: 2. The medicament of claim 1 , wherein the respiratory tract disease is rhinosinusitis.3. The medicament of claim 1 , wherein the respiratory tract disease is caused by an RNA-comprising virus.4. The medicament of claim 3 , wherein the virus is selected from the group consisting of rhinovirus claim 3 , Coxsackie virus claim 3 , respiratory syncytial virus claim 3 , and influenza virus.5. The medicament of claim 1 , wherein the disease is exacerbations of bronchitis and mucoviscidosis claim 1 , which are caused by rhinovirus claim 1 , influenza virus and/or respiratory syncytial virus.7. The pharmaceutical composition of claim 6 , wherein the respiratory tract disease is rhinosinusitis.8. The pharmaceutical composition of claim 6 , wherein the respiratory tract disease is caused by an RNA-comprising virus.9. The pharmaceutical composition of claim 8 , wherein the virus is selected from the group consisting of rhinovirus claim 8 , Coxsackie virus claim 8 , respiratory syncytial virus claim 8 , and influenza.10. The pharmaceutical composition of claim 6 , wherein the disease is exacerbations of bronchitis and mucoviscidosis claim 6 , which are caused by rhinovirus claim 6 , influenza virus and/or respiratory syncytial virus.12. The method of claim 11 , wherein the respiratory tract disease is rhinosinusitis.13. The method of claim 11 , wherein the respiratory tract disease is caused by an RNA-comprising virus.14. The method of claim 13 , wherein the virus is selected from the group consisting of rhinovirus claim 13 , Coxsackie virus claim 13 , respiratory syncytial virus claim 13 , and influenza virus. This application is a continuation of U.S. application Ser. No. 14/783,911 filed Oct. 12, 2015, now allowed, which is a U.S. National Stage application under 35 U.S.C. §371 of International Application PCT/RU2014/000264 (published ...

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Номер записи: 69
18-01-2018 дата публикации

Glutarimide Derivatives, Use Thereof, Pharmaceutical Composition Based Thereon and Methods for Producing Glutarimide Derivatives

Номер: US20180016255A1
Автор: Kromova Tatyana Alexandrovna, Nebolsin Vladimir Evgenievich
Принадлежит:

A medicament or pharmaceutical composition for the treatment of exacerbations of asthma and chronic obstructive pulmonary disease, which is a compound having the following formula: This application is a continuation of U.S. application Ser. No. 14/783,911 filed Oct. 12, 2015, now allowed, which is a U.S. National Stage application under 35 U.S.C. §371 of International Application PCT/RU2014/000264 (published as WO 2014/168522 A1), filed Apr. 10, 2014, which claims priority to Application RU 2013116826, filed Apr. 12, 2013. Benefit of the filing date of each of these prior applications is hereby claimed. Each of these prior applications is hereby incorporated by reference in its entirety.The invention relates to novel biologically active compounds, in particular to glutarimide derivatives or pharmaceutically acceptable salt thereof, to use thereof as agents for the prevention and treatment of upper respiratory tract diseases, and to methods for preparing said compounds.Upper respiratory tract chronic diseases are the most common diseases in children and adults throughout the world. The upper respiratory tract chronic diseases include, in particular, rhinosinusitis.Rhinosinusitis is an inflammation of the mucous tunic of the nose and paranasal sinuses (PNS) and is the most actual problem in the otorhinoryngology (Fokkens W. J., Lund V. J., Mullol J. et al., European Position Paper on Rhinosinusitis and Nasal Polyps. Rhinology 2007; 45; 20:1-139). A cause of rhinosinusitis almost always is mucous congestion, blockage of natural ostia of the PNS, and a disturbance in their ventilation when the mechanism of mucociliary clearance suffers since said mechanism is an important primary innate mechanism protecting the respiratory tract from damaging action of inhaled pollutions, allergens and causal organisms.Acute rhinosinusitis is a frequent complication of an acute respiratory viral infection (ARVI).Today, the rhinosinusitis therapy starts with administration of ...

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Номер записи: 70
18-01-2018 дата публикации

Glutarimide Derivatives, Use Thereof, Pharmaceutical Composition Based Thereon and Methods for Producing Glutarimide Derivatives

Номер: US20180016257A1
Автор: Kromova Tatyana Alexandrovna, Nebolsin Vladimir Evgenievich
Принадлежит:

A method for preparing a compound of formula I: 2. The method of claim 1 , wherein the dehydrating agent is glutaric anhydride claim 1 , and the method is performed under heating in an organic solvent.3. The method of wherein the organic solvent is dimethylformamide4. The method of claim 1 , wherein the dehydrating agent is propionic anhydride claim 1 , and the method is performed under heating in an organic solvent.5. The method of wherein the organic solvent is toluene6. The process of claim 4 , wherein the method is performed with addition of sodium acetate.7. The method of claim 1 , wherein the dehydrating agent is acetic anhydride claim 1 , and the method is performed under heating in an organic solvent.8. The method of wherein the organic solvent is dioxane.9. The process of claim 7 , wherein the method is performed with addition of sodium acetate.10. The method of claim 1 , wherein the dehydrating agent is acetic acid chloroanhydride claim 1 , and the method is performed under heating in an organic solvent.11. The method of wherein the organic solvent is acetic acid12. The method of claim 10 , wherein the dehydrating agent and the solvent are acetic acid anhydride claim 10 , and the method is performed at 90-100° C.13. The method of claim 1 , wherein the dehydrating agent is carbonyldiimidazole. This application is a divisional of U.S. application Ser. No. 14/783,911 filed Oct. 12, 2015, now allowed, which is a U.S. National Stage application under 35 U.S.C. §371 of International Application PCT/RU2014/000264 (published as WO 2014/168522 A1), filed Apr. 10, 2014, which claims priority to Application RU 2013116826, filed Apr. 12, 2013. Benefit of the filing date of each of these prior applications is hereby claimed. Each of these prior applications is hereby incorporated by reference in its entirety.The invention relates to novel biologically active compounds, in particular to glutarimide derivatives or pharmaceutically acceptable salt thereof, to use thereof ...

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Номер записи: 71
18-01-2018 дата публикации

Aminoester derivatives

Номер: US20180016265A1
Автор: Charles Baker-Glenn, Elisabetta Armani, Gabriele Amari, Herve Van De Poel, Naimisha Trivedi, Wesley Blackaby
Принадлежит: Chiesi Farmaceutici SpA

Compounds of formula (I) are both phosphodiesterase 4 (PDE4) enzyme inhibitors and muscarinic M3 receptor antagonists and are useful for the prevention and/or treatment of diseases of the respiratory tract characterized by airway obstruction.

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Номер записи: 72
28-01-2016 дата публикации

Amides of acetic and propionic acids

Номер: US20160022651A1
Автор: Christina Erb, Christoph Methfessel, Frank-Gerhard Bob, Joachim Luithle, Katrin Schnizler, Marja V. Kampen, Timo Flessner
Принадлежит: Bayer Intellectual Property GmbH

The invention relates to novel amides of acetic and propionic acids, methods for production and use thereof for the production of medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning ability and memory.

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Номер записи: 73
28-01-2016 дата публикации

INDOLE AND BENZOFURAN FUSED ISOQUINUCLIDENE DERIVATIVES AND PROCESSES FOR PREPARING THEM

Номер: US20160024075A1
Автор: Moriarty Robert M.
Принадлежит:

Provided herein are indole and benzofuran fused isoquinuclidene derivatives. Also provided herein are processes, preferably enantioselective processes, for preparing such derivatives including processes for preparing (−) and (+) noribogaine or a salt thereof, in substantially enantiomerically pure forms. 110-. (canceled)1716. An isolated enantiomer of a compound of any one of - in substantial enantiomeric excess.20. The compound of claim 11 , wherein Ris C-Calkyl optionally substituted with 1-3 substituents selected from the group consisting of keto claim 11 , halo claim 11 , amino claim 11 , hydroxy claim 11 , cyano claim 11 , nitro claim 11 , —N claim 11 , and —COH or an ester thereof.21. The compound of claim 11 , wherein Ris a non-hydrogen substituent claim 11 , and k is 2.22. The compound of claim 11 , wherein Ris a non-hydrogen substituent claim 11 , and k is 3.24. The compound of claim 18 , wherein Ris methyl claim 18 , ethyl claim 18 , propyl claim 18 , or butyl each optionally substituted with an OMe group claim 18 , OH group claim 18 , an amide claim 18 , or with an amino group.26. The compound of claim 18 , wherein Ris methyl claim 18 , ethyl claim 18 , propyl claim 18 , or butyl each optionally substituted with an OMe group claim 18 , OH group claim 18 , an amide claim 18 , or with an amino group. This application claims the benefit under 35 U.S.C. 119(e) of U.S. Provisional Application Ser. Nos. 61/590,740 filed 1-25-2012 and 61/591,258 filed 1-26-2012 and each of which is hereby incorporated by reference into this application in its entirety.Provided herein are indole and benzofuran fused isoquinuclidene derivatives, and processes, preferably enantioselective processes, for preparing such derivatives including processes for preparing (−) and (+) noribogaine, in substantially enantiomerically pure forms. In certain aspects, the processes provided herein employ the novel isoquinuclidene, R,R 7-oxo-2-azabicyclo[2.2.2]oct-5-ene, or a protected derivative ...

