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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 9369. Отображено 100.
17-05-2012 дата публикации

Radiolabeled cgrp antagonists

Номер: US20120121508A1
Автор: Craig A. Stump, Eric Hostetler, Harold G. Selnick, Ian M. Bell
Принадлежит: Merck Sharp and Dohme LLC

The present invention is directed to radiolabeled CGRP receptor antagonists which are useful for the quantitative imaging of CGRP receptors in mammals.

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Номер записи: 1
17-05-2012 дата публикации

No-Carrier-Added Nucleophilic [F-18] Fluorination of Aromatic Compounds

Номер: US20120123120A1
Автор: Jorge R. Barrio, Nagichettiar Satyamurthy
Принадлежит: UNIVERSITY OF CALIFORNIA

Phenyliodonium ylide derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are shown for use as precursors in aromatic nucleophilic substitution reactions. The iodonium ylide group is substituted by nucleophiles such as halide ions to provide the corresponding haloaryl derivatives. No-carrier-added [F-18]fluoride ion exclusively substitutes the iodonium ylide moiety in these derivatives and provides high specific activity F-18 labeled fluoro derivatives. Protected L-dopa-6-iodonium ylide derivative have been synthesized as a precursors for the preparation of no-carrier-added 6-[F-18]fluoro-L-dopa. The iodonium ylide group in this L-dopa.derivative is nucleophilically substituted by no-carrier-added [F-18]fluoride ion to provide a [F-18]fluoro intermediates which upon acid hydrolysis yielded 6-[F-18]fluoro-L-dopa.

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Номер записи: 2
20-09-2012 дата публикации

Iodine radiolabelling method

Номер: US20120237444A1
Автор: Michelle Avory
Принадлежит: Individual

The present invention provides a novel method of labelling biological targeting molecules (BTMs) of interest with radioiodine. Also provided are novel radioiodinated BTMs prepared using the method, as well as radiopharmaceutical compositions comprising such radioiodinated BTMs. The invention also provides radioiodinated intermediates useful in the method, as well as in vivo imaging methods using the radioiodinated BTMs.

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Номер записи: 3
25-10-2012 дата публикации

Heterodimers of Glutamic Acid

Номер: US20120269726A1
Автор: Craig N. Zimmerman, John W. Babich, Kevin P. Maresca
Принадлежит: Molecular Insight Pharmaceuticals Inc

Compounds of Formula (Ia) wherein R is a C 6 -C 12 substituted or unsubstituted aryl, a C 6 -C 12 substituted or unsubstituted heteroaryl, a C 1 -C 6 substituted or unsubstituted alkyl or —NR′R′, Q is C(O), O, NR′, S, S(O) 2 , C(O) 2 (CH2)p Y is C(O), O, NR′, S, S(O) 2 , C(O) 2 (CH2)p Z is H or C 1 -C 4 alkyl, R′ is H, C(O), S(O) 2 , C(O) 2 , a C 6 -C 12 substituted or unsubstituted aryl, a C 6 -C 12 substituted or unsubstituted heteroaryl or a C 1 -C 6 substituted or unsubstituted alkyl, when substituted, aryl, heteroaryl and alkyl are substituted with halogen, C 1 -C 12 heteroaryl, —NR′R′ or COOZ, which have diagnostic and therapeutic properties, such as the treatment and management of prostate cancer and other diseases related to NAALADase inhibition. Radiolabels can be incorporated into the structure through a variety of prosthetic groups attached at the X amino acid side chain via a carbon or hetero atom linkage.

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Номер записи: 4
10-01-2013 дата публикации

4-hydroxybutyric acid analogs

Номер: US20130012565A1
Автор: Adam J. Morgan, I. Robert Silverman, Roger D. Tung
Принадлежит: Concert Pharmaceuticals Inc

This invention relates to novel derivatives of 4-hydroxybutyric acid and prodrugs thereof, and pharmaceutically acceptable salts of the foregoing. This invention also provides pharmaceutical compositions comprising a compound of this invention and the use of such compositions in methods of treating narcolepsy, fibromyalgia, other disorders or conditions that are beneficially treated by improving nocturnal sleep or by administering sodium oxybate.

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Номер записи: 5
14-03-2013 дата публикации

Lipophilic cationic probe for pet-imaging

Номер: US20130064768A1
Автор: David K. Menon, Franklin I. Aigbirhio, Michael P. Murphy, Robin A. Smith
Принадлежит: CAMBRIDGE ENTERPRISE LTD, Medical Research Council, UNIVERSITY OF OTAGO

The present invention provides an imaging probe which comprises a lipophilic cation, a hydrophobic moiety and a PET nucleus. The present invention also provides a precursor molecule for the production of such an imaging probe and methods for using the probe for analysing mitochondrial membrane potential in a subject.

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Номер записи: 6
28-03-2013 дата публикации

Fluorinated fructose derivatives for pet imaging

Номер: US20130078184A1
Автор: Andrei Manolescu, Brendan TRAYNER, Chris CHEESEMAN, Frederick West, John Mercer, Tina GRANT
Принадлежит: University of Alberta

The present invention is directed to fructose-based radiopharmaceuticals, pharmaceutical compositions comprising same, precursors and methods for preparing same, and methods of using same for diagnostic imaging of cancer cells and non-imaging tracer studies.

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Номер записи: 7
28-03-2013 дата публикации

NITROIMIDAZOLE DERIVATIVES

Номер: US20130078185A1
Автор: ATREYA Chandan Ramaswamy, Kuniyil Kulangara Vijaya Raj
Принадлежит: GE HEALTHCARE LIMITED

The present invention provides novel compounds useful in the treatment and diagnosis of mycobacterial infections. Compounds of the present invention have enhanced biological properties as compared to the related known compounds. The present invention also provides a precursor compound useful in the synthesis of certain compounds of the invention, and a method to obtain these compounds using said precursor compound. Methods of treatment and diagnosis in which the compounds of the invention fmd use are also provided. 2. The compound as defined in wherein Ris methyl.3. The compound as defined in wherein X is —O—.4. (canceled)5. The compound as defined in wherein said radioactive halogen is a gamma-emitting radioactive halogen selected from I claim 1 , I and Br.6. (canceled)7. The compound as defined in wherein said radioactive halogen is a positron-emitting radioactive halogen selected from F claim 1 , F claim 1 , Br claim 1 , Br and I.810.-. (canceled)1519.-. (canceled)20. A pharmaceutical composition comprising the compound as defined in together with a biocompatible carrier in a form suitable for mammalian administration.21. An in vivo imaging method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) administration of the compound as defined in ;'}(b) allowing said compound to bind to the cell wall of any mycobacteria present in said subject;(c) detecting by an in vivo imaging procedure signals emitted by said radioactive halogen;(d) generating an image representative of the location and/or amount of said signals; and,(e) determining the distribution of mycobacteria in said subject wherein said distribution is directly correlated with said signals.22. (canceled)23Mycobacterium tuberculosis.. The in vivo imaging method as defined in wherein said mycobacterium is24Mycobacterium tuberculosis.. The in vivo imaging method as defined in which is carried out repeatedly during the course of a treatment regimen for said subject claim 23 , said regimen ...

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Номер записи: 8
04-04-2013 дата публикации

CARBOXYLATION CATALYSTS

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

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

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Номер записи: 9
11-04-2013 дата публикации

SOLID-PHASE FLUORINATION OF BENZOTHIAZOLES

Номер: US20130089501A1
Автор: BRADY FRANK, GIBSON ALEXANDER MARK, LUTHRA SAJINDER KAUR
Принадлежит:

The invention provides a process for the production of an F-labelled tracer which comprises treatment of a solid support-bound precursor of formula (I) 18-. (canceled)10. A radiopharmaceutical kit for the preparation of an F-labelled tracer for use in PET , which comprises:{'claim-ref': {'@idref': 'CLM-00009', 'claim 9'}, '(i) a vessel containing a compound of formula (I), (Ia), or (Ib) as defined in ; and'}{'sup': 18', '−, '(ii) means for eluting the vessel with a source of F;'}{'sup': 18', '−, '(iii) an ion-exchange cartridge for removal of excess F.'}11. A cartridge for a radiopharmaceutical kit for the preparation of an F-labelled tracer for use in PET which comprises:{'claim-ref': {'@idref': 'CLM-00009', 'claim 9'}, '(i) a vessel containing a compound of formula (I), (Ia), or (Ib) as defined in ; and'}{'sup': 18', '−, '(ii) means for eluting the vessel with a source of F.'}12. A radiopharmaceutical kit for the preparation of an F-labelled tracer for use in PET , which comprises:{'claim-ref': {'@idref': 'CLM-00009', 'claim 9'}, '(i) a vessel containing a compound of formula (III) as defined in ; and'}{'sup': 18', '−, '(ii) means for eluting the vessel with a source of F.'}13. A cartridge for a radiopharmaceutical kit for the preparation of an F-labelled tracer according to for use in PET which comprises:{'claim-ref': {'@idref': 'CLM-00009', 'claim 9'}, '(i) a vessel containing a compound of formula (III) as defined in ; and'}{'sup': '18', '(ii) means for eluting the vessel with a source of F.'}14. A method for obtaining a diagnostic PET image which comprises the step of using a radiopharmaceutical kit according to or a cartridge for a radiopharmaceutical kit according to . The present invention relates to novel solid-phase processes for the production of radiolabelled tracers, in particular for the production of F-labelled benzothiazole compounds which may be suitable for use as Positron Emission Tomography (PET) radiotracers. The invention also comprises ...

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Номер записи: 10
25-04-2013 дата публикации

IMAGING AND RADIOTHERAPY METHODS

Номер: US20130101509A1
Автор: BHALLA RAJIV, Cuthbertson Alan, Iveson Peter Brian, Kuniyil Kulangara Vijaya Raj
Принадлежит:

The present invention relates to in vivo imaging and radiotherapeutic methods and agents which target the enzyme aldehyde dehydrogenase (ALDH) and that are suitable for the in vivo imaging of tumours and treatment of cancer. 2. The method of claim 1 , further comprising identifying ALDH expressing cells within a tumor.7. A pharmaceutical formulation comprising the compound of and a pharmaceutically acceptable excipient. The present invention relates to in vivo imaging and radiotherapeutic methods and agents suitable for the in vivo imaging of tumours and treatment of cancer. It further relates to methods and agents which target the enzyme aldehyde dehydrogenase (ALDH). The agents have utility for in vivo imaging by Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT) imaging, Optical Imaging (OI) and radiotherapy (RT).Recently the stem cell model of cancer has emerged based on the principle that a sub-population of tumour initiating cells are present in the tumour which are distinct from the bulk cells of the tumour. The model predicts that eradication of the bulk of the tumour cells by chemotherapy or radiotherapy will at best result in temporary remission if cancer stem cells are left behind following treatment. It is also known that these stem cell-like populations are more resistant to many of the alkylating agents used in standard chemotherapy regimes [Gordon, M. Y., et al., Leuk. Res. 9, 1017, 1985]. For example, clinical studies have shown the benefit of purging samples with 4-hydroperoxycyclophosphamide (4-HC) before autologous bone marrow transplantation (ABMT) which removes committed progenitor cells but leaves the stem cell population largely intact [Kaizer, H., et al., Blood, 65, 1504-1510, 1985]. In addition, breast cancer studies have demonstrated correlation between ALDH expression in tumour tissue and poor clinical outcome and have also suggested ALDH as a marker of malignant mammary stem cells [Ginestier, C., et al ...

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Номер записи: 11
16-05-2013 дата публикации

Styryl-based compound, composition containing styryl-based compound, and organic light emitting diode including styryl-based compound

Номер: US20130119355A1
Автор: Dae-Yup Shin, Hye-jin Jung, Jin-O Lim, Jong-hyuk Lee, Sang-hyun Han, Seok-Hwan Hwang, Soo-Yon Kim, Young-Kook Kim
Принадлежит: Samsung Display Co Ltd

A styryl-based compound represented by Formula 1, a composition containing the styryl-based compound, and an organic light-emitting diode (OLED) including the styryl-based compound: The styryl-based compound may exhibit high heat resistance and thus an OLED including the same may have low driving voltage, high brightness, high efficiency, and long lifetime.

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Номер записи: 12
16-05-2013 дата публикации

PROCESS FOR THE SPECIFIC ISOTOPIC LABELING OF METHYL GROUPS OF VAL, LEU AND ILE

Номер: US20130122598A1
Автор: AYALA Isabel, Boisbouvier Jérôme, Gans Pierre, HAMELIN Olivier
Принадлежит:

The invention relates to a process for the specific isotopic labeling of Valine, Leucine and Isoleucine amino acids. The process of the invention uses a 2-alkyl-2-hydroxy-3-oxobutanoic acid in which the alkyl substituent in position 2 is ethyl or methyl. The invention can be used for the analysis of proteins, in particular by NMR. 2. The process of further comprising:b) overexpression of the protein by the bacteria in the medium, andc) purification of the protein.3. The process of wherein:{'sup': '1', 'Ris selected from the group consisting of{'sup': 12', '12', '13', '13', '13', '13, 'sub': 3', '3', '3', '3', '2', '2, 'CH, CD, CH, CD, CHD, and CHD,'}{'sup': '2', 'Ris selected from the group consisting of{'sup': 12', '12', '13', '13', '13', '13', '12', '12', '12', '12', '13', '12', '13', '13', '13', '13', '13', '13', '13', '13', '13', '12', '13', '12, 'sub': 3', '3', '3', '3', '2', '2', '3', '2', '3', '2', '3', '2', '3', '2', '3', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'CH, CD, CH, CD, CHD, CHD, CHCD, CDCD, CHCD, CHCD, CDCD, CHDCD, CHDCD, CHDCD, and CHDCD.'}4. The process of claim 1 , wherein the acetolactate compound is selected from the group consisting of:{'sup': 13', '2, 'sub': '3', '2-hydroxy-2-(C)methyl-3-oxo-4(H)butanoic acid (formula 4),'}{'sup': 2', '13, 'sub': '3', '2-hydroxy-2-(H)methyl-3-oxo-4(C)butanoic acid (formula 5),'}{'sup': 2', '13, 'sub': '5', '2-(H)ethyl-2-hydroxy-3-oxo-4-(C)methylbutanoic acid (formula 6),'}{'sup': 13', '2, 'sub': '5', '1,2,3,4-(C)-2-(H)ethyl-2-hydroxy-3-oxobutanoic acid (formula 9),'}{'sup': 13', '13', '2, 'sub': '3', '1,2,3-(C)-2-(C)methyl-2-hydroxy-3-oxo-4-(H)butanoic acid (formula 21),'}{'sup': 13', '2, 'sub': '3', '1,2,3,4-(C)-2-(H)methyl-2-hydroxy-3-oxobutanoic acid (formula 22),'}{'sup': 13', '2', '13', '2, 'sub': 2', '2', '3, '1,2,3-(C)-2-(1′-(H),C)ethyl)-2-hydroxy-3-oxo-4-(H)butanoic acid (formula 24),'}3,4-(13C)-2-(13C)methyl-2-hydroxy-3-oxo-4-(2H3)butanoic acid (formula 36),3,4-(13C)-2-(2H3,13C)methyl-2-hydroxy-3 ...

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Номер записи: 13
06-06-2013 дата публикации

Device for the synthesis of radio-labeled compounds

Номер: US20130144052A1
Автор: Marco Mueller
Принадлежит: ABX advanced biochemical compounds GmbH

The invention relates to a device for the synthesis of radio-labeled compounds, which comprises a reaction vessel for reacting a precursor compound having protective groups with a radioactive isotope to obtain a first reaction product; a first cartridge for hydrolyzing the protective groups of the first reaction product to obtain a second reaction product; and a second cartridge for purifying the second reaction product, wherein the reaction vessel, the first cartridge, and the second cartridge are connected to each other via pipelines. Here it is provided that the first cartridge contains 801 to 1200 mg of a solid carrier and/or the reaction vessel is a reaction vessel made of a temperature-resistant plastic with the plastic having a temperature resistance of at least 120° C.

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Номер записи: 14
13-06-2013 дата публикации

Labeled Alginate Conjugates for Molecular Imaging Applications

Номер: US20130149242A1
Автор: Deckwerth Thomas L., Meglasson Martin D., Ruan Fuqiang
Принадлежит: Ikaria Development Subsidiary One LLC

Described are bifunctional NOTA-based derivatives capable of conjugating with alginate and with metal ions, as well as NOTA-alginate conjugates which can be labeled with stable or radioactive metal ions. Also described are conjugation methods of the bifunctional NOTA-based linker with alginate, and methods of using radiometal-labeled NOTA-alginate conjugates or other radio-labeled alginate conjugates as imaging reagents. 2. The compound of claim 1 , wherein the compound further comprises a stable or radioactive metal ion chelated by the 1 claim 1 ,4 claim 1 ,7-triazacyclononane-1 claim 1 ,4 claim 1 ,7-triacetic acid moiety.3. The compound of claim 2 , wherein the stable or radioactive metal ion comprises a gallium ion.4. The compound of claim 2 , wherein the radioactive metal ion comprises Cu claim 2 , Cu claim 2 , Cu claim 2 , Cu claim 2 , Cu claim 2 , or In.6. The alginate conjugate of claim 5 , wherein the conjugate further comprises a stable or radioactive metal ion chelated by the 1 claim 5 ,4 claim 5 ,7-triazacyclononane-1 claim 5 ,4 claim 5 ,7-triacetic acid moiety of the conjugate.7. The alginate conjugate of claim 6 , wherein the stable or radioactive metal ion comprises a gallium ion.8. The alginate conjugate of claim 6 , wherein the radioactive metal ion comprises Cu claim 6 , Cu claim 6 , Cu claim 6 , Cu claim 6 , Cu claim 6 , or In.9. A method of imaging in a mammal comprising:administering a radio-labeled alginate conjugate to a mammal; andimaging the temporal and spatial distribution of the radio-labeled alginate conjugate.11. The method of claim 10 , wherein the stable or radioactive metal ion comprises a gallium ion.12. The method of claim 10 , wherein the radioactive metal ion comprises Cu claim 10 , Cu claim 10 , Cu claim 10 , Cu claim 10 , Cu claim 10 , or In.13. The method of claim 9 , wherein the alginate is conjugated to an iodinated tyramine or tyramine derivative.14. The method of claim 9 , wherein the radio-labeled alginate conjugate is ...

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Номер записи: 15
13-06-2013 дата публикации

COMPOSITIONS, METHODS, AND SYSTEMS FOR THE SYNTHESIS AND USE OF IMAGING AGENTS

Номер: US20130149244A1
Автор: Benites Pedro, Cesati Richard R., Cheesman Edward H., Lazewatsky Joel, Lee L. Veronica, Looby Richard J., Purohit Ajay, Radeke Heike S.
Принадлежит: Lantheus Medical Imaging, Inc.

