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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 2122. Отображено 100.
07-06-2012 дата публикации

Materials and Methods for the Treatment of Hypertension

Номер: US20120141424A1
Автор: Denis Tvorogov, Georgia Zarkada, Kari Alitalo, Tuomas Tammela
Принадлежит: Vegenics Pty Ltd

The present invention is directed to materials and methods for the treatment of hypertension and ischemia comprising administering at least one therapeutic agent selected from the group consisting of vascular endothelial growth factor-C product and vascular endothelial growth factor-D product, and optionally, when treating hypertension, a standard of care anti-hypertensive agent.

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Номер записи: 1
20-12-2012 дата публикации

Development of Novel Detergents for Use in PCR Systems

Номер: US20120322066A1
Автор: Jonathan Wang, Parul Angrish, Zhiwei Yang
Принадлежит: Life Technologies Corp

This disclosure relates to novel detergents for use in various procedures including, for example, nucleic acid amplification reactions such as polymerase chain reaction (PCR). Methods for preparing the modified detergents are also described.

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Номер записи: 2
14-02-2013 дата публикации

SOLUBLE FMS-LIKE TYROSINE KINASE-1 (sFLT-1) ANTIBODY AND RELATED COMPOSITION, KIT, METHODS OF USING, AND MATERIALS AND METHOD FOR MAKING

Номер: US20130040407A1
Автор: Bryan C. Tieman, David J. Hawksworth, Dominick L. Pucci, Don C. Laird, Joan D. Tyner, Saul A. Datwyler, Sharmila Manoj, Susan E. Brophy, Zhiguang Yu
Принадлежит: ABBOTT LABORATORIES

An isolated antibody that specifically binds to sFlt-1 or a fragment thereof having (i) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO: 2, (ii) a variable light domain region comprising the amino acid sequence of SEQ ID NO: 4, or (iii) both (i) and (ii), a pharmaceutical composition and a kit comprising such an antibody, a method of making such an antibody, a method of determining the presence, amount or concentration of sFlt-1 or a fragment thereof in a test sample, a method of treating a patient in therapeutic or prophylactic need of an antagonist of sFlt-1, an isolated nucleic acid comprising a nucleotide sequence encoding the amino acid sequence of (i) SEQ ID NO: 2, (ii) SEQ ID NO: 4, or (iii) both (i) and (ii), optionally as part of a vector, and a host cell comprising and expressing such a nucleic acid.

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Номер записи: 3
28-03-2013 дата публикации

PYRENYLOXYSULFONIC ACID FLUORESCENT AGENTS

Номер: US20130079497A1
Автор: Haugland Richard, Leung Wai-Yee, LIU Jixiang
Принадлежит: LIFE TECHNOLOGIES CORPORATION

The invention provides a novel class of reactive fluorescent agents that are based on a pyrene sulfonic acid nucleus. The agents are readily incorporated into conjugates with other species by reacting the reactive group with a group of complementary reactivity on the other species of the conjugate. Also provided are methods of using the compounds of the invention to detect and/or quantify an analyte in a sample. In an exemplary embodiment, the invention provides multi-color assays incorporating the compounds of the invention. 125.-. (canceled)27. The compound of wherein s is 1 and t is 2.28. The compound of wherein the linker arm comprises a straight-chain claim 26 , saturated chain of atoms and includes unsubstituted polyalkylene.30. The compound of wherein s is 1 and t is 2.32. The conjugate of wherein s is 1 and t is 2.33. The conjugate of wherein the linker arm comprises a straight-chain claim 31 , saturated chain of atoms and includes unsubstituted polyalkylene.35. The conjugate of claim 34 , wherein the linker arm comprises a cleavable group.36. The conjugate of claim 34 , wherein the linker arm comprises —C(O)NH— claim 34 , —C(O)O— claim 34 , —NH— claim 34 , —S— claim 34 , or —O—.37. The conjugate of claim 34 , wherein s is 1 claim 34 , and t is 2.38. A kit for the detection of an analyte in a sample claim 26 , wherein said kit comprises a compound of .39. A kit for the detection of an analyte in a sample claim 29 , wherein said kit comprises a compound of .40. A kit for the detection of an analyte in a sample claim 31 , wherein said kit comprises a conjugate of .41. A kit for the detection of an analyte in a sample claim 34 , wherein said kit comprises a conjugate of . NOT APPLICABLENOT APPLICABLENOT APPLICABLEThe present invention relates to novel fluorescent compounds that have utility in detecting one or more selected analytes in a sample. The invention is of use in a variety of fields including immunology, diagnostics, molecular biology and fluorescence ...

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Номер записи: 4
28-03-2013 дата публикации

METHOD FOR PRODUCING OPTICALLY ACTIVE 3-AMINOPIPERIDINE OR SALT THEREOF

Номер: US20130079525A1
Автор: MORI Kohei, NISHIYAMA Akira, NOJIRI Masutoshi, TAOKA Naoaki
Принадлежит: KANEKA CORPORATION

The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing. 118.-. (canceled) The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate, and to intermediates useful for producing the 3-aminopiperidine.As methods for producing an optically active 3-aminopiperidine or salt thereof, or a derivative of optically active 3-aminopiperidine, for example, the following methods are known:1) a method, wherein L-ornithine monohydrochloride is methyl-esterified, and then (S)-3-amino piperidone is obtained by chromatography with an ion exchange resin, the (S)-3-amino piperidone is reacted with lithium aluminum hydride to be (S)-3-aminopiperidine, an inorganic salt is removed by filtration, and the target compound is purified (Non-patent Document 1);2) a method, wherein ethyl nipecotate is optically resolved using L-tartaric acid, the nitrogen atom is protected with benzyloxycarbonyl group, the ethyl ester is hydrolyzed in alkaline condition, Curtius rearrangement is carried out using ...

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Номер записи: 5
04-07-2013 дата публикации

BIPHENYL COMPOUNDS USEFUL AS MUSCARINIC RECEPTOR ANTAGONISTS

Номер: US20130172301A1
Автор: Husfeld Craig, Ji Yu-Hua, Li Li, Mammen Mathai, Mu YongQi
Принадлежит: THERAVANCE, INC.

This invention provides compounds of formula I: 214-. (canceled)15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of .16. The pharmaceutical composition of claim 15 , wherein the composition further comprises an agent selected from βadrenergic receptor agonists claim 15 , steroidal anti-inflammatory agents claim 15 , phosphodiesterase-4 inhibitors claim 15 , and combinations thereof.17. The pharmaceutical composition of claim 16 , wherein the composition comprises a βadrenergic receptor agonist and a steroidal anti-inflammatory agent.1823-. (canceled)24. A method for treating a pulmonary disorder claim 1 , the method comprising administering to a patient a therapeutically effective amount of the compound of .25. A method of producing bronchodilation in a patient claim 1 , the method comprising administering to a patient a bronchodilation-producing amount of the compound of .26. A method of treating chronic obstructive pulmonary disease or asthma claim 1 , the method comprising administering to a patient a therapeutically effective amount of the compound of . This application claims the benefit of U.S. Provisional Application No. 60/552,443, filed on Mar. 11, 2004; the entire disclosure of which is incorporated herein by reference in its entirety.1. Field of the InventionThe present invention relates to novel biphenyl compounds having muscarinic receptor antagonist or anticholinergic activity. This invention also relates to pharmaceutical compositions comprising such biphenyl compounds, processes and intermediates for preparing such biphenyl compounds and methods of using such biphenyl compounds to treat pulmonary disorders.2. State of the ArtPulmonary or respiratory disorders, such as chronic obstructive pulmonary disease (COPD) and asthma, afflict many millions of people worldwide and such disorders are a leading cause of morbidity and mortality.Muscarinic receptor antagonists are known to provide bronchoprotective ...

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Номер записи: 6
11-07-2013 дата публикации

PRODRUGS OF A PIPERIDINYL DERIVATIVE AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY

Номер: US20130178444A1
Автор: CARTER Percy H., Cornelius Lyndon A.M., Dhar T.G. Murali, Duncia John V., HYNES John, Nair Satheesh K., Santella Joseph B., Warrier Jayakumar S., Wu Hong
Принадлежит:

The present application describes prodrugs of the compound of formula (I): 3. A pharmaceutical composition comprised of a pharmaceutically acceptable carrier and a therapeutically effective amount of one or more of the compounds of .4. A pharmaceutical composition comprised of a pharmaceutically acceptable carrier and a therapeutically effective amount of one or more of the compounds of .5. A method for modulation of chemokine or chemokine receptor activity comprising administering to a patient in need thereof a therapeutically effective amount of one or more of the compounds of .6. The method of claim 5 , wherein the chemokine or chemokine receptor activity is CCR-1 or CCR-1 receptor activity.7. A method for treating a disorder comprising administering to a patient in need thereof a therapeutically effective amount of one or more of the compounds of ; wherein said disorder is selected from osteoarthritis claim 1 , aneurysm claim 1 , fever claim 1 , cardiovascular effects claim 1 , Crohn's disease claim 1 , congestive heart failure claim 1 , autoimmune diseases claim 1 , HIV-infection claim 1 , HIV-associated dementia claim 1 , psoriasis claim 1 , idiopathic pulmonary fibrosis claim 1 , transplant arteriosclerosis claim 1 , physically- or chemically-induced brain trauma claim 1 , neuropathic pain claim 1 , inflammatory bowel disease claim 1 , alveolitis claim 1 , ulcerative colitis claim 1 , systemic lupus erythematosus claim 1 , nephrotoxic serum nephritis claim 1 , glomerulonephritis claim 1 , asthma claim 1 , multiple sclerosis claim 1 , atherosclerosis claim 1 , rheumatoid arthritis claim 1 , restenosis claim 1 , organ transplantation claim 1 , multiple myeloma claim 1 , colorectal cancer claim 1 , hepatocellular cancer and other cancers.8. A method for treating inflammatory diseases comprising administering to a patient in need thereof a therapeutically effective amount of one or more of the compounds of .9. A method for preparing a medicament for the treatment ...

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Номер записи: 7
29-08-2013 дата публикации

Method To Prepare beta-Functionalized Aliphatic Esters

Номер: US20130225852A1
Автор: Dominik Ohlmann, Lukas J. Goossen, Markus Dierker
Принадлежит: Cognis IP Management GmbH

The invention pertains to a new route to prepare β-functionalized carboxylic acid esters in a one-pot reaction, by reacting an olefinic acid ester in the presence of a catalyst system, comprising a Rh(I)-complex, together with an aryl boron or a diamine as nucleophilic compounds, and under oxygen-free conditions and elevated temperatures.

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Номер записи: 8
26-09-2013 дата публикации

Process for the preparation of enantiomerically enriched cyclic beta-aryl or heteroaryl carbocyclic acids

Номер: US20130253201A1
Автор: Michelangelo Scalone, Patrick Schnider, Stephan Bachmann
Принадлежит: Hoffmann La Roche Inc

The present invention relates to a process for the preparation of cis substituted cyclic β-aryl or heteroaryl carboxylic acid derivatives in high diastereo- and enantioselectivity by enantioselective hydrogenation in accordance with the following scheme wherein X, Ar, n, and m are defined herein and corresponding salts thereof.

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Номер записи: 9
10-10-2013 дата публикации

QUATERNARY HETEROATOM CONTAINING COMPOUNDS

Номер: US20130267699A1
Автор: Behenna Douglas C., Duquette Douglas, Eidamshaus Christian, Liu Yiyang, Stoltz Brian M., Virgil Scott C., White David E., Yurino Taiga
Принадлежит:

The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II): 3. The method of claim 2 , wherein:{'sup': '1', 'Ris selected from halogen and an optionally substituted group selected from alkyl, carbocyclyl, carbocyclylalkyl, cyanoalkyl, aralkyl, heteroaralkyl, hydroxyalkyl, haloalkyl, acylalkyl, alkoxycarbonylalkyl, and aryloxycarbonylalkyl;'}{'sup': 2', '12', '7', '8', '11, 'R, R, R, R, and Rare independently selected at each occurrence from hydrogen, halogen, hydroxyl, haloalkyl, cyano, alkyl, alkoxy, alkylthio, amide, amine, and carbocyclyl;'}{'sup': 3', '4', '5', '13', '14', '15, 'R, R, R, R, R, and Rare independently selected at each occurrence from hydrogen, halogen, haloalkyl, cyano, alkyl, alkoxy, alkylthio, amide, amine, aryloxy, and aralkyloxy;'}{'sup': 6', '9', '10, 'R, R, and Rare independently selected at each occurrence from hydrogen, hydroxyl, and optionally substituted alkyl, alkoxy, alkylthio, aryloxy, carbocyclyl, aryl, arylcarbonyl, aralkylcarbonyl, heteroaryl, aralkyl, heteroaralkyl, aralkyloxy, heteroaryloxy, acyl, arylcarbonyl, aralkylcarbonyl, acyloxy, alkylsulfonyl, arylsulfonyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, and amide.'}4. The method of claim 3 , wherein:{'sup': '1', 'Ris selected from halogen, alkyl, optionally substituted aralkyl, optionally substituted alkoxycarbonylalkyl, optionally substituted cyanoalkyl, and optionally substituted hydroxyalkyl; and'}{'sup': 6', '9', '10, 'R, R, and Rare independently selected at each occurrence from optionally substituted aralkyloxy, aralkoxycarbonyl, heteroaryloxy, acyl, arylcarbonyl, aralkylcarbonyl, arylsulfonyl, alkoxycarbonyl, and aryloxycarbonyl.'}5. The method of claim 4 , wherein:{'sup': '6', 'X is —NR—;'}{'sup': 7', '7, 'Z is selected from —C(O)— and —CRR—;'}{'sup': 8', '8, 'A at each occurrence is —CRR—;'}{'sup': 10', '11', '11, 'W is selected from —NR ...

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Номер записи: 10
07-11-2013 дата публикации

PROLINAMIADE DERIVATIVES AS THROMBIN INHIBITOR, PREPRARATION METHOD AND APPLICATION THEREOF

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

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

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Номер записи: 11
14-11-2013 дата публикации

PROCESS FOR PREPARING CYCLIC AMINE COMPOUNDS

Номер: US20130303771A1
Автор: Hirai Yoshinori, NISHIYAMA Akira
Принадлежит: KANEKA CORPORATION

A cyclic amine compound having a prescribed configuration can be efficiently prepared by reducing an imine derivative in the presence of a sulfonic acid. Specifically, a cyclic amine compound which is substituted with an amino group and a carboxyl group in which both groups are arranged in the trans configuration can be prepared efficiently. 2. The process according to claim 1 , wherein Ris Calkyloxy group claim 1 , Calkenyloxy group claim 1 , Caralkyloxy group claim 1 , Caryloxy group claim 1 , Ctrialkylsilyloxy group claim 1 , amino group claim 1 , Calkylamino group claim 1 , Calkenylamino group claim 1 , Caralkylamino group claim 1 , Carylamino group claim 1 , Cdialkylamino group claim 1 , Cdialkenylamino group claim 1 , Cdiaralkylamino group claim 1 , Cdiarylamino group claim 1 , thiol group claim 1 , Calkylthio group claim 1 , Calkenylthio group claim 1 , Caralkylthio group claim 1 , or Carylthio group.3. The process according to claim 1 , wherein the sulfonic acid is sulfuric acid or camphorsulfonic acid; and the reducing agent is borane.4. The process according to claim 1 , wherein Ris benzyloxy group or dibenzylamino group; Ris hydrogen atom; Ris benzyloxy group; and n is 2.5. The process according to claim 4 , further comprising the steps of forming a salt of said cyclic amine compound and oxalic acid claim 4 , and precipitating the salt as a solid in methanol claim 4 , in ethanol claim 4 , in isopropanol claim 4 , in a mixed solvent containing methanol claim 4 , in a mixed solvent containing ethanol claim 4 , or in a mixed solvent containing isopropanol.7. The process according to claim 6 , wherein P is benzyloxycarbonyl group. The present invention relates to a process for producing a cyclic amine compound, specifically, a cyclic amine compound which has an amino group and a carboxyl group as substituents and their configuration is trans, and especially a trans-5-aminopiperidine-2-carboxylic acid derivative, which is useful for an intermediate for ...

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Номер записи: 12
19-12-2013 дата публикации

CRYSTALLINE FREEBASE FORMS OF A BIPHENYL COMPOUND

Номер: US20130338191A1
Автор: Woollam Grahame
Принадлежит: THERAVANCE, INC.

The invention provides two crystalline freebase forms of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester. The invention also provides pharmaceutical compositions comprising the crystalline freebase or prepared using the crystalline freebases; processes and intermediates for preparing the crystalline freebases; and methods of using the crystalline freebases to treat a pulmonary disorder. 12-. (canceled)3. The method of or , wherein the crystalline freebase is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values selected from 6.6±0.1 , 11.4±0.1 , 13.1±0.1 , 16.1±0.1 , 17.5±0.1 , 18.2±0.1 , 18.6±0.1 , 19.3±0.1 , 19.7±0.1 , 19.9±0.1 , 20.2±0.1 , 20.8±0.1 , 21.1±0.1 , 21.7±0.1 , and 22.3±0.1.4. The method of or , wherein the crystalline freebase is further characterized by a powder x-ray diffraction pattern in which the peak positions are substantially in accordance with the peak positions of the pattern shown in .5. The method of or , wherein the crystalline freebase is further characterized by a differential scanning calorimetry thermogram which shows a melting point of about 125° C.6. The method of or , wherein the crystalline freebase is further characterized by a differential scanning calorimetry thermogram substantially in accordance with that shown in .7. (canceled)8. The method of or , wherein the crystalline freebase is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values selected from 6.6±0.1 , 13.1±0.1 , 15.0±0.1 , 17.3±0.1 , 17.7±0.1 , 18.6±0.1 , 19.7±0.1 , 20.2±0.1 , 20.9±0.1 , 21.4±0.1 , and 22.6±0.1.9. The method of or , wherein the crystalline freebase is further characterized by a powder x-ray diffraction pattern in which the peak positions are substantially in accordance with the peak positions of the pattern shown in .10. The method of or , wherein the crystalline freebase is further characterized by a ...

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Номер записи: 13
02-01-2014 дата публикации

PHENOXYETHYL PIPERIDINE COMPOUNDS

Номер: US20140005226A1
Автор: SCHIFFLER Matthew Allen, York Jeremy Schulenburg
Принадлежит:

The present invention provides a compound of the Formula II: 2. A compound according to wherein Ris H.3. A compound according to wherein Ris H and Ris methyl.8. A method of treating osteoarthritis in a patient claim 1 , comprising administering to a patient in need of such treatment an effective amount of a compound claim 1 , or pharmaceutically acceptable salt thereof claim 1 , as in .9. A method of treating rheumatoid arthritis in a patient claim 1 , comprising administering to a patient in need of such treatment an effective amount of a compound or pharmaceutically acceptable salt thereof claim 1 , as in .10. A method of treating pain associated with osteoarthritis or rheumatoid arthritis in a patient claim 1 , comprising administering to a patient in need of such treatment an effective amount of a compound or a pharmaceutically acceptable salt thereof claim 1 , as in .11. A pharmaceutical composition claim 1 , comprising a compound or a pharmaceutically acceptable salt thereof as in in combination with one or more pharmaceutically acceptable carriers claim 1 , diluents claim 1 , or excipients.12. The pharmaceutical composition according to claim 11 , further comprising one or more other therapeutic agents. The present invention relates to novel phenoxyethyl piperidine compounds, to pharmaceutical compositions comprising the compounds, to methods of using the compounds to treat physiological disorders, and to intermediates and processes useful in the synthesis of the compounds.The present invention is in the field of treatment of inflammatory conditions, such as arthritis, including osteoarthritis and rheumatoid arthritis, and further including pain associated with these conditions. Arthritis affects millions of patients in the United States alone and is a leading cause of disability. Treatments often include NSAIDs (nonsteroidal anti-inflammatory drugs) or COX-2 inhibitors, which may produce untoward cardiovascular and/or gastrointestinal side effects. As such, ...

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Номер записи: 14
27-03-2014 дата публикации

PROCESS INTERMEDIATES AND METHODS FOR THE PREPARATION OF PROCESS INTERMEDIATES FOR THE SYNTHESIS OF ARGATROBAN MONOHYDRATE

Номер: US20140088310A1
Автор: Huber Florian Anton Martin, Ricci Antonio, Stivanello Mariano
Принадлежит: LUNDBECK PHARMACEUTICALS ITALY S.P.A.

Methods are provided for the synthesis of key intermediates for the synthesis of Argatroban monohydrate, ethyl (2R,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl. Such intermediates are also provided. 135-. (canceled)36. An ethyl (2R ,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate comprising in an amount HCl between about 1 mol/mol and about 2 mol/mol.37. A solvate of the compound of having an organic solvent or water content of at least 0.5 mol/mol.38. A dihydrochloride form of the compound of having a weight/weight chloride content between about 12 and about 16%.39. A dihydrochloride form of the compound of claim 36 , wherein said compound is solvated by ethanol and has a weight/weight chloride content between about 11 and about 15%.40. A Method for obtaining ethyl (2R claim 36 ,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl claim 36 , solvated or unsolvated claim 36 , comprising exposing a mixture of ethyl (2R claim 36 ,4R)-1-[(2S)-2-amino-5[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate and ethyl (2S claim 36 ,4S)-1-[(2S)-2-amino-5[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl claim 36 , solvated or unsolvated claim 36 , to an organic or aqueous solvent or to a mixture thereof claim 36 , followed by the selective precipitation and isolation of ethyl (2R claim 36 ,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl claim 36 , solvated or unsolvated.41. The method of comprising:a) exposing a mixture of ethyl (2R,4R)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl]amino]-1-oxopentyl]-4-methylpiperidine-2-carboxylate compounded with HCl, solvated or unsolvated, and ethyl (2S,4S)-1-[(2S)-2-amino-5-[[imino(nitroamino)methyl] ...

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Номер записи: 15
03-01-2019 дата публикации

COMPOSITIONS COMPRISING 4'-O-GLUCURONIDE EPICATECHIN AND METHODS OF MAKING AND USING SUCH COMPOSITIONS

Номер: US20190000868A1
Автор: Actis Goretta Lucas, Camacho Susana, Castaneda Gutierrez Euridice, Le Coutre Johannes, Legrand Coline, Michlig Gonzalez Stephanie, PATIN AMAURY, SILVA ZOLEZZI IRMA
Принадлежит: NESTEC S.A.

Compositions can comprise the flavanol metabolite 4′-O-glucuronide epicatechin (4GEC). In some embodiments, the composition can be used in a method for blood vessel dilation and/or increased delivery of blood flow to tissues in the body, for example by administering the composition to an individual having or at risk of high blood pressure or a cardiovascular disease. In some embodiments, the compositions are used for weight maintenance or weight loss. The compositions are preferably administered orally as a food product in which the 4′-Oglucuronide is present in a concentration of at least 0.01 mg/g of the food product. 1. A method for blood vessel dilation and/or increased delivery of blood flow to tissues in the body , the method comprising administering a composition comprising 4′-O-glucuronide epicatechin to an individual.2. The method of wherein the composition is orally administered to the individual as a food product in which the 4′-O-glucuronide epicatechin is present in a concentration of at least 0.01 mg/g of the food product.3. The method of wherein the composition is administered to the individual at least once a day for at least one week.4. The method of wherein the 4′-O-glucuronide epicatechin is chemically synthesized.5. (canceled)6. The method of wherein the individual has or is at risk of a cardiovascular disease.7. The method of wherein the composition is administered to the individual in an amount that achieves a therapeutic effect selected from the group consisting of reduced blood pressure claim 1 , stimulation of protein synthesis claim 1 , improvement of blood circulation claim 1 , improvement of blood brain circulation claim 1 , increased release of growth factors claim 1 , enhanced immune function claim 1 , and combinations thereof claim 1 , the method comprising administering to the individual a composition comprising 4′-O-glucuronide epicatechin.8. The method of wherein the composition is administered to the individual in an amount that ...