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Номер записи: 74
26-01-2017 дата публикации

NORIBOGAINE SALT TABLETS

Номер: US20170022193A1
Автор: Gless, JR. Richard D., Schinzer William C.
Принадлежит: DEMERX, INC.

Stable noribogaine salt ansolvates are useful for preparing pharmaceutical compositions and for alleviating nociceptive pain in a patient. Such ansolvates can be prepared by slurrying solvated forms, preferably MeOH solvated noribogaine hydrochloride in EtOH/water. 1. A stable pharmaceutically acceptable salt of noribogaine ansolvate.2. The stable salt of noribogaine ansolvate of claim 1 , wherein the salt is a hydrochloride salt.3. The salt of claim 2 , which is crystalline.4. The crystalline salt of claim 3 , characterized by at least one X-ray powder diffraction peak (Cu Kα radiation) selected from 11.6° claim 3 , 12.1° claim 3 , 13.5° claim 3 , 13.9° claim 3 , 14.9° claim 3 , 15.7° claim 3 , 17.1 claim 3 , 17.9° claim 3 , 18.3° claim 3 , 19.8° claim 3 , 20.8° claim 3 , 21.0° claim 3 , 21.9° claim 3 , 22.8° claim 3 , 23.3° claim 3 , 24.9° claim 3 , 25.9° claim 3 , 26.4 claim 3 , 29.3° claim 3 , and 29.8°2θ (each ±0.2 °2θ).5. The crystalline salt of claim 3 , which shows substantially no thermal transitions under 300° C. in its differential scanning calorimetry thermogram.6. The crystalline salt of claim 3 , which shows substantially no weight loss at a temperature under 300° C. in its thermogravimetric analysis thermogram.7. The crystalline ansolvate salt of claim 3 , which has a density that is at least 3% and up to 20% greater than the density of a solvated crystalline hydrochloride salt of noribogaine.8. The crystalline ansolvate salt of claim 3 , which has a unit cell volume of less than about 1800 cubic angstrom claim 3 , or less than about 1750 cubic angstrom claim 3 , or less than 1700±2% cubic angstrom.9. A crystalline noribogaine hydrochloride solvate polymorph characterized by about 4% weight loss at temperatures under 125° C. in its differential scanning calorimetry thermogram.10. The crystalline solvate polymorph of characterized by at least one X-ray powder diffraction peak (Cu Kα radiation) selected from 9.7 claim 9 , 10.2 claim 9 , 12.0 claim 9 , ...

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Номер записи: 75
26-01-2017 дата публикации

STABLE CRYSTALLINE NORIBOGAINE SALT ANSOLVATES

Номер: US20170022194A1
Автор: Gless, JR. Richard D., Schinzer William C.
Принадлежит: DEMERX, INC.

Stable noribogaine salt ansolvates are useful for preparing pharmaceutical compositions and for alleviating nociceptive pain in a patient. Such ansolvates can be prepared by slurrying solvated forms, preferably MeOH solvated noribogaine hydrochloride in EtOH/water. 1. A stable pharmaceutically acceptable salt of noribogaine ansolvate.2. The stable salt of noribogaine ansolvate of claim 1 , wherein the salt is a hydrochloride salt.3. The salt of claim 2 , which is crystalline.4. The crystalline salt of claim 3 , characterized by at least one X-ray powder diffraction peak (Cu Kα radiation) selected from 11.6° claim 3 , 12.1° claim 3 , 13.5° claim 3 , 13.9° claim 3 , 14.9° claim 3 , 15.7° claim 3 , 17.1 claim 3 , 17.9° claim 3 , 18.3° claim 3 , 19.8° claim 3 , 20.8° claim 3 , 21.0° claim 3 , 21.9° claim 3 , 22.8° claim 3 , 23.3° claim 3 , 24.9° claim 3 , 25.9° claim 3 , 26.4 claim 3 , 29.3° claim 3 , and 29.8° 2θ (each ±0.2° 2θ).5. The crystalline salt of claim 3 , which shows substantially no thermal transitions under 300° C. in its differential scanning calorimetry thermogram.6. The crystalline salt of claim 3 , which shows substantially no weight loss at a temperature under 300° C. in its thermogravimetric analysis thermogram.7. The crystalline ansolvate salt of claim 3 , which has a density that is at least 3% and up to 20% greater than the density of a solvated crystalline hydrochloride salt of noribogaine.8. The crystalline ansolvate salt of claim 3 , which has a unit cell volume of less than about 1800 cubic angstrom claim 3 , or less than about 1750 cubic angstrom claim 3 , or less than 1700±2% cubic angstrom.9. A crystalline noribogaine hydrochloride solvate polymorph characterized by about 4% weight loss at temperatures under 125° C. in its differential scanning calorimetry thermogram.10. The crystalline solvate polymorph of characterized by at least one X-ray powder diffraction peak (Cu Kα radiation) selected from 9.7 claim 9 , 10.2 claim 9 , 12.0 claim 9 , ...

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Номер записи: 76
17-04-2014 дата публикации

METHODS AND COMPOSITIONS FOR TREATING AMYLOID-RELATED DISEASES

Номер: US20140107027A1
Автор: Gervais Francine, KONG Xianqi, MIGNEAULT David, VALADE Isabelle, WU Xinfu
Принадлежит: BHI LIMITED PARTNERSHIP

Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease. 1232-. (canceled)234. The compound of claim 233 , wherein Ris hydrogen.235. The compound of claim 233 , wherein Ris straight chain alkyl.236. The compound of claim 233 , wherein Ris t-butyl.237. The compound of claim 233 , wherein Ris carbocyclic.238. The compound of claim 233 , wherein Ris C-Cbicycloalkyl.239. The compound of claim 233 , wherein said bicyclic fused ring group is indolyl.240. The compound of claim 233 , wherein Lis CHCHor absent.251. A method of treating or preventing an amyloid-related disease in a subject comprising administering to a subject in need thereof a compound of in an amount effective to treat or prevent an amyloid related disease.252. The method according to claim 251 , wherein said amyloid-related disease is Alzheimer's disease claim 251 , cerebral amyloid angiopathy claim 251 , inclusion body myositis claim 251 , macular degeneration claim 251 , MCI claim 251 , or Down's syndrome.253. The method according to claim 251 , wherein amyloid fibril formation or deposition claim 251 , neurodegeneration claim 251 , microglial inflammatory response claim 251 , or cellular toxicity is reduced or inhibited upon administration of said compound.254. The method according to claim 251 , wherein said amyloid-related disease is diabetes claim 251 , AA amyloidosis claim 251 , AL amyloidosis claim 251 , or hemodialysis related amyloidosis (βM).255. The method of claim 251 , wherein said subject has Alzheimer's disease claim 251 , Mild Cognitive Impairment claim 251 , or cerebral amyloid angiopathy claim 251 , and stabilization of cognitive function claim 251 , prevention of a further decrease in cognitive function claim 251 , or prevention claim 251 , slowing claim 251 , or stopping of disease progression occurs in said patient upon administration.256. A method for inhibiting amyloid deposition in a subject comprising administering ...