The present invention generally relates to novel synthetic methods, systems, kits, salts, and precursors useful in medical imaging. In some embodiments, the present invention provides compositions comprising an imaging agent precursor, which may be formed using the synthetic methods described herein. An imaging agent may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in F. In some cases, an imaging agent including salt forms (e.g., ascorbate salt) may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs. 4. The composition of claim 3 , wherein X is halide claim 3 , phosphate claim 3 , sulfate claim 3 , trifluoroacetate claim 3 , toluenesulfonate claim 3 , acetate claim 3 , formate claim 3 , citric claim 3 , ascorbate claim 3 , mesylate (methanesulfonate) claim 3 , or benzoate.6. The composition of claim 1 , wherein at least one Ris not hydrogen.921-. (canceled)24. (canceled)2648-. (canceled)49. The method of any one of claims 23 , wherein the step of reacting comprises exposing a compound comprising formula (II) or (IV) to a source of fluoride.50. The method of claim 49 , wherein the source of fluoride is isotopically enriched with F.5158-. (canceled)60. (canceled)62. (canceled)63. The salt of claim 61 , wherein the fluorine is isotopically enriched with F.64. A pharmaceutically acceptable composition comprising a salt of claim 63 , and optionally a pharmaceutically acceptable excipient.65. A kit comprising a salt of and instructions for use66. A method of imaging a subject claim 63 , comprising:{'claim-ref': {'@idref': 'CLM-00063', 'claim 63'}, 'administering a dose of a pharmaceutically acceptable composition comprising a salt of and optionally a pharmaceutically acceptable excipient, to a subject; and'}acquiring at least one image of a portion of the subject.6768-. (canceled)70. The method of ...

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Номер записи: 16
20-06-2013 дата публикации

Method of preparing ethacrynic amide derivatives and application thereof

Номер: US20130156701A1
Автор: Chun Nan Yeh, Chung Shan Yu, Gon-Shen Chen, Hao Lien Huang, Jenn-Tzong Chen, Kang-Wei Chang, Ken-Hong Lin, Li-Wu Chiang, Wei-Ting Wang, Wuu-Jyh Lin, Yin-Cheng Huang
Принадлежит: National Tsing Hua University NTHU

The present invention provides a method for preparing [ 18 F]—N-(4-fluorobutyl)ethacrynic amide which is prepared from radiofluorination and deprotection of the precursor tosylate N-Boc-N-[4-(toluenesulfonyloxy)-butyl)ethacrynic amide], obtained from ethacrynic acid via 6-step synthesis in 39% yield, in a radiochemical yield of 44%, aspecific activity of 48 GBq/μmol and radiochemical purity of 98%. The present invention further provides a composition for positron emission tomography (PET) of an animal models of a tumor liver or a liver disease, comprising [ 18 F]—N-(4-fluorobutyl)ethacrynic amide and a pharmaceutically acceptable carrier.

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Номер записи: 17
18-07-2013 дата публикации

Processes for Making Compounds Useful as Inhibitors of ATR Kinase

Номер: US20130184292A1
Автор: Armando Urbina, Benjamin Joseph Littler, David Andrew Siesel, Francoise Yvonne Theodora Marie Pierard, Jean-Damien Charrier, John Studley, Paul Angell, Robert Michael Hughes, Steven John Durrant, Yi Shi
Принадлежит: Vertex Pharmaceuticals Inc

The present invention relates to processes and intermediates for preparing compounds useful as inhibitors of ATR kinase, such as aminopyrazine-isoxazole derivatives and related molecules. The present invention also relates to compounds useful as inhibitors of ATR protein kinase. The invention relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and solid forms of the compounds of this invention. The compounds of this invention have formula I or II: wherein the variables are as defined herein.

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Номер записи: 18
15-08-2013 дата публикации

Compositions and Methods for Imaging

Номер: US20130209360A1
Автор: Alexander R. Lippert, Christopher J. Chang
Принадлежит: UNIVERSITY OF CALIFORNIA

The present disclosure provides compositions for in vivo imaging of hydrogen peroxide; and methods for detecting hydrogen peroxide in vivo. The compositions and methods find use in various diagnostic applications, which are also provided.

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Номер записи: 19
29-08-2013 дата публикации

MICROREACTOR AND METHOD FOR PREPARING A RADIOLABELED COMPLEX OR A BIOMOLECULE CONJUGATE

Номер: US20130225791A1
Автор: Desai Amit V., Kenis Paul J.A., Önal Birce C., Reichert David E., Wheeler Tobias D., Zeng Dexing
Принадлежит: WASHINGTON UNIVERSITY IN ST. LOUIS

A microreactor for preparing a radiolabeled complex or a biomolecule conjugate comprises a microchannel for fluid flow, where the microchannel comprises a mixing portion comprising one or more passive mixing elements, and a reservoir for incubating a mixed fluid. The reservoir is in fluid communication with the microchannel and is disposed downstream of the mixing portion. A method of preparing a radiolabeled complex includes flowing a radiometal solution comprising a metallic radionuclide through a downstream mixing portion of a microchannel, where the downstream mixing portion includes one or more passive mixing elements, and flowing a ligand solution comprising a bifunctional chelator through the downstream mixing portion. The ligand solution and the radiometal solution are passively mixed while in the downstream mixing portion to initiate a chelation reaction between the metallic radionuclide and the bifunctional chelator. The chelation reaction is completed to form a radiolabeled complex. 1. A method of preparing a radiolabeled complex , the method comprising:flowing a radiometal solution comprising a metallic radionuclide through a downstream mixing portion of a microchannel, the downstream mixing portion including one or more passive mixing elements;flowing a ligand solution comprising a bifunctional chelator through the downstream mixing portion;passively mixing the ligand solution and the radiometal solution while in the downstream mixing portion to form a mixed solution and to initiate a chelation reaction between the metallic radionuclide and the bifunctional chelator; andcompleting the chelation reaction to form a radiolabeled complex.2. The method of claim 1 , further comprising claim 1 , prior to flowing the radiometal solution through the downstream mixing portion of the microchannel claim 1 , flowing a precursor radiometal solution comprising the metallic radionuclide through an upstream mixing portion of the microchannel claim 1 , the upstream ...

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Номер записи: 20
05-09-2013 дата публикации

RADIOLABELLED mGluR2 PET LIGANDS

Номер: US20130230459A1
Автор: Alcázar-Vaca Manuel Jesús, Andrés-Gil José Ignacio, BORMANS Guy Maurits R., Celen Sofie Jeanne Leopoldine, CID-NUNEZ Jose Maria, Koole Michel, Trabanco-Suárez Andrés Avelino
Принадлежит: JANSSEN PHARMACEUTICALS, INC.

The present invention relates to novel, selective, radiolabelled mGluR2 ligands which are useful for imaging and quantifying the metabotropic glutamate receptor mGluR2 in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo and to precursors of said compounds. 3. The compound according to wherein{'sup': '1', 'Ris selected from cyclopropylmethyl and 2,2,2-trifluoroethyl; and'}{'sup': '2', 'Ris selected from chloro and trifluoromethyl.'}4. The compound according to claim 1 , wherein Ris cyclopropylmethyl and Ris chloro.5. The compound according to claim 1 , wherein n is 0 or 2.7. A sterile solution comprising a compound of Formula (I) as defined in .8. (canceled)9. A method of imaging a tissue claim 1 , cells or a host claim 1 , comprising contacting with or administering to a tissue claim 1 , cells or a host claim 1 , a compound of Formula (I) as defined in claim 1 , and imaging the tissue claim 1 , cells or host with a positron-emission tomography imaging system.11. The compound according to claim 10 , wherein n is 0 or 2. The present invention relates to novel, selective, radiolabelled mGluR2 ligands which are useful for imaging and quantifying the metabotropic glutamate receptor mGluR2 in tissues, using positron-emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo and to precursors of said compounds.Glutamate is the major amino acid neurotransmitter in the mammalian central nervous system. Glutamate plays a major role in numerous physiological functions, such as learning and memory but also sensory perception, development ...

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Номер записи: 21
10-10-2013 дата публикации

Purificiation of precursor compound by crystallisation

Номер: US20130267730A1
Автор: Anne Nilsen, Sondre NILSEN
Принадлежит: GE Healthcare Ltd

The invention relates to a process for preparation of radiopharmaceutical precursors, and in particular protected amino acid derivatives which are used as precursors for production of radiolabelled amino acids for use in vivo imaging procedures such as positron emission tomography (PET). Particularly, the invention relates to a process for preparation of a precursor useful in the preparation of the [ 18 F]-1-amino-3-fluorocyclobutanecarboxylic acid ([ 18 F] FACBC) PET tracer.

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Номер записи: 22
17-10-2013 дата публикации

PROCESS SIMPLIFICATION FOR PRECURSOR COMPOUND

Номер: US20130274507A1
Автор: Berg Tom Christian
Принадлежит: GE HEALTHCARE LIMITED

The invention relates to a process for preparation of radiopharmaceutical precursors, and in particular protected amino acid derivatives which are used as precursors for production of radiolabelled amino acids for use in in vivo imaging procedures such as positron emission tomography (PET). Particularly, the invention relates to a process for preparation of a precursor useful in the preparation of the [F]-1-amino-3-fluorocyclobutanecarboxylic acid ([F] FACBC) PET tracer. 2) The method as defined in wherein X is a group represented by the group —O—SO—R.3) The method as defined in wherein Ris selected from the group consisting of toluenesulfonic acid claim 2 , nitrobenzenesulfonic acid claim 2 , benzenesulfonic acid claim 2 , trifluoromethanesulfonic acid claim 2 , fluorosulfonic acid claim 2 , perfluoroalkylsulfonic acid claim 2 , trimethylstannyl and triethylstannyl.4) The method as defined in wherein Ris trifluoromethanesulfonic acid.5) The method as defined in wherein X is halogen.6) The method as defined in wherein said halogen is bromo or chloro.7) The method as defined in wherein Ris ethyl.8) The method as defined in wherein Ris selected from the group consisting of a t-butoxycarbonyl group claim 1 , an allyloxycarbonyl group claim 1 , a phthalimide group and N-benzylideneamine substituent.9) (canceled)11) (canceled)12) (canceled)13) The method as defined in wherein said deprotection comprises removal of Rfollowed by removal of R.14) (canceled)15) The method as defined in wherein Ris ethyl.16) The method as defined in wherein Ris a t-butoxycarbonyl group.18) The method as defined in wherein said deprotection step comprises removal of Et by basis hydrolysis and removal of Boc by acidic hydrolysis.19) The method as defined in wherein steps (c) and (d) are carried out on an automated synthesiser. The present invention relates to a method to obtain radiopharmaceutical precursors, and in particular to protected amino acid derivatives which are used as precursors for ...

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Номер записи: 23
31-10-2013 дата публикации

Fluorinated 2-Amino-4-(Benzylamino)Phenylcarbamate Derivatives

Номер: US20130287686A1
Автор: Ajay Purohit, D. Scott Edwards, Mark E. Duggan, Takeru Furuya
Принадлежит: Scifluor Life Sciences Inc

The invention relates to fluorinated compounds and their use as anti-epileptic, muscle-relaxing, fever-reducing and peripherally analgesically acting medications and as imaging agents. Novel fluorinated 2-amino-4-(benzylamino)phenyl carbamate derivatives of ezogabine and pharmaceutically acceptable salts or solvates thereof and their use are described.

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Номер записи: 24
07-11-2013 дата публикации

Benzoquinoline inhibitors of vesicular monoamine transporter 2

Номер: US20130296360A1
Автор: Manouchehr Shahbaz, Thomas G. Gant
Принадлежит: Auspex Pharmaceuticals Inc

The present invention relates to new benzoquinoline inhibitors of vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions thereof, and methods of use thereof.

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Номер записи: 25
14-11-2013 дата публикации

POLYMER PRECURSORS OF RADIOLABELED COMPOUNDS, AND METHODS OF MAKING AND USING THE SAME

Номер: US20130303757A1
Автор: HUNTER Duncan H., JANABI Mustafa
Принадлежит:

One aspect of the present invention relates to novel compounds that can be used to prepare radiolabeled compounds in an effective manner. A second aspect of the present invention relates to a method of synthesizing radiolabeled compounds. 115-. (canceled)16. A method for preparing a radiolabeled compound , the method comprising: reacting a polymer precursor compound with an oxidant , a radiolabeled compound and optionally a buffer , wherein the compound is selected from the group consisting of:Poly-(4S, 5S)-2-(5-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}-2,3-dihydrobenzofuran-7-yl)-3, 4-dimethyl-5-phenyl-1, 3-oxazolidine-co-divinylbenzene;Poly-5-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}-2, 3-dihydrobenzofuran-7-carbaldehyde-co-divinylbenzene;Poly-5-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}-2, 3-dihydrobenzofuran-7-carboxylic acid-co-divinylbenzene;Poly-(4S, 5S)-2-(4-{dibutyl[2-(3-vinylphenyl)ethyl]stannyl}phenyl)-3, 4-dimethyl-5-pheynyl-1, 3-oxazolidine-co-divinylbenzene; andPoly-(4S, 5S)-2-(4-{dibutyl[2-(4-vinylphenyl)ethyl]stannyl}phenyl)-3, 4-dimethyl-5-phenyl-1, 3-oxazolidine-co-divinylbenzene.17. A method of claim 16 , further comprising a purification of the radiolabeled compound.18. A kit containing a radiolabeling system claim 16 , comprising: a polymer precursor compound and instructions for using said polymer precursor compound claim 16 , wherein said polymer precursor compound comprises the polymer precursor compound of .19. The kit of that further includes a filter or a filtration device.20. The kit of that further includes a chelating agent and optionally an auxiliary molecule.21. A method of synthesizing radiolabeled benzamides on a solid support comprising:a) selecting a solid support comprising at least one compound attached to said solid support which compound comprises a benzoic acid moiety;b) reacting said moiety of said compound attached to said solid support with at least one amine to afford a benzamide bound to a solid support; andc) reacting said ...

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Номер записи: 26
21-11-2013 дата публикации

Morphinan compounds

Номер: US20130310415A1
Автор: Roger Tung
Принадлежит: Concert Pharmaceuticals Inc

This disclosure relates to novel morphinan compounds and their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This disclosure also provides compositions comprising a compound of this disclosure and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a σ 1 receptor agonist that also has NMDA antagonist activity.

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Номер записи: 27
28-11-2013 дата публикации

RADIOIODINATION METHOD

Номер: US20130315824A1
Автор: AVORY MICHELLE, NAIRNE ROBERT JAMES DOMETT, Wadsworth Harry John
Принадлежит: GE HEALTHCARE LIMITED

The present invention provides a novel method of labelling biological targeting molecules (BTMs) of interest with radioiodine. Also provided are functionalised BTMs useful in the method, as well as methods of preparing such functionalised BTMs under mild conditions. 2. The method according to claim 1 , where I* is chosen from I claim 1 , I or I.3. The method according to claim 1 , where BTM is a single amino acid claim 1 , a 3-100 mer peptide claim 1 , an enzyme substrate claim 1 , an enzyme antagonist an enzyme agonist claim 1 , an enzyme inhibitor or a receptor-binding compound.5. The method according to claim 4 , where the click cycloaddition catalyst comprises Cu(I).6. The method according to claim 5 , where the Cu(I) catalyst comprises elemental copper.7. The method of claim 1 , where the functionalised biological targeting molecule is of Formula (Ia) claim 1 , and the radioiodinated product is the conjugate of Formula (IIa).8. The method of claim 1 , which is carried out in an aseptic manner claim 1 , such that the product of Formula (IIa) or (IIb) is obtained as a radiopharmaceutical composition.9. The method of claim 8 , which is carried out using an automated synthesizer apparatus.10. The method of claim 9 , where the automated synthesizer apparatus comprises a single use claim 9 , sterile cassette claim 9 , said cassette comprising the non-radioactive reagents necessary to carry out the method in sterile claim 9 , apyrogenic form.12. The functionalised biological targeting molecule of claim 11 , which is provided in sterile claim 11 , apyrogenic form.13. The functionalised biological targeting molecule of claim 12 , where the sterile form is a pharmaceutical composition comprising said functionalised biological targeting molecule together with a biocompatible carrier medium.1416.-. (canceled) The present invention provides a novel method of labelling biological targeting molecules (BTMs) of interest with radioiodine. Also provided are functionalised BTMs ...

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Номер записи: 28
05-12-2013 дата публикации

ELUENT SOLUTION

Номер: US20130324715A1
Автор: Evje Dag M., Hjelstuen Ole Kristian, Ochsenfeld Liane, Svadberg Anders, Wickstrom Torild
Принадлежит: GE HEALTHCARE LIMITED

The present invention provides a novel method for the preparation of F-fluoride (F) for use in radiofluorination reactions. The method of the invention finds use especially in the preparation of F-labelled positron emission tomography (PET) tracers. The method of the invention is particularly advantageous where bulk solutions are prepared and stored in prefilled vials rather than being freshly prepared on the day of synthesis. Also provided by the present invention is a radiofluorination reaction which comprises the method of the invention, as well as a cassette for use in carrying out the method of the invention and/or the radiofluorination method of the invention on an automated radiosynthesis apparatus. 1) A method for preparation of Ffor use in a radiofluorination reaction wherein said method comprises:{'sup': 18', '−, '(i) trapping an aqueous solution of Fonto an anion exchange column; and,'}{'sup': 18', '−', '18', '−, '(ii) passing an eluent solution through said anion exchange column on which said Fis adsorbed to obtain an Feluent, wherein said eluent solution comprises a cationic counterion in a suitable solvent wherein said suitable solvent comprises an alkanol with the proviso that said eluent solution does not comprise acetonitrile.'}2) (canceled)3) The method as defined in wherein said anion exchange column is a quaternary methylammonium (QMA) column.4) The method as defined in wherein said cationic counterion is a metal complex of a cryptand.5) The method as defined in wherein said metal of said metal complex of a cryptand is potassium.6) The method as defined in wherein said cryptand of said metal complex of a cryptand is Krytofix 222 (K222).7) (canceled)8) The method as defined in wherein said suitable solvent is an aqueous solution of an alkanol.9) The method as defined in wherein said alkanol is methanol.10) The method as defined in which comprises a further step:{'sup': 18', '−, '(iii) drying said Feluted from said column in step (ii).'}11) The ...