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Номер записи: 16
04-01-2018 дата публикации

METHOD FOR PRODUCING 5-HYDROXYPIPERIDINE-2-CARBOXYLIC ACID

Номер: US20180002286A1
Автор: HIDAKA Tsugihiko, MAEDA Tomoko, MURAI Masato, OHTANI TAKASHI, Takehara Jun
Принадлежит: API Corporation

A method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid represented by the formula (10) below: The present application is a Divisional application of U.S. application Ser. No. 15/108,141, filed Jun. 24, 2016, which is a National Stage of international Patent Application No. PCT/JP2014/084518 filed Dec. 26, 2014, which claims priority to Japanese Application No. 2013-272766 filed Dec. 27, 2013. The disclosures of U.S. application Ser. No. 15/108,141 and International Patent Application No. PCT/JP2014/084518 are incorporated by reference herein in their entireties.The present invention relates to a method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid and synthetic intermediates thereof (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid, which is produced by the method of the present invention, is useful as a synthetic intermediate for a β-lactamase inhibitor and the like.(2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid is a useful intermediate for the synthesis of an agent and the like that inhibits β-lactamases in bacteria exhibiting the resistance against the β-lactam class of antibiotics, which β-lactamases are the major cause of the resistance in the bacteria.A production method using glutamic acid or pyroglutamic acid as a starting raw material has been known as a method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid. Specifically, Patent Document 1 describes that a protected 5-hydroxypiperidine-2-carboxylic acid compound as an intermediate of N-protected oxo-azacycloalkylcarboxylic acids is produced from pyroglutamic acid as a starting raw material through the homologation process to increase carbon atoms and the cyclization process.Moreover, Non-Patent Document 1 describes that a protected 5-hydroxypiperidine-2-carboxylic acid compound is produced from glutamine as a starting raw material through the homologation process to increase carbon atoms and the cyclization process.Non-Patent ...

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Номер записи: 17
03-01-2019 дата публикации

CARBOXAMIDE DERIVATIVES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B

Номер: US20190002406A1
Автор: Haché Geerwin Yvonne Paul, Kesteleyn Bart Rudolf Romanie, Raboisson Pierre Jean-Marie Bernard, Vandyck Koen
Принадлежит:

Inhibitors of HBV replication of formula (I) 113.-. (canceled)14. A compound selected from the group consisting of:(S)—N-(3-bromo-4,5-difluorophenyl)-1-(2-oxo-2-(((R)-1,1,1-trifluoropropan-2-yl)amino)acetyl)pyrrolidine-3-carboxamide;(S)—N-(3-bromo-4,5-difluorophenyl)-1-(2-((3-methyloxetan-3-yl)amino)-2-oxoacetyl)pyrrolidine-3-carboxamide;(S)—N-(3-bromo-4,5-difluorophenyl)-1-(2-(tert-butylamino)-2-oxoacetyl)pyrrolidine-3-carboxamide;(3S)—N-(4-fluoro-3-methylphenyl)-1-{[(1-methylethyl)amino] (oxo)acetyl}pyrrolidine-3-carboxamide;(S)-1-(2-(cyclopentylamino)-2-oxoacetyl)-N-(4-fluoro-3-methylphenyl)pyrrolidine-3-carboxamide;(S)—N-(4-fluoro-3-methylphenyl)-1-(2-(((R)-1-hydroxypropan-2-yl)amino)-2-oxoacetyl)pyrrolidine-3-carboxamide;(3S)—N-(4-fluoro-3-methylphenyl)-1-{[(3-methyloxetan-3-yl)amino]-(oxo)acetyl}pyrrolidine-3-carboxamide;(3S)—N-(4-fluoro-3-methylphenyl)-1-[{[(1R)-1-methylpropyl]amino}(oxo)acetyl]pyrrolidine-3-carboxamide;(3S)—N-(4-fluoro-3-methylphenyl)-1-{oxo[(3S)-tetrahydrofuran-3-ylamino]-acetyl}pyrrolidine-3-carboxamide;(2S,3S)—N-(4-fluoro-3-methylphenyl)-2-methyl-1-{[(3-methyloxetan-3-yl)-amino](oxo)acetyl}pyrrolidine-3-carboxamide;(S)—N-(3-chloro-4,5-difluorophenyl)-1-(2-oxo-2-(((R)-1,1,1-trifluoropropan-2-yl)amino)acetyl)pyrrolidine-3-carboxamide;(3S)—N-(4-fluoro-3-methylphenyl)-1-{[(1-methylethyl)amino] (oxo)acetyl}piperidine-3-carboxamide;(S)—N-(3-chloro-4,5-difluorophenyl)-1-(2-oxo-2-((1-(trifluoromethyl) cyclopropyl)amino)acetyl)pyrrolidine-3-carboxamide;(S)—N-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(2-oxo-2-(((R)-1,1,1-trifluoropropan-2-yl)amino)acetyl)pyrrolidine-3-carboxamide;(S)—N-(3-chloro-4-fluorophenyl)-1-(2-oxo-2-(((R)-1,1,1-trifluoropropan-2-yl)amino)acetyl)pyrrolidine-3-carboxamide;(S)—N-(3-chloro-4,5-difluorophenyl)-1-(2-oxo-2-((1,1,1-trifluoro-2-methylpropan-2-yl)amino)acetyl)pyrrolidine-3-carboxamide;N-(4-fluoro-3-methylphenyl)-5-methyl-1-(2-((3-methyloxetan-3-yl)amino)-2-oxoacetyl)pyrrolidine-3-carboxamide;N-(3-chloro-4,5-difluoro- ...

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Номер записи: 18
07-01-2021 дата публикации

PIPECOLIC ESTERS FOR INHIBITION OF THE PROTEASOME

Номер: US20210002220A1
Автор: Gaczynska Maria, Giletto Matt, Osmulski Pawel A., Tepe Jetze
Принадлежит:

The present disclosure relates to chemical compounds that modulate proteasome activity, pharmaceutical compositions containing such compounds, and use of these compounds and compositions for the treatment of disorders of uncontrolled cellular proliferation such as, for example, a cancer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention. 2. The compound of claim 1 , wherein n is 1.34-. (canceled)5. The compound of claim 1 , wherein Ris selected from (CH)Cyand Cy.6. The compound of claim 1 , wherein Ris CHCy.710-. (canceled)1315-. (canceled)16. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of and a pharmaceutically acceptable carrier.1720-. (canceled) This application claims the benefit of U.S. Provisional Application No. 62/623,861, filed on Jan. 30, 2018, the contents of which is incorporated herein by reference in its entirety.The Sequence Listing submitted Jan. 30, 2019 as a text file named “21105_0050P1_ST25.txt,” created on Jan. 30, 2019, and having a size of 496 bytes is hereby incorporated by reference pursuant to 37 C.F.R. § 1.52(e)(5).The proteasome is an essential protease that regulates intracellular processes and maintains biological homeostasis through the proteolytic degradation of misfolded and redundant proteins (Glickman et al. (2002) 82: 373-428). Inhibition of the proteasome induces apoptosis, which has translated in the clinic as a means to treat various cancers, most notably multiple myeloma and mantle cell lymphoma (Jankowska et al. (2013) 19: 1010-1028; Adams, J. (2004) 4: 349-360; Kuhn et al. (2011) 11: 285-295). The activities of the proteasome, the essential, multifunctional human proteolytic assembly, are not infrequently found to be affected by compounds with non-proteasomal primary targets. For example, this is the case with chloroquine (Sprangers et al. (2008) 47: 6727-6734), ...

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Номер записи: 19
13-01-2022 дата публикации

CRYSTALLINE FREEBASE FORMS OF A BIPHENYL COMPOUND

Номер: US20220009890A1
Автор: Woollam Grahame
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

The invention provides two crystalline freebase forms of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester. The invention also provides pharmaceutical compositions comprising the crystalline freebase or prepared using the crystalline freebases; processes and intermediates for preparing the crystalline freebases; and methods of using the crystalline freebases to treat a pulmonary disorder. 120-. (canceled)21. A method for producing bronchodilation in a human , the method comprising:(a) preparing a pharmaceutical composition by dissolving a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester in an aqueous pharmaceutical carrier; wherein the crystalline freebase is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1; and(b) administering the pharmaceutical composition to the human using a nebulizer.22. The method of claim 21 , wherein the crystalline freebase is further characterized by five or more additional diffraction peaks at 2θ values selected from 8.8±0.1 claim 21 , 10.1±0.1 claim 21 , 11.4±0.1 claim 21 , 11.6±0.1 claim 21 , 14.8±0.1 claim 21 , 15.2±0.1 claim 21 , 16.1±0.1 claim 21 , 16.4±0.1 claim 21 , 16.9±0.1 claim 21 , 17.5±0.1 claim 21 , 18.2±0.1 claim 21 , 19.3±0.1 claim 21 , 19.9±0.1 claim 21 , 20.8±0.1 claim 21 , 21.1±0.1 claim 21 , 21.7±0.1 claim 21 , and 22.3±0.1.23. The method of claim 21 , wherein the crystalline freebase is further characterized by a powder x-ray diffraction pattern having peak positions substantially in accordance with the peak positions shown in .24. The method of claim 21 , wherein the crystalline freebase is further characterized by a melting point of about 125° C.25. The method of claim 21 , wherein the crystalline freebase is further characterized by a differential scanning ...

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Номер записи: 20
01-01-2015 дата публикации

ANTIVIRAL COMPOUNDS

Номер: US20150005283A1
Автор: Cheung Adrian Wai-Hing, Schoenfeld Ryan Craig, Yun Weiya, Zhao Shu-Hai
Принадлежит: Hoffmann-La Roche Inc.

The present invention provides compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection. 2. The compound of claim 2 , wherein Ris H and X is CH.3. The compound of claim 2 , wherein n is 2.4. The compound of claim 2 , wherein n is 1.5. The compound of claim 4 , wherein Ris —C(═O)N(R) claim 4 ,6. The compound of claim 4 , wherein Ris monocyclic or bicyclic heteroaryl claim 4 , optionally substituted with one or more R.7. The compound of claim 4 , wherein Ris —C(═O)OR.8. The compound of claim 7 , wherein R is lower alkyl.9. The compound of claim 8 , wherein Ris lower alkyl or cycloalkyl.10. The compound of claim 9 , wherein Ris cyclohexyl.11. A compound selected from the group consisting of:(2S,4S)-1-Cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic acid tert-butyl ester;(2S,4S)-1-(3,3-Dimethyl-butyl)-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic acid methyl ester;(2S,4R)-1-Cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-piperidine-2-carboxylic acid ethyl ester;(2S,4S)-1-Cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic acid ethyl ester;1-Hydroxy-naphthalene-2-carboxylic acid ((3S,5S)-5-benzooxazol-2-yl-1-cyclohexylmethyl-pyrrolidin-3-yl)-amide;(2S,4R)-1-Cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-piperidine-2-carboxylic acid methyl ester;1-Hydroxy-naphthalene-2-carboxylic acid [(3S,5S)-1-cyclohexylmethyl-5-(5-methyl-oxazol-2-yl)-pyrrolidin-3-yl]-amide;1-Hydroxy-naphthalene-2-carboxylic acid [(3S,5S)-1-cyclohexylmethyl-5-(5-phenyl-oxazol-2-yl)-pyrrolidin-3-yl]-amide;1-Hydroxy-naphthalene-2-carboxylic acid ((3S,5S)-1-cyclohexylmethyl-5-oxazol-2-yl-pyrrolidin-3-yl)-amide;(2S,4S)-1-Cyclohexylmethyl-4-[(1-hydroxy-naphthalene-2-carbonyl)-amino]-pyrrolidine-2-carboxylic ...

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Номер записи: 21
14-01-2021 дата публикации

Automated Synthesis of Small Molecules Using Chiral, Non-Racemic Boronates

Номер: US20210009508A1
Автор: Burke Martin D., Gillis Eric P., LI Junqi
Принадлежит:

Provided are methods for making and using chiral, non-racemic protected organoboronic acids, including pinene-derived iminodiacetic acid (PIDA) boronates, to direct and enable stereoselective synthesis of organic molecules. Also provided are methods for purifying PIDA boronates from solution. Also provided are methods for deprotection of boronic acids from their PIDA ligands. The purification and deprotection methods may be used in conjunction with methods for coupling or otherwise reacting boronic acids. Iterative cycles of deprotection, coupling, and purification can be performed to synthesize chiral, non-racemic compounds. The methods are suitable for use in an automated chemical synthesis process. Also provided is an automated small molecule synthesizer apparatus for performing automated stereoselective synthesis of chiral, non-racemic small molecules using iterative cycles of deprotection, coupling, and purification. 1144-. (canceled)145. A method of deprotecting a pinene-derived iminodiacetic acid (PIDA) boronate , comprising:contacting a solution comprising the chiral, non-racemic PIDA boronate and a solvent with a solid-supported ammonium hydroxide reagent, thereby deprotecting the chiral, non-racemic PIDA boronate and forming a boronic acid and a PIDA.146. The method of claim 145 , wherein the solvent comprises THF.147. The method of claim 145 , wherein the solid-supported ammonium hydroxide reagent binds the PIDA.148. The method of claim 145 , further comprising the steps of removing the solvent by filtration claim 145 , leaving the boronic acid and PIDA ligand trapped inside the solid-supported ammonium hydroxide reagent; and adding additional solvent.149. The method of claim 148 , wherein the additional solvent is THF.150. The method of claim 145 , further comprising washing the solid-supported ammonium hydroxide reagent with an organic solution comprising an organic solvent and an acid in a quantity greater than that needed to neutralize the solid- ...

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Номер записи: 22
21-01-2016 дата публикации

AMINO- OR AMMONIUM-CONTAINING SULFONIC ACID, PHOSPHONIC ACID AND CARBOXYLIC ACID DERIVATIVES AND THEIR MEDICAL USE

Номер: US20160016981A1
Автор: Braxmeier Tobias, Friedrichson Tim, Jennings Gary, Knölker Hans-Joachim, Schlechtingen Georg
Принадлежит: GLYCOREGIMMUNE, INC.

The present invention relates to amino- or ammonium-containing sulfonic acid, phosphonic acid and carboxylic acid derivatives, in particular the compounds of formula 1, 2, 3, 4, 5 or 6, and their medical use, including their use in the treatment, prevention or amelioration of an inflammatory, autoimmune and/or allergic disorder.

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Номер записи: 23
15-01-2015 дата публикации

PIPECOLATE-DIKETOAMIDES FOR TREATMENT OF PSYCHIATRIC DISORDERS

Номер: US20150018340A1
Автор: Gopalakrishnan Ranganath, Hausch Felix
Принадлежит:

The present invention relates to compounds having a pipecolate diketoamide scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds together with pharmaceutically acceptable carrier, excipient and/or diluents. Said pipecolate diketoamide compounds can be used for prophylaxis and/or treatment of psychiatric disorders and neurodegenerative diseases, disorders and conditions. 5. Compound according to selected from the group consisting of:2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1S,2R)-1-hydroxy-2-methylcyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid,(S)—((R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)propyl) 1-(2-((1S,2R)-1-hydroxy-2-methylcyclohexyl)-2-oxoacetyl)piperidine-2-carboxylate,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1S,2R)-2-ethyl-1-hydroxy-cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid,(S)—((R)-3-(3,4-dimethoxyphenyl)-1-(3-(2-morpholinoethoxy)phenyl)propyl)1-(2-((1S,2R)-2-ethyl-1-hydroxycyclohexyl)-2-oxoacetyl)piperidine-2-carboxylate,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1S,2S)-1-hydroxy-2-(hydroxyl methyl)cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1R,2R)-1-hydroxy-2-methyl cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-((1R,2R)-2-ethyl-1-hydroxy cyclohexyl)-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-(2-cyclohexyl-2-oxoacetyl)piperidine-2-carbonyloxy)propyl)phenoxy) acetic acid,2-{3-[(1R)-3-(3,4-dimethoxyphenyl)-1-({1-[2-oxo-2-(3,4,5-trimethoxyphenyl)acetyl]piperidin-2-yl}carbonyloxy)propyl]phenoxy}acetic acid,2-(3-((R)-3-(3,4-dimethoxyphenyl)-1-((S)-1-(2-oxo-2-(4-phenoxyphenyl)acetyl)piperidine-2-carbonyloxy)propyl)phenoxy)acetic acid, and2-(3-((R)-3-(3,4-dimethoxyphenyl)-1 ...

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Номер записи: 24
26-01-2017 дата публикации

PROCESSES FOR PREPARING HETEROCYCLIC COMPOUNDS INCLUDING TRANS-7-OXO-6-(SULPHOOXY)-1,6-DIAZABICYCLO[3,2,1]OCTANE-2-CARBOXAMIDE AND SALTS THEREOF

Номер: US20170022160A1
Автор: Boyd Alistair, Cherryman Janette, Dedhiya Mahendra G., Golden Michael, Kalyan Yuriy B., Lawton Graham Richard, Milne David, Phillips Andrew, Racha Saibaba, Ronsheim Melanie Simone, TELFORD Alexander, Zhou Shao Hong
Принадлежит:

The present invention relates to compounds and processes for preparing compounds of Formula (I), 114-. (canceled)16. The compound of claim 15 , wherein R5 is benzyloxy and R6 and R7 are hydrogen.17. The compound of claim 15 , wherein R5 is allyl or trialkylsilyl and R6 and R7 are hydrogen.18. The compound of claim 15 , wherein R5 is benzyloxy and R1 claim 15 , R2 claim 15 , R6 and R7 are hydrogen.19. The compound of claim 15 , wherein R1 is a heterocycle.20. The compound of claim 15 , wherein R7 is amide.21. The compound of claim 15 , herein R1 is piperidinyl claim 15 , R5 is benzyloxy and R2 claim 15 , R6 and R7 are hydrogen.22. The compound of claim 15 , wherein R1 claim 15 , R2 and R6 are hydrogen.23. The compound of claim 15 , wherein R5 is OSOH.24. The compound of claim 15 , wherein R1 claim 15 , R2 and R6 are hydrogen claim 15 , R5 is OSOH and R7 is carbamoyl.25. The compound of claim 15 , wherein R1 is piperidinyl claim 15 , R2 and R6 are hydrogen claim 15 , R5 is OSOh and R7 is carbamoyl.2644-. (canceled)45. A pharmaceutical composition comprising the compound of or a salt thereof claim 15 , and a pharmaceutical acceptable carrier.48. A pharmaceutical composition comprising the compound of or a salt thereof claim 45 , and a pharmaceutical acceptable carrier. This application claims priority under 35 U.S.C. §119, based on U.S. Provisional Application Ser. No. 61/498,522 filed on Jun. 17, 2011, which is hereby incorporated by reference in its entirety.The present invention relates to novel compounds and processes for preparing compounds of Formula (I), including compounds such as trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide and salts thereof (e.g., NXL-104).U.S. Pat. No. 7,112,592 discloses novel heterocyclic compounds and their salts, processes for making the compounds and methods of using the compounds as antibacterial agents. One such compound is sodium salt of trans-7-oxo-6-(sulphooxy)-1,6-diazabicyclo[3,2,1]octane-2-carboxamide. ...

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Номер записи: 25
01-02-2018 дата публикации

S1P MODULATING AGENTS

Номер: US20180028511A1
Автор: Caldwell Richard D., Guckian Kevin M., Kumaravel Gnanasambandam, Lin Edward Yin-Shiang, Ma Bin, MI SHA, Thomas Jermaine, Zheng Guo Zhu
Принадлежит:

Compounds of formula (I) or (II) can modulate the activity of S1P receptors. 132-. (canceled)33. A method for treating stroke in a mammal , comprising administering to said mammal an effective amount of a compound selected from the group consisting of:1-((6-(trans-4-tert-butylcyclohexyloxy)quinazolin-2-yl)methyl)piperidine-4-carboxylic acid;1-(1-(6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)-2,2,2-trifluoroethyl)piperidine-4-carboxylic acid;1-((6-(4-isopropylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(cis-4-tert-butylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(4-butylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(spiro[4.5]decan-8-yloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(cis-4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(trans-4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((6-(trans-4-tert-butylcyclohexyloxy)quinolin-2-yl)methyl)piperidine-4-carboxylic acid;1-(6-(trans-4-tert-butylcyclohexyloxy)-2-naphthoyl)piperidine-4-carboxylic acid;1-((6-((4-tert-butylcyclohexylidene)methyl)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid;1-((2-(trans-4-tert-butylcyclohexyloxy)quinolin-6-yl)methyl)piperidine-4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-ethyl-piperidine-4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-propyl-piperidine- 4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-3-methyl-piperidine-4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-4-phenyl-piperidine-4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-perhydro-azepine-4-carboxylic acid;1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2 ...

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Номер записи: 26
29-01-2015 дата публикации

Pharmaceutical Compositions with Attenuated Release of Phenolic Opioids

Номер: US20150031635A1
Автор: Jenkins Thomas E., Seroogy Julie D., Wray Jonathan W.
Принадлежит:

Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise a phenolic opioid prodrug that provides enzymatically-controlled release of a phenolic opioid, and an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of the phenolic opioid from the prodrug so as to attenuate enzymatic cleavage of the prodrug. 148-. (canceled)49. A pharmaceutical composition , which comprises a trypsin inhibitor and a compound of general formula (II):{'br': None, 'sup': 1', '2', '3', '4', '5, 'sub': 'n', 'X—C(O)—NR—(C(R)(R))—NH—C(O)—CH(R)—NH(R)\u2003\u2003(II)'}or a pharmaceutically acceptable salt thereof, in which:{'sup': 1', '2', '3', '4', '5, 'sub': 'n', 'X represents a residue of a phenolic opioid selected from the group consisting of buprenorphine, dihydroetorphine, diprenorphine, etorphine, hydromorphone, levorphanol, morphine, nalmefene, naloxone, N-methylnaloxone, naltrexone, N-methylnaltrexone, oxymorphone, oripavine, ketobemidone, dezocine, pentazocine, phenazocine, butorphanol, nalbuphine, meptazinol, O-desmethyltramadol, tapentadol, and nalorphine, wherein the hydrogen atom of the phenolic hydroxyl group is replaced by a covalent bond to —C(O)—NR—(C(R)(R))—NH—C(O)—CH(R)—NH(R);'}{'sup': '1', 'Ris selected from alkyl, substituted alkyl, arylalkyl, substituted arylalkyl, aryl and substituted aryl;'}{'sup': '2', 'each Ris independently selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, acyl, and aminoacyl;'}{'sup': '3', 'each Ris independently selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, acyl, and aminoacyl;'}{'sup': 2', '3', '2', '3, 'or Rand Rtogether with the carbon to which they are attached form a cycloalkyl or substituted cycloalkyl group, or two Ror Rgroups on adjacent carbon atoms, together with the carbon atoms to which they are attached, form a cycloalkyl or substituted cycloalkyl group;'}n represents an integer ...

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Номер записи: 27
29-01-2015 дата публикации

CYCLIC AMIDES AS METAP-2 INHIBITORS

Номер: US20150031670A1
Автор: FRIESE-HAMIM Manja, Heinrich Timo, Krier Mireille, SEENISAMY Jeyaprakashnarayanan, Zenke Frank
Принадлежит: Merck Patent GmBH

Compounds of the formula (I), in which R, R, R, R, R, R, X and Y have the meanings indicated in Claim , are inhibitors of methionine aminopeptidase and can be employed for the treatment of tumours. 2. Compounds according to in which{'sub': 2', '2', '2', '2', 'n', '2', '2', 'n', '2', 'n', '2', '2', '2', '2', '2', '2', '2', '2, 'sup': 1', '3', '3, 'Het denotes pyrazinyl, pyrazolyl, benzimidazolyl, pyridyl, indolyl, dihydroindolyl, benzofuranyl, tetrahydropyranyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, indazolyl, imidazolyl, pyrrolyl, oxazolyl, oxadiazolyl, isoxazolyl, benzothiazolyl, piperidin-1-yl, pyrrolidin-1-yl, 3,4-dihydro-2H-pyrido[3,2-b]-1,4-oxazinyl, 3,4-dihydro-2H-benzo-1,4-oxazinyl, benzofuranyl, azetidinyl, 3-azabicylo[3.2.0]hexyl, pyrrolo[2,3-b]pyridinyl, tetrahydrofuranyl, tetrahydro-1,8-naphthyridinyl, 2,3-dihydrobenzoisothiazolyl, 1,2,3,4-tetrahydrobenzothiazinyl or hexahydrobenzo-1,3-dioxolyl, each of which is unsubstituted or mono-, di- or trisubstituted by Hal, A, OA, CN, NH, NHA, NA, NO, CN, COOH, COOA, (CH)CONH, (CH)CONHA, (CH)CONA, NHCOA, COA, CHO, Het, SOA, SONH, SONHA, SONA, CONHNH, CONHAr, ═O and/or Ar,'}and pharmaceutically usable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.3. Compounds according to in which{'sup': '1', 'Hetdenotes pyridazinyl, pyrazolyl, pyridyl, piperazinyl, morpholinyl, pyrimidinyl, furyl, thienyl, imidazolyl, pyrrolyl, oxazolyl, oxadiazolyl, isoxazolyl, thiazolyl, triazolyl, tetrazolyl, thiadiazole, piperidin-1-yl, pyrrolidin-1-yl, tetrahydropyranyl, 1,2-oxazinan-2-yl, 1,2,5-oxadiazinan-2-yl, 1,3-oxazinan-3-yl or hexahydropyrimidinyl, each of which is unsubstituted or mono-, di- or trisubstituted by A and/or OA,'}and pharmaceutically usable salts, tautomers and stereoisomers thereof, including mixtures thereof in all ratios.4. Compounds according to in which{'sup': 2', '4', '4', '2', '2', '4', '2, 'sub': 2', '2', 'n', '2', 'n, 'R ...