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Номер записи: 77
25-01-2018 дата публикации

Glutarimide Derivatives, Use Thereof, Pharmaceutical Composition Based Thereon and Methods for Producing Glutarimide Derivatives

Номер: US20180022728A1
Автор: Kromova Tatyana Alexandrovna, Nebolsin Vladimir Evgenievich
Принадлежит:

A compound having the following formula: 2. A medicament for the treatment of a respiratory tract disease claim 1 , which is a compound or a pharmaceutically acceptable salt thereof of .3. The medicament of claim 2 , wherein the respiratory tract disease is rhinosinusitis.4. The medicament of claim 2 , wherein the respiratory tract disease is caused by an RNA-comprising virus.5. The medicament of claim 4 , wherein the virus is selected from the group consisting of rhinovirus claim 4 , Coxsackie virus claim 4 , and influenza virus.6. The medicament of claim 2 , wherein the disease is exacerbations of asthma claim 2 , chronic obstructive pulmonary disease claim 2 , bronchitis and mucoviscidosis claim 2 , which are caused by rhinovirus claim 2 , influenza virus and/or respiratory syncytial virus.7. A pharmaceutical composition for the treatment of a respiratory tract disease claim 1 , comprising an effective amount of a compound or a pharmaceutically acceptable salt thereof of claim 1 , and a pharmaceutically acceptable carrier.8. The pharmaceutical composition of claim 7 , wherein the respiratory tract disease is rhinosinusitis.9. The pharmaceutical composition of claim 7 , wherein the respiratory tract disease is caused by an RNA-comprising virus.10. The pharmaceutical composition of claim 9 , wherein the virus is selected from the group consisting of rhinovirus claim 9 , Coxsackie virus claim 9 , and influenza.11. The pharmaceutical composition of claim 7 , wherein the disease is exacerbations of asthma claim 7 , chronic obstructive pulmonary disease claim 7 , bronchitis and mucoviscidosis claim 7 , which are caused by rhinovirus claim 7 , influenza virus and/or respiratory syncytial virus.12. A method of treating a respiratory tract disease claim 1 , comprising administering to a patient an effective amount of a compound or a pharmaceutically acceptable salt thereof of .13. The method of claim 12 , wherein the respiratory tract disease is rhinosinusitis.14. The ...

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Номер записи: 78
10-02-2022 дата публикации

QUATERNARY AMMONIUM SALTS AS INHIBITORS OF TRIMETHYLAMINE PRODUCTION

Номер: US20220041641A1
Автор: AJAYI Kehinde, BILLINGS Gabriel, BOGART Elijah, Briggs Timothy, DOUD Devin Forest Reed, GUNASEKERA Dinara Shashanka, LAFRANCE Danny, LIU Jenny, MARTINEZ-DEL CAMPO Ana, NUDEL Kathleen, PECK Spencer Cory, PROUDFOOT John, ROSS Cheri, Taylor Steven, TEFFERA Yohannes, YASUDA Koji
Принадлежит:

Provided are compounds that can inhibit pathogenic, bacterial metabolite production and conjugates of the same. Also provided are pharmaceutical compositions comprising the same and methods of using the same. 5. The compound of claim 4 , wherein Ris Calkyl substituted with —O-(acylated sugar) and is optionally further substituted with oxo.6. The compound of or claim 4 , wherein Ris methyl.7. The compound of any one of claim 4 , claim 4 , and claim 4 , wherein Ris Calkyl.8. The compound of any one of - claim 4 , wherein Ris propargyl.9. The compound of claim 4 , wherein{'sup': '1', 'sub': '2-6', 'Ris Calkyl substituted with —O-(acylated sugar) and is optionally further substituted with oxo;'}{'sup': '2', 'Ris methyl;'}{'sup': '3', 'sub': '1-6', 'Ris Calkyl; and'}{'sup': '4', 'Ris propargyl.'}10. The compound of claim 4 , wherein{'sup': '1', 'sub': '2-6', 'Ris Calkyl substituted with isosorbide and is optionally further substituted with oxo and/or methene;'}{'sup': '2', 'Ris methyl;'}{'sup': '3', 'sub': '1-6', 'Ris Calkyl; and'}{'sup': '4', 'Ris propargyl.'}13. The compound of claim 4 , wherein{'sup': '1', 'sub': 3-4', '1-2, 'Ris Ccycloalkyl Calkyl;'}{'sup': '2', 'sub': '2-6', 'Ris Calkyl optionally substituted with one or two hydroxyl, oxo, and —O-(acylated sugar);'}{'sup': 1', '2', 's', 's, 'sub': 2', 'n, 'or Rand R, together with the nitrogen atom to which both are attached, combine to form a 4- or 5-membered heterocyclic ring optionally substituted with ethynyl or —(CH)—ORor an acylated sugar, wherein n is 0 or 1, Ris hydrogen or an acylated sugar;'}{'sup': '3', 'sub': '1-6', 'Ris Calkyl optionally substituted with a halogen or hydroxyl; and'}{'sup': '4', 'sub': '1-6', 'Ris Calkyl or propargyl.'}14. The compound of claim 13 , wherein Ris Ccycloalkyl Calkyl.15. The compound of or claim 13 , wherein Ris Calkyl optionally substituted with one or two hydroxyl groups.16. The compound of claim 13 , wherein Rand R claim 13 , together with the nitrogen atom to which both ...

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Номер записи: 79
28-01-2021 дата публикации

PROCESS FOR THE PREPARATION OF ISOXAZOLINE COMPOUNDS

Номер: US20210022344A1
Автор: Yang ChunHua
Принадлежит: Boehringer Ingelheim Animal Health USA Inc.

This invention relates to processes for the preparation of antiparasitic isoxazoline compounds enriched in an enantiomer using quinine-based chiral phase transfer catalyst. The invention also relates to novel quinine-based phase transfer catalysts and to a toluene solvent form of the isoxazoline compound of the invention. 2. The process of claim 1 , wherein the compound of formula (I) enriched in one enantiomer is isolated by crystallizing the compound from an aromatic solvent or a mixture of solvents comprising an aromatic solvent.3. The process of claim 2 , wherein the aromatic solvent is selected from the group consisting of toluene claim 2 , ethylbenzene claim 2 , xylenes claim 2 , chlorobenzene claim 2 , o-dichlorobenzene claim 2 , fluorobenzene claim 2 , anisole and mesitylene claim 2 , or a combination thereof.4. The process of claim 3 , wherein the aromatic solvent is toluene.5. The process of claim 1 , wherein prior to isolating the compound of formula (I) enriched in an enantiomer claim 1 , the process further comprises crystallizing racemic compound of formula (I) and removing the solid.7. The process according to claim 1 , wherein Q is —C(O)NHCHC(O)NHCHCF claim 1 , —C(O)CHS(O)CH claim 1 , —C(O)NHCHCHSCHor (—CH—)(—CH—)N(CO)CHS(O)CH.8. The process according to claim 1 , wherein X in the chiral phase transfer catalyst of formula (IIIa) or (IIIb) is a halogen counter ion.9. The process according to claim 7 , wherein X is a chloride counter ion.10. The process according to claim 1 , wherein R in the chiral phase transfer catalyst of formula (IIIa) or (IIIb) is a phenyl group that is substituted by 1 claim 1 , 2 claim 1 , 3 claim 1 , 4 or 5 aralkoxy groups.11. The process according to claim 10 , wherein the aralkoxy group is a benzyloxy group.12. The process according to claim 10 , wherein R is substituted with 3 aralkoxy groups.13. The process according to claim 12 , wherein R is 3 claim 12 ,4 claim 12 ,5-tris(benzyloxy)phenyl.1471-. (canceled)72. The process ...