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Номер записи: 29
19-12-2013 дата публикации

RADIOFLUORINATION METHOD

Номер: US20130338361A1
Автор: Betts Helen May, Khan Imtiaz, ROBINS EDWARD GEORGE
Принадлежит: GE HEALTHCARE LIMITED

Provided by the present invention is a novel method for obtaining an F-labelled compound wherein said compound comprises an F-labelled pyridyl ring. The method of the invention is advantageous over the prior art methods as it provides these compounds in higher radiochemical yields than have been possible with previous methods. Also provided by the present invention is an F-labelled synthon useful in the method of the invention. 4) The method as defined in which further comprises the step:{'sup': 18', '18, '(ii) coupling the F-labelled synthon of Formula Y as defined herein with a cross-coupling partner in a transition metal-mediated coupling reaction to obtain an F-labelled product.'}5) The method as defined in wherein said transition metal is palladium.12) The method as defined in which is automated. The present invention relates to a method for radiosynthesis and more specifically a novel method for the synthesis of F-labelled compounds. The invention also relates to a novel synthon for use in the inventive method of synthesis.In order to expand the range of applications for positron emission tomography (PET) there is an interest in developing synthetic methods for new PET tracers, i.e. biologically useful compounds labelled with C, F or Br. Currently, the most widely-used of these radiotracers for PET imaging is F.Typically, the synthesis of a PET tracer including its purification should be completed within three half-lives of the radiotracer. F has a relatively short half-life of 109.7 minutes and as such methods for its incorporation into a PET tracer demands fast and high-yielding reactions that can be performed on a small scale and under mild conditions.Direct labelling is desirable as it introduces F at the last possible step. However, direct labelling tends only to be possible using [F]fluoride in a nucleophilic substitution reaction can require the presence of activating groups, proton-free conditions and typically high temperatures of above 100° C. The ...

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Номер записи: 30
26-12-2013 дата публикации

RADIOLABELED PDE10A LIGANDS

Номер: US20130343992A1
Автор: Black Lawrence A.
Принадлежит: AbbVie Inc.

Compounds of formula (I) are disclosed 2. The compound of claim 1 , wherein said compound comprises a radiolabel.3. The compound of claim 1 , wherein R comprises a radiolabel.4. The compound of claim 1 , wherein HetAr comprises a radiolabel.7. The compound of claim 6 , wherein R is C-Calkyl.8. The compound of claim 7 , selected from the group consisting of:{'sup': '11', '2-((4-(1-[C]methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-1,5-naphthyridine; and'}{'sup': '18', '2-((4-(1-(2-[F]-fluoroethyl)-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-1,5-naphthyridine.'}10. The compound of claim 9 , wherein R is C-Calkyl.11. The compound of claim 10 , selected from the group consisting of:{'sup': '11', '2-((4-(1-[C]methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-1,6-naphthyridine; and'}{'sup': '18', '2-((4-(1-(2-[F]-fluoroethyl)-4-pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-1,6-naphthyridine.'}13. The compound of claim 12 , wherein R is C-Calkyl.14. The compound of claim 13 , selected from the group consisting of:{'sup': '11', '6-((4-(1-[C]methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)pyrido[3,2-c]pyridazine; and'}{'sup': '18', '6-((4-(1-(2-[F]fluoroethyl)-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)pyrido[3,2-c]pyridazine.'}16. The compound of claim 15 , wherein R is C-Calkyl.17. The compound of claim 16 , selected from the group consisting of:{'sup': '18', '2-((4-(1-(2-[F]fluoroethyl)-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)quinazoline.'}19. The compound of claim 18 , wherein R is C-Calkyl.20. The compound of claim 19 , selected from the group consisting of:{'sup': '11', '2-((4-(1-[C]methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)pyrido[3,2-d]pyrimidine; and'}{'sup': '18', '2-((4-(1-(2-[F]fluoroethyl)-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)pyrido[3,2-d]pyrimidine.'}22. The compound of claim 21 , wherein{'sup': '1', 'Zis CH;'}{'sup': '1', 'sub': 1', '6, 'Ris C-Calkyl; and'}{'sub': 1', '6, 'R is C-Calkyl.'}23. The ...

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Номер записи: 31
26-12-2013 дата публикации

RADIOLABELED 5-HT6 LIGANDS

Номер: US20130343993A1
Автор: Black Lawrence A.
Принадлежит: AbbVie Inc.

Compounds of formula (I) are disclosed 2. The compound of claim 1 , wherein said compound comprises a radiolabel.3. The compound of claim 1 , wherein R comprises a radiolabel.4. The compound of claim 1 , wherein R is hydrogen.5. The compound of claim 1 , wherein R is C-Calkyl.6. The compound of claim 5 , wherein R is CH.7. The compound of claim 5 , wherein R is CHCH.8. The compound of claim 5 , wherein R is CHCHCH.9. The compound of claim 5 , wherein R is CHCHF.10. The compound of claim 5 , wherein R is CHCHCHF.11. The compound of claim 5 , wherein R is C-Chydroxyalkyl.12. The compound of claim 5 , wherein R is —COtBu.13. The compound of claim 1 , selected from the group consisting of:8-(piperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline;8-(1-methylpiperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline;8-(1-ethylpiperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline;8-(1-propylpiperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline;8-(1-(2-fluoroethyl)piperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline;8-(1-(3-fluoropropyl)piperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline;2-(4-(3-(pyridin-2-ylsulfonyl)quinolin-8-yl)piperidin-1-yl)ethanol;3-(4-(3-(pyridin-2-ylsulfonyl)quinolin-8-yl)piperidin-1-yl)propan-1-ol;tert-butyl 4-(3-(pyridin-2-ylsulfonyl)quinolin-8-yl)piperidine-1-carboxylate;{'sup': '11', '8-(1-[C]methylpiperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline;'}{'sup': '11', '8-(1-[1-C]ethylpiperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline;'}{'sup': '11', '8-(1-[1-C]propylpiperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline;'}{'sup': '18', '8-(1-(2-[F]fluoroethyl)piperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline;'}{'sup': '18', '8-(1-(3-[F]fluoropropyl)piperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline; and'}{'sup': '3', '8-(1-([H]methyl)piperidin-4-yl)-3-(pyridin-2-ylsulfonyl)quinoline.'}14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt claim 1 , ester claim 1 , amide ...

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Номер записи: 32
26-12-2013 дата публикации

Pyridine Compounds as Sodium Channel Blockers

Номер: US20130345211A1
Автор: Kyle Donald J., Ni Chiyou, Park Minnie, TAFESSE Laykea
Принадлежит: Purdue Pharma L.P.

The invention relates to substituted pyridine compounds of Formula I: (I) or a pharmaceutically acceptable salt, prodrug, or solvate thereof wherein A, X, A, R, R, R, G, and z are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of sodium channels. Compounds of the present invention are especially useful for treating pain. 2. (canceled)412-. (canceled)1419-. (canceled)23. (canceled)26. (canceled)2829-. (canceled)31. The compound of claim 20 , wherein G is G-7 and n is 2 claim 20 , or a pharmaceutically acceptable salt or solvate thereof.3236-. (canceled)40. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , and a pharmaceutically acceptable carrier.4244-. (canceled)45. The method of claim 41 , wherein a disorder responsive to the blockade of Na1.7 sodium channels is treated.47. (canceled)48. The method of claim 46 , wherein said method is for treating pain.49. The method of claim 46 , wherein said method is for preemptive or palliative treatment of pain.50. The method of claim 48 , wherein said pain is selected from the group consisting of chronic pain claim 48 , inflammatory pain claim 48 , neuropathic pain claim 48 , acute pain claim 48 , and surgical pain.5259-. (canceled)60. The compound of claim 1 , wherein the compound is H claim 1 , C claim 1 , or C radiolabeled claim 1 , or a pharmaceutically acceptable salt or solvate thereof.61. A method of screening a candidate compound for the ability to bind to a binding site on a protein using a radiolabeled compound of claim 60 , comprising a) introducing a fixed concentration of the radiolabeled compound to a soluble or membrane-associated protein or fragment thereof to form a mixture; b) titrating the mixture with a candidate compound; and c) determining the binding of the candidate compound to said binding site.62. A method of ...

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Номер записи: 33
02-01-2014 дата публикации

Method of preparing radioisotope nanostructure with ligand-metal framework and application

Номер: US20140005407A1
Автор: Jin Ho MOON, Jong Bum Kim, Min Seok Oh, Seong-Ho Choi, Sung Hee Jung
Принадлежит: Korea Atomic Energy Research Institute KAERI

This invention relates to a method of preparing a radioisotope nanostructure having a ligand-metal framework, and a radioisotope nanostructure prepared thereby. The method of preparing the radioisotope nanostructure of the invention has a simple preparation process and can thus be applied to mass production of a radioisotope nanostructure. Also, because this radioisotope nanostructure is nano-sized spherical particles and has no reactive group, it can be easily dispersed in a fluid, and this nanostructure is physically and chemically stable and thus can be utilized as a radioisotope tracer in the fields of refineries, chemistry, cement, agriculture, water resources, marine, etc. Furthermore, this nanostructure can be used for diagnosis and/or treatment in medical fields, and can be applied to checking whether a nanomaterial is harmful. In addition, this nanostructure is expected to be applicable in a variety of fields using radioisotopes.

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Номер записи: 34
09-01-2014 дата публикации

Precursor compound connected to solid support for manufacturing 18f radiopharmaceutical, method for manufacturing same, and application thereof

Номер: US20140011961A1
Автор: Byoung-Se Lee, Dae-Yoon Chi, Hye-Rim Kwon, Jae-hak Lee, So-Young Chu, Woon-Jung Jung
Принадлежит: Industry University Cooperation Foundation of Sogang University

The present invention relates to a solid precursor in the form of an organic salt, the solid precursor having a solid support, a method for manufacturing same, and an application thereof. The solid precursor of the present invention enables omission of the [ 18 F]fluoride refining process using additional cartridge, and the use of excessive phase-transfer catalyst, and can easily remove remaining substance after reaction through the solid support inside the precursor. The solid precursor of the present invention is very appropriate for an automated synthesis device as an all-in-one system that can carry out overall process of [ 18 F]fluorosis reaction, when used by charging in a cartridge.

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Номер записи: 35
23-01-2014 дата публикации

Substituted triazolophthalazine derivatives

Номер: US20140024652A1
Автор: Scott L. Harbeson
Принадлежит: Concert Pharmaceuticals Inc

This invention relates to novel substituted triazolophthalazines and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering selective α5 receptor partial or full inverse agonists.

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Номер записи: 36
30-01-2014 дата публикации

Ligands for imaging cardiac innervation

Номер: US20140030189A1
Автор: Ajay Purohit, David S. Casebier, Heike S. Radeke, Michael T. Azure, Ming Yu, Simon P. Robinson, Thomas D. Harris
Принадлежит: ACP Lantern Acquisition Inc, Bristol Myers Squibb Pharma Co, Lantheus Medical Imaging Inc

Novel compounds that find use as imaging agents within nuclear medicine applications (PET imaging) for imaging of cardiac innervation are disclosed. These PET based radiotracers may exhibit increased stability, decreased NE release (thereby reducing side effects), improved quantitative data, and/or high affinity for VMAT over prior radiotracers. Methods of using the compounds to image cardiac innervation are also provided. In some instances the compounds are developed by derivatizing certain compounds with 18F in a variety of positions: aryl, alkyl, a keto, benzylic, beta-alkylethers, gamma-propylalkylethers and beta-proplylalkylethers. Alternatively or additionally, a methyl group a is added to the amine, and/or the catechol functionality is either eliminated or masked as a way of making these compounds more stable.

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Номер записи: 37
06-02-2014 дата публикации

METHOD FOR RAPID PREPARATION OF SUITABLEFLUORIDE FOR NUCLEOPHILICFLUORINATION

Номер: US20140039074A1
Автор: Chi Dae Yoon, Lee Byoung Se, LEE Sang Ju, Oh Seung Ju, Ryu Jin-Sook
Принадлежит: PIRAMAL IMAGING SA

The invention generally relates to the preparation of F-labeled radiopharmaceuticals. In particular, this invention relates to the advanced processes for an efficient eiution of [F]fluoride trapped in a cartridge filled with quaternary ammonium polymer which comprises inert non-basic and non-nucleophilic counter anions. The said methods and polymer cartridges allow the rapid preparation of suitable [F]fluoride solution, which is also less basic to reduce the formation of byproducts, finally to increase radiochemical yield and purity of F-radiopharmaceuticals. 2. quaternary ammonium polymer according to claim 1 , wherein NRis selected from the group consisting of trimethylamine claim 1 , triethylamine claim 1 , tri-n-propylamine claim 1 , tri-n-butylamine claim 1 , N-methylimidazole claim 1 , and pyridine.3. A quaternary ammonium polymer according to claim 1 , wherein the X is selected from the group consisting of methanesulfonate (OMs) claim 1 , trifluoromethanesulfonate (OTf) claim 1 , para-toluenesulfonate (OTs) claim 1 , para-nitrobenzenesulfonate (ONs) claim 1 , tetrafluoroborate (BF) claim 1 , hexafluorophosphate (PF) claim 1 , hexafluoroantimonate (SbF) claim 1 , and N claim 1 ,N-bis(trifluoromethanesulfonyl)amide (N(Tf)).6. A polymer cartridge 6 containing neutral ammonium polystyrene of for solid-phase anion extraction.7. A method for separation of [F]fluoride from aqueous solution claim 6 , wherein [F]fluoride dissolved in aqueous solution is passed through the polymer cartridge of .8. A method for the preparation of an eluting solution for eluting [18F] from a cartridge according to claim 6 , wherein the eluting solution is prepared by composing three ingredients (Ingredient A claim 6 , Ingredient B claim 6 , and Ingredient C) claim 6 , and dissolving in an alcohol solvent.9. A method according to claim 8 , wherein Ingredient A is K222 that is used as a phase transfer catalyst of [F]fluorination in a range from 10 to 20 mg.10. A method according to claim 8 ...

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Номер записи: 38
13-02-2014 дата публикации

Method of utilizing recycled deuterium oxide in the synthesis of deuterated compounds

Номер: US20140046060A1
Автор: Andrew D. Jones, Bernhard J. Paul
Принадлежит: Concert Pharmaceuticals Inc

The present invention provides a method for utilizing recycled deuterium oxide synthesis of deuterated compounds.

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Номер записи: 39
13-03-2014 дата публикации

Isotopically enriched arylsulfonamide ccr3 antagonists

Номер: US20140073649A1
Автор: Garrett Thomas Potter, Tai Wei Ly
Принадлежит: Axikin Pharmaceuticals Inc

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

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Номер записи: 40
13-03-2014 дата публикации

Deuterated cftr potentiators

Номер: US20140073667A1
Автор: Adam J. Morgan
Принадлежит: Individual

This invention relates to compounds of Formula I: and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering a CFTR potentiator.

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Номер записи: 41
27-03-2014 дата публикации

F-18 RADIOLABELED COMPOUNDS FOR DIAGNOSING AND MONITORING KIDNEY FUNCTION

Номер: US20140086837A1
Автор: Abrams Paul G., GOKARAJU Rama Raju, KASINA Sudhakar, SOMEPALLI Venkateswarlu
Принадлежит: KASINA LAILA INNOVA PHARMACEUTICALS PRIVATE LIMITED

The invention relates to F-labeled compounds of formula (I), hydrates, isomers, or pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions. The invention relates to the methods of diagnosing kidney function in humans by PET imaging. 2. The F-labeled compound of formula (I) as claimed in claim 1 , wherein Y claim 1 , Z claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare each H.3. The F-labeled compound of formula (I) as claimed in claim 1 , wherein:{'sup': 1', '2', '3, 'Y, Z, R, R, and Rare each H; and'}{'sup': 4', '5', '4', '5, 'sub': '3', 'one of Ror Ris H and the other of Ror Ris COCH.'}5. The compound of claim 1 , wherein said compound is selected from the group consisting of:2-(4-amino-2-(18)fluorobenzamido)acetic acid;2-(4-acetamido-2-(18)fluorobenzamido)acetic acid;2-(3-amino-4-(18)fluorobenzamido)acetic acid;2-(5-amino-2-chloro-4-(18)fluorobenzamido)acetic acid;2-(5-amino-2-(18)fluorobenzamido)acetic acid;2-(4-amino-3-(18)fluorobenzamido)acetic acid;2-(4-acetamido-3-(18)fluorobenzamido)acetic acid;2-(2-amino-6-(18)fluorobenzamido)acetic acid;2-(2-acetamido-6-(18)fluorobenzamido)acetic acid;(S)-2-(4-amino-2-(18)fluorobenzamido)propanoic acid;(R)-2-(4-amino-2-(18)fluorobenzamido)propanoic acid;(S)-2-(2-amino-6-(18)fluorobenzamido)propanoic acid;(R)-2-(2-amino-6-(18)fluorobenzamido)propanoic acid.8. The process for the preparation of compound of formula (I) as claimed in claim 6 , wherein the chemical reactions are conducted at ambient temperature under thermal or microwave or ultrasonic conditions.9. The process for the preparation of compound of formula (I) as claimed in claim 7 , wherein the chemical reactions are conducted at ambient temperature under thermal or microwave or ultrasonic conditions.10. The process for the preparation of F-labeled compound of formula (I) as claimed in claim 6 , wherein said phase transfer catalyst is selected from 18-crown-6 claim 6 ,15-crown-5 claim 6 , kryptofix-222 claim 6 ...

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Номер записи: 42
06-01-2022 дата публикации

Half-Curcuminoids as Amyloid-Beta PET Imaging Agents

Номер: US20220001036A1
Автор: Moore Anna, Ran Chongzhao, Yang Jian
Принадлежит:

Provided herein are curcumin analogues that are able to interact with amyloid beta (Aβ) and to attenuate the copper-induced crosslinking of Aβ. Also provided herein are methods of using the compounds as imaging agents of amyloid beta and for the treatment of diseases associated with amyloid beta. Methods of preparing unlabeled and radiolabeled compounds useful for interacting with amyloid beta and pharmaceutical compositions are also provided. 2. The method of claim 1 , wherein the imaging technique is selected from the group consisting of fluorescence imaging claim 1 , positron emission tomography imaging claim 1 , magnetic resonance imaging claim 1 , single-photon emission computed tomography claim 1 , positron emission tomography with computed tomography imaging claim 1 , and positron emission tomography with magnetic resonance imaging.3. The method of claim 1 , wherein the imaging technique is selected from the group consisting of fluorescence imaging claim 1 , position emission tomography imaging claim 1 , and single-photon emission computed tomography.5. The method of claim 1 , wherein:{'sup': 4', '5, 'X is BRR;'}{'sup': 1', '1A, 'sub': '6-10', 'Ris selected from the group consisting of Caryl and 5-10 membered heteroaryl, each of which may be optionally substituted by 1, 2, 3, or 4 independently selected Rgroups;'}{'sup': 1A', 'N1', 'N2', '6, 'sub': 1-6', '1-6', '1-6', '1-6', '6-10', '1-6', '1-6', '6-10, 'each Ris independently selected from the group consisting of halo, Calkyl, Chaloalkyl, Calkoxy, Chaloalkoxy, NRR, and Caryl, wherein the Calkyl, Calkoxy, and Caryl are each optionally substituted by 1, 2, 3, or 4 independently selected Rgroups;'}{'sup': 2', '2A, 'sub': 1-6', '3-6, 'Ris selected from the group consisting of Calkyl, Ccycloalkyl, and phenyl, each of which may be optionally substituted by 1, 2, 3, or 4 independently selected Rgroups;'}{'sup': '3', 'Ris H;'}{'sup': 4', '5, 'Rand Rare each halo; and'}m is 1.6. The method of claim 5 , wherein:{'sup ...