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Номер записи: 28
05-02-2015 дата публикации

THROMBIN INHIBITORS

Номер: US20150038498A1
Автор: Biftu Tesfaye, Blizzard Timothy Allen
Принадлежит:

Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: (I) or a pharmaceutically acceptable salt thereof, wherein Q is CH, NR, O, S, S(O) or S(O), wherein Ris H, Calkyl, aryl, or Ccycloalkyl; Ris a heterocycle or —(CRR)1-2NH2, wherein Rand R, each time in which they occur, are independently H, Calkyl, —CHF, —CHF, CFor —CHOH; Ris OH, NHor NHSOCH; and Ris Calkyl. 3. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris tetrazole or —CHNH.4. A compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein Ris —CHNH.5. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris OH.6. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —C(CH).7. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H or CH.8. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.9. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.11. A compound of claim 1 , or pharmaceutically acceptable salt thereof claim 1 , which is(2S)—N-[2-(aminomethyl)-5-chlorobenzyl]-1-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]piperidine-2-carboxamide,(2S)—N-[2-(aminomethyl)-5-chlorobenzyl]-1-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]piperazine-2-carboxamide,(2S)—N-[2-(aminomethyl)-5-chlorobenzyl]-1-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]-4-methylpiperazine-2-carboxamide,(3 S)—N-[2-(aminomethyl)-5-chlorobenzyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]morpholine-3-carboxamide,(3R)—N-[2-(aminomethyl)-5-chlorobenzyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]thiomorpholine-3-carboxamide,(3R)—N-[2-(aminomethyl)-5-chlorobenzyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]thiomorpholine-3-carboxamide 1-oxide, or(3R)—N-[2-(aminomethyl)-5-chlorobenzyl]-4-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]thiomorpholine-3- ...

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Номер записи: 29
11-02-2016 дата публикации

CYTOTOXIC AND ANTI-MITOTIC COMPOUNDS, AND METHODS OF USING THE SAME

Номер: US20160038606A1
Автор: BABCOOK John, Bourque Elyse Marie Josee, HEDBERG Bradley John, HSIEH Tom Han Hsiao, MANDEL Alexander Laurence, RICH James R., Winters Geoffrey C.
Принадлежит:

Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity. 4. The compound according to or , wherein each optionally substituted alkyl , optionally substituted alkylamino , optionally substituted cycloalkyl , optionally substituted aryl , optionally substituted heterocyclyl and optionally substituted heteroaryl is , independently , optionally substituted with ═O , ═S , —OH , —OR , —OCR , —SH , —SR , —SOCR , —NH , —N , —NHR , —N(R) , —NHCOR , —NRCOR , —I , —Br , —Cl , —F , —CN , —COH , —COR , —CHO , —COR , —CONH , —CONHR , —CON(R) , —COSH , —COSR , —NO , —SOH , —SORor —SORwherein each Ris , independently , alkyl optionally substituted with halogen , —OH or —SH.5. The compound according to or , wherein each optionally substituted aryl and optionally substituted heteroaryl is , independently , selected from the group consisting of optionally substituted phenyl , optionally substituted naphthyl , optionally substituted anthracyl , optionally substituted phenanthryl , optionally substituted furyl , optionally substituted pyrrolyl , optionally substituted thiophenyl , optionally substituted benzofuryl , optionally substituted benzothiophenyl , optionally substituted quinolinyl , optionally substituted isoquinolinyl , optionally substituted imidazolyl , optionally substituted thiazolyl , optionally substituted oxazolyl , and optionally substituted pyridinyl.128. The composition according to any one of - wherein R claims 2 , R claims 2 , and R claims 2 , are each methyl.138. The composition according to any one of - claims 2 , wherein Ris H claims 2 , Ris methyl claims 2 , and Ris methyl.1413. A pharmaceutical composition ...

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Номер записи: 30
06-02-2020 дата публикации

S1P MODULATING AGENTS

Номер: US20200038385A1
Автор: Caldwell Richard D., Guckian Kevin, Kumaravel Gnanasambandam, Lin Edward Yin-Shiang, Ma Bin, MI SHA, Thomas Jermaine, Zheng Guo Zhu
Принадлежит:

Compounds of formula (I) or (II) can modulate the activity of S1P receptors. 132-. (canceled)34. The method of claim 33 , wherein the compound is 1-((6-(trans-4-tert-butylcyclohexyloxy)quinazolin-2-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.35. The method of claim 33 , wherein the compound is 1-(1-(6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)-2 claim 33 ,2 claim 33 ,2-trifluoroethyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.36. The method of claim 33 , wherein the compound is 1-((6-(spiro[4.5]decan-8-yloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.37. The method of claim 33 , wherein the compound is 1-((6-(cis-4-ethylcyclohexyloxy)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.38. The method of claim 33 , wherein the compound is 1-((6-(trans-4-tert-butylcyclohexyloxy)quinolin-2-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.39. The method of claim 33 , wherein the compound is 1-(6-(trans-4-tert-butylcyclohexyloxy)-2-naphthoyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.40. The method of claim 33 , wherein the compound is 1-((6-((4-tert-butylcyclohexylidene)methyl)naphthalen-2-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.41. The method of claim 33 , wherein the compound is 1-((2-(trans-4-tert-butylcyclohexyloxy)quinolin-6-yl)methyl)piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.42. The method of claim 33 , wherein the compound is 1-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-ylmethyl]-3-methyl-piperidine-4-carboxylic acid claim 33 , or a pharmaceutically acceptable salt thereof.43. The method of claim 33 , wherein the compound is 1-[6-(4-tert-butyl- ...

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Номер записи: 31
15-02-2018 дата публикации

Process for preparing piperidine-4-carbothioamide hydrochloride

Номер: US20180044294A1
Автор: Bruenjes Marco, Ford Mark James
Принадлежит: Bayer CropScience Aktiengesellschaft

The present invention describes a novel process for preparing piperidine-4-carbothioamide hydrochloride. 2. Process according to claim 1 , wherein the base used is triethylamine claim 1 , 3-picoline claim 1 , di-n-butylamine or n-butylamine.3. Process according to claim 1 , wherein the base used is triethylamine.4. Process according to claim 1 , wherein the reaction is conducted in a closed reaction vessel.5. Process according to claim 1 , wherein the reaction is conducted at a reaction temperature of ≧0° C. claim 1 , optionally at 20° C. to 100° C. claim 1 , optionally at 40° C. to 80° C.6. Process according to claim 1 , wherein the solvent is a primary claim 1 , secondary or tertiary alcohol or a mixture thereof or any of said alcohols mixed with one or more further solvents.7. Process according to claim 1 , wherein the solvent is an alcohol having 1 to 10 carbon atoms.8. Process according to claim 1 , wherein the solvent is methanol claim 1 , ethanol claim 1 , isopropanol claim 1 , tert-butanol claim 1 , i-butanol claim 1 , n-butanol claim 1 , cyclopentanol or cyclohexanol. The present invention relates to a novel process for preparing piperidine-4-carbothioamide hydrochloride (I).Piperidine-4-carbothioamide derivatives are important precursors for active pharmaceutical and agrochemical ingredients (cf. WO 2008/013622, WO 2011/072207 and WO 2011/076699).The preparation of 4-cyanopiperidine, as a starting material for the preparation of piperidine-4-carbothioamide, generally proceeds from the piperidine-4-carbamide and is known from various literature references and patents (J. Org. Chem. 1957, 22, 984-986; US 2006/0084808). Dewatering, for example by means of phosphorus oxychloride or thionyl chloride, at first gives rise to the corresponding 4-cyanopiperidine hydrochloride which, after neutralization with a suitable base and subsequent extraction, gives access to the free amine (4-cyanopiperidine).The preparation of piperidine-4-thioamide is again effected with ...

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Номер записи: 32
03-03-2022 дата публикации

Novel high penetration drugs and their compositions thereof for treatment of parkinson diseases

Номер: US20220064157A1
Автор: Chongxi Yu, Lina Xu
Принадлежит: Techfields Pharma Co Ltd

One aspect of the invention provides a composition of novel high penetration compositions (HPC) or a high penetration prodrug (HPP) for treatment of Parkinson's disease. The HPCs/HPPs are capable of being converted to parent active drugs or drug metabolites after crossing the biological barrier and thus can render treatments for the conditions that the parent drugs or metabolites can. Additionally, the HPPs are capable of reaching areas that parent drugs may not be able to access or to render a sufficient concentration at the target areas and therefore render novel treatments. The HPCs/HPPs can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

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Номер записи: 33
14-02-2019 дата публикации

TRANS-ISOMERIC HETEROCYCLIC COMPOUNDS AND PREPARATION THEREOF

Номер: US20190047956A1
Автор: Chen Wen-Chang, Chou Shan-Yen, Hsu Han-Pei, Hsu Ming-Chu, Lin Chu-Chung, Yen Chi-Feng
Принадлежит:

A trans-isomeric compound of formula (I) below or a pharmaceutically acceptable salt thereof: 2. The compound of claim 1 , wherein Ris C-Calkyl.3. The compound of claim 2 , wherein Ris methyl.8. The method of claim b claim 2 , wherein Ris C-Calkyl.9. The method of claim 8 , wherein Ris methyl.10. The method of claim 6 , wherein the palladium catalyst is Pd(OH)/C claim 6 , Pd/C claim 6 , Pd(OAc) claim 6 , Pd/AlO claim 6 , or a combination thereof claim 6 , optionally containing Pt/C or Rh/C; and the content of palladium in the palladium catalyst is 0.01 wt % to 30 wt %.11. The method of claim 6 , wherein the inert solvent is HO claim 6 , a C-Cester claim 6 , a C-Ccycloalkane claim 6 , tetrahydrofuran (THF) claim 6 , dimethylformamide (DMF) claim 6 , acetonitrile claim 6 , a C-Calcohol claim 6 , an alkylene glycol monoalkyl ether claim 6 , an alkylene glycol monoalkyl ether carboxylate claim 6 , an amide-based solvent claim 6 , an organic acid claim 6 , or a combination thereof claim 6 , optionally combined with one or more inorganic acids.12. The method of claim 11 , wherein the inert solvent is HO claim 11 , a C-Cester claim 11 , a C-Ccycloalkane claim 11 , THF claim 11 , DMF claim 11 , a C-Calcohol claim 11 , propylene glycol monomethyl ether claim 11 , propylene glycol monomethyl ether acetate claim 11 , N claim 11 ,N-dimethylacetamide claim 11 , a C-Ccarboxylic acid claim 11 , a C-Csulfonic acid claim 11 , or a combination thereof claim 11 , optionally combined with hydrochloric acid.13. The method of claim 12 , wherein the inert solvent is HO claim 12 , methanol claim 12 , ethanol claim 12 , isopropanol claim 12 , formic acid claim 12 , acetic acid claim 12 , ethyl acetate claim 12 , methanesulfonic acid claim 12 , or a combination thereof claim 12 , optionally combined with hydrochloric acid.14. The method of claim 11 , wherein the inert solvent is an organic acid or a combination of the organic acid with one or more solvents selected from the group consisting ...

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Номер записи: 34
14-02-2019 дата публикации

BIPHENYL COMPOUNDS USEFUL AS MUSCARINIC RECEPTOR ANTAGONISTS

Номер: US20190047957A1
Автор: Husfeld Craig, Ji YuHua, Li Li, Mammen Mathai, Mu YongQi
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

This invention provides compounds of formula I:

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Номер записи: 35
14-02-2019 дата публикации

SYNTHETIC PROCESSES AND INTERMEDIATES

Номер: US20190048024A1
Автор: Athunuri Savi Rami Reddy, Korrakuti Thrisulapani, Parhi Ajit S., Ponnaiah Ravi, Seelam Pullarao, Soni Anil Kumar, Sunkari Sudhakar
Принадлежит: TAXIS PHARMACEUTICALS, INC.

The invention provides synthetic processes and synthetic intermediates that can be used to prepare a compound of formula (I): or a salt thereof. 4. The method of further comprising preparing a nitro pyridine of formula f by reacting 2-chloro-3-nitro-5-(trifluoromethyl)pyridine with thiourea to provide the nitro pyridine of formula f.9. The method of further comprising preparing the compound of formula a by converting a 2 claim 8 ,4-difluorophenol to the compound of formula a. This application claims priority to Indian Application No. 201641006639 filed on 25 Feb. 2016. The entire contents of the foregoing are incorporated herein by reference.International Patent Application Publication Number WO 2014/074932 reports a series of soluable compounds that are useful as antibiotic agents. One of these compounds, the compound of formula (I):is currently being evaluated for potential use as an antibacterial agent in humans.Currently there is a need for improved synthetic processes and new synthetic intermediates that can be used to prepare commercial quantities of the compound of formula (I).The invention provides synthetic processes and synthetic intermediates that can be used to prepare a compound of formula (I) or a salt thereof. These processes and intermediates allow commercial quantities of the compound to be prepared in a cost effective and enviornmentally acceptable manner. Accordingly, these processes and intermediates will facilitate the commercial development of the compound of formula (I).In one embodiment the invention provides a method for preparing a compound of formula (I):comprising reacting a phenol of formula e:with a chloride of formula h:to provide the compound of formula (I).In one embodiment the invention provides a method for preparing a chloride of formula hby reacting the amino pyridine of formula g:with chloroacetic acid:to provide the chloride of formula h.In one embodiment the invention provides a method for preparing an amino pyridine of ...

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Номер записи: 36
25-02-2021 дата публикации

TREPROSTINIL PRODRUGS

Номер: US20210054009A1
Автор: Batra Hitesh, GUO LIANG, Phares Kenneth Robert
Принадлежит: United Therapeutics Corporation

Provided are novel prodrugs of treprostinil, as well as methods of making and methods of using these prodrugs. 146-. (canceled)48. A pharmaceutical composition claim 47 , comprising (A) an effective amount of the compound of and (B) a pharmaceutically acceptable carrier.49. A method of treating pulmonary hypertension comprising administering to a subject in need thereof the composition of .50. The method of claim 49 , wherein the composition is administered orally.51. The method of claim 49 , wherein the subject has detectable treprostinil plasma levels for at least 24 hours following said administration.52. The method of claim 49 , wherein the composition is administered by an injection.53. The method of claim 52 , wherein the administration is performed subcutaneously.54. The method of claim 53 , wherein said administration is continuous subcutaneous administration.55. The method of claim 52 , wherein said administration results in no or less pain at a site of the injection compared to administering treprostinil.56. The method of claim 49 , wherein the subject is a human being.57. The method of claim 49 , wherein upon said administration said compound converts to a metabolic product claim 49 , which consists essentially of treprostinil.58. The method of claim 57 , wherein said metabolic product consists of treprostinil.61. The method of claim 60 , wherein Ris C-Calkylene and each of Rand Rare H.62. The method of claim 49 , wherein Ris —C(O)—CHR—N(R) claim 49 , wherein Ris the side group of an amino acid.63. The method of claim 62 , wherein the amino acid is alanine claim 62 , valine or glycine.64. The method of claim 49 , wherein Ris a third drug moiety linked to the compound via an ester.65. The method of claim 49 , wherein the second drug moiety is a pain relief drug moiety.66. The method of claim 49 , wherein the second drug moiety is a nonsteroidal anti-inflammatory drug moiety.67. The method of claim 66 , wherein the second drug moiety is selected from the ...

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Номер записи: 37
05-03-2015 дата публикации

NIPECOTIC ACID DERIVATIVE AND USE THEREOF FOR MEDICAL PURPOSES

Номер: US20150065717A1
Автор: Asaoka Yoshiji, Hayashi Shinnosuke, KATO Yuko, Nishimura Yutaka, Yamada Masateru, YAMADA Naohiro, Yamamoto Masashi, Yamazaki Aiko
Принадлежит:

A compound has an sEH-inhibiting activity and provides a pharmaceutical having a therapeutic effect and a prophylactic effect on chronic renal disease and pulmonary hypertension based on the sEH-inhibiting action. The nipecotic acid derivatives are represented by the chemical formula below and pharmaceutically acceptable salts thereof. 16.-. (canceled)8. The nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to claim 7 , wherein{'sup': 2', '3', '2', '3, 'sub': 1', '6', '2', 'l, 'Rand Reach independently represents a hydrogen atom or C-Calkyl, or together represent —(CH)—, with the proviso that Rand Rdo not simultaneously represent a hydrogen atom;'}{'sup': '4', 'Rrepresents a substituent in the 2-position of the benzene ring; and'}{'sup': '5', 'Rrepresents a substituent in the 4-position of the benzene ring.'}9. The nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to claim 7 , wherein{'sup': 1', '6', '7', '6', '7, 'sub': '2', 'Rrepresents —N(R)C(═O)Ror —N(R)S(═O)R;'}{'sup': '4', 'sub': 1', '6, 'Rrepresents a halogen atom, or C-Calkyl or alkyloxy;'}{'sup': '5', 'sub': 1', '6, 'Rrepresents a halogen atom, cyano, or C-Calkyl or alkyloxy; and'}{'sup': '6', 'Rrepresents a hydrogen atom.'}10. A pharmaceutical comprising as an effective component the nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to .11. A soluble epoxide hydrolase inhibitor comprising as an effective component the nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to .12. A therapeutic or prophylactic agent for chronic renal disease or pulmonary hypertension claim 7 , said agent comprising as an effective component the nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to .13. The nipecotic acid derivative or a pharmaceutically acceptable salt thereof according to claim 8 , wherein{'sup': 1', '6', '7', '6', '7, 'sub': '2', 'Rrepresents —N(R)C(═O) ...

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Номер записи: 38
17-03-2022 дата публикации

OPIOID HAPTENS, CONJUGATES, VACCINES, AND METHODS OF GENERATING ANTIBODIES

Номер: US20220081400A1
Автор: Bremer Paul, Janda Kim D., Natori Yoshihiro
Принадлежит:

The disclosure provides, inter alia, opioid haptens, opioid hapten conjugates, opioid vaccines, methods of treating or preventing opioid use disorder, methods of treating opioid overdose, and methods of generating and/or isolating antibodies selective for opioids. 168-. (canceled)70. The compound of claim 69 , wherein Xis keyhole limpet hemocyanin.71. The compound of claim 69 , wherein Xis tetanus toxoid.72. The compound of claim 69 , wherein Xis CRM197.73. The compound of claim 69 , wherein Xis diphtheria toxoid.74. The compound of claim 69 , wherein Xis a synthetic peptide carrier.75. The compound of claim 69 , wherein z is an integer from 2 to 4.76. The compound of claim 69 , wherein z is an integer of 3.77. A vaccine comprising the compound of and an aluminum salt.78. The vaccine of claim 77 , wherein the aluminum salt is aluminum sulfate claim 77 , aluminum phosphate claim 77 , aluminum hydroxyphosphate claim 77 , aluminum hydroxide claim 77 , or potassium aluminum sulfate.79. The vaccine of claim 77 , wherein the aluminum salt is aluminum phosphate or aluminum hydroxide.80. The vaccine of claim 77 , further comprising a toll-like receptor agonist.81. The vaccine of claim 80 , wherein the toll-like receptor agonist is a CpG oligodeoxynucleotide (ODN).82. The vaccine of claim 81 , wherein the CpG ODN is CpG ODN 1585 claim 81 , CpG ODN 2216 claim 81 , CpG ODN 2336 claim 81 , CpG ODN 1668 claim 81 , CpG ODN 1826 claim 81 , CpG ODN 2006 claim 81 , CpG ODN 2007 claim 81 , CpG ODN BW006 claim 81 , CpG ODN D-SL01 claim 81 , CpG ODN 2395 claim 81 , CpG ODN M362 claim 81 , or CpG ODN D-SL03.83. The vaccine of claim 81 , wherein the CpG ODN is CpG ODN 2006.84. A vaccine comprising the compound of and an aluminum salt.85. The vaccine of claim 84 , wherein the aluminum salt is aluminum sulfate claim 84 , aluminum phosphate claim 84 , aluminum hydroxyphosphate claim 84 , aluminum hydroxide claim 84 , or potassium aluminum sulfate.86. The vaccine of claim 84 , further ...

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Номер записи: 39
08-03-2018 дата публикации

IMMUNE CHECKPOINT INHIBITORS, COMPOSITIONS AND METHODS THEREOF

Номер: US20180065917A1
Автор: ALMASSY Robert J., Webber Stephen E.
Принадлежит:

The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis aryl.3. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Xis aryl optionally substituted by halogen claim 1 , (C-C)alkyl or (C-C)haloalkyl.4. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Yis NH(R) or N(R)(R).5. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris (C-C)alkyl or halogen.6. The compound of claim 5 , or a stereoisomer claim 5 , a tautomer or a pharmaceutically acceptable salt thereof claim 5 , wherein Ris CH.7. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare independently H claim 1 , (C-C)alkyl or Rand Rcombine together with the nitrogen atom to form a heterocyclyl.8. The compound of claim 7 , or a stereoisomer claim 7 , a tautomer or a pharmaceutically acceptable salt thereof claim 7 , wherein Rand Rare independently H or (C-C)alkyl claim 7 , wherein (C-C)alkyl is optionally substituted by OH or C(O)OH.9. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rcombine together with the nitrogen atom to form a heterocyclyl claim 1 , optionally substituted by C(O)OH.10. The compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable salt thereof claim 1 , wherein “n” is 1.11. A compound of claim 1 , or a stereoisomer claim 1 , a tautomer or a pharmaceutically acceptable ...

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Номер записи: 40
08-03-2018 дата публикации

CARBOXAMIDE DERIVATIVES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B

Номер: US20180065929A1
Автор: Haché Geerwin Yvonne Paul, Kesteleyn Bart Rudolf Romanie, Raboisson Pierre Jean-Marie Bernard, Vandyck Koen
Принадлежит:

Inhibitors of HBV replication of formula (I) 112-. (canceled)16. The compound of claim 13 , wherein each of Ra claim 13 , Rb claim 13 , Rc claim 13 , Rd claim 13 , Re claim 13 , Rf claim 13 , Rg claim 13 , Rh and Ri is hydrogen.17. The compound of claim 13 , wherein at least one of Ra claim 13 , Rb claim 13 , Rc claim 13 , Rd claim 13 , Re claim 13 , Rf and Rg is methyl.18. The compound of claim 13 , wherein Ris fluoro.19. The compound of claim 13 , wherein Ris selected from the group consisting of fluoro claim 13 , chloro claim 13 , —CHF claim 13 , —CHF claim 13 , —CF claim 13 , —CN and methyl.20. The compound of claim 13 , wherein Ris selected from the group consisting of fluoro claim 13 , chloro and bromo.21. The compound of claim 13 , wherein Ris fluoro; Ris selected from the group consisting of fluoro claim 13 , chloro claim 13 , —CHF claim 13 , —CHF claim 13 , —CF claim 13 , —CN and methyl; and Ris selected from the group consisting of fluoro claim 13 , chloro and bromo.22. The compound of claim 13 , wherein Ris fluoro and Ris methyl.23. The compound of claim 13 , wherein Ris fluoro; Ris selected from the group consisting of fluoro and chloro; and Ris selected from the group consisting of hydrogen claim 13 , fluoro and chloro.24. The compound of claim 13 , wherein Ris a branched C-Calkyl optionally substituted with one or more fluoro.25. The compound of claim 13 , wherein Ris selected from the group consisting of —CH(CH) claim 13 , —CH(CH) claim 13 , —CH(CH) claim 13 , —(CH)(CH)CH claim 13 , —(CH)(CH)CH—OH claim 13 , —CH(CH)CF claim 13 , CH(CH)CF.26. The compound of claim 13 , wherein Ris —CH(CH).27. The compound of claim 13 , wherein Ris —CH(CH)CF.28. The compound of claim 13 , wherein Ris fluoro; and Ris —CH(CH)CF.29. The compound of claim 13 , wherein Ris a 4-5 membered saturated ring containing one oxygen claim 13 , said 4-5 membered saturated ring optionally substituted with methyl.30. A pharmaceutical composition comprising the compound of and a ...