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Номер записи: 80
29-01-2015 дата публикации

Substituted Pyrazolo [1,5-A] Pyrimidine Compounds as TRK Kinase Inhibitors

Номер: US20150031667A1
Автор: Allen Shelley, Andrews Steven Wade, Condroski Kevin Ronald, Haas Julia, Huang Lily, Jiang Yutong, Krecher Timothy, Seo Jeongbeob
Принадлежит:

Compounds of Formula I: 2. The method of claim 1 , wherein:{'sup': '1', 'Ris H or -(1-6C alkyl);'}{'sup': 2', '1', '1', '2', '2', '1, 'sub': 2', '2', '2', '2', '2, 'Ris H, -(1-6C)alkyl, -(1-6C)fluoroalkyl, -(1-6C)hydroxyalkyl, -(2-6C)dihydroxyalkyl, -(1-6C alkyl)CN, -(1-6C alkyl)SONH, -(1-6C alkyl)NHSO(1-3C alkyl), -(1-6C alkyl)NH, -(1-6C alkyl)NH(1-4C alkyl), -(1-6C alkyl)N(1-4C alkyl), -(1-6C alkyl)hetCyc, -(1-6C alkyl)hetAr, hetAr, hetCyc, —O(1-6C alkyl), —O(3-6C cycloalkyl), Cyc, or a bridged 7-membered cycloalkyl ring,'}{'sup': 1', '2, 'sub': 2', '2, 'or NRRforms a 4-6 membered azacyclic ring optionally substituted with one or more substituents independently selected from -(1-6C)alkyl, —OH, —COH and -(1-3C alkyl)COH;'}{'sup': 1', '1, 'hetCycis a 5-6 membered heterocyclic ring having 1-2 ring heteroatoms independently selected from N and O, wherein hetCycis optionally substituted with oxo;'}{'sup': 2', '2, 'sub': 2', '2', '2, 'hetCycis a 6 membered carbon-linked heterocyclic ring having 1-2 ring heteroatoms independently selected from N and O, wherein hetCycis optionally substituted with F, SONH, or SO(1-3C alkyl);'}{'sup': '1', 'hetAris a 5-membered heteroaryl ring having 1-2 ring heteroatoms independently selected from N and O and optionally substituted with -(1-4C)alkyl;'}{'sup': '2', 'hetAris a 5-6 membered heteroaryl ring having 1-2 ring nitrogen atoms and optionally substituted with one or more substituents independently selected from -(1-4C)alkyl;'}{'sup': '1', 'sub': '2', 'Cycis 3-6 membered cycloalkyl ring which is optionally substituted with one or more substituents independently selected from -(1-4C alkyl), —OH, —OMe, —COH and -(1-4C alkyl)OH;'}{'sub': 3', '2, 'sup': '3', 'Y is (i) phenyl optionally substituted with one or more substituents independently selected from halogen, -(1-4C)alkoxy, —CF—CHF, —O(1-4C alkyl)hetCycand —O(1-4C alkyl)O(1-3C alkyl), or (ii) a 5-6 membered heteroaryl ring having a ring heteroatom selected from N and S, wherein said ...

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Номер записи: 81
29-01-2015 дата публикации

DIAZABICYCLO[3.3.1]NONANES, METHODS OF SYNTHESIS, AND USES THEREOF

Номер: US20150031675A1
Автор: Strachan Jon-Paul, Yohannes Daniel
Принадлежит:

The present invention relates to compounds that bind to and modulate the activity of neuronal nicotinic acetylcholine receptors, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central nervous system (CNS). 2. (canceled)3. A method for treatment of central nervous system disorders and dysfunctions claim 1 , comprising administering to a mammal in need of such treatment claim 1 , a therapeutically effective amount of the compound according to .4. The method of claim 3 , wherein the disorder is selected from the group consisting of age-associated memory impairment claim 3 , mild cognitive impairment claim 3 , pre-senile dementia claim 3 , early onset Alzheimer's disease claim 3 , senile dementia claim 3 , dementia of the Alzheimer's type claim 3 , Lewy body dementia claim 3 , vascular dementia claim 3 , Alzheimer's disease claim 3 , stroke claim 3 , AIDS dementia complex claim 3 , attention deficit disorder claim 3 , attention deficit hyperactivity disorder claim 3 , dyslexia claim 3 , schizophrenia claim 3 , schizophreniform disorder claim 3 , schizoaffective disorder claim 3 , cognitive deficits in schizophrenia claim 3 , and cognitive dysfunction in schizophrenia.5. The method of claim 4 , wherein the disorder is selected from the group consisting of mild to moderate dementia of the Alzheimer's type claim 4 , attention deficit disorder claim 4 , attention deficit hyperactivity disorder claim 4 , mild cognitive impairment claim 4 , age-associated memory impairment claim 4 , cognitive deficits in schizophrenia claim 4 , and cognitive dysfunction in schizophrenia.6. A pharmaceutical composition comprising a compound according to claim 1 , and one or more pharmaceutically acceptable carrier.7. (canceled)8. A method of treating inflammation claim 1 , the inflammatory ...

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Номер записи: 82
02-02-2017 дата публикации

NOVEL SUBSTITUTED IMIDAZOQUINOLINES

Номер: US20170029422A1
Автор: CHAURE Ganesh S., GEKELER Volker, Hofmann Hans-Peter, JAGTAP Anil P., KULKARNI Sanjeev A., Maier Thomas, ZIMMERMANN Astrid
Принадлежит: 4SC AG

Imidazoquinolines of formula I that contain substituted amine or amide functionality at 1-position and that are effective as Toll like Receptor 7 activators are disclosed. These compounds are useful as anticancer agents. 2. The compound of formula I according to claim 1 , wherein Ris selected from the group consisting of alkyl claim 1 , alkenyl claim 1 , aryl claim 1 , heteroaryl claim 1 , cycloalkyl claim 1 , and heterocyclyl claim 1 ,{'sub': '3', 'each of which may be unsubstituted or substituted by one or more substituents selected from group consisting of: —H, alkyl, alkenyl, alkoxy, halogen, —OH, —N, trifluromethyl, -alkyl-aryl, —O-alkyl-aryl, —CO-aryl, aryl, heterocyclyl, heteroaryl, —CO-heteroaryl, —CO-substituted aryl, —CO-substituted heteroaryl, —CO—O-alkyl, —CO—N-alkyl, —CO—N-aryl.'}3. The compound of formula I according to claim 1 , wherein Ris selected from the group consisting of alkyl claim 1 , alkynyl claim 1 , aryl claim 1 , alkoxy claim 1 , heterocyclyl and heteroaryl claim 1 , each of which may be optionally substituted by one or more substituents which are selected from the group consisting of: —H claim 1 , —OH claim 1 , halogen claim 1 , —CO—N(R) claim 1 , —N(R) claim 1 , —CO—Calkyl claim 1 , —CO—O—Calkyl claim 1 , —N claim 1 , optionally substituted aryl claim 1 , heterocyclyl and —CO-aryl claim 1 ,{'sub': 4', '1-10', '1-10, 'wherein each Ris independently selected from the group consisting of: —H, —Calkyl, —Calkyl-aryl, or aryl.'}4. The compound of formula I according to claim 1 , wherein Ris substituted by one or more substituents which are selected from the group consisting of: —H claim 1 , —OH claim 1 , halogen claim 1 , —CN claim 1 , —NO claim 1 , —COOH claim 1 , —SH claim 1 , —CO—Calkyl claim 1 , —CO—O—Calkyl claim 1 , —N claim 1 , optionally substituted aryl claim 1 , heterocyclyl claim 1 , —CO-aryl and —CO-heterocyclyl.5. The compound of formula I according to claim 1 , wherein Ris hydrogen.6. The compounds of formula I according to ...

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Номер записи: 83
29-01-2015 дата публикации

BIS-QUARTERNARY CINCHONA ALKALOID SALTS AS ASYMMETRIC PHASE TRANSFER CATALYSTS

Номер: US20150031891A1
Автор: Xiang Bangping, Yasuda Nobuyoshi
Принадлежит: Merck Sharp & Dohme Corp.

The invention is directed to novel bis-quarternary cinchona alkaloid salts and the use of bis-quarternary cinchona alkaloid salts in asymmetric phase transfer catalysis. The present invention is directed to novel bis-quarternary cinchona alkaloid salts and the use of bis-quarternary cinchona alkaloid salts in asymmetric phase transfer catalysis. On certain substrates and under specific reaction conditions, the inventors have discovered that the use of bis-quarternary cinchona alkaloid salts in asymmetric phase transfer catalysis surprisingly provides for a more active and efficient process as compared to mono-quarternary catalysts. 2. The process of wherein said bis-quaternary cinchona alkaloid salt is used as a phase transfer catalyst in one of the following asymmetric reactions:(1) alkylation with an electrophilic alkylating agent,(2) Michael addition with an electron deficient olefin,(3) aldol reaction with an aldehyde,(4) Mannich reaction with a α-imino ester,(5) Darzens reaction with an aldehyde,(6) Neber rearrangement of an oxime into an α-aminoketone,(7) epoxidation of an electron deficient olefin,(8) aziridination of an electron deficient olefin,(9) dihydroxylation of an electron deficient olefins,(10) fluorination of a carbonyl substrate, and(11) sulfenylation of a β-keto sulfoxide.4. The process according to wherein:{'sup': A', 'B, 'claim-text': (i) hydrogen,', '(ii) halogen,', {'sup': '7', '(iii) OR,'}, {'sup': '7', 'sub': '2', '(iv) N(R),'}, '(v) CN,', {'sub': 1-8', '2-8', '3', '2', '2', '2', '2', '2', '2', '2, 'sup': 7', '7', '7', '7', '7', '7', '7', '8', '7', '8, '(vi) Calkyl or Calkenyl, either of which optionally bears up to 3 substituents independently selected from halogen, OH, CN, CF, OR, SR8, SOR8, SON(R), COR, COR, CON(R), N(R), NRCORand NRSOR; and'}, {'sub': 3-10', '3-10', '1-4', '1-4', '1-4', '3', '2', '2', '2', '2', '2', '2', '2, 'sup': 8', '7', '8', '8', '7', '7', '7', '7', '7', '7', '8', '7', '8, '(vii) Ccycloalkyl, CcycloalkylCalkyl, Het, ...