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Номер записи: 43
02-01-2020 дата публикации

5-DEUTERO-2,4-THIAZOLIDINEDIONE DERIVATIVES AND COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME

Номер: US20200000788A1
Автор: DEWITT Sheila, Jacques Vincent, van der Ploeg Leonardus
Принадлежит:

The invention provides 5-deuterium-enriched 2,4-thiazolidinediones (e.g., 5-[4-[2-(5-ethyl-2-pyridyl)-2-oxoethoxy]benzyl]-5-deutero-thiazolidine-2,4-dione), deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treatment using the same. 12-. (canceled)858-. (canceled)59. The compound of claim 5 , wherein Ris D.60. The compound of claim 6 , wherein Ris D.61. The deuterium-enriched compound of claim 59 , or a stereoisomer or pharmaceutically acceptable salt form thereof claim 59 , wherein Ris ethyl; and Z is H or D claim 59 , provided that the abundance of deuterium in Z is at least 50%.62. The deuterium-enriched compound of claim 59 , wherein the abundance of deuterium in Z is at least 80%.63. The deuterium-enriched compound of claim 59 , wherein the abundance of deuterium in Z is at least 95%.64. The deuterium-enriched compound of claim 60 , or a pharmaceutically acceptable salt form thereof claim 60 , wherein Ris ethyl; and wherein the compound has an enantiomeric excess claim 60 , with respect to the C—Z carbon claim 60 , of at least 80% claim 60 , and Z is H or D claim 60 , provided that the abundance of deuterium in Z is at least 50%.65. The deuterium-enriched compound of claim 64 , wherein the abundance of deuterium in Z is at least 80%.66. The deuterium-enriched compound of claim 64 , wherein the abundance of deuterium in Z is at least 95%.67. The deuterium-enriched compound of claim 64 , wherein the compound has an enantiomeric excess claim 64 , with respect to the C—Z carbon claim 64 , of at least 90%.68. The deuterium-enriched compound of claim 64 , wherein the compound has an enantiomeric excess claim 64 , with respect to the C—Z carbon claim 64 , of at least 95%.69. The deuterium-enriched compound of claim 7 , wherein the compound has an enantiomeric excess claim 7 , with respect to the C(RR) carbon claim 7 , of at least 80%.70. The deuterium-enriched compound of claim 7 , wherein the ...

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Номер записи: 44
04-01-2018 дата публикации

RADIOACTIVE IODINE LABELED PYRIDO[1,2-a]BENZOIMIDAZOLE DERIVATIVE COMPOUND

Номер: US20180000974A1
Автор: Ihara Masafumi, Ono Masahiro, Saji Hideo, Seki Ikuya
Принадлежит:

The present invention relates to a radioactive iodine-labeled pyrido[1,2-a]benzimidazole derivative compound represented by a definite general formula or a salt thereof, or a radiopharmaceutical comprising the same. 2. The radioactive iodine-labeled compound or a salt thereof according to claim 1 , wherein the radioactive iodophenyl group is a substituent having a phenyl group which hydrogen atom at position 4 is substituted with a radioactive iodine atom.3. The radioactive iodine-labeled compound or a salt thereof according to claim 1 , wherein the radioactive iodine atom is I claim 1 , I claim 1 , I claim 1 , or I.4. A radiopharmaceutical comprising a radioactive iodine-labeled compound or a salt thereof according to .5. The radiopharmaceutical according to claim 4 , which is for use in single photon emission computed tomography (SPECT).6. A diagnostic agent for Alzheimer's disease comprising a radioactive iodine-labeled compound or a salt thereof according to . The present invention relates to a radioactive iodine-labeled pyrido[1,2-a]benzimidazole derivative compound or a salt thereof, and a radiopharmaceutical comprising the same.Accumulation of senile plaque (SP) composed mainly of amyloid β protein (Aβ) and neurofibrillary tangle (NFT) composed mainly of tau protein is found in the brain with Alzheimer's disease (AD). Since the accumulation of NFT exhibits high correlation with clinical symptoms, as compared with SP, development of radioactive molecule imaging probes for nuclear medicine diagnosis targeting the tau protein has received attention recently.For example, Patent Document 1 describes radioactive iodine-labeled compounds comprising rhodanine and thiohydantoin derivatives having affinity for the tau protein.Also, Patent Documents 2 and 3 describe compounds having binding activity against both of the Aβ and the tau protein. Specifically, Patent Document 2 describes a radioactive iodine-labeled compound having styrylbenzimidazole as a nucleus, and ...

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Номер записи: 45
07-01-2016 дата публикации

Methods and compositions for radiohalogen protein labeling

Номер: US20160002121A1
Автор: Charles Andrew Boswell, Jan Marik, Leslie A. Khawli, Simon Williams
Принадлежит: Genentech Inc

Methods and compositions are provided for labeling proteins with radiohalogen-label reagents. Radiohalogen-labeled proteins may be used for imaging studies, as therapeutics and in diagnostic tests. The [ 125 I] HIP-DOTA label reagent 6 is prepared by an efficient and convenient process.

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Номер записи: 46
05-01-2017 дата публикации

INDAZOLES AND USE THEREOF

Номер: US20170001986A1
Автор: Yu Jianming
Принадлежит:

In one aspect, the present disclosure provides indazoles of Formula I: (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R, R, R, R, Z, Z, Z, and G are defined as set forth in the specification. Further, the present disclosure also provides compounds of Formulae II and IA, and the pharmaceutically acceptable salts and solvates thereof. The present disclosure is also directed to the use of compounds of Formulae I, II, and IA, and the pharmaceutically acceptable salts and solvates thereof, to treat a disorder responsive to the blockade of sodium channels. In one embodiment, compounds of the present disclosure are especially useful for treating pain. 2. The compound of claim 1 , wherein G is dihydroxyalkyl claim 1 , or a pharmaceutically acceptable salt or solvate thereof.4. (canceled)6. The compound of claim 5 , wherein:{'sup': '2', 'Zis selected from the group consisting of N and CH;'}{'sup': '3', 'Ris selected from the group consisting of hydrogen and alkyl; and'}{'sup': '4', 'Ris selected from the group consisting of hydrogen, halogen, alkyl, and haloalkyl,'}or a pharmaceutically acceptable salt or solvate thereof.7. The compound of claim 1 , wherein Ris hydrogen claim 1 , and Zis N claim 1 , or a pharmaceutically acceptable salt or solvate thereof.89-. (canceled)10. The compound of claim 1 , wherein G is —(CHR)—C═O)E claim 1 , E is —NRR claim 1 , and Rand Rare hydrogen claim 1 , or a pharmaceutically acceptable salt or solvate thereof.11. The compound of claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , hydroxyalkyl claim 1 , and —X—R claim 1 , or a pharmaceutically acceptable salt or solvate thereof.12. The compound of claim 11 , wherein Ris hydrogen claim 11 , or a pharmaceutically acceptable salt or solvate thereof.13. (canceled)15. The compound of claim 11 , wherein Ris —X—R claim 11 , wherein X is —O— or —NH— claim 11 , or a pharmaceutically acceptable salt or solvate thereof.1619-. (canceled)21. The ...

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Номер записи: 47
07-01-2016 дата публикации

2',6'-DIOXO-3'-DEUTERO-PIPERDIN-3-YL-ISOINDOLINE COMPOUNDS

Номер: US20160002202A1
Автор: DEWITT Sheila
Принадлежит:

The present application describes 2-(2′,6′-dioxo-3′-deutero-piperidin-3′-yl)isoindoles, deuterated derivatives thereof, stereoisomers thereof, pharmaceutically acceptable salt forms thereof, and methods of treating using the same. 13-. (canceled)524-. (canceled)25. The deuterium-enriched compound of claim 4 , wherein X is C═O.26. The deuterium-enriched compound of claim 4 , wherein Ris aryl.27. The deuterium-enriched compound of claim 25 , wherein Ris aryl.28. The deuterium-enriched compound of claim 26 , wherein said aryl is phenyl.29. The deuterium-enriched compound of claim 27 , wherein said aryl is phenyl.30. The deuterium-enriched compound of claim 27 , wherein Ris (CH).31. The deuterium-enriched compound of claim 29 , wherein Ris (CH).32. The deuterium-enriched compound of claim 27 , wherein Ris (C-C)heterocycloalkyl.33. The deuterium-enriched compound of claim 30 , wherein Ris (C-C)heterocycloalkyl.34. The deuterium-enriched compound of claim 31 , wherein Ris (C-C)heterocycloalkyl.35. The deuterium-enriched compound of claim 33 , wherein (C-C)heterocycloalkyl is morpholinyl.36. The deuterium-enriched compound of claim 34 , wherein (C-C)heterocycloalkyl is morpholinyl.37. The deuterium-enriched compound of claim 33 , wherein the abundance of deuterium in Z is at least 90%.38. The deuterium-enriched compound of claim 34 , wherein the abundance of deuterium in Z is at least 90%.39. The deuterium-enriched compound of claim 36 , wherein the abundance of deuterium in Z is at least 90%.40. The deuterium-enriched compound of claim 33 , wherein R-Rare H claim 33 , and Ris H.41. The deuterium-enriched compound of claim 34 , wherein R-Rare H claim 34 , and Ris H.42. The deuterium-enriched compound of claim 36 , wherein R-Rare H claim 36 , and Ris H.43. The deuterium-enriched compound of claim 39 , wherein R-Rare H claim 39 , and Ris H.441. A pharmaceutical composition comprising a deuterium-enriched compound of claim and one or more excipients.45. A pharmaceutical ...

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Номер записи: 48
03-01-2019 дата публикации

Purification method

Номер: US20190002363A1
Автор: Janne Olsen FRENVIK, Olav B. Ryan
Принадлежит: Bayer AG

The invention provides a method for the purification of complexed 227Th from a mixture comprising complexed 227Th and 223Ra (complexed or in solution), said method comprising: i) preparing a first solution comprising a mixture of complexed 227Th ions and 223Ra ions in a first aqueous buffer; ii) loading said first solution onto a separation material; iii) eluting complexed 227Th from said separation material whereby to generate a second solution comprising complexed 227Th; iv) Optionally rinsing said separation material using a first aqueous washing medium; The invention additionally provides a purified 227Th solution, a pharmaceutical product and its use in treatment of disease such as cancer and a kit for generation of such a product.

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Номер записи: 49
05-01-2017 дата публикации

CYCLOPROPYL MODULATORS OF P2Y12 RECEPTOR

Номер: US20170002015A1
Автор: Rao Tadimeti, Zhang Chengzhi
Принадлежит:

The present invention relates to new cyclopropyl modulators of P2Y12 receptor activity, pharmaceutical compositions thereof, and methods of use thereof. 2. The compound or salt thereof of wherein each position represented as D has deuterium enrichment of no less than about 50%.3. The compound or salt thereof of wherein each position represented as D has deuterium enrichment of no less than about 90%.4. The compound or salt thereof of wherein each position represented as D has deuterium enrichment of no less than about 98%.5. A method of treating a P2Y12 receptor-mediated disorder comprising administering to a patient in need thereof claim 1 , a therapeutically effective amount of a compound or salt thereof as recited in .6. The method of claim 5 , wherein said disorder is arterial thrombosis or coronary artery disease.7. The method of claim 5 , further comprising administering an additional therapeutic agent.8. The method of wherein said additional therapeutic agent is an alpha adrenergic receptor antagonist claim 7 , a beta adrenergic receptor antagonist claim 7 , an angiotensin II receptor antagonist claim 7 , an angiotensin-converting enzyme inhibitor claim 7 , an anti-arrhythmic claim 7 , an antithrombotic claim 7 , an antiplatelet agent claim 7 , a calcium channel blocker claim 7 , a fibrate claim 7 , or a HMG-CoA reductase inhibitor.9. The method of wherein said alpha adrenergic receptor antagonist is abanoquil claim 8 , adimolol claim 8 , ajmalicine claim 8 , alfuzosin claim 8 , amosulalol claim 8 , arotinolol claim 8 , atiprosin claim 8 , benoxathian claim 8 , buflomedil claim 8 , bunazosin claim 8 , carvedilol claim 8 , CI-926 claim 8 , corynanthine claim 8 , dapiprazole claim 8 , DL-017 claim 8 , domesticine claim 8 , doxazosin claim 8 , eugenodilol claim 8 , fenspiride claim 8 , GYKI-12 claim 8 ,743 claim 8 , GYKI-16 claim 8 ,084 claim 8 , indoramin claim 8 , ketanserin claim 8 , L-765 claim 8 ,314 claim 8 , labetalol claim 8 , mephendioxan claim 8 , ...

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Номер записи: 50
03-01-2019 дата публикации

Compositions for binding sphingosine-1-phosphate receptor 1 (s1p1), imaging of s1p1, and methods of use thereof

Номер: US20190002450A1
Автор: Adam Rosenberg, Hui Liu, Junbin Han, Zhude Tu
Принадлежит: Washington University in St Louis WUSTL

Among the various aspects of the present disclosure is the provision of a compositions for binding sphingosine-1-phosphate receptor 1 (S1P1), imaging of S1P1, and methods of use thereof. Provided are imaging agents for imaging S1P1 and S1P1 associated diseases, disorders, and conditions. Also provided are therapeutic compositions and methods for the treatment of S1P1 associated diseases, disorders, and conditions.

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Номер записи: 51
02-01-2020 дата публикации

AZETIDINYLOXYPHENYLPYRROLIDINE COMPOUNDS

Номер: US20200002318A1
Автор: DENG Gary G., HUANG Danwen, JESUDASON Cynthia Darshini, Odingo Joshua O.
Принадлежит:

The invention provides certain azetidinyloxyphenylpyrrolidine compounds, particularly compounds of formula I, and pharmaceutical compositions thereof. The invention further provides methods of using a compound of formula I to treat overactive bladder. 4. The compound or salt of wherein Ris Cl.6. The compound which is (2S)-3-[(3S claim 3 ,4S)-3-[(1R)-1-hydroxyethyl]-4-(4-methoxy-3-{[1-(5-chloropyridin-2-yl)azetidin-3-yl]oxy}phenyl)-3-methylpyrrolidin-1-yl]-3-oxopropane-1 claim 3 ,2-diol.8. A pharmaceutical composition comprising a compound of or claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , and a pharmaceutically acceptable carrier claim 3 , diluent or excipient.9. A method of treating overactive bladder comprising administrating to a patient in need thereof an effective amount of a compound of or claim 3 , or a pharmaceutically acceptable salt thereof.10. A method of treating overactive bladder comprising administrating to a patient in need thereof an effective amount of a compound of or claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , in combination with an effective amount of tadalafil.11. (canceled)12. (canceled)13. (canceled) The invention provides certain azetidinyloxyphenylpyrrolidine compounds, pharmaceutical compositions thereof, methods of using the same, and processes for preparing the same.Overactive bladder (OAB) is a symptomatically defined medical condition referring to the symptoms of urinary frequency and urgency, with or without urge incontinence. OAB is a condition that adversely affects the quality of life and social functioning of approximately 17 percent of the adult population. In spite of progress made for OAB treatment, many patients suffer with OAB for years without resolution. The first-line treatment for OAB are antimuscarinic drugs which have a good initial response, but experience diminishing patient compliance over the long term due to adverse effects and decreasing efficacy. There remains a ...

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Номер записи: 52
07-01-2021 дата публикации

Creatine prodrugs, compositions and methods of use thereof

Номер: US20210002211A1
Автор: Alexandra Trotier-Faurion, Arjun NATESAN, David Lapointe, Emil D. Kakkis, Mike E. Lizarzaburu, Paul Lee, Sharyl FYFFE-MARICICH, William F. Brubaker, Yiumo CHAN
Принадлежит: Ultragenyx Pharmaceutical Inc

The present disclosure provides creatine prodrug analogs and their compositions useful for the treatment of creatine deficiencies.

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Номер записи: 53
07-01-2021 дата публикации

COMPOUNDS, COMPOSITIONS, AND METHODS

Номер: US20210002260A1
Автор: de Vicente Fidalgo Javier, Estrada Anthony A., Feng Jianwen A., Lyssikatos Joseph P., Sweeney Zachary K.
Принадлежит: Denali Therapeutics Inc.

The present disclosure relates generally to LRRK2 inhibitors, or a pharmaceutically acceptable salt, deuterated analog, prodrug, tautomer, stereoisomer, or mixture of stereoisomers thereof, and methods of making and using thereof. 131.-. (canceled)33. The method of claim 32 , wherein Rand Rare methyl.34. The method of claim 32 , wherein at least one of Rand Ris hydrogen.35. The method of claim 34 , wherein both Rand Rare hydrogen.36. The method of claim 32 , wherein Ris optionally substituted cyclopropyl or optionally substituted cyclobutyl.37. The method of claim 36 , wherein Ris cyclopropyl independently substituted with one or more halo claim 36 , hydroxy claim 36 , cyano claim 36 , or heteroaryl.38. The method of claim 36 , wherein Ris cyclopropyl claim 36 , cyclobutyl claim 36 , hydroxycylobut-3-yl claim 36 , cyanocylobut-3-yl claim 36 , triazol-2yl-cyclobut-3-yl claim 36 , triazol-1-yl-cyclobut-3-yl claim 36 , or fluorocyclobut-3-yl.39. The method of claim 32 , wherein Ris CD claim 32 , ethyl claim 32 , prop-2-yl claim 32 , or methyl optionally substituted with halo.40. The method of claim 32 , wherein Ris halo claim 32 , cyano claim 32 , or Calkyl optionally substituted with one or more halo.41. The method of claim 40 , wherein Ris bromo.42. The method of claim 40 , wherein Ris —CF.43. The method of claim 32 , wherein Ris optionally substituted cycloalkyl claim 32 , optionally substituted Calkoxy claim 32 , or —N(R)(R).44. The method of claim 43 , wherein Ris optionally substituted Calkyl.45. The method of claim 43 , wherein Ris H and Ris ethyl.46. The method of claim 32 , wherein Ris cyclopropyl claim 32 , methoxy claim 32 , 1 claim 32 ,1-difluoroeth-2-ylamino claim 32 , cyclopropylamino claim 32 , —NH(CH) claim 32 , or —NH(CHCH).47. The method of claim 32 , wherein Ris hydrogen.48. The method of claim 32 , wherein Ris cycloalkyl independently substituted with one or more hydroxy claim 32 , cyano claim 32 , or heteroaryl; Ris halo or Chaloalkyl; Ris —N(R)(R) ...