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Номер записи: 41
12-03-2015 дата публикации

Methods for Treating Depressive Symptoms

Номер: US20150072971A1
Автор: Blumberg Laura Cook, Deaver Dan, Eyerman David, Wynn Thomas
Принадлежит: ALKERMES PHARMA IRELAND LIMITED

The present application relates methods for treating a depressive symptom comprising administering an effective amount of a μ opioid receptor agonist or a pharmaceutically acceptable salt thereof to a subject in need thereof. Non-limiting examples of such agonist include the compounds of Formulas I, II, III, and IV, as well as the compounds of Table A. 10. The method of claim 1 , wherein the compound is a μ opioid receptor agonist that exhibits an Emax of 5% to 45% in a GTPγS binding assay.11. The method of claim 10 , wherein the Emax is 15% to 35% in a GTPγS binding assay.12. The method of claim 10 , wherein said agonist has a low risk of opioid dependence claim 10 , opioid addiction claim 10 , and/or symptoms of opioid withdrawal.13. The method of claim 1 , wherein the compound exhibits a maximal dopamine efflux in the nucleus accumbens of 125% to 300% over base line in a rat.14. (canceled)15. The method of claim 1 , wherein the compound does not attenuate thermal pain in a rodent hot plate model when administered at a dose of at least 1 mg/kg.16. (canceled)17. (canceled)18. A method of treating a depressive symptom in a subject in need thereof claim 1 , the method comprising administering to the subject an effective amount of a μ opioid receptor agonist that exhibits an Emax of 5% to 45% in a GTPγS binding assay.19. (canceled)20. (canceled)21. A method of treating a depressive symptom in a subject in need thereof claim 1 , the method comprising administering to the subject an effective amount of a compound that exhibits a maximal dopamine efflux in the nucleus accumbens of 125% to 300% over base line in a rat.22. (canceled)23. A method of treating a depressive symptom in a subject in need thereof claim 1 , the method comprising administering to the subject an effective amount of a compound that does not attenuate thermal pain in a rodent hot plate model when administered at a dose of at least 1 mg/kg.24. (canceled)25. (canceled)26. (canceled)27. The method of ...

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Номер записи: 42
12-03-2015 дата публикации

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Номер: US20150072984A1
Автор: Qian Xiangping
Принадлежит:

Chemical entities that are curcumin derivatives, pharmaceutical compositions and methods of treatment of cancer are described. 2. At least one chemical entity of wherein Ris chosen from hydrogen claim 1 , optionally substituted alkyl claim 1 , optionally substituted cycloalkyl claim 1 , and optionally substituted heterocycloalkyl.3. At least one chemical entity of wherein Ris chosen from optionally substituted alkyl claim 1 , optionally substituted cycloalkyl claim 1 , and optionally substituted heterocycloalkyl.4. At least one chemical entity of wherein Rand Rare independently chosen from optionally substituted alkyl.5. At least one chemical entity of wherein Rand Rare joined together to form an optionally substituted 4- to 8-membered heterocycloalkyl ring.6. At least one chemical entity of wherein Rand Rare joined together to form an optionally substituted pyrrolidin-1-yl claim 5 , morpholin-1-yl claim 5 , piperidin-1-yl claim 5 , piperazin-1-yl claim 5 , 1 claim 5 ,4-diazepan-1-yl claim 5 , and 1 claim 5 ,4-diazocan-1-yl.7. At least one chemical entity of any one of to wherein Ris chosen from hydrogen claim 5 , optionally substituted alkyl claim 5 , optionally substituted cycloalkyl claim 5 , optionally substituted heterocycloalkyl claim 5 , optionally substituted aryl claim 5 , optionally substituted heteroaryl claim 5 , optionally substituted aminocarbonyl claim 5 , and optionally substituted phosphato.8. At least one chemical entity of wherein Ris chosen from hydrogen claim 7 , optionally substituted lower alkyl claim 7 , and optionally substituted aminocarbonyl.9. At least one chemical entity of wherein Ris hydrogen.10. At least one chemical entity of wherein Ris optionally substituted lower alkyl.11. At least one chemical entity of wherein Ris methyl.12. At least one chemical entity of wherein Ris lower alkyl substituted with hydroxyl or amino.13. At least one chemical entity of wherein Ris optionally substituted aminocarbonyl.14. At least one chemical ...

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Номер записи: 43
15-03-2018 дата публикации

PROCESSES AND INTERMEDIATES IN THE PREPARATION OF C5aR ANTAGONISTS

Номер: US20180072668A1
Автор: Fan Pingchen, KALISIAK Jaroslaw, Krasinski Antoni, LUI Rebecca M., Powers Jay, Punna Sreenivas, Tanaka Hiroko, Zhang Penglie
Принадлежит:

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds. 18.-. (canceled).10. A compound of claim 9 , in salt form as a L-DTTA salt.11. A compound of claim 9 , wherein Ris CF.12. A compound of claim 9 , wherein Ris Cl.13. A compound of claim 9 , in salt form as a bis L-DTTA salt.15. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris F claim 14 , and Ris CH.16. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris Cl claim 14 , and Ris H.17. A method in accordance with claim 14 , wherein Ris Cl claim 14 , Ris F claim 14 , and Ris CH.18. A method in accordance with claim 14 , wherein LG is halogen.1920.-. (canceled). This application is a continuation of U.S. patent application Ser. No. 14/867,669 filed Sep. 28, 2015, which application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/057,107, filed Sep. 29, 2014, each of which is incorporated herein by reference.NOT APPLICABLEThe complement system plays a central role in the clearance of immune complexes and in immune responses to infectious agents, foreign antigens, virus infected cells and tumor cells. Inappropriate or excessive activation of the complement system can lead to harmful, and even potentially life-threatening consequences due to severe inflammation and resulting tissue destruction. These consequences are clinically manifested in various disorders including septic shock; myocardial, as well as, intestinal ischemia/reperfusion injury; graft rejection; organ failure; nephritis; pathological inflammation; and autoimmune diseases.The activation of the complement pathway generates biologically active fragments of complement proteins, e.g. C3a, C4a and C5a anaphylatoxins and C5b-9 membrane attack complexes (MAC), all which mediate inflammatory responses by affecting leukocyte chemotaxis; activating macrophages, neutrophils, platelets, mast cells and endothelial cells; and increasing vascular permeability, ...

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Номер записи: 44
07-03-2019 дата публикации

Octahydroanthracene Compound, Preparation Method and Application Thereof

Номер: US20190071393A1
Автор: BAO Xuefei, CHEN Guoliang, FANG Wuhong, GAO Jinheng, REN Fulong, YUAN Chunling, ZHANG Daiming, ZHENG Zhonghui, ZHOU Linbo, ZOU Libo
Принадлежит:

An octahydroanthracene compound having the structure shown in formula (I) and (II), preparation method and application thereof are disclosed. The octahydroanthracene compound has a good therapeutic effect on tumors and neurodegenerative diseases. The preparation of the octahydroanthracene compound is mainly carried out by using benzene as a starting material, and being subjected to Friedel-Crafts reaction, nitration, reduction, (sulfo-) amide formation, reduction, urea formation or amide formation, thus obtaining a target compound. 2. The octahydroanthracene compound and the pharmaceutically acceptable salts of the octahydroanthracene compound of claim 1 , whereinthe Linker is a substituted/unsubstituted phenyl group, pyridine, furan, pyrrole, thiazole or thiophene; wherein a substituent of the substituted phenyl group, pyridine, furan, pyrrole, thiazole or thiophene is a C1-C6 alkyl group or a C1-C6 alkoxy group.3. The octahydroanthracene compound and the pharmaceutically acceptable salts of the octahydroanthracene compound of claim 1 , wherein the nitrogen-free structural fragment is C1-C10 alkyl group.5. The octahydroanthracene compound and the pharmaceutically acceptable salts of the octahydroanthracene compound of claim 1 , wherein X is hydrogen claim 1 , methyl or ethyl.6. An octahydroanthracene compound and pharmaceutically acceptable salts of the octahydroanthracene compound claim 1 , selecting from:4-[(1,1,4,4,5,5,8,8-octamethyl-1,2,3,4,5,6,7,8-octahydro-9-anthryl) carbamoyl] methyl benzoate;4-[(1,1,4,4,5,5,8,8-octamethyl-1,2,3,4,5,6,7,8-octahydro-9-anthryl) carbamoyl] benzoic acid;N-hydroxy-4-[(1,1,4,4,5,5,8,8-octamethyl-1,2,3,4,5,6,7,8-octahydro-9-anthryl) carbamoyl] benzamide;N-(2-aminophenyl)-4-[(1,1,4,4,5,5,8,8-octamethyl-1,2,3,4 5,6,7,8-octahydro-9-anthryl) carbamoyl] benzamide;N[2-(N,N-diethylamino)]ethyl-4-[(1,1,4,4,5,5,8,8-octamethyl-1,2,3,4,5,6,7,8-octahydro-9-anthryl) carbamoyl] benzamide;N-(2-amino) ethyl -4[(1,1,4,4,5,5,8,8-octamethyl-1,2,3,4,5 ...

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Номер записи: 45
31-03-2022 дата публикации

FREE BASE CRYSTALLINE FORM OF A COMPLEMENT COMPONENT C5a RECEPTOR

Номер: US20220096453A1
Автор: Krasinski Antoni, LUI Rebecca M., Singh Rajinder, YAU Kwok, Zeng Yibin, Zhang Penglie
Принадлежит:

Provided herein is a free base crystalline form of a complement component 5a receptor having the formula of Compound 1 12.-. (canceled)3. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by XRPD peaks at 12.4 claim 11 , 15.2 claim 11 , 16.1 claim 11 , 24.4 claim 11 , and 24.7 degrees 2θ (±0.2 degrees 2θ)4. The method of claim 11 , wherein the free base crystalline form of Compound 1 is characterized by an X-ray powder diffraction pattern substantially in accordance with .5. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a differential scanning calorimetry thermogram (DSC) comprising an endothermic peak at around 216° C.6. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a melting point onset of about 213° C. as determined by differential scanning calorimetry thermogram (DSC).7. The method of claim 11 , wherein the free base crystalline form of Compound 1 is further characterized by a DSC substantially in accordance with .810.-. (canceled)12. The method of claim 11 , wherein the disease or disorder is an inflammatory disease or disorder.13. The method of claim 12 , wherein the disease or disorder is selected from the group consisting of neutropenia claim 12 , sepsis claim 12 , septic shock claim 12 , Alzheimer's disease claim 12 , multiple sclerosis claim 12 , stroke claim 12 , inflammatory bowel disease claim 12 , age-related macular degeneration claim 12 , chronic obstructive pulmonary disorder claim 12 , inflammation associated with burns claim 12 , lung injury claim 12 , osteoarthritis claim 12 , atopic dermatitis claim 12 , chronic urticaria claim 12 , ischemia-reperfusion injury claim 12 , acute respiratory distress syndrome claim 12 , systemic inflammatory response syndrome claim 12 , multiple organ dysfunction syndrome claim 12 , tissue graft rejection claim 12 , cancer and hyperacute ...

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Номер записи: 46
31-03-2022 дата публикации

METHOD FOR TREATING SARCOIDOSIS-ASSOCIATED PULMONARY HYPERTENSION

Номер: US20220096475A1
Автор: PACK Thomas, Rajagopal Sudarshan
Принадлежит:

There is a method of treating or preventing sarcoidosis-associated pulmonary hypertension in a patient. The method has the step of administering to the patient a therapeutically effective amount of one or more compounds: (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof, or (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroeth-oxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof, or a combination of the foregoing. 1. A method of treating or preventing sarcoidosis-associated pulmonary hypertension in a human patient comprising administering to the patient a therapeutically effective amount of about 1 mg/kg/day to about 50 mg/kg/day of a compound selected from the group consisting of (i) (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1 ,1′-biphenyl]-2-yl)-2 ,2 ,2-trifluoroethoxy)pyrimidin-4-yl)-2 ,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof , (ii) (S)-8-(2-amino-6-((R)-1-(5-chloro-[1 ,1′-biphenyl]-2-yl)-2 ,2 ,2-trifluoroeth-oxy)pyrimidin-4-yl)-2 ,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof , and (iii) a combination of the foregoing.2. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered orally.3. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered orally by a dosage form selected from the group consisting of capsules claim 1 , tablets claim 1 , powders claim 1 , and granules.4. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered orally in the form of a liquid.5. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered one to four times per day.6. The method of claim 1 , wherein ...

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Номер записи: 47
23-03-2017 дата публикации

CRYSTALLINE FREEBASE FORMS OF A BIPHENYL COMPOUND

Номер: US20170081283A1
Автор: Woollam Grahame
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

The invention provides two crystalline freebase forms of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester. The invention also provides pharmaceutical compositions comprising the crystalline freebase or prepared using the crystalline freebases; processes and intermediates for preparing the crystalline freebases; and methods of using the crystalline freebases to treat a pulmonary disorder. 1. Crystalline freebase Form III of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl)piperidin-4-yl ester characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1 , 13.1±0.1 , 18.6±0.1 , 19.7±0.1 , and 20.2±0.1; and further characterized by having five or more additional diffraction peaks at 2θ values selected from 8.8±0.1 , 10.1±0.1 , 11.4±0.1 , 11.6±0.1 , 14.8±0.1 , 15.2±0.1 , 16.1±0.1 , 16.4±0.1 , 16.9±0.1 , 17.5±0.1 , 18.2±0.1 , 19.3±0.1 , 19.9±0.1 , 20.8±0.1 , 21.1±0.1 , 21.7±0.1 , and 22.3±0.1.2. (canceled)3. Crystalline freebase Form III of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values selected from 6.6±0.1 , 11.4±0.1 , 13.1±0.1 , 16.1±0.1 , 17.5±0.1 , 18.2±0.1 , 18.6±0.1 , 19.3±0.1 , 19.7±0.1 , 19.9±0.1 , 20.2±0.1 , 20.8±0.1 , 21.1±0.1 , 21.7±0.1 , and 22.3±0.1.420-. (canceled)21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and crystalline freebase Form III of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1 , 13.1±0.1 , 18.6±0.1 , 19.7±0.1 , and 20.2±0.1; and further characterized by having five or more additional diffraction peaks at 2θ values ...

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Номер записи: 48
31-03-2016 дата публикации

PROCESSES AND INTERMEDIATES IN THE PREPARATION OF C5aR ANTAGONISTS

Номер: US20160090357A1
Автор: Fan Pingchen, Kalisiak Jarek, Krasinski Antoni, LUI Rebecca, Powers Jay, Punna Sreenivas, Tanaka Hiroko, Zhang Penglie
Принадлежит:

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds. 2. A compound of claim 1 , in salt form as a bis L-DTTA salt.6. A method of any of claim 1 , or claim 1 , wherein Ris CF claim 1 , Ris F claim 1 , and Ris CH.7. A method of any of claim 1 , or claim 1 , wherein Ris CF claim 1 , Ris Cl claim 1 , and Ris H.8. A method of any of claim 1 , or claim 1 , wherein Ris Cl claim 1 , Ris F claim 1 , and Ris CH.10. A compound of claim 9 , in salt form as a L-DTTA salt.11. A compound of claim 9 , wherein Ris CF.12. A compound of claim 9 , wherein Ris Cl.13. A compound of claim 9 , in salt form as a bis L-DTTA salt.15. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris F claim 14 , and Ris CH.16. A method in accordance with claim 14 , wherein Ris CF claim 14 , Ris Cl claim 14 , and Ris H.17. A method in accordance with claim 14 , wherein Ris Cl claim 14 , Ris F claim 14 , and Ris CH.18. A method in accordance with claim 14 , wherein LG is halogen. This application claims the benefit of priority to U.S. Provisional Application Ser. No. 62/057,107, filed Sep. 29, 2014, the entire content of which is incorporated herein by reference.NOT APPLICABLENOT APPLICABLEThe complement system plays a central role in the clearance of immune complexes and in immune responses to infectious agents, foreign antigens, virus infected cells and tumor cells. Inappropriate or excessive activation of the complement system can lead to harmful, and even potentially life-threatening consequences due to severe inflammation and resulting tissue destruction. These consequences are clinically manifested in various disorders including septic shock; myocardial, as well as, intestinal ischemia/reperfusion injury; graft rejection; organ failure; nephritis; pathological inflammation; and autoimmune diseases.The activation of the complement pathway generates biologically active fragments of complement proteins, e.g. C3a, C4a and C5a anaphylatoxins and ...

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Номер записи: 49
21-03-2019 дата публикации

Alpha-Ketoamide Inhibitors Of Cysteine Proteases

Номер: US20190085024A1
Автор: Addis Russ, Gaboury Janet, Greenbaum Doron, Kulkami Swapnil, Meinhardt Nataline
Принадлежит:

The disclosure provides compounds comprising a α-ketoamide linkage that is terminated on each end by an amino acid, such as compounds of Formula (I), wherein RA-RC are defined herein. Also provided are compositions containing these compounds and methods of inhibiting calpain activity, treating a calpain-mediated disorder, inhibiting cathepsin-B, cathepsin-L, cathepsin-S, or cathepsin-L activity, and methods of treating a cathepsin-B, cathepsin-L, cathepsin-S, or cathepsin-L mediated disorder using these compounds and compositions. 1. A compound comprising an α-ketoamide linkage that is terminated on each end by an amino acid.4. The compound of claim 3 , wherein Ris OH or NH.5. The compound of claim 3 , wherein Ris NH(optionally substituted Calkyl) such as NH(methyl) claim 3 , NH(ethyl) claim 3 , NH(propyl) claim 3 , NH(butyl) claim 3 , NH(pentyl) claim 3 , or NH(hexyl) or N(optionally substituted Calkyl)such as N(methyl) claim 3 , N(ethyl) claim 3 , N(propyl) claim 3 , N(butyl) claim 3 , N(pentyl) claim 3 , or N(hexyl).6. The compound of claim 3 , wherein Ris NH(optionally substituted Calkyl-optionally substituted aryl) or NH(optionally substituted Calkyl-optionally substituted heterocyclyl).7. The compound of claim 3 , wherein Ris NH(optionally substituted Calkyl) substituted with C(O)OH claim 3 , C(O)O(Calkyl) claim 3 , or C(O)NH.8. The compound of claim 3 , wherein Ris NH(optionally substituted Ccycloalkyl) such as NH(cyclopentyl).9. The compound of claim 3 , wherein Ris heteroaryl such as pyrrolidinyl or thiazolyl.10. The compound of claim 3 , wherein Ris NH(optionally substituted Calkyl-optionally substituted aryl)C(O)NHsuch as NH(benzyl)C(O)NH.11. The compound of claim 3 , wherein Ris NH-(optionally substituted Calkyl)C(O)NH-(optionally substituted Calkyl-optionally substituted heterocyclyl) such as NH—(Calkyl)C(O)NH—Calkylmorpholinyl.12. The compound of claim 3 , wherein Ris NH-(optionally substituted Calkyl)C(O)NH-optionally substituted Calkyl-optionally ...

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Номер записи: 50
05-05-2022 дата публикации

Quaternary ammonium salt compound, preparation method therefor and use thereof

Номер: US20220135526A1
Автор: Bowen KE, Jin Liu, Jun Yang, Lei Tang, Wensheng Zhang
Принадлежит: West China Hospital of Sichuan University

A quaternary ammonium salt compound of formula I is fast-acting and has a long-term local anaesthetic effect after a single administration, the sensory nerve block time being longer than the motor nerve block time, has both a long-acting local anaesthetic effect and a selective local anaesthetic effect, and also significantly reduces the side effects of quaternary ammonium salt compounds with the structural features of surfactants and is highly safe; thus, the compound of formula I and the pharmaceutically acceptable salt thereof can be used for the preparation of saft drugs having a long-term local anaesthetic effect and a selective local anaesthetic effect

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Номер записи: 51
19-03-2020 дата публикации

PROCESS FOR THE PREPARATION OF ENANTIOMERICALLY ENRICHED 3-AMINOPIPERIDINE

Номер: US20200087257A1
Автор: Andrushko Vasyl, Kantor Mark, Meier Viktor, Reuter Karl, Stolz Florian, Wedel Tobias
Принадлежит: REUTER CHEMISCHE APPARATEBAU KG

The present invention relates to a process for the preparation of enantiomerically enriched 3-aminopiperidine, as in particular of its R-enantiomer (R)-3-aminopiperidine. The invention also relates to an enantiomerically enriched intermediate of said process and to specific acid-addition salts of 3-aminopiperidine (hereinafter also APIP) that are useful for obtaining a single enantiomer of APIP, and to crystalline (R)-3-aminopiperidine-dihydrochloride-monohydrateand crystalline (S)-3-aminopiperidine-dihydrochloride-monohydrate. 2. The process according to claim 1 , wherein the carboxylic acid A is selected from (S)-2-phenyl sulfonylamino-propionic acid claim 1 , (S)-2-(4-methylphenyl)sulfonylamino-propionic acid claim 1 , (S)-2-(4-chlorophenyl)sulfonylamino-propionic acid claim 1 , (R)-2-(3-phenylureido)-propionic acid and (R)-2-(3-(4-chlorophenyl)ureido)-propionic acid.3. A process for enantiomeric enrichment of 3-aminopiperidine with regard to its S-enantiomer claim 1 , the process comprising the fractional crystallization of 3-aminopiperidine in the form of its acid-addition salt with a chiral carboxylic acid A from a solution claim 1 , suspension or emulsion containing a mixture of the enantiomers of 3-aminopiperidine claim 1 , in particular a racemic mixture of the enantiomers of 3-aminopiperidine claim 1 ,{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'where the chiral carboxylic acid A is the compound of the formula A, as defined in , where the chiral carboxylic acid A has an enantiomeric excess with regard to one of its enantiomers.'}4. The process according to claim 3 , wherein the carboxylic acid A is selected from (R)-2-phenyl sulfonylamino-propionic acid claim 3 , (R)-2-(4-methylphenyl)sulfonylamino-propionic acid claim 3 , (R)-2-(4-chlorophenyl)sulfonylamino-propionic acid claim 3 , (S)-2-(3-phenylureido)-propionic acid and (S)-2-(3-(4-chlorophenyl)ureido)-propionic acid.5. The acid-addition salt of 3-aminopiperidine with the chiral carboxylic acid A ...

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Номер записи: 52
19-03-2020 дата публикации

CHEMOSELECTIVE METHYLENE HYDROXYLATION IN AROMATIC MOLECULES

Номер: US20200087331A1
Автор: White M. Christina, Zhao Jinpeng
Принадлежит:

A chemoselective and reactive Mn(CF-PDP) catalyst system that enables for the first time the strategic advantages of late-stage aliphatic C—H hydroxylation to be leveraged in aromatic compounds. This discovery will benefit small molecule therapeutics by enabling the rapid diversification of aromatic drugs and natural products and identification of their metabolites. 2. The complex of wherein the complex is an (S claim 1 ,S) enantiomer.3. The complex of wherein the complex is an (R claim 1 ,R) enantiomer.4. The complex of wherein the complex is a salt and the anion of the salt is Cl claim 1 , Br claim 1 , AcO claim 1 , TfO claim 1 , CFCO claim 1 , BF claim 1 , ClO claim 1 , ReO claim 1 , AsF claim 1 , PF claim 1 , or SbF.5. The complex of wherein Land Lare each independently chloro claim 1 , acetone claim 1 , acetonitrile claim 1 , or a terminal oxo bridge; or Land Ltogether are a carboxylate group.6. The complex of wherein each Gand each Gis independently (C-C)alkyl substituted with one or more halo groups.7. The complex of wherein each Gis independently chloro claim 1 , methyl claim 1 , ethyl claim 1 , isopropyl claim 1 , teat-butyl claim 1 , —OCH claim 1 , —C(═O)OCH claim 1 , —C(═O)OC(CH) claim 1 , —CF claim 1 , —CFCH claim 1 , or —CFCF.8. The complex of wherein each Gis independently chloro claim 7 , methyl claim 7 , ethyl claim 7 , isopropyl claim 7 , teat-butyl claim 7 , —OCH claim 7 , —C(═O)OCH claim 7 , —C(═O)OC(CH) claim 7 , —CF claim 7 , —CFCH claim 7 , or —CFCF.9. The complex of wherein x and y are each independently 2 or 3; or{'sup': 3', '4, 'wherein Gand Gare at the 4-position of the pyridyl moiety of Formula I.'}11. The complex of wherein each Gand each Gis independently chloro claim 10 , methyl claim 10 , ethyl claim 10 , isopropyl claim 10 , teat-butyl claim 10 , —OCH claim 10 , —C(═O)OCH claim 10 , —C(═O)OC(CH) claim 10 , —CF claim 10 , —CFCH claim 10 , or —CFCF.12. The complex of wherein z is 0.13. The complex of wherein Rand Rare each —CH—.15. The ...