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Номер записи: 84
31-01-2019 дата публикации

METHOD OF PREPARING GLUCOSYLCERAMIDE SYNTHASE INHIBITORS

Номер: US20190031652A1
Автор: Gimi Rayomand, Reardon Michael, Siegel Craig S., Zhao Jin
Принадлежит: Genzyme Corporation

The invention relates to a method of preparing inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer. 122.-. (canceled)24. (canceled) The invention relates to a method of preparing inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.Glucosylceramide synthase (GCS) is a pivotal enzyme which catalyzes the initial glycosylation step in the biosynthesis of glucosylceramide-base glycosphingolipids (GSLs) namely via the pivotal transfer of glucose from UDP-glucose (UDP-Glc) to ceramide to form glucosylceramide. GCS is a transmembrane, type III integral protein localized in the cis/medial Golgi. Glycosphingolipids (GSLs) are believed to be integral for the dynamics of many cell membrane events, including cellular interactions, signaling and trafficking. Synthesis of GSL structures has been shown (see, Yamashita et al., Proc. Natl. Acad. Sci. USA 1999, 96(16), 9142-9147) to be essential for embryonic development and for the differentiation of some tissues. Ceramide plays a central role in sphingolipid metabolism and downregulation of GCS activity has been shown to have marked effects on the sphingolipid pattern with diminished expression of glycosphingolipids. Sphingolipids (SLs) have a biomodulatory role in physiological as well as pathological cardiovascular conditions. In particular, sphingolipids and their regulating enzymes appear to play a role in adaptive responses to chronic hypoxia in the neonatal rat heart (see, El Alwanit et al., Prostaglandins & Other Lipid Mediators 2005, 78(1-4), 249-263).GCS inhibitors have been proposed for the treatment of a variety of diseases (see for example, WO2005068426). Such treatments include ...

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Номер записи: 85
11-02-2016 дата публикации

Salt forms of (s)-quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate

Номер: US20160039805A1
Автор: Craig S. Siegel, Jin Zhao
Принадлежит: Genzyme Corp

The present invention relates to novel salt forms of (S)-Quinuclidin-3-yl(2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate useful as an inhibitor of glucosylceramide synthase (GCS) and for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.

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Номер записи: 86
11-02-2016 дата публикации

METHOD OF PREPARING GLUCOSYLCERAMIDE SYNTHASE INHIBITORS

Номер: US20160039806A1
Автор: Gimi Rayomand, Reardon Michael, Siegel Craig S., Zhao Jin
Принадлежит:

The invention relates to a method of preparing inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer. 4. A method according to , or , wherein n is 1; t is 0; y is 1 and z is 1.5. A method according to claim 4 , wherein Xis CRR.6. A method according to claim 5 , wherein Rand Rare each methyl.7. A method according to claim 6 , wherein Ais (C-C)heteroaryl.8. A method according to claim 7 , wherein Ais thiophene claim 7 , thiazole claim 7 , isothiazole claim 7 , furane claim 7 , oxazole claim 7 , isoxazole claim 7 , pyrrole claim 7 , imidazole claim 7 , pyrazole claim 7 , triazole claim 7 , pyridine claim 7 , pymiridine claim 7 , pyridazine claim 7 , indole claim 7 , benzotiazole claim 7 , benzoisoxazole claim 7 , benzopyrazole claim 7 , benzoimidazole claim 7 , benzofuran claim 7 , benzooxazole or benzoisoxazole.9. A method according to claim 8 , wherein Ais thiazole.10. A method according to claim 9 , wherein Ris H.11. A method according to claim 10 , wherein Xis a direct bond.12. A method according to claim 11 , wherein Ais (C-C)aryl.13. A method according to claim 12 , wherein Ais phenyl.14. A method according to claim 13 , wherein the phenyl group is substituted by halo.15. A method according to claim 14 , wherein the halo group is fluoro.16. A method according to claim 15 , wherein Ris hydrogen. The invention relates to a method of preparing inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.Glucosylceramide synthase (GCS) is a pivotal enzyme which catalyzes the initial glycosylation step in the biosynthesis of glucosylceramide-base glycosphingolipids (GSLs) namely via the pivotal transfer of glucose from UDP-glucose (UDP-Glc) to ...

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Номер записи: 87
07-02-2019 дата публикации

HETEROARYL CARBOXAMIDES

Номер: US20190040057A1
Автор: Böss Frank-Gerhard, Erb Christina, Hendrix Martin, Krüger Joachim, Luithle Joachim, Methfessel Christoph, Schreiber Rudy, Wiese Welf-Burkhard
Принадлежит:

The invention relates to novel heteroaryl carboxamides, processes for their preparation, and their use for producing medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning and/or memory. 19-. (canceled)10: A method of treating a cognitive impairment in a patient in need thereof , comprising administering to the patient a compound selected from the group consisting of:N-(1-Azabicyclo[2.2.2]oct-3-yl)-6-quinolinecarboxamide hydrochloride;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenazinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-7-quinolinecarboxamide hydrochloride;N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-6-quinolinecarboxamide hydrochloride;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-methyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl]-2-propyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-4-methyl-6-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-propyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-ethyl-4-methyl-7-quinolinecarboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-(tetrahydro-2H-pyran-2-yl)-6-quinoline-carboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-4-(tetrahydro-2H-pyran-2-yl)-7-quinoline-carboxamide;N-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenyl-6-quinolinecarboxamide; andN-(1-Azabicyclo[2.2.2]oct-3-yl)-2-phenyl-7-quinolinecarboxamide;or a salt thereof.11: The method of claim 10 , wherein the cognitive impairment is Alzheimer's disease.12: The method of claim 10 , wherein the cognitive impairment is schizophrenia.13: The method of claim 10 , wherein the method improves perception claim 10 , concentration claim 10 , learning claim 10 , or memory.14: A method of treating a cognitive impairment in a patient in need thereof claim 10 , ...

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Номер записи: 88
12-02-2015 дата публикации

(2S,3R)-N-2-3-PYRIDINYLMETHYL-1-AZABICYCLO 2.2.2 OCT-3-YL BENZOFURAN-2-CARBOXAMIDE, NOVEL SALT FORMS, AND METHODS OF USE THEREOF

Номер: US20150045386A1
Автор: Bencherif Merouane, Benson Lisa, Dull Gary Maurice, Federov Nikolai, Gatto Gregory J., Jordan Kristen G., Mazurov Anatoly A., Miao Lan, Munoz Julio A., Pfeffier Inigo, Pfeiffer Sondra, Phillips Teresa
Принадлежит:

The present invention relates to (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide, novel salt forms thereof, methods for its preparation, novel intermediates, and methods for treating a wide variety of conditions and disorders, including those associated with dysfunction of the central and autonomic nervous systems. 1. A method for treating a neurodegenerative disorder comprising administering a compound (2S ,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide or a pharmaceutically acceptable salt thereof , substantially free of (2S ,3S)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , (2R ,3S)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , (2R ,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide , and pharmaceutically acceptable salts thereof.2. The method of claim 1 , wherein the treatment is for dementia.3. The method of claim 1 , wherein the treatment is for ataxia. The present invention is a continuation of U.S. patent application Ser. No. 13/947,157 filed Jul. 22, 2013, which is a continuation of U.S. patent application Ser. No. 13/116,080, filed May 26, 2011, now U.S. Pat. No. 8,541,446, issued Sep. 24, 2013, which is a continuation of U.S. patent application Ser. No. 12/184,312, filed Aug. 1, 2008, now U.S. Pat. No. 7,981,906 issued Jul. 19, 2011, which claims benefit to U.S. Provisional Application Nos. 60/971,654, filed Sep. 12, 2007, 60/953,610, filed Aug. 2, 2007, 60/953,613, filed Aug. 2, 2007, and 60/953,614 filed Aug. 2, 2007, each of which is incorporated herein by reference in its entirety.The present invention relates to (2S,3R)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide, novel salt forms thereof, methods for its preparation, novel intermediates, and methods for treating a wide variety of conditions and disorders, including those associated ...