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Номер записи: 54
02-01-2020 дата публикации

METHODS AND COMPOSITIONS FOR IMAGING AMYLOID DEPOSITS

Номер: US20200002410A1
Автор: Lentzsch Suzanne, Mintz Akiva
Принадлежит:

Methods and diagnostic compositions for detection of amyloid deposits using a chimeric (e.g., mouse-human) antibody or antigen-binding fragment thereof linked to a detectable label are disclosed. 1. An in vivo method of detecting the presence , location and/or quantity of amyloid deposits in a patient suspected of having amyloid deposits which comprises administering to the patient an antibody or antigen binding fragment having a detectable molecule linked thereto , the antibody or antigen-binding fragment comprising:{'sub': 'H', 'a variable heavy chain (V) comprising: a complementarity determining region (CDR) H1 comprising SEQ ID NO: 53; a CDRH2 comprising SEQ ID NO: 53; and a CDRH3 comprising SEQ ID NO: 54; and'}{'sub': 'K', 'a variable light chain (V) comprising a CDRL1 comprising SEQ ID NO: 49; a CDRL2 comprising SEQ ID NO: 50; and a CDRL3 comprising SEQ ID NO: 51; and'}detecting the presence, location, and/or quantity of amyloid deposits by detecting the detectable label bound to the amyloid deposits by diagnostic imaging.2. The method of wherein the antibody or antigen binding fragment comprises a chimeric mouse-human antibody which comprises a Vregion comprising SEQ ID NO: 47 and a Vregion comprising SEQ ID NO: 48.3. The method of wherein the method of detection is positron emission spectroscopy (PET).4. The method of claim 3 , wherein the detectable label is I.5. The method of claim 3 , wherein the detectable label is Zr.6. The method of wherein the antibody is chimeric 11-1F4.{'claim-ref': {'@idref': 'CLM-00005', 'claim 5'}, 'The method of wherein the antibody is chimeric 11-1F4.'}7. The method of wherein the antibody is CAEL-101.8. The method of wherein the antibody is CAEL-101.9. The method of claim 1 , wherein the amyloid deposits are in the heart.10. A composition for detecting the presence claim 1 , location claim 1 , and/or quantity of amyloid deposits in a subject which comprises an antibody or antigen binding fragment having a detectable molecule ...

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Номер записи: 55
01-01-2015 дата публикации

HETEROCYCLIC COMPOUNDS AS IMAGING PROBES OF TAU PATHOLOGY

Номер: US20150004100A1
Автор: GLASER MATTHIAS EBERHARD, Johansson Saga, Jones Clare, Jose Jinto, Mokkapati Umamaheshwar P., Nairne James, Newington Ian Martin, Rangswamy Chitralekha, WYNN DUNCAN
Принадлежит: GE HEALTHCARE LIMITED

Pyridazinone compounds of Formula I: (I) wherein: R′ is alkyl or Ar, optionally substituted with at least one alkyl, halogen, hydroxyl, alkoxy, haloalkoxy, acid, ester, amino, nitro, amide, or alkoxyhalo; 2 R is independently alkyi, alkynyl, ester, amino, amide, acid, aryl, heteroaryl, aminoalkyl, —C(=0)alkyl, —C(=0)aryl, —C(=0)heteroaryl, —C(=0)heterocycloalkyl, —C(=0)heterocycloalkylAr, —C(=0)(CH)halo, —C(═O)(CH)nheterocyclyl, or —SĈAr, optionally substituted with at least one alkyi, alkylhalo, halogen, nitro, aryl, heteroaryl, or heteroaryl(CH)nhalo; Rand Rare independently hydrogen, alkyi, alkenyl, alkynyl, aryl, heteroaryl; Ar is an aryl, heteroaryl, cycloalkyl, heterocycloalkyl group; n is an integer from 0-10; or a radiolabeled derivative thereof. The compounds are useful as imaging probes of Tau pathology in Alzheimer's disease are described. Compositions and methods of making such compounds are also described. 3. (canceled)10. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. (canceled)17. A composition comprising a compound according to and a pharmaceutically acceptable carrier or excipient.18. (canceled)19. A method of imaging using a compound according to or a pharmaceutical composition thereof.20. A method of detecting tau aggregates in vitro and/or in vivo using a compound according to or a pharmaceutical composition thereof.21. (canceled)22. (canceled)23. (canceled) The present invention relates to radiolabeled pyridazinone compounds, compositions thereof, methods of making such compounds and their use as imaging probes of Tau pathology especially as it relates to Alzheimer's Disease. Compounds of the present invention may be used for Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) imaging.Alzheimer's disease (AD) is the most common cause of dementia in the elderly. It is definitively diagnosed and staged on the basis of post-mortem neuropathology. The pathological hallmark of AD is a ...

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Номер записи: 56
13-01-2022 дата публикации

RADIOLABELLED AND NONRADIOLABELLED PEGYLATED COMPOUNDS AND USES THEREOF

Номер: US20220008563A1
Автор: Lam Phuc Quang, Liang Christopher, Martinez Stephanie, Mondal Rommani, Mukherjee Jogeshwar
Принадлежит:

The disclosure provides compounds for detecting neurodegeneration and/or identifying and monitoring the progression of inflammation in neurodegenerative diseases. The disclosure further provides compounds that inhibit the activity of monoamine oxidases, and uses thereof. 2. The compound of claim 1 , wherein R-Ris selected from —ORand H claim 1 , and one of R-Ris —OR.3. The compound of claim 2 , wherein R claim 2 , Rand Rare H claim 2 , and Ris —OR.4. The compound of claim 1 , wherein R-Ris selected from —OR claim 1 , a radiohalogen claim 1 , and H claim 1 , and wherein one of R-Ris —ORand one of R-Ris I or I.5. The compound of claim 1 , wherein Rand Rare H claim 1 , Ris —OR claim 1 , and Ris a radiohalogen.6. The compound of claim 5 , wherein Ris I or I.7. The compound of claim 1 , wherein R-Ris selected from At and H claim 1 , and one of R-Ris a radiohalogen.8. The compound of claim 7 , wherein R claim 7 , R claim 7 , and Rare H claim 7 , and Ris a radiohalogen.9. The compound of claim 8 , wherein Ris I claim 8 , I or At.10. The compound of claim 1 , wherein R-Ris selected from —ORand H claim 1 , and one of R-Ris —OR.11. The compound of claim 1 , wherein X is a radiohalogen selected from I claim 1 , At claim 1 , I claim 1 , I claim 1 , and Br.12. The compound of claim 11 , wherein X is F.14. A method of imaging neurodegeneration in a postmortem brain specimen claim 11 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'contacting a postmortem brain specimen from a subject who has a neurodegenerative disorder or is suspected of having a neurodegenerative disorder with a compound of ,'}detecting and/or quantitating binding of the compound to brain tissue comprising neurodegeneration using an imaging technique that detects radioactivity emitted by the compound.15. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier claim 1 , diluent claim 1 , and/or excipient claim 1 , wherein the compound comprises a ...

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Номер записи: 57
13-01-2022 дата публикации

Radiolabeled GRPR-Antagonists for Diagnostic Imaging and Treatment of GRPR-Positive Cancer

Номер: US20220008568A1
Автор: de Jong Hendriks Marion, Maina-Nock Theodosia, Nock Berthold Artur
Принадлежит: Advanced Accelerator Applications International SA

The present invention relates to probes for use in the detection, imaging, diagnosis, targeting, treatment, etc. of cancers expressing the gastrin releasing peptide receptor (GRPR). For example, such probes may be molecules conjugated to detectable labels which are preferably moieties suitable for detection by gamma imaging and SPECT or by positron emission tomography (PET) or magnetic resonance imaging (MRI) or fluorescence spectroscopy or optical imaging methods. 119-. (canceled)23. A method of treating primary and/or metastatic GRPR-positive cancer in a human subject comprising administering the radiolabeled GRPR-antagonist as claimed in to the human subject.24. A method of treating primary and/or metastatic GRPR-positive cancer in a human subject comprising administering the radiolabeled GRPR-antagonist as claimed in to the human subject.25. A method of treating primary and/or metastatic GRPR-positive cancer in a human subject comprising administering the radiolabeled GRPR-antagonist as claimed in to the human subject.26. The method as claimed in claim 23 , wherein the primary and/or metastatic GRPR-positive cancer is selected from prostate cancer claim 23 , breast cancer claim 23 , small cell lung cancer claim 23 , colon carcinoma claim 23 , gastrointestinal stromal tumors claim 23 , gastrinoma claim 23 , renal cell carcinomas claim 23 , gastroenteropancreatic neuroendocrine tumors claim 23 , oesophageal squamous cell tumors claim 23 , neuroblastomas claim 23 , head and neck squamous cell carcinomas claim 23 , as well as in ovarian claim 23 , endometrial and pancreatic tumors displaying neoplasia-related vasculature that is GRPR-positive.27. The method as claimed in claim 24 , wherein the primary and/or metastatic GRPR-positive cancer is selected from prostate cancer claim 24 , breast cancer claim 24 , small cell lung cancer claim 24 , colon carcinoma claim 24 , gastrointestinal stromal tumors claim 24 , gastrinoma claim 24 , renal cell carcinomas claim 24 , ...

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Номер записи: 58
13-01-2022 дата публикации

Deuterated compounds, compositions, and methods of use

Номер: US20220009950A1
Автор: Mikhail Sergeevich Shchepinov
Принадлежит: Retrotope Inc

Deuterated polyunsaturated fatty acid (“PUFA”) compounds, compositions, and uses of the compounds for reducing lipid autooxidation and the treatment of various diseases and conditions are provided.

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Номер записи: 59
20-01-2022 дата публикации

COMPOSITIONS, METHODS, AND SYSTEMS FOR THE SYNTHESIS AND USE OF IMAGING AGENTS

Номер: US20220017459A1
Автор: Benites Pedro, Lazewatsky Joel, Lee L. Veronica, Purohit Ajay, Radeke Heike S.
Принадлежит: Lantheus Medical Imaging, Inc.

The present invention generally relates to novel synthetic methods, systems, kits, salts, and precursors useful in medical imaging. In some embodiments, the present invention provides compositions comprising an imaging agent precursor, which may be formed using the synthetic methods described herein. An imaging agent may be converted to an imaging agent using the methods described herein. In some cases, the imaging agent is enriched in F. In some cases, an imaging agent including salt forms (e.g., ascorbate salt) may be used to image an area of interest in a subject, including, but not limited to, the heart, cardiovascular system, cardiac vessels, brain, and other organs. 1102-. (canceled)104. The method of claim 103 , wherein the maximum dose of the compound or pharmaceutically acceptable salt thereof that is administered to the subject is approximately 13 mCi or less claim 103 , is between approximately 10 mCi and approximately 13 mCi claim 103 , or is between approximately 8 mCi and approximately 10 mCi.105. The method of claim 103 , wherein the portion of the subject being imaged is at least a portion of the cardiovascular system claim 103 , or at least a portion of a tumor claim 103 , or is at least a portion of the heart.106. The method of claim 103 , further comprising determining the presence or absence of a cardiovascular disease or condition in the subject.107. The method of claim 103 , further comprising:{'claim-ref': {'@idref': 'CLM-00103', 'claim 103'}, 'administering a second dose of the compound or pharmaceutically acceptable salt thereof to the subject at a time subsequent to the dose of ; and'}acquiring at least one image of the portion of the subject after the administration of the second dose.108. The method of claim 107 , further comprising:comparing the at least one image acquired after the first dose with the at least one image acquired after the second dose; anddetermining the presence or absence of differences between the cardiac sympathetic ...

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Номер записи: 60
12-01-2017 дата публикации

HEATSEAL

Номер: US20170007728A1
Автор: Dumont Philippe, KUCI SALI, Mosdzianowski Christoph
Принадлежит:

The present invention relates to systems and methods to facilitate replacement between runs of a kit or cassette from an automated radiosynthesis device located in a hot cell. The method and apparatus of the invention enable automated disconnection of the outlet line by sealing the tubing hermetically by means of heat and by cutting the tubing where it is sealed in such a way that there is no risk of environmental contamination with radioactive material. The invention enables disconnection of the outlet line without manual intervention before opening the shielded enclosure. 1. A method comprising:(i) providing a kit that can be fitted to an automated radiosynthesis device in order to synthesise a positron emission tomography (PET) tracer and one or more sections of thermoplastic tubing;(ii) fitting said kit and said one or more sections of thermoplastic tubing to the automated radiosynthesis device;(iii) introducing a PET isotope into said kit to carry out a radiochemical process to form a radiolabelled product;(iv) transferring said radiolabelled product from said kit to a product collection device and/or a product processing device; and,(v) heat sealing and cutting said one or more sections of thermoplastic tubing.2. The method as defined in wherein said product collection device is a product collection vial.3. The method as defined in wherein said product processing device is a chromatography device claim 2 , a dispensing device or a quality control device.4. The method as defined in wherein each of said radiosynthesis device claim 3 , product collection device and product processing device is contained within a shielded enclosure.5. The method as defined in wherein said shielded enclosure is a hot cell.6. The method as defined in wherein said automated radiosynthesis device is contained within a first shielded enclosure and said product collection device and/or said product processing device are contained within a second shielded enclosure.7. The method as ...

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Номер записи: 61
12-01-2017 дата публикации

OXINDOLE DERIVATIVES CARRYING A PIPERIDYL-SUBSTITUTED AZETIDINYL SUBSTITUENT AND USE THEREOF FOR TREATING VASOPRESSINE-RELATED DISEASES

Номер: US20170008875A1
Автор: Geneste Hervé, Hornberger Wilfried, Hutchins Charles W., Jantos Katja, Kling Andreas, LAPLANCHE Loic, van Gaalen Marcel
Принадлежит:

The present invention relates to novel substituted oxindole derivatives of formula (I) wherein the variables are as defined in the claims and description; to pharmaceutical compositions comprising them, and to their use for treatment of vasopressin-related disorders. 2. The compound of claim 1 , wherein at least one hydrogen atom has been replaced by a deuterium atom.3. The compound of claim 1 , wherein Xis C—Rand R claim 1 , Rand R claim 1 , independently of each other claim 1 , are selected from the group consisting of hydrogen claim 1 , halogen claim 1 , C-C-alkyl claim 1 , fluorinated C-C-alkyl claim 1 , C-C-alkoxy and fluorinated C-C-alkoxy.4. The compound of claim 3 , wherein R claim 3 , Rand R claim 3 , independently of each other claim 3 , are selected from the group consisting of hydrogen claim 3 , fluorine and methoxy.5. The compound of claim 4 , wherein Ris selected from hydrogen claim 4 , fluorine and methoxy.6. The compound of claim 4 , wherein Ris selected from the group consisting of hydrogen claim 4 , fluorine and methoxy.7. The compound of claim 4 , wherein Ris hydrogen or fluorine.8. The compound of claim 1 , wherein Xis N and Rand R claim 1 , independently of each other claim 1 , are selected from the group consisting of hydrogen claim 1 , halogen claim 1 , C-C-alkyl claim 1 , fluorinated C-C-alkyl claim 1 , C-C-alkoxy and fluorinated C-C-alkoxy.9. The compound of claim 8 , wherein Ris selected from the group consisting of hydrogen claim 8 , fluorine and methoxy.10. The compound of claim 8 , wherein Ris selected from the group consisting of hydrogen claim 8 , fluorine and methoxy.11. The compound of claim 1 , wherein Ris selected from the group consisting of methoxy and ethoxy.12. The compound of claim 1 , wherein Ris hydrogen or methoxy.13. The compound of claim 1 , wherein Ris selected from the group consisting of cyano claim 1 , fluorine and chlorine.14. The compound of claim 1 , wherein Ris hydrogen or fluorine.15. The compound of claim 1 , ...

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Номер записи: 62
12-01-2017 дата публикации

PYRIDINES AND PYRIMIDINES AND USE THEREOF

Номер: US20170008882A1
Автор: Lynch Stephen M.
Принадлежит:

The present disclosure provides pyridines and pyrimidines of Formula I and pharmaceutically acceptable salts and solvates thereof: wherein A, G, W, W, W, and Rare defined as set forth in the specification. The present disclosure also provides uses of the compounds of Formula I and pharmaceutically acceptable salts and solvates thereof. In certain embodiments, Compounds of the present disclosure are useful for treating pain. In another embodiment, Compounds of the present disclosure are useful for treating a disorder responsive to blockade of sodium channels, or alleviating symptoms of the disorder. 36-. (canceled)910-. (canceled)11. The compound of claim 1 , wherein Ris selected from the group consisting of alkyl claim 1 , optionally substituted cycloalkyl claim 1 , optionally substituted heterocyclo claim 1 , optionally substituted aryl claim 1 , optionally substituted heteroaryl claim 1 , and —SOR claim 1 , or a pharmaceutically acceptable salt or solvate thereof.12. The compound of claim 11 , wherein Ris optionally substituted phenyl or (C-C)alkyl claim 11 , or a pharmaceutically acceptable salt or solvate thereof.13. (canceled)1517-. (canceled)18. The compound of claim 1 , wherein Wis N claim 1 , Wis CH claim 1 , and Wis CH claim 1 , or a pharmaceutically acceptable salt or solvate thereof.19. The compound of claim 1 , wherein Wis N claim 1 , Wis N claim 1 , and Wis CH claim 1 , or a pharmaceutically acceptable salt or solvate thereof.20. (canceled)22. The compound of claim 1 , wherein G is —C(═O)E claim 1 , or a pharmaceutically acceptable salt or solvate thereof.23. (canceled)2530-. (canceled)31. The compound of claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , hydroxyalkyl claim 1 , and —X—R claim 1 , or a pharmaceutically acceptable salt or solvate thereof.32. (canceled)3438-. (canceled)40. The compound of selected from the group consisting of:6-(1-(4-(Trifluoromethyl)phenyl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-yl)picolinamide ...