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Номер записи: 53
23-04-2015 дата публикации

PROCESSES FOR PREPARING HETEROCYCLIC COMPOUNDS INCLUDING TRANS-7-OXO-6-(SULPHOOXY)-1,6-DIAZABICYCLO[3,2,1]OCTANE-2-CARBOXAMIDE AND SALTS THEREOF

Номер: US20150112070A1
Автор: Boyd Alistair, Cherryman Janette, Dedhiya Mahendra G., Golden Michael, Kalyan Yuriy B., Lawton Graham Richard, Milne David, Phillips Andrew, Racha Saibaba, Ronsheim Melanie Simone, TELFORD Alexander, Zhou Shao Hong
Принадлежит: FOREST LABORATORIES HOLDINGS LTD.

The present invention relates to compounds and processes for preparing compounds of Formula (I), 2. The process of claim 1 , wherein R1 claim 1 , R2 and R7 are hydrogen and R3 is OSOH.3. The process of claim 1 , wherein R1 is piperidinyl claim 1 , R2 and R7 are hydrogen and R3 is OSOH.4. The process of claim 1 , wherein R4 is benzyloxy.5. The process of claim 1 , wherein R5 is benzyloxy and R6 and R7 are hydrogen.6. The process of claim 1 , wherein R5 is allyl or trialkylsilyl and R6 is hydrogen.7. The process of claim 1 , comprising treating the compound of Formula (III) with 9-fluorenylmethoxycarbonyl.8. The process of claim 1 , comprising treating the compound of Formula (III) with N claim 1 ,N-carbonyl diimidazole.9. The process of claim 1 , further comprising treating the compound formed after treatment of compound of Formula (III) with a SOcomplex.10. The process of claim 1 , wherein the compound of Formula (I) is trans-7-oxo-6-(sulphooxy)-1 claim 1 ,6-diazabicyclo[3 claim 1 ,2 claim 1 ,1]octane-2-carboxamide or a pharmaceutically acceptable salt thereof.11. The process of claim 1 , wherein the compound of Formula (I) is sodium ({[(2S claim 1 ,5R)-2-carbamoyl-7-oxo-1 claim 1 ,6-diazabicyclo[3.2.1]oct-6-yl]oxy}sulphonyl)oxidanide.12. The process of claim 1 , wherein the compound of Formula (II) is benzyl (2S claim 1 ,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate.13. The process of claim 1 , wherein the compound of Formula (III) is (2S claim 1 ,5R)-5-[(benzyloxy)amino]piperidine-2-carboxamide.14. The process of claim 13 , comprising treating (2S claim 13 ,5R)-5-[(benzyloxy)amino]piperidine-2-carboxamide to prepare (2S claim 13 ,5R)-6-(benzyloxy)-7-oxo-1 claim 13 ,6-diazabicyclo[3.2.1]octane-2-carboxamide.16. The compound of claim 15 , wherein R5 is benzyloxy and R6 and R7 are hydrogen.17. The compound of claim 15 , wherein R5 is allyl or trialkylsilyl and R6 and R7 are hydrogen.18. The compound of claim 15 , wherein R5 is benzyloxy and R1 claim ...

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Номер записи: 54
20-04-2017 дата публикации

GLYCOSIDASE INHIBITORS AND USES THEREOF

Номер: US20170107180A1
Автор: McEachern Ernest J., Selnick Harold G., Vocadlo David J., Zhou Yuanxi
Принадлежит:

The invention provides compounds for inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc. 2. (canceled)3. The compound of wherein the compound is selected from the following group:(2S,3R,4S,5R,6R)—N-ethyl-3,4,5-trihydroxy-6-(hydroxymethyl)piperidine-2-carboxamide;(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-N,1-dimethylpiperidine-2-carboxamide;(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-N-methyl-1-(5-methylhexyl)piperidine-2-carboxamide;(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-N-methyl-1-(3-phenylpropyl)piperidine-2-carboxamide;(2S,3R,4S,5R,6R)—N-ethyl-3,4,5-trihydroxy-6-(hydroxymethyl)-1-(3-phenylpropyl)piperidine-2-carboxamide;(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-N-methyl-1-(4-phenylbutyl)piperidine-2-carboxamide;(2S,3R,4S,5R,6R)-1-((E)-3-([1,1′-biphenyl]-4-yl)allyl)-3,4,5-trihydroxy-6-(hydroxymethyl)-N-methylpiperidine-2-carboxamide;(2S,3R,4S,5R,6R)-1-(3-([1,1′-biphenyl]-4-yl)propyl)-3,4,5-trihydroxy-6-(hydroxymethyl)-N-methylpiperidine-2-carboxamide (2S,3R,4S)-1-hexyl-3,4-dihydroxy-N-methylpiperidine-2-carboxamide;(2S,3R,4S,5R)-3,4,5-trihydroxy-N-methylpiperidine-2-carboxamide;(2S,3R,4S,5R)-3,4,5-trihydroxy-N,1-dimethylpiperidine-2-carboxamide;(2S,3R,4S,5R)-3,4,5-trihydroxy-1-methylpiperidine-2-carboxamide;(2S,3R,4S,5R)—N-ethyl-3,4,5-trihydroxypiperidine-2-carboxamide;(2S,3R,4S,5R)—N-ethyl-3,4,5-trihydroxy-1-methylpiperidine-2-carboxamide;(2S,3R,4S,5R,6R)—N-ethyl-3,4,5-trihydroxy-6-methylpiperidine-2-carboxamide;(2S,3R,4S,5R,6R)—N-ethyl-3,4,5-trihydroxy-6-methyl-1-phenethylpiperidine-2-carboxamide;(2S,3R,4S,5R)—N-ethyl-3,4,5-trihydroxy-1-(3-phenylpropyl)piperidine-2-carboxamide;(2S,3S,4R,5S,6R)—N-ethyl-4-fluoro-3,5-dihydroxy-6-methyl-1-phenethylpiperidine-2-carboxamide;(2R, ...

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Номер записи: 55
10-07-2014 дата публикации

Pyrenyloxysulfonic acid fluorescent agents

Номер: US20140193926A1
Автор: Jixiang Liu, Richard Haugland, Wai-Yee Leung
Принадлежит: Life Technologies Corp

The invention provides a novel class of reactive fluorescent agents that are based on a pyrene sulfonic acid nucleus. The agents are readily incorporated into conjugates with other species by reacting the reactive group with a group of complementary reactivity on the other species of the conjugate. Also provided are methods of using the compounds of the invention to detect and/or quantify an analyte in a sample. In an exemplary embodiment, the invention provides multi-color assays incorporating the compounds of the invention.

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Номер записи: 56
09-04-2020 дата публикации

SYNTHETIC PEPTIDES, PRODRUGS, PHARMACEUTICAL COMPOSITIONS AND USES

Номер: US20200108118A1
Автор: Borges da Silva Perla Villani, da Silva Carolina Nunes, de Castro Pimenta Adriano Monteiro, de Melo Braga Marcella Nunes, de Paula Junior Iron Francisco, dos Santos da Silva Diego Allonso Rodrigues, França do Nascimento Caio Victor Machado, Garcia Maria Elena de Lima Perez, Gross Gerhard Max, Lacativa Paulo Gustavo Sampaio
Принадлежит:

The present invention relates to smooth muscle tone modulating synthetic peptides. It also refers to pharmaceutical compositions containing such peptides and to the uses thereof in the treatment of disturbances in which the modulation of the smooth muscle tone is beneficial. 3. The peptide of claim 2 , wherein the pharmacologically active peptide sequence of formula (2) is SEQ ID NO: 17 claim 2 , SEQ ID NO: 18 claim 2 , SEQ ID NO: 19 claim 2 , SEQ ID NO: 20 claim 2 , SEQ ID NO: 22 claim 2 , SEQ ID NO: 23 claim 2 , SEQ ID NO: 24 or SEQ NO ID: 5.4. The peptide of claim 1 , wherein the pharmacologically active peptide sequence of formula (2) has from 15 to 18 contiguous amino acid residues claim 1 , with the proviso that it does not consist in SEQ ID NO: 27.5. The peptide of claim 1 , wherein the pharmacologically active peptide sequence of formula (2) has 18 contiguous amino acid residues claim 1 , with the proviso that it does not consist in SEQ ID NO: 27.6. The peptide of claim 1 , further comprising at least a second peptide or protein claim 1 , with the proviso that it does not consist in SEQ ID NO: 27.8. The peptide of claim 7 , wherein H claim 7 , acetyl claim 7 , chloride claim 7 , or trifluoroacetyl is covalently bonded to the N-terminus of —Z—X—Z′—.9. A peptide of claim 7 , wherein OH or NHis covalently bonded to the C-terminus of —Z—X—Z′—.10. (canceled)11. A peptide of claim 1 , wherein the peptide is linked to a half-life enhancing moiety selected from the group consisting of albumin-binding moieties.12. The peptide of claim 11 , wherein the N-terminus is covalently bonded to an acetyl claim 11 , and wherein the C-terminus is covalently bonded to an NH.13. A peptide of claim 1 , in the form of a multimer claim 1 , comprising two or more peptides having a sequence of formula (2) interspaced by amino acid-based cleavable linkers.14. A pharmaceutical composition claim 1 , comprising one or more peptides defined in any of and a pharmaceutically acceptable ...

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Номер записи: 57
13-05-2021 дата публикации

AMORPHOUS FORM OF A COMPLEMENT COMPONENT C5a RECEPTOR

Номер: US20210139426A1
Автор: LELETI Manmohan Reddy, LUI Rebecca M., LUONG Kenken, Singh Rajinder, YAU Kwok, Zeng Yibin, Zhang Penglie
Принадлежит:

Provided herein is an amorphous form of a complement component 5a receptor having the formula of Compound 1 2. The amorphous form of Compound 1 according to claim 1 , characterized by an X-ray powder diffraction pattern substantially in accordance with .3. The amorphous form of Compound 1 according to claim 1 , further characterized by a glass transition temperature of about 108° C. claim 1 , as determined by differential scanning calorimetry.4. The amorphous form of Compound 1 according to claim 1 , further characterized by a differential scanning calorimetry (DSC) thermogram substantially in accordance with .5. The amorphous form of Compound 1 according to claim 1 , further characterized by a weight loss of about 0.015% up heating to around 235° C. claim 1 , as measured by thermal gravimetric analysis (TGA).6. The amorphous form of Compound 1 according to claim 1 , further characterized a thermal gravimetric analysis (TGA) thermogram substantially in accordance with .7. The amorphous form of Compound 1 according to claim 1 , further characterized by a weight gain of about 0.44% after undergoing a dynamic vapor sorption (DVS) cycle from about 0% relative humidity (RH) to about 95% RH at 25° C.8. The amorphous form of Compound 1 according to claim 1 , further characterized by a weight gain of about 0.31% after undergoing a dynamic vapor sorption (DVS) cycle from about 0% relative humidity (RH) to about 65% RH at 25° C.9. The amorphous form of Compound 1 according to claim 1 , further characterized by a dynamic vapor sorption (DVS) plot that does not exhibit any hysteresis between adsorption and desorption.10. The amorphous form of Compound 1 according to claim 1 , further characterized by a dynamic vapor sorption (DVS) plot substantially in accordance with .11. The amorphous form of Compound 1 according to claim 1 , further characterized by a scanning electron microscopy (SEM) image having predominantly spherical particles.12. The amorphous form of Compound 1 ...

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Номер записи: 58
13-05-2021 дата публикации

SALT FORMS OF A COMPLEMENT COMPONENT C5A RECEPTOR

Номер: US20210139427A1
Автор: LUI Rebecca M., ROTH Howard S., Singh Rajinder, Yang Ju, YAU Kwok, Zeng Yibin, Zhang Penglie
Принадлежит:

Provided herein are salt forms of a complement component 5a receptor having the formula of Compound 1 1. The salt form of claim 139 , wherein the salt form is a besylate salt.2. The besylate salt of claim 1 , in a single crystalline form which is substantially free of other crystalline or amorphous forms.3. The besylate salt of claim 2 , wherein the single crystalline form is besylate salt Form I.4. The besylate salt Form I claim 3 , according to claim 3 , characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 10.9 claim 3 , 13.3 claim 3 , 16.2 claim 3 , 17.6 and 21.8 degrees 2θ (±0.2 degrees 2θ).5. The besylate salt Form I claim 4 , according to claim 4 , further characterized by XRPD peaks at 6.6 claim 4 , 7.6 claim 4 , 14.5 claim 4 , 16.2 claim 4 , and 28.2 degrees 2θ (±0.2 degrees 2θ).6. The besylate salt Form I claim 4 , according to claim 4 , characterized by an X-ray powder diffraction pattern substantially in accordance with .7. The besylate salt Form I claim 4 , according to claim 4 , further characterized by a differential scanning calorimetry thermogram (DSC) comprising an endothermic peak at around 207.2° C.8. The besylate salt Form I claim 4 , according to claim 4 , further characterized by a melting point onset of about 200.6° C. as determined by differential scanning calorimetry thermogram (DSC).9. The besylate salt Form I claim 4 , according to claim 4 , wherein said DSC thermogram is substantially in accordance with .10. The besylate salt Form I claim 4 , according to claim 4 , further characterized by a weight loss of about 0.14% upon heating to around 202.9° C. claim 4 , as measured by thermal gravimetric analysis (TGA).11. The besylate salt Form I claim 4 , according to claim 4 , further characterized a thermal gravimetric analysis (TGA) thermogram substantially in accordance with .12. The besylate salt Form I claim 4 , according to claim 4 , further characterized by a weight gain of about 0.5% after undergoing a dynamic ...

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Номер записи: 59
03-05-2018 дата публикации

PROCESSES FOR CONVERTING CARBOXAMIDES TO THIOCARBOXAMIDES

Номер: US20180118675A1
Автор: GRENDZE Martin P., MURUGAN Ramiah
Принадлежит: Vertellus Holdings LLC

Process for converting a carboxamide to a thiocarboxamide includes reacting (a) a substrate that comprises a heteroatom-containing moiety and a carboxamide moiety with (b) a dialkyl dithiophosphate and/or a salt thereof. The heteroatom-containing moiety includes a heteroatom selected from the group consisting of N, O, and S. Processes for preparing piperidine-4-thiocarboxamide are described. 1. A process for converting a carboxamide to a thiocarboxamide , the process comprising:reacting (a) a substrate that comprises a heteroatom-containing moiety and a carboxamide moiety with (b) a dialkyl dithiophosphate and/or a salt thereof;wherein the heteroatom-containing moiety comprises a heteroatom selected from the group consisting of N, O, and S.5. The process of claim 1 , wherein the heteroatom-containing moiety comprises a nitrogen atom.6. The process of claim 1 , wherein the heteroatom-containing moiety comprises a heterocyclic moiety selected from the group consisting of aziridine claim 1 , azirine claim 1 , diazirine claim 1 , oxaziridine claim 1 , azetidine claim 1 , azete claim 1 , diazetidine claim 1 , pyrrolidine claim 1 , pyrrole claim 1 , imidazolidine claim 1 , imidazole claim 1 , pyrazolidine claim 1 , pyrazole claim 1 , oxazolidine claim 1 , oxazole claim 1 , isoxazolidine claim 1 , isoxazole claim 1 , thiazolidine claim 1 , thiazole claim 1 , isothiazolidine claim 1 , isothiazole claim 1 , triazoles claim 1 , furazan claim 1 , oxadiazole claim 1 , thiadiazole claim 1 , dithiazole claim 1 , tetrazole claim 1 , piperidine claim 1 , pyridine claim 1 , piperazine claim 1 , diazines claim 1 , morpholine claim 1 , oxazine claim 1 , thiomorpholine claim 1 , thiazine claim 1 , triazine claim 1 , tetrazine claim 1 , azepane claim 1 , azepine claim 1 , homopiperazine claim 1 , diazepine claim 1 , thiazepine claim 1 , azocane claim 1 , azocine claim 1 , tetrahydropyran claim 1 , and combinations thereof.9. The process of claim 8 , wherein Rand Rare hydrogen.10. The ...

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Номер записи: 60
07-05-2015 дата публикации

BIGUANIDE COMPOUNDS AND USE THEREOF

Номер: US20150126518A1
Автор: HEO Hye Jin, Jeong Jae Kap, KIM Hong Woo, KIM Seo-il, Lee Hong Bum, LEE Ji Sun, Lee Young Woo, Park Ji Hyun
Принадлежит: HANALL BIOPHARMA CO., LTD.

The present invention relates to biguanide compounds and use thereof, more particularly, to biguanide derivatives exhibiting excellent effects for inhibition of cancer cell proliferation and inhibition of cancer metastasis and recurrence, a method for preparing the same, a pharmaceutical composition containing the same as an active ingredient, and a method of prevention or treatment of cancer comprising the step of administering an effective amount of the composition to a subject in need thereof. 2. The compound according to claim 1 , wherein the compound is selected from the group consisting of:N1-pyrrolidine-N5-(benzo[1,3]dioxol-5-ylmethyl)biguanide,N1-pyrrolidine-N5-(4-methoxy)phenyl biguanide,N1-pyrrolidine-N5-(3-chloro-4-methoxy)phenyl biguanide,N1-pyrrolidine-N5-(2,6-difluoro-N5-methyl)phenyl biguanide,N1-pyrrolidine-N5-(4-dimethylamino)phenyl biguanide,N1-pyrrolidine-N5-(4-isopropyl)phenyl biguanide,N1-pyrrolidine-N5-(3-phenoxy)phenyl biguanide,N1-pyrrolidine-N5-(N-biphenyl-3-yl)biguanide,N1-pyrrolidine-N5-(N-biphenyl-4-yl)biguanide,N1-pyrrolidine-N5-(4′-fluorobiphenyl-3-yl)biguanide,N1-pyrrolidine-N5-(3′-fluorobiphenyl-4-yl)biguanide,N1-pyrrolidine-N5-(4-fluoro)phenethyl biguanide,N1-pyrrolidine-N5-(2-phenylpropane-2-yl)biguanide,N1-pyrrolidine-N5-(5,6,7,8-tetrahydronaphthalene-2-yl)biguanide,N1-pyrrolidine-N5-((1,2,3,4-tetrahydronaphthalene-1-yl)biguanide,N1-(S)-2-methyl pyrrolidine-N5-(4-(trifluoromethoxy)phenyl biguanide,N1-(S)-3-hydroxy pyrrolidine-N5-(4-trifluoromethoxy)phenyl biguanide,N1-(R)-3-hydroxy pyrrolidine-N5-(4-trifluoromethoxy)phenyl biguanide,N-ethyl-4-((3-(imino(pyrrolidin-1-yl)methyl)guanidino)methyl)benzamide,N-ethyl-3-((3-(imino(pyrrolidin-1-yl)methyl)guanidino)methyl)benzamide,N1-pyrrolidine-N5-(4-(2-aminoethyl)phenyl biguanide,N—(N-(4-(2-oxo-2-(piperidin-1-yl)ethylthio)phenyl)carbamimidoyl)pyrrolidine-1-carboximidamide, andS)-3-hydroxy-N—(N-(4-(2-oxo-2-(piperidin-1-yl)ethylthio)phenyl)carbamimidoyl)pyrrolidine-1-carboximidamide.3. The ...

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Номер записи: 61
04-05-2017 дата публикации

Method for producing heterocyclic compound

Номер: US20170121286A1
Автор: Hironori Yamashita, Kazuhiro Miwa
Принадлежит: Takeda Pharmaceutical Co Ltd

Provided is a production method of a synthetic intermediate for a heterocyclic compound having a renin inhibitory activity and useful as a prophylactic or therapeutic drug for diabetic nephropathy, hypertension and the like. A production method of a compound represented by the formula (III-1a), the formula (III-1b), the formula (III-1c) and/or the formula (III-1d); wherein each symbol is as described in DESCRIPTION, or a salt thereof, including reacting a compound represented by the formula (Ia) or (Ib): wherein each symbol is as described in DESCRIPTION, or a salt thereof with a compound represented by the formula (II): wherein each symbol is as described in DESCRIPTION, or a salt thereof, in the presence of an aluminum compound and a chiral amine compound.

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Номер записи: 62
16-04-2020 дата публикации

NOVEL PIPERAZINE AND PIPERIDINE DERIVATIVES, THEIR SYNTHESIS AND USE THEREOF IN INHIBITING VDAC OLIGOMERIZATION, APOPTOSIS AND MITOCHONDRIA DYSFUNCTION

Номер: US20200115348A1
Автор: LEV GRUZMAN Arie, SHOSHAN-BARMATZ Varda
Принадлежит:

Provided herein piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction. Also provided methods of treatment of diseases associated with said processes, e.g. Alzheimer's and Parkinson's diseases. 3. A pharmaceutical composition containing the compound according to together with one or more pharmaceutically acceptable excipients.4. A method of making a medicament comprising formulating a compound according to with one or more pharmaceutically acceptable excipients.5. A method for treating a disease or disorder associated with enhanced apoptosis comprising administering to a subject in need thereof a therapeutically effective amount of the compound according to .6. A method for treating a disease or disorder a disease or disorder selected from the list consisting of neurodegenerative diseases and disorders claim 1 , cardiovascular diseases and disorders claim 1 , Alzheimer's disease claim 1 , Parkinson's disease claim 1 , cardiac hypertrophy claim 1 , heart failure claim 1 , myocardial infarction claim 1 , ischemia/reperfusion injury claim 1 , apoptosis claim 1 , autophagy of cardiac myocytes claim 1 , atrial fibrillation (AF) claim 1 , and cardiac arrhythmia comprising administering to a subject in need thereof a therapeutically effective amount of the compound according to . This application is a continuation-in-part of U.S. application Ser. No. 15/567,807 filed Oct. 19, 2017, which is the U.S. national phase of International Application No. PCT/IL2016/051020 filed Sep. 13, 2016, which designated the U.S. and claims priority to U.S. Provisional Application No. 62/217,986 filed Sep. 14, 2015, the entire contents of each of which are hereby incorporated by reference.The invention relates to use of small organic compounds interacting with the Voltage-Dependent Anion Channel (VDAC), reducing its channel conductance and acting as inhibitors of VDAC oligomerization, associated with ...