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Номер записи: 89
18-02-2021 дата публикации

COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE

Номер: US20210047333A1
Автор: "ODonnell Michael", AHMAD Nadia, Boyall Dean, Charrier Jean-Damien, Davis Chris, Davis Rebecca, Durrant Steven, ETXEBARRIA I JARDI Gorka, Fraysse Damien, Jimenez Juan-Miguel, KAY David, Knegtel Ronald, Marie Francoise, Middleton Donald, PANESAR Maninder, PIERARD, Pinder Joanne, Shaw David, Storck Pierre-Henri, Studley John, Twin Heather
Принадлежит:

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. 1188-. (canceled)190. The process of claim 189 , wherein the suitable conditions to form an amine comprise reacting the compound of formula 27 under Buchwald-Hartwig amination conditions.192. The process of claim 191 , wherein suitable halogen exchange conditions comprise reacting the compound of formula 18 with potassium fluoride in the presence of an aprotic solvent and a phase transfer catalyst.193. The process of claim 192 , wherein the aprotic solvent is independently selected from DMSO claim 192 , DMF claim 192 , and sulfolane.194. The process of claim 192 , wherein the phase transfer catalyst is MeNCl.195. The process of claim 191 , wherein suitable displacement conditions comprise reacting the compound of formula 32 with a compound of formula 22 in the presence of a base.196. The process of claim 195 , wherein the base is an aliphatic amine.197. The process of claim 196 , wherein the aliphatic amine is DIPEA.199. The process of claim 198 , wherein suitable halogenation conditions comprise 1) reacting the compound of formula 31 with a base to generate an anion; and 2) reacting the anion with a chlorinating agent.200. The process of claim 199 , wherein the base is LDA.201. The process of claim 199 , wherein the chlorinating agent is 1 claim 199 ,1 claim 199 ,1 claim ...

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Номер записи: 90
18-02-2016 дата публикации

HETEROCYCLIC COMPOUND AND USE THEREOF

Номер: US20160046601A1
Автор: Fukase Yoshiyuki, Imaeda Yasuhiro, Iwanaga Kouichi, KUROITA Takanobu, Taya Naohiro, Tokuhara Hidekazu
Принадлежит:

Compounds represented by the formulas 34-. (canceled)7. (canceled)920-. (canceled)21. 1-(2-Fluorophenyl)-5-(4-methoxybutyl)-N-(2-methylpropyl)-N-[(3S ,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]-1H-1 ,2 ,3-triazole-4-carboxamide or a salt thereof.2231-. (canceled) The present invention relates to a heterocyclic compound and the like, which has a superior renin inhibitory activity and is useful as an agent for the prophylaxis or treatment of hypertension, various organ damages attributable to hypertension, and the like.Hypertension is one of representative lifestyle-related diseases. Hypertension which is left untreated for long time lays a heavy burden on the cardiovascular system and results in arteriosclerosis to progress, thus causing various disorders in important organs, such as cerebral hemorrhage, cerebral infarction, cardiac failure, angina pectoris, myocardial infarction, renal failure and the like. Accordingly, the purpose of treating hypertension lies not only in lowering the blood pressure, but also in improving and/or preventing disorders in important organs including brain, heart and kidney, by controlling the blood pressure. As a method of treating hypertension, there are available fundamental treatments based on improvement in the lifestyle, such as dietetic therapy, exercise therapy and the like, as well as an attempt to control the blood pressure by positive pharmaceutical intervention.The renin-angiotensin (RA) system is a system of biosynthesis of angiotensin II (AII), which is a major vasopressor factor, and takes an important role in the control of the blood pressure and the amount of body fluid. AII exhibits a strong vasoconstrictive effect brought by the intervention of AII receptors on the cellular membrane, thus raising the blood pressure, and also promotes cellular propagation or production of extracellular matrix by directly acting on the AII receptors in the cardiac cells or renal cells. Therefore, drugs inhibiting increase in the ...

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Номер записи: 91
16-02-2017 дата публикации

NOVEL DISUBSTITUTED 1, 2, 4-TRIAZINE COMPOUND

Номер: US20170044115A1
Автор: AKAHOSHI Fumihiko, ONDA Yuichi, SAKAKIBARA Ryo, SASAKI Wataru, USHIROGOCHI Hideki
Принадлежит: MITSUBISHI TANABE PHARMA CORPORATION

This invention provides a novel disubstituted 1,2,4-triazine compound or a pharmaceutically acceptable salt thereof, which has an aldosterone synthetase inhibitory activity and is useful for preventing and/or treating various diseases or conditions associated with aldosterone; a method for preparing it; use of it; as well as a pharmaceutical composition comprising it as an active ingredient. A compound of the general formula [I]: 2. The compound according to claim 1 , [{'sup': '1', 'a substituent of (1) a cycloalkyl group which may be substituted, (2) an aryl group which may be partially hydrogenated and may be substituted, and (3) a heteroaryl group which may be partially hydrogenated and may be substituted, represented by ring Ain the above formula (A-1) is 1-3 groups selected independently from the group consisting of a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkoxyalkyl group, an alkoxy group, and an alkylenedioxy group which may be substituted with 1-2 halogen atoms,'}, 'an aryl moiety in the aryl group which may be partially hydrogenated and may be substituted is 6- to 10-membered monocyclic or bicyclic aryl,', 'a heteroaryl moiety in the heteroaryl group which may be partially hydrogenated and may be substituted is 5- to 10-membered monocyclic or bicyclic heteroaryl which contains 1-2 heteroatoms selected independently from the group consisting of a sulfur atom, an oxygen atom, and a nitrogen atom;', {'sup': '2', 'ring Ain the above formula (A-2) is a 6- to 10-membered monocyclic or bicyclic aryl group which may be substituted with (a) a cycloalkyl group, or (b) a halogen atom,'}, {'sup': '1', 'Qis a single bond, an oxygen atom, or —NH—;'}, {'sup': 'B', 'Ris'}, '(a) a monocyclic cycloalkyl group,', '(b) an isoindolinyl group,', '(c) a group represented by the above formula (B-1):', {'sup': '1', 'wherein ring Aris a 6- to 10-membered monocyclic or bicyclic aryl group,'}, '(d) a group represented by the above formula (B-2):', {'sup': ...

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Номер записи: 92
16-02-2017 дата публикации

Oxaspiro[2.5]Octane Derivatives and Analogs

Номер: US20170044122A1
Автор: Chaffee Stuart, Vath James E.
Принадлежит: Zafgen, Inc.

The invention provides oxaspiro[2.5]octane derivatives and analogs, methods for preparation thereof, intermediates thereto, pharmaceutical compositions, and uses thereof in the treatment of various disorders and conditions, such as overweight and obesity. 4. The compound of claim 1 , wherein Ris Cstraight saturated alkyl.5. The compound of claim 1 , wherein Ris selected from the group consisting of Cstraight saturated alkyl or Cstraight saturated alkyl.6. The compound of claim 1 , wherein Ris Calkylene substituted on the terminal end by —C(O)OH claim 1 , —C(O)—O-Me claim 1 , or C(O)-Et.8. A pharmaceutically acceptable composition comprising a compound of and a pharmaceutically acceptable excipient.9. A method of treating and/or controlling obesity claim 1 , comprising administering to a patient in need thereof an effective amount of the compound of .10. The method of claim 9 , wherein the patient is a human.11. The method of claim 10 , wherein the patient has a body mass index greater than or equal to about 25 kg/mbefore the administration.12. The method of claim 1 , wherein after administration claim 1 , thioredoxin 1 is not significantly present in the testes of male patient.14. The compound of claim 13 , wherein Z is C. This application is a continuation of U.S. patent application Ser. No. 14/003,906, filed Oct. 29, 2014, which is a national stage filing under U.S.C. §371 of PCT/US2012/028068, filed Mar. 7, 2012, which claims priority to U.S. Provisional Patent Application No. 61/450,301 filed Mar. 8, 2011, all of which are hereby incorporated by reference in their entirety.Over 1.1 billion people worldwide are reported to be overweight. Obesity is estimated to affect over 90 million people in the United States alone. Twenty-five percent of the population in the United States over the age of twenty is considered clinically obese. While being overweight or obese presents problems (for example restriction of mobility, discomfort in tight spaces such as theater or ...