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Номер записи: 63
12-01-2017 дата публикации

Cot modulators and methods of use thereof

Номер: US20170008905A1
Автор: Chien-Hung Chou, Christopher T. Clark, Elizabeth M. Bacon, Gary Phillips, Gayatri BALAN, James G. Taylor, Jeromy J. Cottell, John O. Link, Kirk L. Stevens, Musong Kim, Nathan E. Wright, Neil H. Squires, Scott D. Schroeder, Sheila M. Zipfel, Thorsten A. Kirschberg, William J. Watkins
Принадлежит: Gilead Sciences Inc

The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof.

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Номер записи: 64
14-01-2021 дата публикации

IN VIVO IMAGING OF MATRIX METALLOPROTEINASES IN LUNG DISEASE

Номер: US20210008231A1
Автор: "DArmiento Jeanine", GOLDKLANG Monica, Johnson Lynne, Tekabe Yared
Принадлежит: The Trustees of Columbia University in the City of New York

The present invention provides a method of imaging a subject's lung which comprises contacting the subject's lung with a matrix metalloproteinase inhibitor labeled with a radioisotope under conditions such that the inhibitor binds to matrix metalloproteinase in the lung, and then imaging the radiolabeled inhibitor bound to matrix metalloproteinase in the subject's lung. 1. A method of imaging a subject's lung which comprises contacting the subject's lung with a matrix metalloproteinase inhibitor labeled with a radioisotope under conditions such that the inhibitor binds to matrix metalloproteinase in the lung , and then imaging the radiolabeled inhibitor bound to matrix metalloproteinase in the subject's lung so as to image the subject's lung.2. The method of claim 1 , wherein the matrix metalloproteinase inhibitor is Ro 32-3555 or a modified form of CGS27023A.3. The method of claim 2 , wherein the radioisotope is I-123.4. The method of claim 3 , wherein the matrix metalloproteinase inhibitor is Ro 32-3555.5. The method of claim 3 , wherein the matrix metalloproteinase inhibitor is a modified form of CGS27023A.8. The method of claim 1 , wherein the subject is claim 1 , or is suspected of being claim 1 , afflicted with a destructive lung disease.9. (canceled)10. The method of claim 8 , wherein the destructive lung disease is chronic obstructive pulmonary disease (COPD) claim 8 , lymphangioleiomyomatosis (LAM) claim 8 , idiopathic pulmonary fibrosis (IPF) claim 8 , or acute lung injury (ALI).11. The method of claim 8 , wherein the destructive lung disease is emphysema.12. The method of claim 1 , wherein the imaging is single-photon emission computed tomography (SPECT) imaging.13. The method of claim 1 , wherein the contacting comprises administering to the subject an imageable amount of the matrix metalloproteinase inhibitor labeled with a radioisotope.14. (canceled)15. The method of claim 1 , wherein the imaging is effected with a computer tomography (CT) scanner.167 ...

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Номер записи: 65
11-01-2018 дата публикации

Radiosynthesiser Add-On Device

Номер: US20180008950A1
Автор: Dumont Philippe
Принадлежит: GE HEALTHCARE LIMITED

The present invention relates to an automated radiosynthesis device adapted for the addition of multiple additional components. The automated radiosynthesis device of the invention enables a wider range of radiochemical synthetic processes to be carried out in an automated fashion. 1. An automated radiosynthesis device comprising:(i) a plurality of connectors for removably attaching a disposable kit;(ii) a plurality of actuators to selectively control moving parts of said disposable kit;(iii) a control unit for directing the selective control of the moving parts of said disposable kit by said plurality of actuators;(iv) a reaction vessel heating well;(v) an inert gas conduit;(vi) a vacuum conduit;(vii) a radioisotope conduit;(viii) means to fix add-on devices onto the radiosynthesis device at various locations.2. The automated radiosynthesis device as defined in claim 1 , wherein said plurality of connectors is selected from the group comprising fasteners and fluidic connectors.3. The automated radiosynthesis device as defined in claim 2 , wherein said fluidic connectors are selected from the group comprising push-on type connectors claim 2 , luer slip connectors or luer screw connectors.4. The automated radiosynthesis device as defined in claim 1 , wherein said disposable kit is suitable for the synthesis of a radiotracer compound.5. The automated radiosynthesis device as defined in claim 4 , wherein said radiotracer compound is a positron-emission tomography (PET) tracer.6. The automated radiosynthesis device as defined in claim 5 , wherein said radiotracer compound is an F-labelled PET tracer.7. The automated radiosynthesis device as defined in claim 1 , wherein said disposable kit is a single-use cassette.8. The automated radiosynthesis device as defined in claim 1 , wherein said plurality of actuators is selected from the group comprising rotatable arms for stopcocks of valves claim 1 , linear actuators claim 1 , arms that press onto reagent vials and pinch ...

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Номер записи: 66
10-01-2019 дата публикации

LABELED INHIBITORS OF PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA), THEIR USE AS IMAGING AGENTS AND PHARMACEUTICAL AGENTS FOR THE TREATMENT OF PROSTATE CANCER

Номер: US20190008988A1
Автор: BAUDER-WÜST Ulrike, Benesova Martina, EDER Matthias, EISENHUT Michael, Haberkorn Uwe, KLIEM Hans-Christian, Kopka Klaus, KRATOCHWIL Clemens, Mier Walter, Schäfer Martin
Принадлежит:

The present invention generally relates to the field of radiopharmaceuticals and their use in nuclear medicine as tracers, imaging agents and for the treatment of various disease states of prostate cancer. Thus, the present invention concerns compounds that are represented by the general Formulae (Ia) or (Ib). 114-. (canceled)16. The compound of claim 15 , wherein Chelator is a radical of:1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid (DOTA);N,N″-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N″-diacetic acid (HBED-CC);1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA);2-(4,7-bis(carboxymethyl)-1,4,7-triazonan-1-yl)pentanedioic acid (NODAGA);2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)pentanedioic acid (DOTAGA);1,4,7-triazacyclononane phosphinic acid (TRAP);1,4,7-triazacyclononane-1-[methyl(2-carboxyethyl)phosphinic acid]-4,7-bis[methyl(2-hydroxymethyl)phosphinic acid] (NOPO);3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA);N′-{5-[Acetyl(hydroxy)amino]pentyl}-N-[5-({4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoyl}amino)pentyl]-N-hydroxysuccinamide (DFO);diethylenetriaminepentaacetic acid (DTPA);trans-cyclohexyl-diethylenetriaminepentaacetic acid (CHX-DTPA);1-oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid (oxo-Do3A);p-isothiocyanatobenzyl-DTPA (SCN-Bz-DTPA);1-(p-isothiocyanatobenzyI)-3-methyl-DTPA (1B3M);2-(p-isothiocyanatobenzyI)-4-methyl-DTPA (1M3B); or1-(2)-methyl-4-isocyanatobenzyl-DTPA (MX-DTPA).18. A radiolabeled compound of .19. A radiolabeled compound of .20. A metal complex comprising a radionuclide and a compound of .21. The metal complex of claim 20 , wherein the radionuclide is selected from Zr claim 20 , Sc claim 20 , In claim 20 , Y claim 20 , Ga claim 20 , Lu claim 20 , Tc claim 20 , Cu claim 20 , Cu claim 20 , Gd claim 20 , Gd claim 20 , Gd claim 20 , Bi claim 20 , or Ac.22. A pharmaceutical composition comprising the compound of or a pharmaceutically acceptable ...

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Номер записи: 67
27-01-2022 дата публикации

COMPOSITIONS AND METHODS FOR INHIBITION OF THE JAK PATHWAY

Номер: US20220024907A1
Автор: Chen Yan, Ding Pingyu, Heckrodt Thilo J., Li Hui, McMurtrie Darren John, Singh Rajinder, Taylor Vanessa, Yen Rose
Принадлежит: Rigel Pharmaceuticals, Inc.

Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful. Also disclosed are methods of making the compounds. 1. A pharmaceutical composition , comprising:a means for inhibiting a Janus kinase (JAK); anda pharmaceutically acceptable excipient.2. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is a liquid carrier.3. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is a solid carrier.4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for oral administration claim 1 , parenteral administration claim 1 , inhalation spray nasal administration claim 1 , vaginal administration claim 1 , rectal administration claim 1 , sublingual administration claim 1 , urethral administration claim 1 , or topical administration.5. The pharmaceutical composition of claim 4 , wherein parenteral administration is selected from intramuscular claim 4 , intraperitoneal claim 4 , intravenous claim 4 , ICV claim 4 , intracisternal injection or infusion claim 4 , subcutaneous injection claim 4 , or implant administration.6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a gel claim 1 , ointment claim 1 , cream claim 1 , aerosol claim 1 , a semi-solid claim 1 , a solid claim 1 , a powder claim 1 , a tablet claim 1 , a suppository claim 1 , a pill claim 1 , a soft elastic capsule claim 1 , a jelly claim 1 , a hard gelatin capsule claim 1 , a solution claim 1 , a suspension claim 1 , or a combination thereof.7. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipient is selected from binding agents claim 1 , fillers claim 1 , lubricants claim 1 , disintegrants claim 1 , ...

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Номер записи: 68
27-01-2022 дата публикации

Process for Making Biologically Active Compounds and Intermediates Thereof

Номер: US20220024910A1
Автор: Makriyannis Alexandros, Vemuri Kiran
Принадлежит:

A process of manufacturing biologically active compounds, their analogs, pharmaceutically acceptable salts, solvates, polymorphs, isotopic variants, and intermediates thereof. Notably, the compounds of the formula IA, 1B, 1C. 1D. 1E, 1F and IG for which novel processes have been disclosed, selectively act on the cannabinoid receptors, and with high affinity. The processes for the preparation of the compounds enable the syntheses of cannabinoid modulators on a large-scale that are eco-friendly and economically viable. Additionally, the processes disclosed enable the synthesis of cannabinoid modulators with high purity and in high yield for their use in making drug substance and drug products. 8. The process of claim 1 , wherein X1 is —SO2- claim 1 , —O— or —CH2-.9. The process of claim 7 , wherein X1 is —SO2- claim 7 , —O— or —CH2-. The present invention relates to a chemical process for the preparation of compounds of one of Formulae I, IA, IB, IC, ID, IE, 1F. and 1G. and IV, IVA, IVB, IVC, V and VI and intermediates thereof.More specifically, the invention relates to a chemical process for the preparation of 5-[4-(4-cyano-1-butyn-1-yl)phenyl]-1-(2,4-dichlorophenyl)-N-(1,1-dioxido-4-thiomorpholinyl)-4-methyl-1H-pyrazole-3-carboxamide and 5-(4-(4-cyanobut-1-yn-1-yl)phenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-morpholino-1H-pyrazole-3-carboxamide and their analogs, solvates, polymorphs and isotopic variations thereof.Compounds of this class with unique pharmacological properties and therapeutic value have been disclosed in WO200674445, WO2008154015 and WO2010104488.Disclosed herein are processes for the preparation of compounds comprising, reacting a compound of Formula II with a compound of Formula III to provide a compound of Formula VII, second by reacting a compound of Formula VII with an alkyne in the presence of a palladium reagent and copper (I) iodide, in a basic medium and in an aprotic solvent to obtain a product of Formula I, third by hydrolysis of a compound ...

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Номер записи: 69
27-01-2022 дата публикации

Deuterium-Substituted 7-Substituted-2-(Benzylamino)-6-Ozopurine Compounds and Uses Thereof

Номер: US20220024925A1
Автор: Yu Xiang Y.
Принадлежит:

The invention relates to compounds of formula (I): The compounds are useful as antibacterial agents, especially again -associated diseases. 2. The compound of claim 1 , wherein at least one of Y claim 1 , Y claim 1 , Y claim 1 , and Yis deuterium.4. The compound of claim 2 , wherein the level of deuterium incorporation at each of Y claim 2 , Y claim 2 , Y claim 2 , and Ydesignated as deuterium is at least 52.5% claim 2 , at least 75% claim 2 , at least 82.5% claim 2 , at least 90% claim 2 , at least 95% claim 2 , at least 97% claim 2 , at least 98% claim 2 , or at least 99%.5. The compound of claim 1 , wherein at least one of least one of Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Yand Yis deuterium.7. The compound of claim 5 , wherein the level of deuterium incorporation at each of Y Y claim 5 , Y claim 5 , Y claim 5 , Y claim 5 , Yand Ydesignated as deuterium is at least 52.5% claim 5 , at least 75% claim 5 , at least 82.5% claim 5 , at least 90% claim 5 , at least 95% claim 5 , at least 97% claim 5 , at least 98% claim 5 , or at least 99%.8. The compound of claim 1 , wherein at least one of Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Y claim 1 , Yand Yis deuterium.10. The compound of claim 8 , wherein the level of deuterium incorporation at each of Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Y claim 8 , Yand Ydesignated as deuterium is at least 52.5% claim 8 , at least 75% claim 8 , at least 82.5% claim 8 , at least 90% claim 8 , at least 95% claim 8 , at least 97% claim 8 , at least 98% claim 8 , or at least 99%.12. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.13Clostridium difficileClostridium difficile. A method of inhibiting ...

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Номер записи: 70
09-01-2020 дата публикации

RADIOACTIVE FLUORINE-LABELED PRECURSOR COMPOUND, AND METHOD FOR PRODUCING RADIOACTIVE FLUORINE-LABELED COMPOUND USING SAME

Номер: US20200009273A1
Автор: Ichikawa Hiroaki, KIRIU Masato, Okumura Yuki, Tanaka Hiroshi
Принадлежит:

There is provided a labeling precursor compound represented by the general formula (2): 15.-. (canceled)7. The labeling precursor compound according to claim 6 , wherein the radioactive fluorine-labeled compound represented by the general formula (1) has a clogP of −1.4 to 5.0 claim 6 , and a difference in clogP between the radioactive fluorine-labeled compound represented by the general formula (1) and the precursor compound represented by the general formula (2) is 2 or more.11. The production method according to claim 10 , further comprising:{'sup': '18', 'a step of adding a reaction mixture containing a radioactive fluorine-labeled compound represented by the general formula (1) to a reverse-phase cartridge column, said reaction mixture being obtained by the reaction of the labeling precursor compound with [F]fluoride ion; and'}a step of eluting the radioactive fluorine-labeled compound represented by the general formula (1) from the reverse-phase cartridge column. The present invention relates a novel radioactive fluorine-labeling precursor compound and a production method of a radioactive fluorine-labeled compound using the precursor compound.Conventionally, a radioactive fluorine-labeling reaction is often performed by preparing a labeling precursor compound which is a compound having a leaving group bonded to a site to be fluorine-labeled of a target substrate and performing a nucleophilic substitution reaction in which radioactive fluoride ion F is allowed to react with the labeling precursor compound. In general, this reaction is performed by using a small amount of radioactive fluoride ion F with respect to a large amount of labeling precursor compound. Therefore, purification of the obtained radioactive fluorine-labeled compound is usually performed by separating a large amount of unreacted labeling precursor compound by a high-performance liquid chromatography (HPLC) method.However, the HPLC method is cumbersome and takes time, and thus causes ...

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Номер записи: 71
11-01-2018 дата публикации

CONTRAST AGENTS FOR MYOCARDIAL PERFUSION IMAGING

Номер: US20180009763A1
Автор: Casebier David S., Purohit Ajay, Radeke Heike S.
Принадлежит: Lantheus Medical Imaging, Inc.

The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging. 125-. (canceled)27. A composition , comprising:{'claim-ref': {'@idref': 'CLM-00026', 'claim 26'}, 'the compound of and a solvent.'}29. A composition comprising:{'claim-ref': {'@idref': 'CLM-00028', 'claim 28'}, 'the compound of and a solvent.'}31. The precursor compound of claim 30 , wherein the precursor compound is provided in a solution.32. The precursor compound of claim 30 , wherein the precursor compound is provided as a solid preparation.33. The precursor compound of claim 32 , wherein the solid preparation is a lyophilized solid. The present application claims the benefit of priority under 35 U.S.C. §119(e) from the provisional application 60/544,861 filed Feb. 13, 2004, the contents of which are herein incorporated by reference.The present disclosure relates to novel compounds comprising imaging moieties, and their use for diagnosing certain disorders in a patient.Mitochondria are membrane-enclosed organelles distributed through the cytosol of most eukaryotic cells. Mitochondria are especially concentrated in myocardium tissue.Complex 1 (“MC-1”) is a membrane-bound protein complex of 46 dissimilar subunits. This enzyme complex is one of three energy-transducing complexes that constitute the respiratory chain in mammalian mitochondria. This NADH-ubiquinone oxidoreductase is the point of entry for the majority of electrons that traverse the respiratory chain, eventually resulting in the reduction of oxygen to water (1992, 25, 253-324).Known inhibitors of MC-1 include deguelin, piericidin A, ubicidin-3, rolliniastatin-1, rolliniastatin-2 (bullatacin), capsaicin, pyridaben, fenpyroximate, amytal, MPP+, quinolines, and quinolones (1998, 1364, 222-235).The present disclosure is based, in ...

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Номер записи: 72
11-01-2018 дата публикации

Novel organic compounds for organic light-emitting diode and organic light-emitting diode including the same

Номер: US20180009776A1
Автор: CHA Soon-wook, KIM Hee-Dae, PARK Sang-Woo, PARK Seok-Bae, SHIN Yoona
Принадлежит:

The present invention relates to a compound for organic light-emitting diodes that can operate organic light-emitting diodes at a low driving voltage and an organic light-emitting diode comprising the same and, more particularly, to a compound for use as a fluorescent host in organic light-emitting diodes, which can bring about excellent diode properties by operating organic light-emitting diodes at a low driving voltage, and an organic light-emitting diode comprising the same. 3. The organic luminescent compound as set forth in claim 1 , wherein at least one of the substituents R1 to R5 in Chemical Formula A contains a deuterium.4. The organic luminescent compound as set forth in claim 4 , wherein R1 is a deuterium and k is 5.5. The organic luminescent compound as set forth in claim 3 , wherein R2 and/or R3 is a deuterium claim 3 , and l is 2 or greater claim 3 , or m is 2 or greater.6. The organic luminescent compound as set forth in claim 3 , wherein R4 and/or R5 is a deuterium claim 3 , and n is 2 or greater or o is 2 or greater.8. An organic light-emitting diode comprising:a first electrode;a second electrode facing the first electrode; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'an organic layer interposed therebetween, wherein the organic layer contains at least one organic luminescent compound of any one of .'}9. The organic light-emitting diode as set forth in claim 8 , wherein the organic layer comprises at least one of a hole injecting layer claim 8 , a hole transport layer claim 8 , a functional layer capable of both hole injection and hole transport claim 8 , a light-emitting layer claim 8 , an electron transport layer claim 8 , and an electron injecting layer.10. The organic light-emitting diode as set forth in claim 9 , wherein the organic layer interposed between the first electrode and the second electrode is a light-emitting layer composed of a host and a dopant claim 9 , the organic luminescent compound serving as the host.11. The ...