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Номер записи: 63
25-04-2019 дата публикации

DEVELOPMENT OF NOVEL DETERGENTS FOR USE IN PCR SYSTEMS

Номер: US20190119739A1
Автор: Angrish Parul, Wang Jonathan, Yang Zhiwei
Принадлежит:

This disclosure relates to novel detergents for use in various procedures including, for example, nucleic acid amplification reactions such as polymerase chain reaction (PCR). Methods for preparing the modified detergents are also described. 2. The compound of claim 1 , wherein:{'sup': '1', 'sub': 8', '16', '8', '16, 'Ris a (C-C) alkyl or (C-C) substituted alkyl;'}{'sup': 2', '3, 'sub': '3', 'Rand Rare each independently H or CH;'}{'sup': 4', '5', '3', '5, 'sub': 2', 'n', '2', 'n', '1', '30', '1', '30', '1', '30', '1', '30, 'Rand Rare each independently H, (CH)NH, (CH)N, or, alternatively, Ris taken together with Rto form a 5- or 6-membered ring which is optionally substituted with at least one (C-C) alkyl, (C-C) substituted alkyl, (C-C) heteroalkyl, (C-C) substituted heteroalkyl; and'}each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30.5. The composition of claim 4 , wherein:{'sup': '1', 'sub': 8', '16', '8', '16, 'Ris a (C-C) alkyl or (C-C) substituted alkyl;'}{'sup': 2', '3, 'sub': '3', 'Rand Rare each independently H or CH;'}{'sup': 4', '5', '3', '5, 'sub': 2', 'n', '2', 'n', '1', '30', '1', '30', '1', '30', '1', '30, 'Rand Rare each independently H, (CH)NH, (CH)N, or, alternatively, Ris taken together with Rto form a 5- or 6-membered ring which is optionally substituted with at least one (C-C) alkyl, (C-C) substituted alkyl, (C-C) heteroalkyl, (C-C) substituted heteroalkyl; and'}each n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30.7. The composition of claim 4 , wherein said polymerase is thermostable.9. The kit of claim 8 , wherein:{'sup': '1', 'sub': 8', '16', '8', '16, 'Ris a (C-C) alkyl or (C-C) substituted alkyl;'}{'sup': 2', '3, 'sub': '3', 'Rand Rare each independently H or CH;'}{'sup': 4', '5', '3', '5, 'sub': 2', 'n', '2', 'n', '1', '30', '1', '30', '1', '30', '1', '30, 'Rand Rare each ...

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Номер записи: 64
19-05-2016 дата публикации

COMPOUNDS FOR BINDING TO THE PLATELET SPECIFIC GLYCOPROTEIN IIb/IIIa AND THEIR USE FOR IMAGING OF THROMBI

Номер: US20160137629A1
Автор: Berger Markus, Krüger Martin, Lohrke Jessica, Reinhardt Michael, SIEBENEICHER Holger
Принадлежит: PIRAMAL IMAGING SA

The present invention relates to novel fluorine containing compounds, methods for their preparation, the intermediates of the synthesis, their use as diagnostic agents, especially for imaging of thrombi. The invention relates to positron emission tomography (PET) agents and associated precursor reagents, and methods for producing such radiolaveled agents for imaging of thrombi in a mammalian body. More particularly, the invention relates to small nonpeptide, high-affinity, specific-binding glycoprotein 11b/IIIa antagonists for imaging of thrombi. 16.-. (canceled)11. Compounds of Formula I according to claim 7 , selected from:tert-butyl 4-{3-[(3R)-3-({(1S)-3-methoxy-1-[3-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)-phenyl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate,tert-butyl 4-{3-[(3R)-3-({3-methoxy-1-[4-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate,tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[4-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)phenyl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate,tert-butyl 4-{3-[(3R)-3-({(1S)-3-methoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylat,tert-butyl 4-{3-[(3R)-3-({(1S)-3-tert-butoxy-1-[5-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)pyridin-3-yl]-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate,tert-butyl 4-{3-[(3R)-3-{[3-methoxy-1-{5-[4-(2-{[(4-methylphenyl)sulfonyl]oxy}ethoxy)-phenyl]pyridin-3-yl}-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate,tert-butyl 4-{3-[(3R)-3-{[(1S)-3-tert-butoxy-1-{5-[4-(2-{[(4-methylphenyl)sulfonyl]oxy}-ethoxy)phenyl]pyridin-3-yl}-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate;tert-butyl 4-{3-[(3R)-3-({1-[5-(4-chloro-3-cyanophenyl)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl} ...

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Номер записи: 65
18-05-2017 дата публикации

PREPARATION OF PIPERIDINE-4-CARBOTHIOAMIDE

Номер: US20170137381A1
Автор: BRÜNJES Marco, Ford Mark James
Принадлежит: Bayer CropScience Aktiengesellschaft

The present invention describes a novel process for preparing piperidine-4-carbothioamide. 2. The process according to claim 1 , characterized in that the reaction is carried out in a sealed reaction vessel.3. The process according to claim 1 , characterized in that the reaction is carried out at a reaction temperature of ≧0° C.4. The process according to claim 1 , characterized in that the solvent comprises a primary alcohol claim 1 , a secondary alcohol claim 1 , a tertiary alcohol claim 1 , or a mixture thereof.5. The process according to claim 1 , characterized in that the solvent is an alcohol comprising from 1 to 10 carbon atoms.6. The process according to claim 1 , characterized in that the solvent is methanol claim 1 , ethanol claim 1 , isopropanol claim 1 , tert-butanol claim 1 , i-butanol claim 1 , n-butanol claim 1 , cyclopentanol claim 1 , or cyclohexanol.7. Use of the compound of formula (I) according to for preparing active pharmaceutical and agrochemical ingredients.8. Use of the compound of formula (I) according to for preparing active agrochemical ingredients.9. Use of the compound of formula (I) according to for preparing active fungicidal ingredients.10. The process according to claim 1 , characterized in that the reaction is carried out at a reaction temperature from 20° C. to 100° C.11. The process according to claim 1 , characterized in that the reaction is carried out at a reaction temperature from 40° C. to 80° C. The present invention relates to a novel process for preparing piperidine-4-carbothioamide.Piperidine-4-carbothioamide derivatives are important precursors for active pharmaceutical and agrochemical ingredients (cf. WO 2008/013622, WO 2011/072207 and WO 2011/076699).The processes referred to in WO 2008/013622 and WO 2011/072207 and, inter alia, also in WO 2011/146182, WO 2009/094407 and US 2010/0240619 for preparing piperidine-4-carbothioamide derivatives all employ N-substituted 4-cyanopiperidine as starting material. However, the ...

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Номер записи: 66
26-05-2016 дата публикации

CRYSTALLINE FREEBASE FORMS OF A BIPHENYL COMPOUND

Номер: US20160143897A1
Автор: Woollam Grahame
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

The invention provides two crystalline freebase forms of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester. The invention also provides pharmaceutical compositions comprising the crystalline freebase or prepared using the crystalline freebases; processes and intermediates for preparing the crystalline freebases; and methods of using the crystalline freebases to treat a pulmonary disorder. 12-. (canceled)3. The composition of claim 13 , wherein the crystalline compound is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values selected from 6.6±0.1 claim 13 , 11.4±0.1 claim 13 , 13.1±0.1 claim 13 , 16.1±0.1 claim 13 , 17.5±0.1 claim 13 , 18.2±0.1 claim 13 , 18.6±0.1 claim 13 , 19.3±0.1 claim 13 , 19.7±0.1 claim 13 , 19.9±0.1 claim 13 , 20.2±0.1 claim 13 , 20.8±0.1 claim 13 , 21.1±0.1 claim 13 , 21.7±0.1 claim 13 , and 22.3±0.1.411-. (canceled)12. A pharmaceutical composition comprising a pharmaceutically acceptable dry powder excipient and a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1 claim 13 , 13.1±0.1 claim 13 , 18.6±0.1 claim 13 , 19.7±0.1 claim 13 , and 20.2±0.1; and further characterized by having five or more additional diffraction peaks at 2θ values selected from 8.8±0.1 claim 13 , 10.1±0.1 claim 13 , 11.4±0.1 claim 13 , 11.6±0.1 claim 13 , 14.8±0.1 claim 13 , 15.2±0.1 claim 13 , 16.1±0.1 claim 13 , 16.4±0.1 claim 13 , 16.9±0.1 claim 13 , 17.5±0.1 claim 13 , 18.2±0.1 claim 13 , 19.3±0.1 claim 13 , 19.9±0.1 claim 13 , 20.8±0.1 claim 13 , 21.1±0.1 claim 13 , 21.7±0.1 claim 13 , and 22.3±0.1.13. The composition of claim 12 , which further comprises an agent selected from βadrenergic receptor agonists claim 12 , steroidal anti-inflammatory agents claim 12 , ...

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Номер записи: 67
30-04-2020 дата публикации

Process for the Separation of Optical Isomers of Racemic 3-Alkylpiperidine-Carboxylic Acid Ethyl Esters

Номер: US20200131126A1
Автор: FAIGL Ferenc, MÁTRA VÖLGYI Béla, MIZSÁK Ágnes
Принадлежит:

The subject-matter of the invention is process for the separation of optical isomers of racemic 3-alk-3-carboxylic acid ethyl esters of formula rac-I with the resolving agent (II) (−)-2,3:4,5-di-O-izopropylidene-2-keto-L-gulonic acid (hereinafter: diacetone-L-ketogulonic acid). 1. A process for the preparation of the high enantiomerically pure optical isomers ((R)-Ia-c and (S)-Ia-c) of the 3-alkylpiperidine-3-carboxylic acid ethyl esters of formula rac-I (wherein in the formula I the meaning of R can be methyl group (Ia) , ethyl group (Ib) or isopropyl group (Ic)) characterized in that the rac-Ia-c amines are dissolved separately in a suitable organic solvent , preferably in acetone at a temperature between 0° C. and 56° C. , reacted with an amount of 0.8-1.2 molequivalent of (−)-2 ,3:4 ,6-di-O-isopropylidene-2-keto-L-gulonic acid (diacetone-L-ketogulonic acid) resolving agent of formula II , preferably with the monohydrate thereof and after dissolving the resolving agent optionally , the solution is seeded with pure diastereomeric salt prepared from Ia-c enantiomers having appropriate configuration and resolving agent II , then after cooling of the mixture , the diastereomeric salt is separated by filtration and the appropriate high enantiomeric purity (R)-Ia or (R)-Ib or (S)-Ic enantiomers are liberated either from the crystalline (R)-Ia.II or (R)-Ib.II or (S)-Ic.II salts directly or after their recrystallization from an organic solvent , preferably from isopropanol , and optionally obtain therefrom the crystalline (R)-Ia.HCl , (R)-Ib.HCl and (S)-Ic.HCl salts in an organic solvent with hydrochloric acid which are separated by filtration and isolate the high enantiomeric purity crystalline products of (S)-Ia.HCl , (S)-Ib.HCl and (R)-Ic.HCl by the separation from the (S>>R)-Ia.II , (S>>R)-Ia.II and (R>>S)-Ia.II salts remaining in the residues obtained from the filtrate of the diastereomeric salt formation and recrystallization in the same manner as the crystalline ...

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Номер записи: 68
30-04-2020 дата публикации

Intermediates for the preparation of remifentanil hydrochloride

Номер: US20200131127A1
Автор: Janka Králová, Lubos Slízik, Norbert Varga, Pavol Valachovic
Принадлежит: Hameln Pharma Plus GmbH

A new intermediate for synthesizing 1-substituted-4-[phenyl(propanoyl)amino]piperidine-4-carbonitrile derivatives is laid open. Specifically set out is a method for use of this intermediate in the preparation of remifentanil. The enclosed shorter process offers a greater yield of products with higher purity as compared to methods reported in the prior art.

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Номер записи: 69
26-05-2016 дата публикации

COMPOUNDS AND COMPOUNDS FOR USE IN METHODS FOR TREATING DISEASES OR CONDITIONS MEDIATED BY PROTEIN DISULFIDE ISOMERASE

Номер: US20160145209A1
Автор: Dandapani Sivaraman, Flaumenhaft Robert, Munoz Benito, Nag Partha Pratim, Pilyugina Tatiana, PU JUN
Принадлежит:

The invention provides compounds of formula (I) that inhibit PDI, for use in methods to treat or prevent a disease or condition in a subject that would benefit by inhibition of PDI. Formula (I) 2. The compound according to claim 1 , wherein Ris OH.3. The compound according to claim 1 , wherein Ris H or Cl.4. The compound according to claim 3 , wherein Rand Rare both H or claim 3 , taken together with the carbon atom to which they are attached claim 3 , form a carbonyl group.5. The compound according to claim 4 , wherein Ris OR claim 4 , wherein Ris substituted or unsubstituted alkyl.6. The compound according to claim 5 , wherein W is ethylene.7. The compound according to claim 6 , wherein X is O.8. The compound according to claim 7 , wherein Ris substituted or unsubstituted aryl.11. A pharmaceutical composition comprising a compound according to and a pharmaceutically acceptable excipient or solvent.13. The method according to claim 12 , wherein the method is for treating thrombosis claim 12 , thrombotic diseases claim 12 , infectious diseases claim 12 , cancer claim 12 , inflammation claim 12 , platelet aggregation and/or fibrin generation.15. The method according to claim 12 , wherein Ris OH.16. The method according to claim 15 , wherein Ris H or Cl.17. The method according to claim 16 , wherein Rand Rare H claim 16 , or taken together with the carbon atom to which they are attached form a carbonyl group.18. The method according to claim 17 , wherein Ris OR claim 17 , wherein Ris substituted or unsubstituted alkyl.19. The method according to claim 18 , wherein W is ethylene.20. The method according to claim 19 , wherein X is O.21. The method according to claim 20 , wherein Ris substituted or unsubstituted aryl. This application claims the benefit of U.S. Provisional Application No. 61/837,820, filed Jun. 21, 2013, the entire teachings of which are incorporated herein by reference.This invention was supported in part by the United States Government under National ...

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Номер записи: 70
16-05-2019 дата публикации

DEUTERATED COMPOUNDS AS IMMUNOMODULATORS

Номер: US20190144389A1
Автор: Fan Pingchen, LUI Rebecca M., Mali Venkat Reddy, Singh Rajinder, Zeng Yibin, Zhang Penglie
Принадлежит:

Compounds are provided to modulate the C5a receptor. The compounds have the following Formula (I):

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Номер записи: 71
16-05-2019 дата публикации

BIGUANIDE COMPOUNDS AND USE THEREOF

Номер: US20190144464A1
Автор: HEO Hye Jin, Jeong Jae Kap, KIM Hong Woo, KIM Seo-il, Lee Hong Bum, LEE Ji Sun, Lee Young Woo, Park Ji Hyun
Принадлежит:

The present invention relates to biguanide compounds and use thereof, more particularly, to biguanide derivatives exhibiting excellent effects for inhibition of cancer cell proliferation and inhibition of cancer metastasis and recurrence, a method for preparing the same, a pharmaceutical composition containing the same as an active ingredient, and a method of prevention or treatment of cancer comprising the step of administering an effective amount of the composition to a subject in need thereof. 2. The compound according to claim 1 , wherein the compound is selected from the group consisting of:N1-pyrrolidine-N5-(benzo[1,3]dioxol-5-ylmethyl) biguanide,N1-pyrrolidine-N5-(4-methoxy)phenyl biguanide,N1-pyrrolidine-N5-(3-chloro-4-methoxy)phenyl biguanide,N1-pyrrolidine-N5-(2,6-difluorophenyl)-N-methyl)phenyl biguanide,N1-pyrrolidine-N5-(4-dimethylamino)phenyl biguanide,N1-pyrrolidine-N5-(4-isopropyl)phenyl biguanide,N1-pyrrolidine-N5-(3-phenoxy)phenyl biguanide,N1-pyrrolidine-N5-(N-biphenyl-3-yl) biguanide,N1-pyrrolidine-N5-(N-biphenyl-4-yl) biguanide,N1-pyrrolidine-N5-(4′-fluorobiphenyl-3-yl) biguanide,N1-pyrrolidine-N5-(3′-fluorobiphenyl-4-yl) biguanide,N1-pyrrolidine-N5-(4-fluoro)phenethyl biguanide,N1-pyrrolidine-N5-(2-phenylpropane-2-yl) biguanide,N1-pyrrolidine-N5-(5,6,7,8-tetrahydronaphthalene-2-yl) biguanide,N1-pyrrolidine-N5-((1,2,3,4-tetrahydronaphthalene-1-yl) biguanide,N1-(S)-2-methyl pyrrolidine-N5-(4-(trifluoromethoxy)phenyl biguanide,N1-(S)-3-hydroxy pyrrolidine-N5-(4-trifluoromethoxy)phenyl biguanide,N1-(R)-3-hydroxy pyrrolidine-N5-(4-trifluoromethoxy)phenyl biguanide,N1-3-hydroxy methyl pyrrolidine-N5-(4-trifluoromethoxy)phenyl biguanide,N1-pyrrolidine-N5-4-benzamide biguanide,N1-pyrrolidine-N5-4-methyl-N-ethyl benzamide biguanide,N1-pyrrolidine-N5-4-(2-oxo-2-(piperidine-1-yl)ethyl thio)phenyl, andN1-(S)-2-hydroxy pyrrolidine-N5-4-(2-oxo-2-(piperidine-1-yl)ethyl thio)phenyl biguanide.3. The compound according to claim 1 , wherein the compound of ...

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Номер записи: 72
07-06-2018 дата публикации

SMALL MOLECULE BASED ANTIBODY-RECRUITING COMPOUNDS FOR CANCER TREATMENT

Номер: US20180155332A1
Автор: Rullo Anthony, Spiegel David
Принадлежит:

The present invention relates to chimeric (including bifunctional) compounds, compositions comprising those compounds and methods of treating cancer in a patient or subject, especially including metastatic cancer where cancer cells exhibit overexpression (heightened expression) of cell surface urokinase-type plasminogen activator receptor (urokinase receptor) compared to normal (non-cancerous) cells. The compounds bind to the urokinase-type plasminogen activator receptor (uPAR) on the surface of a cancer cell, including a metastatic cancer cell, and consequently recruit native antibodies of the patient or subject where the antibodies can selectively degrade and/or deactivate targeted cancer cells through antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) against a large number and variety of cancers, thus providing cancer cell death and an inhibition of growth, elaboration and/or metastasis of the cancer, including remission and cure of the patient's cancer. 1. A compound according to the general formula:{'img': {'@id': 'CUSTOM-CHARACTER-00021', '@he': '3.22mm', '@wi': '4.57mm', '@file': 'US20180155332A1-20180607-P00001.TIF', '@alt': 'custom-character', '@img-content': 'character', '@img-format': 'tif'}, 'Where is a moiety which binds to an active site of urokinase-type plasminogen activator receptor (uPAR) on the surface of cancer cells of a patient or subject;'}{'img': {'@id': 'CUSTOM-CHARACTER-00022', '@he': '3.22mm', '@wi': '3.89mm', '@file': 'US20180155332A1-20180607-P00002.TIF', '@alt': 'custom-character', '@img-content': 'character', '@img-format': 'tif'}, 'is an antibody binding moiety comprising a hapten which is capable of binding to an antibody in said patient or subject (preferably an endogenous antibody which pre-exists in the patient or subject without having to be raised prior to therapy);'}{'img': [{'@id': 'CUSTOM-CHARACTER-00023', '@he': '3.22mm', '@wi': '4.57mm ...

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Номер записи: 73
07-06-2018 дата публикации

THERAPEUTIC AGENT AND THERAPEUTIC METHOD FOR PULMONARY HYPERTENSION

Номер: US20180155434A1
Автор: EHARA Hiromi, FUJINO Ikuko, IKUTANI Masashi, Ogawa Shinya, TAKATSU Kiyoshi
Принадлежит:

The present invention relates to a therapeutic agent for pulmonary hypertension comprising an interleukin-5 receptor (hereinafter, abbreviated to “IL-5R”)-inhibiting compound and therapeutic method therefor. More specifically, the present invention relates to a therapeutic agent for pulmonary hypertension comprising an antibody or an antibody fragment capable of specifically binding to the extracellular region of IL-5R and a therapeutic method therefor. 115-. (canceled)16. A method for treating pulmonary hypertension , comprising administering an antibody or an antibody fragment thereof which binds to the extracellular region of an interleukin-5 receptor (IL-5R) to inhibit an IL-5R-expressing cell.17. The method according to claim 16 , wherein the antibody removes an IL-5R-expressing cell.18. The method according to claim 16 , wherein the antibody has antibody-dependent cellular cytotoxic activity (ADCC activity).19. The method according to claim 16 , wherein the antibody has IL-5R-neutralizing activity.20. The method according to claim 16 , wherein the antibody inhibits group 2 innate lymphoid cell (ILC2)-dependent IL-5R-expressing cell growth.21. The method according to claim 16 , wherein the method is characterized by at least one of the following (i) to (iii):(i) the IL-5R-expressing cell is at least one cell of an eosinophil, a basophil, and a mast cell;(ii) the method inhibits the growth of a vascular smooth muscle cell; and(iii) the method inhibits pulmonary vascular remodeling.22. The method according to claim 16 , wherein the antibody is any one antibody selected from a monoclonal antibody and a recombinant antibody.23. The method according to claim 16 , wherein the antibody comprises a human Fc region or a human constant region.24. The method according to claim 16 , wherein the antibody comprises heavy chain (H chain) CDR1 to CDR3 respectively comprising the amino acid sequences represented by SEQ ID NOs: 1 to 3 and light chain (L chain) CDR1 to CDR3 ...

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Номер записи: 74
08-06-2017 дата публикации

AUTOMATED SYNTHESIS OF SMALL MOLECULES USING CHIRAL, NON-RACEMIC BORONATES

Номер: US20170158614A1
Автор: Burke Martin D., Gillis Eric P., LI Junqi
Принадлежит:

Provided are methods for making and using chiral, non-racemic protected organoboronic acids, including pinene-derived iminodiacetic acid (PIDA) boronates, to direct and enable stereoselective synthesis of organic molecules. Also provided are methods for purifying PIDA boronates from solution. Also provided are methods for deprotection of boronic acids from their PIDA ligands. The purification and deprotection methods may be used in conjunction with methods for coupling or otherwise reacting boronic acids. Iterative cycles of deprotection, coupling, and purification can be performed to synthesize chiral, non-racemic compounds. The methods are suitable for use in an automated chemical synthesis process. Also provided is an automated small molecule synthesizer apparatus for performing automated stereoselective synthesis of chiral, non-racemic small molecules using iterative cycles of deprotection, coupling, and purification. 14-. (canceled)6. The compound of claim 5 , wherein R* is a chiral group of at least 90% enantiomeric excess.7. The compound of claim 5 , wherein R* is a chiral group of at least 95% enantiomeric excess.14. The compound of claim 5 , wherein Rand R claim 5 , taken together claim 5 , form a 5-10-membered cycloalkyl or aromatic ring claim 5 , or form a 5-10-membered heterocyclic or heteroaromatic ring comprising 1-3 heteroatoms independently selected from the group consisting of O claim 5 , N claim 5 , and S.21. (canceled)22. The compound of claim 5 , wherein m is 0.2329-. (canceled)31. The compound of claim 30 , wherein the carbon atom marked “*” in formula (IV) is a chiral carbon atom of at least 90% enantiomeric excess.32164-. (canceled) This application is a continuation of U.S. patent application Ser. No. 14/692,088, filed on Apr. 21, 2015, now U.S. Pat. No. 9,388,131, which is a divisional of U.S. patent application Ser. No. 14/112,985, filed on Dec. 12, 2013, now U.S. Pat. No. 9,012,658, which is a §371 national stage application based on ...

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Номер записи: 75
08-06-2017 дата публикации

CARBOXAMIDE DERIVATIVES AND THE USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF HEPATITIS B

Номер: US20170158634A1
Автор: Haché Geerwin Yvonne Paul, Kesteleyn Bart Rudolf Romanie, Raboisson Pierre Jean-Marie Bernard, Vandyck Koen
Принадлежит:

Inhibitors of HBV replication of formula (I) 3. A compound according to or , wherein Ris selected from hydrogen , Fluoro , Chloro , —CHF , —CN , —CFor methyl.4. A compound according to anyone of to wherein at least two of R , Rand Rare Fluoro , Chloro or Bromo.5. A compound according to any one of the previous claims wherein Ris methyl.6. A compound according to any one of the previous claims wherein Rcontains a 3-7 membered saturated ring optionally containing one oxygen , such 3-7 membered saturated ring optionally substituted with methyl.7. A compound according to any one of the previous claims wherein Ris a 4 or 5 membered saturated ring containing one oxygen , such 4 or 5 membered saturated ring optionally substituted with methyl.8. A compound according to any one of to , wherein Ris a branched C-Calkyl optionally substituted with one or more Fluoro.11. A compound according to any one of the previous claims for use in the prevention or treatment of an HBV infection in a mammal.12. A pharmaceutical composition comprising a compound according to any of to , and a pharmaceutically acceptable carrier.13. A compound according to any one of to , or a pharmaceutical composition according to in combination with at least one other anti-HBV agent. The Hepatitis B virus (HBV) is an enveloped, partially double-stranded DNA (dsDNA) virus of the Hepadnavirus family (). Its genome contains 4 overlapping reading frames: the precore/core gene; the polymerase gene; the L, M, and S genes, which encode for the 3 envelope proteins; and the X gene.Upon infection, the partially double-stranded DNA genome (the relaxed circular DNA; rcDNA) is converted to a covalently closed circular DNA (cccDNA) in the nucleus of the host cell and the viral mRNAs are transcribed. Once encapsidated, the pregenomic RNA (pgRNA), which also codes for core protein and Pol, serves as the template for reverse transcription, which regenerates the partially dsDNA genome (rcDNA) in the nucleocapsid.HBV has ...