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Номер записи: 93
16-02-2017 дата публикации

Geminal Substituted Aminobenzisoxazole Compounds as Agonists of Alpha7-Nicotinic Acetylcholine Receptors

Номер: US20170044155A1
Автор: Acharya Raksha, Burnett Duane A., Bursavich Matthew Gregory, Cook Andrew Simon, HARRISON Bryce Alden, McRiner Andrew J.
Принадлежит:

The present invention relates to novel geminal substituted aminobenzisoxazole compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of α7-nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom. 2. The compound of claim 1 , wherein Rindependently represents —H claim 1 , -D claim 1 , or halogen radical.35-. (canceled)6. The compound of claim 1 , wherein Rindependently represents —H claim 1 , -D claim 1 , or halogen radical.713-. (canceled)14. The compound of claim 1 , wherein Rindependently represents —F claim 1 , —Cl claim 1 , —Br claim 1 , —CN claim 1 , —CH claim 1 , —CHCH claim 1 , cyclopropyl radical claim 1 , —CHF claim 1 , —CHF claim 1 , —CF claim 1 , —CHCF claim 1 , —OCH claim 1 , —OCHCH claim 1 , —OCH(CH) claim 1 , —O-cyclopropyl claim 1 , or —OCF.15. (canceled)16. The compound of claim 1 , wherein Rindependently represents —F claim 1 , —Cl claim 1 , —CH claim 1 , or —OCH.1718-. (canceled)19. The compound of claim 1 , wherein Rindependently represents —H claim 1 , -D claim 1 , —F claim 1 , —Cl claim 1 , —CN claim 1 , —CH claim 1 , —CH(CH) claim 1 , cyclopropyl radical claim 1 , cyclobutyl radical claim 1 , —CHF claim 1 , —CHF claim 1 , —CF claim 1 , —CHCF claim 1 , —OCH claim 1 , —OCHCH claim 1 , —OCH(CH) claim 1 , —O-cyclopropyl claim 1 , —OCF claim 1 , or —OCHCF.20. (canceled)21. The compound of claim 1 , wherein Rindependently represents —H claim 1 , -D claim 1 , —F claim 1 , —Cl claim 1 , —CH claim 1 , or —OCH.22. The compound of claim 1 , wherein Rand Rindependently represent —H or -D.2326-. (canceled)27. The compound of claim 1 , wherein ...

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Номер записи: 94
13-02-2020 дата публикации

CINCHONINE-DERIVED CATALYSTS AND METHODS OF USING SAME

Номер: US20200048243A1
Автор: Deng Li, WU YONGWEI
Принадлежит: BRANDEIS UNIVERSITY

The present invention includes certain conchinine-derived phase-transfer catalysts of formula (I), compositions comprising the same, and methods of promoting asymmetric addition reactions using the same. 2. The compound of claim 1 , wherein Ris selected from the group consisting of alkyl claim 1 , alkoxy and aryl.3. The compound of claim 1 , wherein Rand Rare independently selected from the group consisting of alkyl claim 1 , alkoxy and aryl.4. The compound of claim 1 , wherein Ris aryl.5. The compound of claim 1 , wherein at least one selected from the group consisting of Rand Ris aryl claim 1 , which is independently optionally substituted with at least one sub stituent selected from alkyl claim 1 , alkoxy claim 1 , —S(alkyl) claim 1 , and —OSiR.6. The compound of claim 5 , wherein Rand Rare both independently aryl claim 5 , each of which is independently optionally substituted with at least one substituent selected from alkyl claim 5 , alkoxy claim 5 , —S(alkyl) claim 5 , and —OSiR.7. The compound of claim 1 , wherein Ris selected from the group consisting of alkyl claim 1 , alkoxy claim 1 , aryloxy claim 1 , —S(alkyl) claim 1 , —S(aryl) claim 1 , —OSiRand —NR.8. The compound of claim 7 , wherein Ris selected from the group consisting of alkoxy and —OSiR.9. The compound of claim 7 , wherein each occurrence of R is independently alkyl.10. The compound of claim 1 , wherein Ris selected from the group consisting of 3 claim 1 ,5-dimethoxyphenyl claim 1 , 3-phenyl-phenyl claim 1 , 3 claim 1 ,5-diphenyl-phenyl claim 1 , 3 claim 1 ,5-(4-methoxyphenyl)-phenyl claim 1 , 3 claim 1 ,5-diphenyl-4-methoxy-phenyl and 3 claim 1 ,5-diphenyl-4-(t-butyldimetylsiloxy)-phenyl.11. The compound of claim 1 , wherein Ris selected from the group consisting of unsubstituted alkyl claim 1 , unsubstituted alkenyl and unsubstituted alkynyl.12. The compound of claim 11 , wherein Ris selected from the group consisting of unsubstituted alkyl and unsubstituted alkenyl.13. The compound of claim ...

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Номер записи: 95
13-02-2020 дата публикации

GLUCOSYLCERAMIDE SYNTHASE INHIBITORS

Номер: US20200048266A1
Автор: "OSHEA Thomas", BOURQUE Elyse, CABRERA-SALAZAR Mario, CELATKA Cassandra, Cheng Seng, CROMWELL Mary A., Good Andrew, HIRTH Bradford, JANCSICS Katherine, LEONARD JOHN P., Li Lingyun, LILLIE James, Liu Hanlan, MAKINO Elina, Marshall John, MASON Paul, METZ Markus, MORSHED Fazeela, SCHEULE Ronald, Skerlj Renato, WANG Bing, Xiang Yibin, Zhao Zhong
Принадлежит:

The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer. 2271-. (canceled)273. A method for treating a disease or disorder mediated by glucosylceramide synthase (GCS) or a disease or disorder in which GCS is implicated in a subject in need of such treatment claim 1 , the method comprising the step of administering to the subject an effective amount of a compound according to .275. The method according to claim 274 , wherein Rand Rare each methyl.276. The method according to claim 274 , wherein Ris H.277. The method according to claim 274 , Xis a direct bond278. The method according to claim 274 , Xis a CRR.279. The method according to claim 278 , wherein Rand Rare each methyl.280. The method according to claim 274 , wherein Ais (C-C)aryl.281. The method according to claim 274 , wherein Ais (C-C)heteroaryl.282. The method according to claim 281 , wherein Ais pyridine.283. The method according to claim 274 , wherein Ais (C-C)heterocycloalkyl.284. The method according to claim 283 , wherein Ais pyrrolidinyl claim 283 , tetrahydrofuranyl claim 283 , dihydrofuranyl claim 283 , tetrahydropyranyl claim 283 , pyranyl claim 283 , thiopyranyl claim 283 , aziridinyl claim 283 , azetidinyl claim 283 , oxiranyl claim 283 , methylenedioxyl claim 283 , chromenyl claim 283 , barbituryl claim 283 , isoxazolidinyl claim 283 , 1 claim 283 ,3-oxazolidin-3-yl claim 283 , isothiazolidinyl claim 283 , 1 claim 283 ,3-thiazolidin-3-yl claim 283 , 1 claim 283 ,2-pyrazolidin-2-yl claim 283 , 1 claim 283 ,3-pyrazolidin-1-yl claim 283 , piperidinyl claim 283 , thiomorpholinyl claim 283 , 1 claim 283 ,2-tetrahydrothiazin-2-yl claim 283 , 1 claim 283 ,3-tetrahydrothiazin-3-yl claim 283 , tetrahydrothiadiazinyl claim 283 , morpholinyl claim 283 , 1 claim 283 ,2-tetrahydrodiazin-2-yl claim 283 , 1 claim 283 ...

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Номер записи: 96
22-02-2018 дата публикации

QUINUCLIDINE DERIVATIVE

Номер: US20180051018A1
Автор: MIZUSHIMA Tohru, Yamakawa Naoki, YAMASHITA Yasunobu
Принадлежит: LTT Bio-Pharma Co., Ltd.