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Номер записи: 73
11-01-2018 дата публикации

DEUTERATED ORGANIC COMPOUND, MIXTURE AND COMPOSITION CONTAINING SAID COMPOUND, AND ORGANIC ELECTRONIC DEVICE

Номер: US20180010040A1
Автор: Huang Hong, Pan Junyou, YAN Xiaolin
Принадлежит:

The present disclosure discloses a deuterated organic compound and a formulation and an organic electronic device containing the same, wherein the deuterated organic compound has the following structural formula: 113-. (canceled)15. The organic compound according to claim 14 , wherein (S1-T1)≦0.25 eV.16. The organic compound according to claim 14 , wherein at least one H atom in at least one electron donor group D is substituted by deuterium.17. The organic compound according to claim 14 , wherein at least one H atom in at least one electron acceptor group A is substituted by deuterium.18. The organic compound according to claim 14 , wherein at least one H atom in Ar is substituted by deuterium.22. The organic compound according to claim 14 , wherein more than 20% of the H atoms are substituted by deuterium.24. A mixture comprising at least one organic compound according to and further an organic functional material selected from a hole-injection or hole-transport material claim 14 , a hole-blocking material claim 14 , an electron-injection or electron-transport material claim 14 , an electron-blocking material claim 14 , an organic host material claim 14 , a singlet emitter claim 14 , and a triplet emitter.26. The formulation according to claim 25 , wherein the organic solvent selecting from methanol claim 25 , ethanol claim 25 , 2-methoxyethanol claim 25 , dichloromethane claim 25 , trichloromethane claim 25 , chlorobenzene claim 25 , o-dichlorobenzene claim 25 , tetrahydrofuran claim 25 , anisole claim 25 , morpholine claim 25 , toluene claim 25 , o-xylene claim 25 , m-xylene claim 25 , p-xylene claim 25 , 1 claim 25 ,4-dioxahexane claim 25 , acetone claim 25 , methyl ethyl ketone claim 25 , 1 claim 25 ,2-dichloroethane claim 25 , 3-phenoxytoluene claim 25 , 1 claim 25 ,1 claim 25 ,1-trichloroethane claim 25 , 1 claim 25 ,1 claim 25 ,2 claim 25 ,2-tetrachloroethane claim 25 , ethyl acetate claim 25 , butyl acetate claim 25 , dimethylformamide claim 25 , ...

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Номер записи: 74
14-01-2021 дата публикации

ORGANIC COMPOUNDS

Номер: US20210009592A1
Автор: Davis Robert, Li Peng, ZHANG QIANG
Принадлежит:

The invention relates to particular deuterated substituted heterocycle fused gamma-carbolines, in free, solid, pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving the 5-HTreceptor, the serotonin transporter (SERT), pathways involving the dopamine Dand Dreceptor signaling system, and/or the μ-opioid receptor. 2. A compound according to claim 1 , wherein Z is O.3. A compound according to claim 1 , wherein Z is —C(O).4. A compound according to claim 1 , wherein Ris methyl.5. A compound according to claim 1 , wherein Ris H and Ris D.6. A compound according to claim 1 , wherein Ris D and Ris D.7. A compound according to claim 1 , wherein Ris H and Ris H.8. A compound according to claim 1 , wherein any one claim 1 , or any two claim 1 , or any three of Rto Ris D.9. A compound according to claim 1 , wherein any one claim 1 , or any two claim 1 , any three claim 1 , any four claim 1 , any five or any six of Rto Ris D.10. A compound according to claim 1 , wherein all four of Rto Ris D.11. A compound according to claim 1 , wherein all six of Rto Ris D.12. A compound according to claim 1 , in the form of a salt claim 1 , e.g. claim 1 , in the form of a pharmaceutically acceptable salt.13. A compound according to claim 1 , having greater than 50% incorporation of deuterium at one or more of the indicated positions of the structure (i.e. claim 1 , greater than 50 atom % D) claim 1 , e.g. claim 1 , greater than 60% claim 1 , or greater than 70% claim 1 , or greater than 80% claim 1 , or greater than 90% or greater than 95% claim 1 , or greater than 96% claim 1 , or greater than 97% claim 1 , or greater than 98% claim 1 , or greater than 99%.14. A pharmaceutical composition comprising a compound according to claim 1 , in free or pharmaceutically acceptable salt form claim 1 , in admixture with a pharmaceutically acceptable diluent or carrier.15. The ...

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Номер записи: 75
14-01-2021 дата публикации

[18F] FMAU LABELING FOR PET IMAGING OF CANCER PATIENTS

Номер: US20210009624A1
Автор: Chen Kai, Conti Peter S.
Принадлежит:

Provided herein are methods and labeling kits for synthesizing 2′-deoxy-2′-[F]fluoro-5-methyl-1-beta-D-arabino-furanosyl-uracil in a one-pot reaction in compliance with CGMP. Also disclosed are labeling kits that can be assembled in an automated synthesis system to enable such a reaction. 1. A system for producing 2′-deoxy-2′-[F]fluoro-5-methyl-1-beta-D-arabinofuranosyl-uracil ([F]FMAU) comprising:2-trifluoromethane-sulfonyl-1,3,5-tri-O-benzoyl ribofuranose;2,4-bis-trimethylsilyl-5-methyl-uracil, a Friedel-Crafts catalyst, and hexamethyldisilizane;an eluent;{'sup': '18', 'an inlet for receiving [F]-fluoride fluoride produced via a cyclotron; and'}{'sup': '18', 'an [F]FMAU collection device.'}2. The system of claim 1 , wherein the Friedel-Crafts catalyst is trimethylsilyl trifluoromethanesulfonate.3. The system of claim 1 , wherein the system is configured for automated one-pot synthesis.4. The system of claim 1 , wherein the system is in compliance with CGPMs.5. The system of claim 1 , further comprising tetrabutylammonium fluoride and acetonitrile.6. The system of claim 1 , further comprising sodium methoxide and methanol.7. The system of claim 1 , further comprising a carrier claim 1 , excipient claim 1 , diluent claim 1 , or a combination thereof.8. An automated synthesis module (ASM) for synthesizing 2′-deoxy-2′[F]fluoro-5-methyl-1-beta-D-arabinofuranosyl-uracil ([F]FMAU) in compliance with CGMPs comprising:a first container for holding 2-trifluoromethane-sulfonyl-1,3,5-tri-O-benzoyl ribofuranose;a second container for holding 2,4-bis-trimethylsilyl-5-methyl-uracil, a Friedel-Crafts catalyst, and hexamethyldisilizane;a third container for holding an eluent;{'sup': '18', 'an inlet for receiving [F]-fluoride produced via a cyclotron; and'}{'sup': '18', 'a fourth container for collecting [F]FMAU.'}9. The ASM of claim 8 , wherein the Friedel-Crafts catalyst is trimethylsilyl trifluoromethanesulfonate.10. The ASM of claim 8 , wherein the system is configured for ...

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Номер записи: 76
10-01-2019 дата публикации

18/19F-LABELLED COMPOUNDS WHICH TARGET THE PROSTATE SPECIFIC MEMBRANE ANTIGEN

Номер: US20190010171A1
Автор: BENARD Francois, KUO Hsiou-ting, LEPAGE Mathieu, LIN Kuo-shyan, LIU Zhibo, PAN Jinhe, Perrin David, ROXIN Aron
Принадлежит:

This disclosure relates to novel compounds comprising a zwitterionic trifluoroborate prosthetic group which target prostate-specific membrane antigen (PSMA), e.g. in prostate cancer. The compounds have Formula I, wherein each R1 is an anionic group, L is a linker and R2B-F3 is —N(R)CHBF, a pyridinium group substituted with BFor methyl BF, or an azole group substituted with methyl BF3. Methods and uses of imaging and treating PSMA-expressing cancers are also disclosed. 3. The compound of claim 1 , wherein Ris COH.7. The compound of claim 1 ,{'sup': '4', 'sub': 2', '2', '2', '2', '2', '2, 'wherein Ris absent, —CH—, —CHCH— or —CHCHCH.'}8. The compound of claim 1 ,{'sup': '5', 'wherein Ris —S—, —NHC(O)—, —C(O)—, —C(O)O— or —OC(O)—.'}13. The compound of claim 1 , in which at least one fluorine in the —BFmoiety is F.14. A method of imaging prostate specific membrane antigen (PSMA)-expressing cancer in a subject claim 1 , the method comprising:{'claim-ref': {'@idref': 'CLM-00013', 'claim 13'}, 'administering to the subject a composition comprising the compound of and a pharmaceutically acceptable excipient; and'}imaging tissue of the subject using positron emission tomography (PET).15. A method of treating prostate specific membrane antigen (PSMA)-expressing cancer in a subject claim 1 , the method comprising: administering to the subject a composition comprising the compound of and a pharmaceutically acceptable excipient.16. The method of claim 14 , wherein the cancer is prostate cancer claim 14 , renal cancer claim 14 , breast cancer claim 14 , thyroid cancer claim 14 , gastric cancer claim 14 , colorectal cancer claim 14 , bladder cancer claim 14 , pancreatic cancer claim 14 , lung cancer claim 14 , liver cancer claim 14 , brain tumor claim 14 , melanoma claim 14 , neuroendocrine tumor claim 14 , ovarian cancer or sarcoma. The present invention relates to novel fluorine-labeled compounds as well as uses/methods for these compounds, including but not limited to uses/ ...

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Номер записи: 77
09-01-2020 дата публикации

PYRIDONE DERIVATIVES HAVING TETRAHYDROPYRANYLMETHYL GROUPS

Номер: US20200010458A1
Автор: ANDO Yosuke, Haginoya Noriyasu, HAYAKAWA Miho, JIMBO Takeshi, KOBAYASHI Katsuhiro, Nakamura Koichi, Ota Masahiro, Suzuki Takashi, TSUKADA Tomoharu
Принадлежит:

The present disclosure provides novel compounds or salts thereof, or crystals of the compounds or the salts, which inhibit Axl and are useful in the treatment of a disease caused by hyperfunction of Axl, the treatment of a disease associated with hyperfunction of Axl, and/or the treatment of a disease involving hyperfunction of Axl. 2. The method of claim 1 , wherein the compound of formula (I) is administered to patient having lung cancer or non-small cell lung cancer.4. The method of claim 3 , wherein the cancer is lung cancer or non-small cell lung cancer.7. The method of claim 6 , wherein the compound of formula (I) is administered to patient having lung cancer or non-small cell lung cancer.9. The combination of claim 8 , wherein the compound of formula (I) claim 8 , or the pharmaceutically acceptable salt thereof claim 8 , and the tyrosine kinase inhibitor are separately contained in different formulations.10. The combination of claim 8 , wherein the compound of formula (I) claim 8 , or the pharmaceutically acceptable salt thereof claim 8 , and the tyrosine kinase inhibitor are contained in a single formulation.13. A methanesulfonate claim 11 , phosphate claim 11 , naphthalene-1 claim 11 ,5-disulfonate claim 11 , or sulfate of the compound of .15. The method of claim 14 , wherein the compound of formula (I) claim 14 , or the pharmaceutically acceptable salt thereof claim 14 , and the tyrosine kinase inhibitor are administered at the same time.16. The method of claim 14 , wherein the compound of formula (I) claim 14 , or the pharmaceutically acceptable salt thereof claim 14 , and the tyrosine kinase inhibitor are administered at different times.17. The method of claim 14 , wherein the cancer is lung cancer or non-small cell lung cancer. This application is a continuation of U.S. patent application Ser. No. 15/036,981, filed May 16, 2016, entitled “PYRIDONE DERIVATIVES HAVING TETRAHYDROPYRANYLMETHYL GROUPS,” which is a national stage application under 35 U.S.C. § ...

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Номер записи: 78
15-01-2015 дата публикации

Compound for organic optoelectronic device organic light emitting diode including the same and display including the organic light emitting diode

Номер: US20150014656A1
Автор: Eun-Jae Jeong, Eun-young Lee, Hye-jin Jung, Jin-O Lim, Jong-hyuk Lee, Jun-Ha Park, Sang-hyun Han, Seok-Hwan Hwang, Soo-Youn Kim, Young-Kook Kim
Принадлежит: Samsung Display Co Ltd

A compound for an organic optoelectronic device is represented by the following Chemical Formula 1. wherein R 1 , R 2 , R 3 , R 4 , Ar 1 , Ar 2 , Ar 3 , L 1 , L 2 , L 3 , n 1 , n 2 , and n 3 are further defined in the specification.

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Номер записи: 79
10-01-2019 дата публикации

Process for producing Gallium-68 through the irradiation of a solution target

Номер: US20190013108A1
Автор: ABRUNHOSA Antero, ALVES Francisco, ALVES Vítor
Принадлежит:

The present disclosure relates to a process for purifying and concentrating Ga isotope produced by the irradiation with an accelerated particle beam of a Zn target in solution. The process according to the present disclosure allows for the production of pure and concentrated Ga isotope in hydrochloric acid solution. The present disclosure also relates to a disposable cassette for performing the steps of purification and concentration of the process. 1. A process for producing and purifying Gallium radioisotope , the process comprising:irradiating a target containing a target solution comprising zinc using an accelerated particle beam;diluting the irradiated target solution with water;feeding the diluted target solution into a strong cation exchanger;washing the strong cation exchanger;eluting zinc isotopes from the strong cation exchanger with a zinc elution solution including acetone;washing the strong cation exchanger;{'sup': '68', 'eluting Gallium isotope from the strong cation exchanger with hydrochloric acid solution to obtain an eluted solution;'}feeding the eluted solution into a strong anion exchanger,washing the strong anion exchanger; and{'sup': '68', 'eluting Gallium isotope from the strong anion exchanger with hydrochloric acid solution to obtain a final solution'}wherein the irradiated target solution is diluted at least 5 volume times with water.2. The process according to claim 1 , wherein the irradiated target solution is diluted at least 10 volume times with water.3. The process according to claim 1 , further comprising:complementing the eluted solution with another hydrochloric acid solution to obtain a complemented solution, wherein the complementing is performed before feeding said the eluted solution into the strong anion exchanger.4. The process according to claim 3 , wherein the complemented solution includes a molarity in hydrochloric acid between 7 M and 10 M.5. The process according to claim 1 , wherein the accelerated particle beam is a ...

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Номер записи: 80
19-01-2017 дата публикации

DEUTERATED IBRUTINIB

Номер: US20170015670A1
Автор: Morgan Adam J., Tung Roger D.
Принадлежит:

The present invention in one embodiment provides a compound of Formula I: 2. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare each hydrogen.3. The compound of claim 1 , wherein Y claim 1 , Y claim 1 , and Yare each deuterium.413.-. (canceled)14. The compound of claim 1 , wherein each Yis hydrogen and each Yis hydrogen.15. The compound of claim 1 , wherein each Yis deuterium and each Yis deuterium.17. (canceled)18. A pharmaceutical composition comprising the compound of or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.19. A method of inhibiting BTK in a cell claim 1 , comprising contacting the cell with a compound of .20. A method of treating a disease selected from the group consisting of chronic lymphocytic leukemia claim 1 , mantle cell lymphoma claim 1 , and multiple myeloma claim 1 , comprising administering to a subject in need of such treatment a compound of .21. The compound of claim 1 , wherein the deuterium incorporation at each designated deuterium atom is at least 95%.22. The compound of claim 1 , wherein the deuterium incorporation at each designated deuterium atom is at least 97%. This application is a continuation of U.S. application Ser. No. 14/418,831, which is the U.S. National Stage of International Application No. PCT/US2013/052721, which designated the United States and was filed on Jul. 30, 2013, published in English, which claims the benefit of U.S. Provisional Application No. 61/677,307, filed on Jul. 30, 2012. The entire teachings of the above applications are incorporated herein by reference.Many current medicines suffer from poor absorption, distribution, metabolism and/or excretion (ADME) properties that prevent their wider use or limit their use in certain indications. Poor ADME properties are also a major reason for the failure of drug candidates in clinical trials. While formulation technologies and prodrug strategies can be employed in some cases to improve certain ADME ...

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Номер записи: 81
19-01-2017 дата публикации

METHOD FOR PRODUCING 4-BORONO-L-PHENYLALANINE HAVING 18F ATOM INTRODUCED THEREINTO, AND PRECURSOR OF 4-BORONO-L-PHENYLALANINE HAVING 18F ATOM INTRODUCED THEREINTO

Номер: US20170015684A1
Автор: ISHINO Yuko, KIRIHATA Mitsunori, NAKASHIMA Hideki, OHTA Yoichiro, TAGUCHI Yusuke, Takenaka Hiroshi, UEDA Sayuri, UEHARA Kohki, YOSHIKAWA Tomohiro
Принадлежит:

F-labeled 4-boronophenylalanine (BPA) can be produced by preparing and further processing a precursor of F-labeled BPA represented by the following formula: 2. The compound according to claim 1 , wherein X represents F claim 1 , and M represents an alkali metal ion claim 1 , an ammonium ion claim 1 , a tetraalkylammonium ion claim 1 , a tetraarylammonium ion claim 1 , a tetraalkylphosphonium ion claim 1 , a tetraarylphosphonium ion claim 1 , or an imidazolium ion.5. The method for producing F-labeled BPA according to claim 4 , wherein X represents F claim 4 , and M represents an alkali metal ion claim 4 , an ammonium ion claim 4 , a tetraalkylammonium ion claim 4 , a tetraarylammonium ion claim 4 , a tetraalkylphosphonium ion claim 4 , a tetraarylphosphonium ion claim 4 , or an imidazolium ion. The present invention relates to a method for producing 4-borono-L-phenylalanine having 18F atom introduced thereinto (fluorinated BPA) (BPA:4-Boronophenylalanine), and precursors thereof.At present, attention has been paid to positron emission tomography (PET) as a technique that is high in sensitivity to be excellent in quantitatively determining performance and can form images easily in light of a principle thereof. This technique has widely been used. The half value period of PET diagnostic reagents (tracers) used for diagnoses is short, and the tracers are each administrated in a fine amount so that any living body is hardly exposed to radiation based thereon. Therefore, this inspecting method is a low invasive inspecting method, thus is greatly advantageous to PET. Furthermore, PET is highly sensitive even to tumors that are not easily determined by CT (computed tomography) or MRI (magnetic resonance imaging), and tumor tissues thereof can be evaluated according to images.18F-labeled BPA, in which a 18F-fluorine atom is introduced into BPA, which is a boronated amino acid used as a boron reagent for BNCT (boron neutron capture therapy), was developed as a molecular ...