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Номер записи: 76
18-06-2015 дата публикации

Neprilysin inhibitors

Номер: US20150166469A1
Автор: Adam D. Hughes, Erik FENSTER, Melissa Fleury
Принадлежит: Theravance Biopharma R&D Ip Llc

In one aspect, the invention relates to compounds having the formula: where R 1 -R 5 and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

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Номер записи: 77
18-06-2015 дата публикации

METHOD FOR PRODUCING OPTICALLY ACTIVE 3-AMINOPIPERIDINE OR SALT THEREOF

Номер: US20150166481A1
Автор: MORI Kohei, NISHIYAMA Akira, NOJIRI Masutoshi, TAOKA Naoaki
Принадлежит: KANEKA CORPORATION

The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing. 121-. (canceled) The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate, and to intermediates useful for producing the 3-aminopiperidine.As methods for producing an optically active 3-aminopiperidine or salt thereof, or a derivative of optically active 3-aminopiperidine, for example, the following methods are known:1) a method, wherein L-ornithine monohydrochloride is methyl-esterified, and then (S)-3-amino piperidone is obtained by chromatography with an ion exchange resin, the (S)-3-amino piperidone is reacted with lithium aluminum hydride to be (S)-3-aminopiperidine, an inorganic salt is removed by filtration, and the target compound is purified (Non-patent Document 1);2) a method, wherein ethyl nipecotate is optically resolved using L-tartaric acid, the nitrogen atom is protected with benzyloxycarbonyl group, the ethyl ester is hydrolyzed in alkaline condition, Curtius rearrangement is carried out using ...

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Номер записи: 78
18-06-2015 дата публикации

NITROGEN CONTAINING COMPOUNDS AND THEIR USE

Номер: US20150166537A1
Автор: Bhagwat Sachin, Birajdar Satish, PATIL Vijaykumar Jagdishwar, Tadiparthi Ravikumar
Принадлежит: WOCKHARDT LTD.

Compounds of Formula (I), their preparation and use in preventing or treating bacterial infections are disclosed. 2. A process according to claim 1 , wherein compound of Formula (III) is obtained by reacting a compound of Formula (II) with 1-hydroxybenzotriazole ammonium salt in presence of dicyclohexylcarbodiimide.3. A process according to claim 1 , wherein compound of Formula (VI) is obtained by reacting a compound of Formula (V) with trimethylsulfoxonium iodide and sodium hydride in presence of triethylamine and dimethylsulfoxide.4. A process according to claim 1 , wherein compound of Formula (XIII) is obtained by cyclizing a compound of Formula (XII) with triphosgene in presence of triethylamine and N claim 1 ,N-dimethylaminopyridine claim 1 , followed by purification using column chromatography.5. A process according to claim 4 , wherein eluent used for column chromatography is mixture of ethyl acetate and hexane.7. A process according to claim 6 , wherein the racemic isomers of compound of Formula (XI) are isolated by treating with methanol.9. A process according to claim 8 , wherein sulfonation of a compound of Formula (XIIIa) is achieved by using sulfur trioxide dimethylformamide complex.10. A process according to claim 8 , wherein compound of Formula (XIIIb) is passed through a column packed with Amberlite sodium to provide a compound of Formula (I).11. A compound of Formula (I) in crystalline form.12. A process of preparing a compound of Formula (I) in crystalline form claim 8 , said process comprising crystallizing a compound of Formula (I) from one or more solvents selected from acetone claim 8 , ethanol claim 8 , water claim 8 , acetonitrile claim 8 , toluene or tetrahydrofuran.13. A compound of Formula (I) according to having X-ray powder diffraction peaks at: 5.18 (±0.2) claim 11 , 5.33 (±0.2) claim 11 , 10.21 (±0.2) claim 11 , 17.52 (±0.2) claim 11 , 18.57 (±0.2) claim 11 , 19.37 (±0.2) claim 11 , 20.29 (±0.2) claim 11 , 25.40 (±0.2) claim 11 , 26.39 ...

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Номер записи: 79
21-05-2020 дата публикации

METHOD FOR TREATING PULMONARY ARTERIAL HYPERTENSION AND ASSOCIATED PULMONARY ARTERIAL HYPERTENSION

Номер: US20200155552A1
Автор: ALONSO-GALICIA Magdalena, Carpenter David, PACK Thomas, RHODES Melissa, RURKA Julie, WRING Steve
Принадлежит: ALTAVANT SCIENCES GmbH

There is a method of treating or preventing pulmonary arterial hypertension or associated pulmonary arterial hypertension in a patient. The method has the step of systemically administering to the patient a therapeutically effective amount of one or more compounds: (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof, or (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroeth-oxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof, or a combination of the foregoing. There is also a method of treating or preventing pulmonary arterial hypertension or associated pulmonary arterial hypertension in a patient by systemically administering a therapeutically effective amount of a THP1 inhibitor from about 1 mg/kg/day to about 50 mg/kg/day 1. A method of treating or preventing pulmonary arterial hypertension or associated pulmonary arterial hypertension in a patient comprising systemically administering to the patient a therapeutically effective amount of a compound selected from the group consisting of (i) (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1 ,1′-biphenyl]-2-yl)-2 ,2 ,2-trifluoroethoxy)pyrimidin-4-yl)-2 ,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof , (ii) (S)-8-(2-amino-6-((R)-1-(5-chloro-[1 ,1′-biphenyl]-2-yl)-2 ,2 ,2-trifluoroeth-oxy)pyrimidin-4-yl)-2 ,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof , and (iii) a combination of the foregoing , wherein the therapeutically effective amount is about 1 mg/kg/day to about 50 mg/kg/day.2. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered orally.3. The method of claim 2 , wherein the compound or pharmaceutically acceptable salt thereof is administered orally by a dosage form selected from ...

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Номер записи: 80
29-09-2022 дата публикации

BIPHENYL COMPOUNDS USEFUL AS MUSCARINIC RECEPTOR ANTAGONISTS

Номер: US20220306579A1
Автор: Husfeld Craig, Ji YuHua, Li Li, Mammen Mathai, Mu YongQi
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

This invention provides compounds of formula I: 126.-. (canceled)28. The process of claim 27 , wherein step (b) is carried out at a temperature of 0 to 10 ° C.29. The process of claim 27 , wherein step (a) is carried out at room temperature.31. The process of claim 30 , further comprising contacting biphenyl-2-ylcarbamic acid piperidin-4-yl ester and N-benzyl-N-methylaminoacetaldehyde in the presence of sodium triacetoxyborohydride to form Compound 3.32. The process of claim 27 , further comprising contacting Compound 1 in the presence of an acid to form a salt of Compound 1.33. The method of claim 32 , wherein the acid is phosphoric acid claim 32 , sulfuric acid claim 32 , or oxalic acid. This application claims the benefit of U.S. Provisional Application No. 60/552,443, filed on Mar. 11, 2004; the entire disclosure of which is incorporated herein by reference in its entirety.The present invention relates to novel biphenyl compounds having muscarinic receptor antagonist or anticholinergic activity. This invention also relates to pharmaceutical compositions comprising such biphenyl compounds, processes and intermediates for preparing such biphenyl compounds and methods of using such biphenyl compounds to treat pulmonary disorders.Pulmonary or respiratory disorders, such as chronic obstructive pulmonary disease (COPD) and asthma, afflict many millions of people worldwide and such disorders are a leading cause of morbidity and mortality.Muscarinic receptor antagonists are known to provide bronchoprotective effects and therefore, such compounds are useful for treating respiratory disorders, such as COPD and asthma. When used to treat such disorders, muscarinic receptor antagonists are typically administered by inhalation. However, even when administered by inhalation, a significant amount of the muscarinic receptor antagonist is often absorbed into the systemic circulation resulting in systemic side effects, such as dry mouth, mydriasis and cardiovascular side effects. ...

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Номер записи: 81
29-09-2022 дата публикации

CRYSTALLINE FREEBASE FORMS OF A BIPHENYL COMPOUND

Номер: US20220306580A1
Автор: Woollam Grahame
Принадлежит:

The invention provides two crystalline freebase forms of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester. The invention also provides pharmaceutical compositions comprising the crystalline freebase or prepared using the crystalline freebases; processes and intermediates for preparing the crystalline freebases; and methods of using the crystalline freebases to treat a pulmonary disorder. 120-. (canceled)21. A process for preparing a pharmaceutical composition , the process comprising:dissolving a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl)piperidin-4-yl ester in a solvent to form a solution; wherein the crystalline freebase is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.122. The process of claim 21 , further comprising combining the solution with an aqueous pharmaceutical carrier.23. The process of claim 21 , wherein the solvent is an aqueous pharmaceutical carrier.24. The process of claim 21 , wherein the crystalline freebase is further characterized by five or more additional diffraction peaks at 20 values selected from 8.8±0.1 claim 21 , 10.1±0.1 claim 21 , 11.4±0.1 claim 21 , 11.6±0.1 claim 21 , 14.8±0.1 claim 21 , 15.2±0.1 claim 21 , 16.1±0.1 claim 21 , 16.4±0.1 claim 21 , 16.9±0.1 claim 21 , 17.5±0.1 claim 21 , 18.2±0.1 claim 21 , 19.3±0.1 claim 21 , 19.9±0.1 claim 21 , 20.8±0.1 claim 21 , 21.1±0.1 claim 21 , 21.7±0.1 claim 21 , and 22.3±0.1.25. The process of claim 21 , wherein the crystalline freebase is further characterized by a powder x-ray diffraction pattern having peak positions in accordance with the peak positions shown in .26. The process of claim 21 , wherein the crystalline freebase is further characterized by a melting point of about 125° C.27. The process of claim 21 , wherein the crystalline freebase is ...

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Номер записи: 82
22-06-2017 дата публикации

PROCESS FOR PREPARATION OF SODIUM (2S, 5R)-6-(BENZYLOXY)-7-OXO-1,6-DIAZABICYCLO[3.2.1]OCTANE-2-CARBOXYLATE

Номер: US20170174686A1
Автор: Birajdar Satish, PATEL Mahesh Vithalbhai, PATIL Vijaykumar Jagdishwar, Shaikh Mohammad Usman, Tadiparthi Ravikumar
Принадлежит: WOCKHARDT LIMITED

2. The process according to claim 1 , wherein the compound of Formula (IV) is obtained by treating the compound of Formula (II) with trimethylsilyl chloride in presence of methanol.4. The process according to claim 3 , wherein the compound of Formula (II) is converted to the compound of Formula (III) in presence of hydrochloric acid.6. The process according to claim 5 , wherein the compound of Formula (VII) is obtained by reacting the compound of Formula (VI) with 4-methoxybenzyl alcohol in presence of a carboxylic group activating agent.7. The process according to claim 6 , wherein the carboxylic group activating agent is selected from the group consisting of 1 -ethyl-3-(3-methylaminopropyl)carbodiimide hydrochloride claim 6 , 1-hydroxy benzotriazole claim 6 , dicyclohexylcarbodiimide claim 6 , carbonyldiimidazole; and a mixture thereof.8. The process according to claim 5 , wherein cyclization is carried out in presence of triphosgene claim 5 , triethylamine and 4-dimethylaminopyridine.10. (canceled)13. The process according to claim 1 , wherein cyclization is carried out in presence of triphosgene claim 1 , triethylamine and 4-dimethylaminopyridine. This application claims priority to Indian Patent Application No. 1192/MUM/2014 filed on Mar. 29, 2014, the disclosures of which are incorporated herein by reference in its entirety as if fully rewritten herein.The invention relates to a process for preparation of sodium (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate.A compound of Formula (I), chemically known as sodium (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate, can be used as an intermediate in the synthesis of several antibacterial compounds and is disclosed in PCT International Patent Application No. PCT/IB2013/059264. The present invention discloses a process for preparation of a compound of Formula (I).In one general aspect, there is provided a process for preparation of a compound of Formula (I), said ...

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Номер записи: 83
02-07-2015 дата публикации

NOVEL COMPOUNDS FOR USE IN PCR SYSTEMS AND APPLICATIONS THEREOF

Номер: US20150184145A1
Автор: Angrish Parul, Yang Zhiwei
Принадлежит:

This disclosure relates to novel compounds for use in various compositions, kits and methods, including, for example, use in polymerase storage buffers and in nucleic acid synthesis or amplification reactions such as a polymerase chain reaction (PCR). Methods for preparing the novel compounds are also described. 3. A composition comprising a polymerase and the compound of .4. The composition of claim 3 , wherein said polymerase is thermostable.5. The composition of claim 3 , comprising one or more of the following:a) at least one nucleotide triphosphateb) DTTc) KCl{'sup': '2', 'd) MgCl'}e) Kathonf) EDTAg) gelatinh) Trisi) glycerolj) BSA6. The composition of claim 3 , further comprising a polymerase inhibitor.7. The composition of claim 6 , wherein said polymerase inhibitor is at least one oligonucleotide inhibitor.8. The composition of claim 6 , wherein said polymerase inhibitor is at least one antibody inhibitor.9. The composition of claim 3 , wherein said polymerase is stable for at least about one month to about three years.10. A kit comprising a storage or reaction composition comprising a polymerase and the compound of .11. The kit of claim 10 , wherein said polymerase is thermostable.12Thermus aquaticus. The kit of claim 11 , wherein said polymerase is a polymerase isolated from (Taq) polymerase.13. The kit of claim 11 , further comprising a polymerase inhibitor.14. A method for increasing the efficiency of a polymerase claim 11 , said method comprising the steps of:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, 'a) mixing a target nucleic acid with at least one polymerase, at least one primer, dNTPs, and the compound according to ; and,'}b) amplifying said target nucleic acid.15. The method of claim 14 , wherein said increased efficiency is the same as the efficiency when the polymerase is in the presence of NP-40 and/or Tween® 20 instead of said compound.16. The method of claim 14 , wherein said increased efficiency is greater than the efficiency when the ...

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Номер записи: 84
28-06-2018 дата публикации

BIPHENYL COMPOUNDS USEFUL AS MUSCARINIC RECEPTOR ANTAGONISTS

Номер: US20180179161A1
Автор: Husfeld Craig, Ji YuHua, Li Li, Mammen Mathai, Mu YongQi
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

This invention provides compounds of formula I: 126-. (canceled)27. A method of treating a pulmonary disorder in a mammal , the method comprising administering to the mammal a pharmaceutical composition comprising a pharmaceutically acceptable carrier and biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester or a pharmaceutically acceptable salt thereof; wherein the pharmaceutical composition is administered to the mammal in an amount sufficient to provide about 10 μg/day to about 200 μg/day of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]-methylamino}ethyl)piperidin-4-yl ester or a pharmaceutically acceptable salt thereof.28. The method of claim 27 , wherein the pulmonary disorder is chronic obstructive pulmonary disease.29. The method of claim 27 , wherein the pulmonary disorder is asthma.30. The method of claim 27 , wherein the pharmaceutical composition is administered by inhalation.31. The method of claim 27 , wherein the pharmaceutical composition is administered using a nebulizer inhaler.32. The method of claim 27 , wherein the pharmaceutical composition is administered in a single daily dose.33. The method of claim 27 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable aqueous carrier.34. The method of claim 33 , wherein the pharmaceutical composition has a pH in the range of from 3 to 8.35. The method of claim 33 , wherein the pharmaceutical composition further comprises a buffer.36. The method of claim 35 , wherein the buffer is a sodium chloride citric acid buffer.37. The method of claim 33 , wherein the pharmaceutical composition is an isotonic aqueous solution.38. The method of claim 37 , wherein the isotonic aqueous solution comprises about 0.05 μg/mL to about 10 mg/mL of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester or a pharmaceutically acceptable salt thereof. ...

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Номер записи: 85
18-09-2014 дата публикации

MATRIX METALLOPROTEASE (MMP) TARGETED AGENTS FOR IMAGING AND THERAPY

Номер: US20140271465A1
Автор: Chinen Lori, Dyszlewski Mary, Freskos John N., Knight Hector, SCHMIDT Michelle
Принадлежит: Mallinckrodt LLC

The present invention provides compound conjugates of matrix metalloprotease inhibitors and linked metal chelators which are useful for imaging solid tumors and treating and diagnosing certain types of diseases such as cancer. 1. A compound conjugate comprising a matrix metalloprotease inhibitor (MMPi) portion and a linked metal chelator portion.2. The conjugate of claim 1 , wherein the MMPi is linked to the metal chelator portion by a bifunctional linker.9. The conjugate of claim 1 , and further comprising a radionuclide.10. The conjugate of claim 9 , wherein said radionuclide is selected from the group consisting of Ac claim 9 , As claim 9 , At claim 9 , B claim 9 , Ba claim 9 , Bi claim 9 , Br claim 9 , Br claim 9 , C claim 9 , Cd claim 9 , Cu claim 9 , Cu claim 9 , Cu claim 9 , F claim 9 , Ga claim 9 , Ga claim 9 , H claim 9 , I claim 9 , I claim 9 , I claim 9 , I claim 9 , In claim 9 , Lu claim 9 , N claim 9 , O claim 9 , P claim 9 , P claim 9 , Pb claim 9 , Pd claim 9 , re claim 9 , Re claim 9 , Sc claim 9 , Sm claim 9 , Sr claim 9 , Tc claim 9 , Y and Y.11. The conjugate of claim 9 , wherein said radionuclide is selected from the group consisting of In and Tc.12. The conjugate of claim 1 , and further comprising a lanthanide.13. The conjugate of claim 1 , and further comprising a lipid claim 1 , a liposome claim 1 , a micelle claim 1 , a lipid-coated bubble claim 1 , or a block copolymer micelle.14. The conjugate of claim 13 , wherein said lipid is a phospholipid claim 13 , glycolipid claim 13 , sphingolipid claim 13 , or cholesterol.15. The conjugate of claim 1 , and further comprising a stealth agent.16. The conjugate of claim 15 , wherein said stealth agent is poly(ethylene glycol).17. A pharmaceutical composition comprising a conjugate of .18. A method of diagnosing the presence of solid tumors in a patient claim 1 , the method comprising the following steps:administering a compound conjugate comprising a matrix metalloprotease inhibitor (MMPi) portion ...

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Номер записи: 86
09-07-2015 дата публикации

ANTI-PROLIFERATIVE COMPOUNDS AND USES THEREOF

Номер: US20150191417A1
Автор: Anderson Kenneth C., Gorgun Gullu, Hideshima Teru, Mazitschek Ralph
Принадлежит:

The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, tautomers, stereoisomers, solvates, hydrates, polymorphs, and compositions thereof. Also provided are methods and kits involving the inventive compounds for treating proliferative diseases (e.g., cancers (e.g., breast cancer, prostate cancer, lung cancer, and ovarian cancer), benign neoplasms, angiogenesis, inflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound of the invention may enhance the anti-tumor immune response by inhibiting or eliminating the immune suppression mediated by immune suppressor myeloid cells (MDSCs), inducing apoptosis, and/or inhibit or down-regulate proteins (e.g., epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), X-linked inhibitor of apoptosis protein (XIAP), and heat shock protein 90 (Hsp90)) in the subject. 25-. (canceled)6. The compound of claim 1 , wherein Ring A is a phenyl ring.7. The compound of claim 1 , wherein Ring B is a phenyl ring.8. (canceled)9. The compound of claim 1 , wherein Rings A claim 1 , B claim 1 , and C are each a phenyl ring.1219-. (canceled)23. The compound of claim 1 , wherein at least one Ris —C(═O)R.2430-. (canceled)31. The compound of claim 1 , wherein j claim 1 , k claim 1 , and m are each 0.35. (canceled)39. (canceled)41. (canceled)42. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , tautomer claim 1 , stereoisomer claim 1 , solvate claim 1 , hydrate claim 1 , or polymorph thereof claim 1 , and optionally a pharmaceutically acceptable excipient.4348-. (canceled)49. A method of treating a proliferative disease in a subject claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering to the subject a therapeutically effective amount of a compound of , or a pharmaceutically ...

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Номер записи: 87
09-07-2015 дата публикации

4-(AZACYCLOALKYL)BENZENE-1,3-DIOL COMPOUNDS AS TYROSINASE INHIBITORS, PROCESS FOR THE PREPARATION THEREOF AND USE THEREOF IN HUMAN MEDICINE AND IN COSMETICS

Номер: US20150191451A1
Автор: BOITEAU Jean-Guy, Bouquet Karine, Millois Barbuis Corinne, Talano Sandrine
Принадлежит:

4-(Azacycloalkyl)benzene-1,3-diol compounds are described corresponding to general formula (I) below: 223.-. (canceled) This application is a continuation of copending U.S. patent application Ser. No. 14/200,954, filed Mar. 7, 2014, which is a continuation of U.S. patent application Ser. No. 13/611,546, filed Sep. 12, 2012, now U.S. Pat. No. 8,697,726, which is a continuation of U.S. patent application Ser. No. 13/131,363, filed Sep. 12, 2011, now U.S. Pat. No. 8,299,259, which is a National Stage of PCT/EP2009/066268, filed Dec. 2, 2009, and designating the United States (published in the English language on Jun. 10, 2010 as WO 2010/063774 A1; the title and abstract were also published in English), which claims benefit of U.S. Provisional Patent Application No. 61/193,460, filed Dec. 2, 2008 and also claims priority under 35 U.S.C. §119 to French Patent Application No. 0858207, filed Dec. 2, 2008, each of the earlier applications being hereby expressly incorporated by reference in their entirety and each assigned to the assignee hereof.The invention relates to novel 4-(azacycloalkyl)benzene-1,3-diol compounds as industrial and useful products. It also relates to the process for the preparation thereof and to the use thereof, as tyrosinase inhibitors, in pharmaceutical or cosmetic compositions for use in the treatment or prevention of pigmentary disorders.Skin pigmentation, in particular human skin pigmentation, is the result of melanin synthesis by dendritic cells, melanocytes. Melanocytes contain organelles called melanosomes which transfer melanin into the upper layers of keratinocytes which are then transported to the surface of the skin through differentiation of the epidermis (Gilchrest B A, Park H Y, Eller M S, Yaar M, Mechanisms of ultraviolet light-induced pigmentation. Photochem Photobiol 1996; 63: 1-10; Hearing V J, Tsukamoto K, Enzymatic control of pigmentation in mammals. FASEB J 1991; 5: 2902-2909).Among the enzymes of melanogenesis, tyrosinase is a ...

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Номер записи: 88
05-07-2018 дата публикации

CRYSTALLINE FREEBASE FORMS OF A BIPHENYL COMPOUND

Номер: US20180186740A1
Автор: Woollam Grahame
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

The invention provides two crystalline freebase forms of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester. The invention also provides pharmaceutical compositions comprising the crystalline freebase or prepared using the crystalline freebases; processes and intermediates for preparing the crystalline freebases; and methods of using the crystalline freebases to treat a pulmonary disorder. 120-. (canceled)21. A method for preparing a pharmaceutical composition for use in a nebulizer inhaler , the method comprising dissolving a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}-ethyl)piperidin-4-yl ester in an aqueous pharmaceutical carrier to form an aqueous nebulizer solution; wherein the crystalline freebase is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1 , 13.1±0.1 , 18.6±0.1 , 19.7±0.1 , and 20.2±0.1.22. The method of claim 21 , wherein the crystalline freebase is further characterized by five or more additional diffraction peaks at 2θ values selected from 8.8±0.1 claim 21 , 10.1±0.1 claim 21 , 11.4±0.1 claim 21 , 11.6±0.1 claim 21 , 14.8±0.1 claim 21 , 15.2±0.1 claim 21 , 16.1±0.1 claim 21 , 16.4±0.1 claim 21 , 16.9±0.1 claim 21 , 17.5±0.1 claim 21 , 18.2±0.1 claim 21 , 19.3±0.1 claim 21 , 19.9±0.1 claim 21 , 20.8±0.1 claim 21 , 21.1±0.1 claim 21 , 21.7±0.1 claim 21 , and 22.3±0.1.23. The method of claim 21 , wherein the crystalline freebase is further characterized by a powder x-ray diffraction pattern having peak positions substantially in accordance with the peak positions shown in .24. The method of claim 21 , wherein the crystalline freebase is further characterized by a melting point of about 125° C.25. The method of claim 21 , wherein the crystalline freebase is further characterized by a differential scanning calorimetry thermogram substantially in accordance with that ...