Provided is a novel therapeutic agent for chronic obstructive pulmonary disease. 2: The quinuclidine derivative according to claim 1 , wherein:m is an integer of 2 to 5;l is a number of 0 or 1; andn is a number of 0 or 1.3: The quinuclidine derivative according to claim 1 , wherein n is 0.4: The quinuclidine derivative according to claim 1 , wherein:m is 3; andl is 0.5: The quinuclidine derivative according to claim 1 , wherein the quinuclidine derivative is an (R) isomer.6: A medicament claim 1 , comprising the quinuclidine derivative according to as an active ingredient.7: The medicament according to claim 6 , wherein the medicament is a therapeutic agent for chronic obstructive pulmonary disease.8: A pharmaceutical composition claim 1 , comprising the quinuclidine derivative according to claim 1 , and a pharmaceutically acceptable carrier.911-. (canceled)12: A method for treating chronic obstructive pulmonary disease claim 1 , the method comprising administering an effective amount of the quinuclidine derivative according to . The present invention relates to a quinuclidine derivative, and to a medicament containing the quinuclidine derivative.Chronic obstructive pulmonary disease (COPD) is a generic term for diseases that have been conventionally called chronic bronchitis or emphysema. COPD is a chronic disease of the lungs, which is caused by long-term inhalation exposure of harmful substances mainly containing tobacco smoke, and is said to be a lifestyle-related disease that occurs in middle-aged or older people against the background of smoking habit.In the drug therapy for COPD, a bronchodilator (an anticholinergic drug, a β-agonist, or a theophylline drug) is mainly used, and an inhaled anticholinergic drug or an inhaled β-agonist that mainly dilates the bronchi for a long time is used. In addition, an inhaled corticosteroid is used in severe cases.In recent years, as a drug effective for the treatment of COPD, for example, a quinuclidine derivative as a ...

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Номер записи: 97
13-02-2020 дата публикации

RESIST COMPOSITION AND PATTERNING PROCESS

Номер: US20200050105A1
Автор: Fujiwara Takayuki, Hatakeyama Jun, OHASHI Masaki
Принадлежит: SHIN-ETSU CHEMICAL CO., LTD.

A resist composition comprising a base polymer and a quencher in the form of an amine compound having an iodized aromatic ring bonded to the nitrogen atom via a divalent hydrocarbon group offers a high sensitivity and minimal LWR or improved CDU, independent of whether it is of positive or negative tone. 1. A resist composition comprising a base polymer and a quencher , the quencher being an amine compound having an iodine-substituted aromatic ring bonded to the nitrogen atom via a C-Cdivalent hydrocarbon group which may contain at least one moiety selected from ester bond and ether bond.3. The resist composition of claim 1 , further comprising an acid generator capable of generating a sulfonic acid claim 1 , imide acid or methide acid.4. The resist composition of claim 1 , further comprising an organic solvent.6. The resist composition of which is a chemically amplified positive resist composition.7. The resist composition of wherein the base polymer is free of an acid labile group.8. The resist composition of which is a chemically amplified negative resist composition.10. The resist composition of claim 1 , further comprising a surfactant.11. The resist composition of claim 1 , further comprising a quencher other than the amine compound.12. A process for forming a pattern comprising the steps of applying the resist composition of onto a substrate claim 1 , baking to form a resist film claim 1 , exposing the resist film to high-energy radiation claim 1 , and developing the exposed resist film in a developer.13. The process of wherein the high-energy radiation is ArF excimer laser radiation of wavelength 193 nm or KrF excimer laser radiation of wavelength 248 nm.14. The process of wherein the high-energy radiation is EB or EUV of wavelength 3 to 15 nm. This non-provisional application claims priority under 35 U.S.C. § 119(a) on Patent Application No. 2018-150050 filed in Japan on Aug. 9, 2018, the entire contents of which are hereby incorporated by reference.This ...

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Номер записи: 98
26-02-2015 дата публикации

SMALL MOLECULE INDUCERS OF GDNF AS POTENTIAL NEW THERAPEUTICS FOR NEUROPSYCHIATRIC DISORDERS

Номер: US20150056699A1
Автор: Carrera Ignacio, Karpowicz Richard, Kruegel Andrew, Li Shu, Li Xiaoguang, Rakshit Souvik, Sames Dalibor
Принадлежит: The Trustees of Columbia University in the City of New York

This invention provides a compound having the structure 34-. (canceled)8. (canceled)1112-. (canceled)14. (canceled)1822-. (canceled)2426-. (canceled)2832-. (canceled)34. (canceled)36. (canceled)3844-. (canceled)4647-. (canceled)5052-. (canceled)54. (canceled) Throughout this application, certain publications are referenced in parentheses. Full citations for these publications may be found immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to describe more fully the state of the art to which this invention relates.Neurotrophic factors play important roles not only in the development of the nervous system, but also in maintenance of its function and plasticity. GDNF (Glial cell line-Derived Neurotrophic Factor) is essential for growth, development and plasticity of dopamine and motor neurons as well as other brain cell populations (Airaksinen, M. S. et al. 2002). In the brain, GDNF is released by both neurons and glia cells. Although the signaling mechanisms underlying the expression and release of GDNF are not fully mapped, the released GDNF exerts its function on the brain cells and neurocircuitry through a receptor complex, comprised of GFRα1 (GDNF Family Receptor α1) and receptor tyrosine kinase RET (Trupp, M. et al. 1997). On the basis of the trophic and repair effects GDNF has on neural cells, it was considered as a potential therapeutic agent for several neurological disorders. However, GDNF is a protein and thus not readily administered to the brain. Consequently, small molecule inducers of GDNF release are of interest as potential therapeutics, most notably in the context of Parkinson's disease and neuropathic pain. In the latter case, GDNF's effectiveness has been ascribed to the ability of GDNF signaling to reset the function of several sodium channel subunits (modified in response to injury) (Boucher, T. J. et al. 2000).Recently, it has been shown ...

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Номер записи: 99
10-03-2022 дата публикации

QUINUCLIDINE-3-ONE DERIVATIVES AND THEIR USE IN CANCER TREATMENT

Номер: US20220071970A1
Автор: Blizzard Tim, Hagberg Lars, Ringom Rune
Принадлежит:

The invention relates to certain substituted quinuclidine-3-one compounds for use in the treatment of hyperproliferative disease, such as cancer, and diseases associated with inflammation. More particularly, the present invention relates to certain substituted 3-quinuclidinones, pharmaceutically acceptable salts thereof, pharmaceutical compositions containing the same, and to methods for using such compounds. In this manner, these compounds are of use for treating hyperproliferative diseases and inflammatory diseases. 3. A compound according to claim 2 , wherein{'sup': '1a', 'sub': ['1', '6', '1', '6', '1', '6'], '#text': 'Ris selected from the group consisting of H, C-Calkyl and C-Chaloalkyl, said alkyl and haloalkyl being optionally substituted with one or more C-Calkoxy; and'}{'sup': '2a', 'sub': ['1', '6'], '#text': 'Ris C-Chaloalkyl;'}or an enantiomer, mixture of enantiomers, pharmaceutically acceptable salt, hydrate, solvate or combination thereof.4. A compound according to or claim 2 , wherein{'sup': '1a', 'sub': ['1', '6', '1', '6'], '#text': 'Ris selected from the group consisting of H and C-Calkyl, said alkyl being optionally substituted with one or more C-Calkoxy; and'}{'sup': '2a', 'sub': ['1', '6'], '#text': 'Ris C-Chaloalkyl;'}or an enantiomer, mixture of enantiomers, pharmaceutically acceptable salt, hydrate, solvate or combination thereof.5. A compound according to any one of - claim 2 , wherein{'sup': '1a', '#text': 'Ris selected from the group consisting of H and ethyl; and'}{'sup': '2a', '#text': 'Ris selected from the group consisting of trihalomethyl and dihalomethyl;'}or an enantiomer, mixture of enantiomers, pharmaceutically acceptable salt, hydrate, solvate or combination thereof.6. A compound according to claim 2 , wherein Ris H claim 2 , or an enantiomer claim 2 , mixture of enantiomers claim 2 , pharmaceutically acceptable salt claim 2 , hydrate claim 2 , solvate or combination thereof.7. A compound according to claim 2 , wherein Ris ethyl ...

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Номер записи: 100