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Номер записи: 89
23-07-2015 дата публикации

Prodrugs of Compounds that Enhance Antifungal Activity and Compositions of Said Prodrugs

Номер: US20150203517A1
Автор: Ajamian Alain, Chantigny Yves Andre, Deziel Robert, Raeppel Franck, Raeppel Stéphane, Vaisburg Arkadii
Принадлежит:

The invention relates to prodrugs for use in the inhibition of histone deacetylase. The prodrugs of the present invention have good aqueous solubility and good aqueous stability. The prodrugs of the invention advantageously are metabolized to the active ingredient in plasma or in the blood stream of a warm-blooded animal. The invention also provides compositions and, and methods for making the prodrugs, and methods for using the prodrugs to treat fungal infections. 1. A compound of the formula{'br': None, 'sup': 2', '2', 'x, 'Cy-L-Ar—Y—C(O)N(R)—Z'} Cy is —H, cycloalkyl, aryl, heteroaryl, or heterocyclyl, any of which is optionally substituted, provided that Cy is not a (spirocycloalkyl)heterocyclyl;', {'sup': '2', 'sub': 1', '6', '2', '6', '2, 'Lis C-Csaturated alkylene or C-Calkenylene, wherein the alkylene or alkenylene optionally is substituted, and wherein one or two of the carbon atoms of the alkylene is optionally replaced by O; NR′, R′ being alkyl, acyl, or hydrogen; S; S(O); or S(O);'}, 'Ar is arylene, wherein said arylene optionally is additionally substituted and optionally is fused to an aryl or heteroaryl ring, or to a saturated or partially unsaturated cycloalkyl or heterocyclic ring, any of which is optionally substituted; and', {'sup': '2', 'Yis a chemical bond or a straight- or branched-chain saturated alkylene, which is optionally substituted, provided that the alkylene is not substituted with a substituent of the formula —C(O)R wherein R comprises an α-amino acyl moiety;'}], 'or a pharmaceutically acceptable salts thereof, wherein'}{'sup': x', '20, 'Ris —H, OH, or —R;'}{'sup': 20', '21, 'Z is —O—Ror —Rwherein'}{'sup': '20', 'claim-text': [{'sup': '10', '—C(O)—R,'}, {'sup': 40', '41, 'sub': 'n', '—C(O)-[C(R)(R)]OP(O)(OH)(OH),'}, {'sup': 31', '40', '41, 'sub': n', '2, '—C(O)N(R)[C(R)(R)]SOOH, or'}, {'sup': 40', '41', '40', '41', '42, 'sub': n', 'n, '—C(O)NH[C(R)(R)]C(O)O[C(R)(R)]R;'}], 'each —Ris'}{'sup': '10', 'claim-text': [{'sup': 40', '41', '42, ...

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Номер записи: 90
18-06-2020 дата публикации

METHOD FOR TREATING SARCOIDOSIS-ASSOCIATED PULMONARY HYPERTENSION

Номер: US20200188398A1
Автор: PACK Thomas, Rajagopal Sudarshan
Принадлежит: ALTAVANT SCIENCES GmbH

There is a method of treating or preventing sarcoidosis-associated pulmonary hypertension in a patient. The method has the step of administering to the patient a therapeutically effective amount of one or more compounds: (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof, or (S)-8-(2-amino-6-((R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroeth-oxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof, or a combination of the foregoing. 1. A method of treating or preventing sarcoidosis-associated pulmonary hypertension in a patient comprising administering to the patient a therapeutically effective amount of a compound selected from the group consisting of (i) (S)-ethyl 8-(2-amino-6-((R)-1-(5-chloro-[1 ,1′-biphenyl]-2-yl)-2 ,2 ,2-trifluoroethoxy)pyrimidin-4-yl)-2 ,8-diazaspiro[4.5]decane-3-carboxylate or a pharmaceutically acceptable salt thereof , (ii) (S)-8-(2-amino-6-((R)-1-(5-chloro-[1 ,1′-biphenyl]-2-yl)-2 ,2 ,2-trifluoroeth-oxy)pyrimidin-4-yl)-2 ,8-diazaspiro[4.5]decane-3-carboxylic acid or a pharmaceutically acceptable salt thereof , and (iii) a combination of the foregoing.2. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered orally.3. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered orally by a dosage form selected from the group consisting of capsules claim 1 , tablets claim 1 , powders claim 1 , and granules.4. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered orally in the form of a liquid.5. The method of claim 1 , wherein the compound or pharmaceutically acceptable salt thereof is administered one to four times per day.6. The method of claim 1 , wherein the compound is (S)-ethyl 8-(2-amino-6-((R)-1-(5- ...

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Номер записи: 91
21-07-2016 дата публикации

COMPOSITIONS AND METHODS FOR THE TREATMENT OF INFLAMMATION AND PAIN

Номер: US20160207886A1
Автор: Kandula Mahesh
Принадлежит:

The invention relates to the compounds of formula V or its pharmaceutical acceptable polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula V and methods for the treatment of inflammation and pain may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, lozenge, spray, intravenous, oral solution, buccal mucosal layer tablet, parenteral administration, syrup, or injection. Such compositions may be used to treatment of pain, oral mucosal inflammatory or oral infectious diseases. 2. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.3. The pharmaceutical composition of claim 2 , wherein said pharmaceutical composition is formulated to treat inflammation mediated pain in a patient in need thereof with an effective amount of said pharmaceutical composition claim 2 , and wherein said pharmaceutical composition is administered to the patient in need by oral administration claim 2 , delayed release or sustained release claim 2 , transmucosal administration claim 2 , syrup claim 2 , lozenge claim 2 , spray claim 2 , mucoadhesive claim 2 , buccal formulation claim 2 , mucoadhesive tablet claim 2 , topical administration claim 2 , parenteral administration claim 2 , injection claim 2 , subdermal administration claim 2 , oral solution claim 2 , rectal administration claim 2 , buccal administration or transdermal administration.4. The pharmaceutical composition of claim 3 , wherein said inflammation mediated pain is caused by oral mucositis claim 3 , oral ulceration claim 3 , oral inflammation claim 3 , oral infection claim 3 , oral wounds claim 3 , dental surgery claim 3 , post-tosillectomy claim 3 , odontostomatology claim 3 , gingivitis claim 3 , stomatitis claim 3 , glossitis claim 3 , aphthous ulcers claim 3 , pharyngitis claim 3 , tonsillitis claim 3 , radiation or intubation mucositis.5. A method of ...

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Номер записи: 92
20-07-2017 дата публикации

BIPHENYL COMPOUNDS USEFUL AS MUSCARINIC RECEPTOR ANTAGONISTS

Номер: US20170204061A1
Автор: Husfeld Craig, Ji YuHua, Li Li, Mammen Mathai, Mu YongQi
Принадлежит: THERAVANCE BIOPHARMA R&D IP, LLC

This invention provides compounds of formula I: 126-. (canceled)30. A method of treating a pulmonary disorder in a patient , the method comprising administering to the patient a compound of or ; or a pharmaceutical composition of .31. The method of claim 30 , wherein the pulmonary disorder is chronic obstructive pulmonary disease.32. The method of claim 30 , wherein the pulmonary disorder is asthma.33. A method of producing bronchodilation in a patient claim 30 , the method comprising administering to the patient a bronchodilation-producing amount of a compound of or ; or a pharmaceutical composition of . This application claims the benefit of U.S. Provisional Application No. 60/552,443, filed on Mar. 11, 2004; the entire disclosure of which is incorporated herein by reference in its entirety.Field of the InventionThe present invention relates to novel biphenyl compounds having muscarinic receptor antagonist or anticholinergic activity. This invention also relates to pharmaceutical compositions comprising such biphenyl compounds, processes and intermediates for preparing such biphenyl compounds and methods of using such biphenyl compounds to treat pulmonary disorders.State of the ArtPulmonary or respiratory disorders, such as chronic obstructive pulmonary disease (COPD) and asthma, afflict many millions of people worldwide and such disorders are a leading cause of morbidity and mortality.Muscarinic receptor antagonists are known to provide bronchoprotective effects and therefore, such compounds are useful for treating respiratory disorders, such as COPD and asthma. When used to treat such disorders, muscarinic receptor antagonists are typically administered by inhalation. However, even when administered by inhalation, a significant amount of the muscarinic receptor antagonist is often absorbed into the systemic circulation resulting in systemic side effects, such as dry mouth, mydriasis and cardiovascular side effects.Additionally, many inhaled muscarinic receptor ...

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Номер записи: 93
02-10-2014 дата публикации

NITROGEN CONTAINING COMPOUNDS AND THEIR USE

Номер: US20140296526A1
Автор: Bhagwat Sachin, Birajdar Satish, PATIL Vijaykumar Jagdishwar, Tadiparthi Ravikumar
Принадлежит: WOCKHARDT LIMITED

Compounds of Formula (I), their preparation and use in preventing or treating bacterial infections are disclosed. 2. A process according to claim 1 , wherein compound of Formula (III) is obtained by reacting a compound of Formula (II) with 1-hydroxybenzotriazole ammonium salt in presence of dicyclohexylcarbodiimde.3. A process according to claim 1 , wherein compound of Formula (VI) is obtained by reacting a compound of Formula (V) with trimethylsulfoxonium iodide and sodium hydride in presence of triethylamine and dimethylsulfoxide.4. A process according to claim 1 , wherein compound of Formula (XIII) is obtained by cyclizing a compound of Formula (XII) with triphosgene in presence of triethylamine and N claim 1 ,N-dimethylaminopyridine claim 1 , followed by purification using column chromatography.5. A process according to claim 4 , wherein eluent used for column chromatography is mixture of ethyl acetate and hexane.7. A process according to claim 6 , wherein the racemic isomers of compound of Formula (XI) are isolated by treating with methanol.9. A process according to claim 8 , wherein sulfonation of a compound of Formula (XIIIa) is achieved by using sulfur trioxide dimethylformamide complex.10. A process according to claim 8 , wherein compound of Formula (XIIIb) is passed through a column packed with Amberlite sodium to provide a compound of Formula (I).11. A compound of Formula (I) in crystalline form.12. A process of preparing a compound of Formula (I) in crystalline form claim 8 , said process comprising crystallizing a compound of Formula (I) from one or more solvents selected from acetone claim 8 , ethanol claim 8 , water claim 8 , acetonitrile claim 8 , toluene or tetrahydrofuran.13. A compound of Formula (I) according to having X-ray powder diffraction peaks at: 5.18 (±0.2) claim 11 , 5.33 (±0.2) claim 11 , 10.21 (±0.2) claim 11 , 17.52 (±0.2) claim 11 , 18.57 (±0.2) claim 11 , 19.37 (±0.2) claim 11 , 20.29 (±0.2) claim 11 , 25.40 (±0.2) claim 11 , 26.39 ...

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Номер записи: 94
09-10-2014 дата публикации

PROCESS FOR PREPARING A COMPOUND USEFUL FOR PRODUCING AN OPTICALLY ACTIVE DIAZABICYCLOOCTANE COMPOUND

Номер: US20140303375A1
Автор: ABE Takao, OKUE Masayuki, SAKAMAKI Yoshiaki
Принадлежит: Meiji Seika Pharma. Co., Ltd.

A process for preparing the compound of the following formula (E): This application is a divisional application of application Ser. No. 13/173,002 filed on Jun. 30, 2011. This application claims the benefit under 35 USC 119(e)(i) of provisional application Ser. No. 61/459,954 filed on Dec. 22, 2010. The entire contents of each of application Ser. No. 13/173,002 and provisional application Ser. No. 61/459,954 are incorporated by reference herein.The present invention relates to an optically active diazabicyclooctane derivative defined by formula (F) below, which is useful as a pharmaceutical intermediate for β-lactamase inhibitor, and a process for preparing the same.Penicillins and cephalosporins are β-lactam antibiotics which are most widely and frequently used in the clinic. However, the development of resistance to β-lactam antibiotics by various pathogens severely has had a damaging effect on maintaining the effective treatment of bacterial infections. The most significant known mechanism related to the development of bacterial resistance is the production of class A, C, and D β-lactamases having a serine residue at the active center. These enzymes decompose the β-lactam antibiotic, resulting in the loss of the antimicrobial activities. Class A β-lactamases preferentially hydrolyze penicillins while class C β-lactamases have a substrate profile favoring cephalosporins. As commercially available β-lactamase inhibitors, clavulanic acid, sulbactam, and tazobactam are known, and these inhibitors are effective mainly against class A β-lactamase producing bacteria, and used as a mixture with a penicillin antibiotic. However, 250 types or more of β-lactamases have been reported to date, and among them, in addition to the expansion of class C β-lactamases as well as extended-spectrum β-lactamase (ESBL) belonging to class A and D β-lactamases, further resistant bacteria which produce class A KPC-2β-lactamase decomposing even carbapenem as a last resort for β-lactam ...

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Номер записи: 95
02-08-2018 дата публикации

NK 1 ANTAGONISTS

Номер: US20180215729A1
Автор: Huang Xianhai, Palani Anandan, Paliwal Sunil, Rao Ashwin U., Shah Sapna S., Shih Neng-Yang, Tsui Hon-Chung, Wang Cheng, Wrobleski Michelle Laci, Xiao Dong
Принадлежит:

A compound having the general structure shown in Formula I: 4. The method of claim 3 , further comprising administering to the patient an effective amount of at least one anti-depressant agent and/or at least one anti-anxiety agent.5. The method of claim 4 , further comprising:administering to the patient an effective amount of at least one selective serotonin reuptake inhibitor, andwherein the physiological disorder, symptom or disease is depression.6. The method according to claim 5 , further comprising:{'sub': 1', '3', '2c, 'administering an effective amount of at least one active ingredient selected from the group consisting of other NKreceptor antagonists, selective serotonin reuptake inhibitors, dopamine receptor agonists, serotonin 5-HTreceptor antagonists, serotonin 5-HTreceptor agonists, nociceptin receptor agonists, glucocorticoids and inhibitors of multidrug resistance protein 5; and'}wherein the physiological disorder, symptom or disease is selected from the group consisting of: a respiratory disease, depression, anxiety, phobia, bipolar disorder, alcohol dependence, psychoactive substance abuse, nociception, psychosis, schizophrenia, stress related disorder, obsessive/compulsive disorder, bulimia, anorexia nervosa, binge eating, sleep disorder, mania, premenstrual syndrome, gastrointestinal disorder, obesity, headache, neuropathic pain, post-operative pain, chronic pain syndrome, bladder disorder or genitourinary disorder. This application is a Continuation of U.S. application Ser. No. 15/293,962 filed Oct. 14, 2016, which is a Continuation of U.S. application Ser. No. 14/304,163 filed Jun. 13, 2014, now U.S. Pat. No. 9,469,629, which is a Continuation of U.S. application Ser. No. 13/245,403 filed Sep. 26, 2011, now U.S. Pat. No. 8,754,216, which is a Continuation of U.S. application Ser. No. 12/750,420 filed Mar. 30, 2010, now U.S. Pat. No. 8,026,364, which is a Divisional on U.S. application Ser. No. 11/172,289 filed Jun. 30, 2005, now U.S. Pat. No. 7 ...

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Номер записи: 96
20-08-2015 дата публикации

CHEMICAL PROCESS

Номер: US20150232423A1
Автор: Hossner Frank, Strachan John Bryce
Принадлежит:

The present invention relates to a process for the preparation of umeclidinium bromide, and to processes for preparing intermediates used in the preparation of umeclidinium bromide. 121-. (canceled)23. A process according to claim 22 , wherein Ris ethyl.24. A process according to claim 22 , wherein X is Cl or Br.25. A process according to claim 22 , wherein the reagent in step (b) is selected from the group consisting of thionyl chloride claim 22 , sulfonyl halides claim 22 , such as sulfonyl chlorides claim 22 , sulfonyl anhydrides and phosphorus halides.26. A process according to claim 25 , wherein the reagent in step (b) is selected from the group consisting of thionyl chloride claim 25 , p-toluenesulfonyl chloride claim 25 , methanesulfonyl chloride claim 25 , methanesulfonic anhydride claim 25 , p-toluenesulfonic anhydride claim 25 , trifluoromethanesulfonic anhydride claim 25 , phosphoryl chloride claim 25 , phosphorus tribromide and phosphorus pentachloride.27. A process according to claim 26 , wherein the reagent is thionyl chloride.28. A process according to claim 22 , wherein steps (a) and (b) are carried out in a suitable solvent.29. A process according to claim 28 , wherein the solvent is toluene.30. A process according to claim 22 , wherein the base is DBU. The present invention relates to a process for the preparation of umeclidinium bromide, and to processes for preparing intermediates used in the preparation of umeclidinium bromide.International Patent Publication Number WO 2005/104745 (Glaxo Group Limited), filed 27 April 2005, discloses muscarinic acetylcholine receptor antagonists. In particular, WO 2005/104745 discloses 4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane bromide, of formula (I), and a process for the preparation of this compound (Example 84):4-[Hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl)}1-azoniabicyclo[2.2.2]octane bromide may also be referred to as umeclidinium bromide. ...

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Номер записи: 97
23-10-2014 дата публикации

DESIGN, SYNTHESIS AND EVALUATION OF PROCASPASE ACTIVATING COMPOUNDS AS PERSONALIZED ANTI-CANCER DRUGS

Номер: US20140315915A1
Автор: Fan Timothy M., HERGENROTHER Paul J., Hsu Danny Chung, Novotny Chris J., Peterson Quinn Patrick, West Diana C.
Принадлежит: The Board of Trustees of the University of Illinois

Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed that have lower neurotoxicity effects than other compounds. 2. The method of wherein{'sup': 10', '11', '12', '13', '14, 'one of R, R, R, R, and Rcontains a polar group selected from the group consisting of: a sulfonamide group, a nitro group, an amino group, a carboxylate group, a sulfonyl group, and an aryl sulfonyl group;'}{'sup': 10', '11', '12', '13', '14, 'the others of R, R, R, R, and Rare each independently selected from the group consisting of: hydrogen, halogen, a hydroxyl group, a sulfonamide group, a nitro group, an amino group, a carboxylate group, a sulfonyl group, an aryl sulfonyl group, and C1-C6 alkoxy; and'}{'sup': 3', '7', '8', '9, 'R, R, R, Rare each independently hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy or C2-C6 alkenyl.'}3. The method of wherein X is oxygen and Ris hydrogen.4. The method of wherein Ris methoxy or allyl.8. The method of wherein Ra and Rare each hydrogen and q is 0.9. The method of wherein Ris allyl claim 7 , X is O and Ris hydrogen.10. The method of wherein R claim 1 , Rand Rare methoxy.11. The method of wherein Ris allyl claim 1 , X is O and Ris hydrogen.12. The method of wherein one or two of X claim 1 , X claim 1 , X claim 1 , X claim 1 , and Xare N.15. The method of wherein the compound of Formula (FX1) is a procaspase activator compound having a log BB of −0.4 to −2.19. The method of wherein the procaspase activator compound has a log BB of −0.4 to −2.21. The method of where the cancer is breast cancer claim 18 , lymphoma claim 18 , adrenal cancer claim 18 , renal cancer claim 18 , melanoma claim 18 , leukemia claim 18 , neuroblastoma claim 18 , lung cancer or brain cancer.22. The method of where ...

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Номер записи: 98
09-08-2018 дата публикации

IONIZABLE CATIONIC LIPID FOR RNA DELIVERY

Номер: US20180222863A1
Автор: Chivukula Padmanabh, Payne Joseph E., Tanis Steven P.
Принадлежит:

What is described is a compound 2. The compound of claim 1 , wherein Lis a bond.3. The compound of claim 2 , wherein X is S.4. The compound of claim 2 , wherein X is O.5. The compound of claim 2 , wherein each of Rand Ris a linear alkyl.6. The compound of claim 2 , wherein each of Rand Ris a linear alkyl or alkenyl.7. The compound of claim 2 , wherein one or both of Land Lis a linear alkylene.8. The compound of claim 2 , wherein each of Land Lis a bond.9. The compound of claim 8 , wherein Lis a bond.10. A method of making the compound of claim 9 , comprising a step of reacting pyrrolidine-3 claim 9 ,4-dicarboxylic acid with a protecting group.11. The compound of claim 8 , wherein Lis a methylene.12. A method of synthesis of the compound of claim 11 , wherein piperidine-3 claim 11 ,5-dicarboxylic acid group is a starting material.13. The compound of claim 1 , wherein Lis an alkylene.14. The compound of claim 12 , wherein X is S.15. The compound of claim 12 , wherein X is O.16. The compound of claim 12 , wherein each of Rand Ris a linear alkyl.17. The compound of claim 12 , wherein each of Rand Ris a linear alkyl or alkenyl.18. The compound of claim 12 , wherein each of Land Lis a linear alkylene.19. The compound of claim 17 , wherein Lis a bond.20. The compound of claim 17 , wherein Lis a methylene. This application claims benefit under 35 U.S.C. § 119(e) of Provisional U.S. Patent Application No. 62/457,060, filed Feb. 9, 2017, the contents of which is incorporated herein by reference in its entirety.A number of different types of nucleic acids are currently being developed as therapeutics for the treatment of a number of diseases. These nucleic acids include DNA in gene therapy, plasmids-based interfering nucleic acids, small interfering nucleic acids for use in RNA interference (RNAi), including siRNA, miRNA, antisense molecules, ribozymes and aptamers. As these molecules are being developed, there has been developed a need to produce them in a form that is stable ...

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Номер записи: 99
10-08-2017 дата публикации

APOE4-TARGETED THERAPUTICS THAT INCREASE SIRT1

Номер: US20170226059A1
Автор: Bredesen Dale E., Campagna Jesus, Jagodzinska Barbara, John Varghese, Jung Michael E., Pham Johnny, Rao Rammohan, Theendakara Veena P.
Принадлежит:

A link between ApoE4 allele and sirtuins expression level is identified that is believed to be associated with elevated risk for the promotion of processing of amyloid precursor protein (APP) by the non-amyloidogenic pathway in a mammal leading to elevated risk for Alzheimer's disease. Compounds are identified that upregulate sirtuins (e.g., SirT1) expression levels and appear to be useful in the treatment and/or prophylaxis of MCI and/or Alzheimer's disease. 2. The compound of claim 1 , wherein said compound is not any of compounds 1 claim 1 , 2 claim 1 , 4 claim 1 , 5 claim 1 , 6 claim 1 , 7 claim 1 , 8 claim 1 , 11 claim 1 , and 15 in Table 6.4. The compound according to any one of - claim 1 , wherein Rand Rare independently selected from the group consisting of hydrogen claim 1 , methyl claim 1 , ethyl claim 1 , propyl claim 1 , and butyl.7. The compound according to any one of - claim 1 , wherein Ris CH.8. The compound of claim 7 , wherein Ris H.9. The compound of claim 7 , wherein Ris CH.10. The compound according to any one of - claim 7 , wherein Ris O.11. The compound according to any one of - claim 7 , wherein Ris NHR.12. The compound according to any one of - claim 7 , wherein Ris NH.13. The compound according to any one of - claim 7 , wherein Rand Rare independently selected from the group consisting of hydrogen claim 7 , halogen claim 7 , and CH.14. The compound of claim 13 , wherein Rand Rare independently selected from the group consisting of H claim 13 , Cl claim 13 , and F.15. The compound of claim 13 , wherein Rand Rare both Cl.16. The compound of claim 13 , wherein Rand Rare both F.17. The compound of claim 13 , wherein Ris Cl and Ris F claim 13 , or Ris F and Ris Cl.18. The compound of claim 13 , wherein Ris H and Ris F.19. The compound of claim 13 , wherein Ris H and Ris Cl.20. The compound of claim 13 , wherein Ris H and Ris CH.21. The compound according to any one of - claim 13 , wherein Ris selected from the group consisting of H claim 13 , CH ...

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Номер записи: 100