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Номер записи: 82
19-01-2017 дата публикации

ZIRCONIUM-89 OXINE COMPLEX AS A CELL LABELING AGENT FOR POSITRON EMISSION TOMOGRAPHY

Номер: US20170015685A1
Автор: Choyke Peter L., Griffiths Gary L., Sato Noriko, Wu Haitao
Принадлежит: THE UNITED STATES OF AMERICA, AS REPREESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERV

The invention provides a method of preparing a Zr-oxine complex of the formula. The invention also provides a method of labeling a cell with the Zr-oxine complex and a method for detecting a biological cell in a subject comprising administering the Zr-oxine complex to the subject. 2. The method of claim 1 , wherein the solution of oxine comprises polysorbate 80 claim 1 , dimethylsulfoxide claim 1 , ethanol claim 1 , or a combination thereof.3. The method of claim 1 , wherein the organic solvent is chloroform.4. The method of claim 1 , wherein the alkaline solution comprises sodium bicarbonate.6. (canceled)7. The method of wherein the Zr-oxine complex-labeled cells or microorganisms are washed free of non-internalized Zr.8. The method of claim 5 , wherein the cell is a healthy cell.9. The method of claim 8 , wherein the healthy cell is a T cell claim 8 , a natural killer (NK) cell claim 8 , a dendritic cell claim 8 , a macrophage claim 8 , a monocyte claim 8 , a B cell claim 8 , a myeloid cell claim 8 , a platelet claim 8 , a stem cell claim 8 , a progenitor cell claim 8 , a mesenchymal cell claim 8 , an epithelial cell claim 8 , a neural cell claim 8 , a skeletal myoblast claim 8 , or a pancreatic islet cell.10. The method of claim 5 , wherein the buffer solution further comprises a second labeling agent claim 5 , whereby the cell is labeled with both Zr-oxine complex and the second labeling agent.1113-. (canceled)15. The biological cell of claim 14 , which is further labeled with a superparamagnetic nanoparticle claim 14 , F claim 14 , or optical dye.16. A method of detecting a biological cell in a subject comprising administering to the subject the biological cell of and examining at least a portion of the subject by PET imaging claim 14 , thereby detecting the labeled biological cell in the subject.17. (canceled)18. The method of claim 16 , wherein examining at least a portion of the subject by PET imaging comprises tracking the migration of the biological cell ...

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Номер записи: 83
17-01-2019 дата публикации

DEUTERATED ANALOGS OF PRIDOPIDINE USEFUL AS DOPAMINERGIC STABILIZERS

Номер: US20190015401A1
Автор: Sonesson Clas
Принадлежит: Teva Pharmaceuticals International GmbH

The present invention provides novel deuterated analogs of Pridopidine, i.e. 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine. Pridopidine is a drug substance currently in clinical development for the treatment of Huntington's disease. 2. The deuterated analog according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1', '2, 'R-Rrepresent deuterium (D); and'}{'sup': 3', '23, 'all of R-Rrepresent hydrogen (H).'}3. The deuterated analog according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1', '7, 'at least one of R-Rrepresents deuterium (D); and'}{'sup': 1', '23, 'the remaining of R-Rrepresent hydrogen (H).'}4. The deuterated analog according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 1', '7, 'all of R-Rrepresent deuterium (D); and'}{'sup': 8', '23, 'all of R-Rrepresent hydrogen (H).'}5. The deuterated analog according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 8', '9', '10', '11, 'R, R, Rand Rrepresent deuterium (D); and'}{'sup': 1', '7', '12', '23, 'all of R-Rand R-Rrepresent hydrogen (H).'}6. The deuterated analog according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': '12', 'Rrepresents deuterium (D); and'}{'sup': 1', '11', '13', '23, 'all of R-Rand R-Rrepresent hydrogen (H).'}7. The deuterated analog according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein{'sup': 17', '20, 'R-Rrepresent deuterium (D); and'}{'sup': 1', '16', '21', '23, 'all of R-Rand R-Rrepresent hydrogen (H).'}8. A pharmaceutical composition claim 1 , comprising a therapeutically effective amount of a deuterated analog of 4-(3-methanesulfonyl-phenyl)-1-propyl-piperidine according to any one of - claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , together with at least one pharmaceutically acceptable carrier claim 1 , excipient or diluent.9. The deuterated ...

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Номер записи: 84
17-01-2019 дата публикации

DEUTERATED ANALOGS OF ETIFOXINE, THEIR DERIVATIVES AND USES THEREOF

Номер: US20190015419A1
Автор: Dasse Olivier
Принадлежит:

This invention relates to deuterated analogs of etifoxine of Formula 1, solvates, prodrugs, and pharmaceutically acceptable salts thereof, as well as to methods for their preparation and use, and to pharmaceutical compositions. Briefly, this invention is generally directed to deuterated analogs of etifoxine as well as to methods for their preparation and use, and to pharmaceutical compositions containing the same. 2. The compound of wherein the compound is: 6-chloro-N-(ethyl-d)-4-methyl-4-phenyl-4H-3 claim 1 ,1-benzoxazin-2-amine claim 1 , 6-chloro-N-(ethyl-d)-4-methyl-4-(phenyl-d)-4H-3 claim 1 ,1-benzoxazin-2-amine claim 1 , 6-chloro-N-(ethyl-d5)-4-(methyl-d3)-4-(phenyl-d5)-4H-3 claim 1 ,1-benzoxazin-2-amine or 6-chloro-N-(ethyl-1 claim 1 ,1-d2)-4-methyl-4-phenyl-4H-3 claim 1 ,1-benzoxazin-2-amine or a pharmaceutically acceptable salt claim 1 , solvate or prodrug thereof.3. The compound of claim 1 , wherein said compound is an enantiomerically pure S-etifoxine analog claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate or prodrug thereof.4. The compound of claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.5. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable excipient.6. A method of modulating the GABAreceptor complex in a subject in need thereof comprising administering to said subject an effective amount of the compound of .7. A method of increasing endogenous neurosteroid and/or neuroactive steroid levels in a subject in need thereof comprising administering to said subject an effective amount of the compound of .8. The compound of claim 1 , wherein a deuterium is present at an abundance that is at least 3340 times greater than the natural abundance of deuterium.9. The compound of claim 1 , wherein said compound is an enantiomerically pure R-etifoxine analog claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate or prodrug thereof. This application is ...

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Номер записи: 85
18-01-2018 дата публикации

DEUTERIUM-SUBSTITUTED OXADIAZOLES

Номер: US20180016244A1
Автор: CHAKMA Justin, Zhang Chengzhi
Принадлежит:

Described are deuterated modulators of S1P1 receptors, pharmaceutical compositions thereof, and methods of use thereof. 156-. (canceled)58. The compound as recited in claim 57 , wherein Ris deuterium.59. The compound as recited in claim 57 , wherein R-Rare deuterium.60. The compound as recited in claim 57 , wherein R-Rare deuterium.61. The compound as recited in claim 57 , wherein Ris deuterium.62. The compound as recited in claim 57 , wherein Rand Rare deuterium.63. The compound as recited in claim 57 , wherein R-Rare deuterium.64. The compound as recited in claim 57 , wherein R-Rare deuterium.65. The compound as recited in claim 57 , wherein R-Rare deuterium.66. The compound as recited in claim 57 , wherein Rand R-Rare deuterium.67. The compound as recited in claim 57 , wherein R-Rand R-Rare deuterium.68. The compound as recited in wherein at least one of R-Rindependently has deuterium enrichment of no less than about 10%.73. The compound as recited in claim 72 , wherein each position represented as D has deuterium enrichment of no less than about 10%.74. The compound as recited in claim 73 , wherein each position represented as D has deuterium enrichment of no less than about 10%.75. A pharmaceutical composition comprising a compound as recited in together with a pharmaceutically acceptable carrier.76. A method of treatment or prevention of a S1P1 receptor-mediated disorder comprising the administration claim 57 , to a patient in need thereof claim 57 , of a therapeutically effective amount of a compound as recited in . This application claims the benefit of U.S. Provisional Application No. 62/143,489, filed on Apr. 6, 2015, the disclosure of which is hereby incorporated by reference in its entirety.Disclosed herein are new oxadiazole compounds and compositions and their application as pharmaceuticals for the treatment or prevention of disorders. Methods of modulation of sphingosine-1-phosphate subtype 1 receptor (S1P1 receptor) activity in a subject are also ...

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Номер записи: 86
18-01-2018 дата публикации

2-(2,4,5-SUBSTITUTED ANILINE) PYRIMIDINE DERIVATIVE, PHARMACEUTICAL COMPOSITION AND USE THEREOF

Номер: US20180016258A1
Автор: JI Aining, JIANG Mingyu, Zhu Xiaoyun
Принадлежит:

Disclosed are a 2-(2,4,5-substituted aniline) pyrimidine derivative, a pharmaceutical composition and a use thereof. The pharmaceutical composition comprises a therapeutically effective amount of the 2-(2,4,5-substituted aniline) pyrimidine derivative, a solvate, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. Also disclosed is a use of the 2-(2,4,5-substituted aniline) pyrimidine derivative, a solvate, or a pharmaceutically acceptable salt thereof in the preparation of drugs for treating cancers. The compounds of the present invention have a relatively high solubility in water and a relatively high permeability, and/or a relatively low binding ability to plasma proteins, and at the same time have a relatively low toxicity characteristic and a relatively high anti-tumor activity. 2. The 2-(2 claim 1 ,4 claim 1 ,5-substituted aniline)pyrimidine derivative represented by formula I claim 1 , or the solvate claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , wherein claim 1 , the methyl substituted by 1 to 3 of deuterium atom(s) is a tri-deuterated methyl.3. The 2-(2 claim 1 ,4 claim 1 ,5-substituted aniline)pyrimidine derivative represented by formula I claim 1 , or the solvate claim 1 , or the pharmaceutically acceptable salt thereof according to claim 1 , which is selected from the group consisting of{'sub': '3', 'N-(2-{2-dimethylaminoethyl-methylamino}-4-methoxy-5-{[4-(1-(D-methyl)indol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide;'}{'sub': '3', 'N-(2-{2-dimethylaminoethyl-methylamino}-4-(D-methoxy)-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide;'}{'sub': '3', 'N-(2-{2-dimethylaminoethyl-(D-methyl)amino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide;'}{'sub': '3', 'N-(2-{2-di(D-methyl)aminoethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)-2-acrylamide;'}{'sub': '3', 'N-(2-{2-[methyl(D-methyl)amino]ethyl- ...

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Номер записи: 87
18-01-2018 дата публикации

Deuterated tic10

Номер: US20180016277A1
Автор: I. Robert Silverman
Принадлежит: Concert Pharmaceuticals Inc

This invention relates to novel imidazo[1,2-a]pyrido[3,4-e]pyrimidin-5(1H)-one compounds, and pharmaceutically acceptable salts thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions alone or in combination with other therapeutics in the treatment of diseases and conditions that are beneficially treated by administering an inducer of the gene encoding tumor necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL) superfamily member 10.

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Номер записи: 88
21-01-2021 дата публикации

METHOD FOR MANUFACTURING NOVEL NITROGEN-CONTAINING COMPOUND OR SALT THEREOF AND MANUFACTURING INTERMEDIATE OF NOVEL NITROGEN-CONTAINING COMPOUND OR SALT THEREOF

Номер: US20210015802A1
Автор: FUKUNAGA Hirofumi, Nakagawa Daisuke, SEKINE Shinichiro, SHINJO Sachiko, YAMAKAWA Takayuki
Принадлежит: FUJIFILM Corporation

A compound represented by Formula [3] or a salt thereof and a method of making the same, 2. The compound according to or a salt thereof claim 1 ,{'sup': '7', 'sub': '1-6', 'wherein Ris a Calkyl group which can be substituted or a benzyl group which can be substituted.'} This application is a Divisional of U.S. application Ser. No. 15/712,815, filed Sep. 22, 2017, which is a Continuation of National Phase of PCT International Application PCT/JP2016/059729 filed on Mar. 25, 2016, which claims priority under 35 U.S.C 119(a) to Japanese Patent Application No. 2015-062306 filed on Mar. 25, 2015. Each of the above application(s) is hereby expressly incorporated by reference, in its entirety, into the present application.The present invention relates to a method for manufacturing a novel nitrogen-containing compound or a salt thereof and a manufacturing intermediate of the compound or a salt thereof.Integrins are a kind of cell adhesion receptors which constitute a family of heterodimeric glycoprotein complexes formed of α and β subunits and are mainly involved in the cell adhesion to extracellular matrix and the transmission of information from extracellular matrix.Among the integrins, integrins ανβand ανβwhich are vitronectin receptors are known to be expressed at a low level on epithelial cells or matured endothelial cells while hyper-expressed in various tumor cells or new blood vessels. The hyper-expression of integrins ανβand ανβis considered to be involved in the exacerbation of cancer such as infiltration or metastasis accompanying tumor angiogenesis and be highly correlated to the malignancy (Nature Reviews cancer, Vol. 10, pp. 9˜23, 2010). It has been revealed that the hyper-expression of integrin is observed in cancer such as head and neck cancer, colorectal cancer, breast cancer, small cell lung cancer, non-small cell lung cancer, glioblastoma, malignant melanoma, pancreatic cancer, and prostatic cancer (Clin. Cancer Res. Vol. 12, pp. 3942˜3949, 2006). ...

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Номер записи: 89
17-01-2019 дата публикации

DEUTERATED IDEBENONE

Номер: US20190016657A1
Автор: Tung Roger D.
Принадлежит:

The present invention in one embodiment provides a compound of Formula I: 2. The compound of claim 1 , wherein each of R claim 1 , Rand Ris independently selected from CHand CD.3. The compound of claim 1 , wherein each Yis deuterium.4. The compound of claim 1 , wherein each Yis hydrogen.5. The compound of claim 1 , wherein each Yis hydrogen.6. The compound of claim 1 , wherein each Yis deuterium.7. The compound of claim 1 , wherein each Yis hydrogen.8. The compound of claim 1 , wherein each Yis deuterium.9. The compound of claim 1 , wherein Ris CH.10. The compound of claim 1 , wherein Ris CD.11. The compound of claim 1 , wherein Ris CH.12. The compound of claim 1 , wherein Ris CD.13. The compound of claim 1 , wherein Ris CH.14. The compound of claim 1 , wherein Ris CD.15. The compound of claim 1 , wherein each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; each Yis deuterium; and each Yis deuterium.19. The compound of claim 1 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.20. A pharmaceutical composition comprising the compound of or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.21. A method of reducing oxidative toxicity in mitochondria claim 1 , comprising contacting mitochondria with a compound of .22. A method of treating a condition that is Duchenne's muscular dystrophy or multiple sclerosis claim 1 , comprising administering to a subject in need of such treatment a compound of .23. The method of claim 22 , wherein the condition is primary progressive multiple sclerosis. This application is a continuation of U.S. application Ser. No. 14/414,039, filed on Jan. 9, 2015, which is the U.S. National Stage of International Application No. PCT/US2013/050302, filed on Jul. 12, 2013, published in English, which claims the benefit of U.S. Provisional Application No. 61/670,716, ...

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Номер записи: 90
21-01-2021 дата публикации

STABILISED RADIOLABELLING REACTION

Номер: US20210017098A1
Автор: CLARKE Alan P., Engell Torgrim, Grigg Julian, Jackson Alexander, KAHN Alexander Imtiaz, MCROBBIE Walter Graeme
Принадлежит:

The present invention provides a method for the synthesis of an injectable composition comprising a [F]-labelled pyridaben derivative that is advantageous over prior methods. In particular, the method of the present invention comprises a method of radiosynthesis that permits a more facile purification using solid phase extraction (SPE). 1. A method comprising reacting a precursor compound with F-fluoride in the presence of (2 ,2 ,6 ,6-Tetramethylpiperidin-1-yl)oxyl (TEMPO) to obtain an F-labelled compound wherein: {'br': None, 'BTM-LINKER-LG \u2003\u2003(I)'}, 'said precursor compound is of Formula Iwherein:BTM is an analogue of pyridaben;LINKER is an alkylene or an alkoxyalkylene; and,LG is a sulfonate-containing leaving group; and{'sup': '18', 'claim-text': {'br': None, 'sup': '18', 'BTM-LINKER-F \u2003\u2003(II)'}, 'said F-labelled compound is of Formula IIwherein BTM and LINKER are as defined for Formula I.3. The method as defined in wherein Ris Calkyl.4. The method as defined in wherein Ris methyl claim 2 , ethyl claim 2 , propyl claim 2 , n-butyl claim 2 , s-butyl claim 2 , or t-butyl.5. The method as defined in wherein Ris halo.6. The method as defined in wherein Ris chloro.7. The method as defined in wherein W is heteroalkylene.8. The method as defined in wherein W is alkoxyalkylene.11. The method as defined in wherein LG is selected from mesylate claim 1 , tosylate claim 1 , triflate claim 1 , nosylate claim 1 , or 1 claim 1 ,2-cyclic sulfate.12. The method as defined in wherein LG is tosylate.13. The method as defined in wherein said precursor compound is dissolved in acetonitrile.14. The method as defined in wherein said TEMPO is present in a molar ratio to the precursor compound of between 0.01:1 and 5:1.15. The method as defined in wherein the starting radioactivity is at least 100 GBq.16. The method as defined in wherein the starting radioactivity is between 100-1000 GBq.17. The method as defined in wherein the starting radioactivity is between 100-750 ...

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Номер записи: 91
21-01-2021 дата публикации

RADIOLABELING OF POLYPEPTIDES

Номер: US20210017099A1
Автор: Dudkin Vadim, Erhardt Joseph, GOLDBERG Shalom, McDevitt Theresa, Salter Rhys
Принадлежит:

Improved methods of radiolabeling antibodies using click chemistry are described. Also described are pharmaceutical compositions and uses related to the radiolabeled antibodies produced by the methods. 1. A method of labeling a polypeptide with a radiometal ion , the method comprising:a. providing a modified polypeptide comprising the polypeptide covalently linked to a first click reaction partner;b. providing a radiocomplex comprising the radiometal ion associated with a chelating moiety, wherein the chelating moiety comprises a chelant covalently linked to a second click reaction partner; andc. contacting the modified polypeptide with the radiocomplex under a condition to allow the first click reaction partner to react with the second click reaction partner to thereby label the polypeptide with the radiometal ion.2. The method of claim 1 , wherein one of the first and second click reaction partners comprises an alkyne group claim 1 , and the other click reaction partner comprises an azide claim 1 , or wherein one of the first and second click reaction partners comprises an alkene group claim 1 , and the other click reaction partner comprises a diene.3. The method of claim 1 , wherein the polypeptide is an antibody claim 1 , or an antigen binding fragment thereof.4. The method of claim 3 , wherein the antibody is an anti-PSMA monoclonal antibody.5. The method of claim 1 , wherein the radiometal ion is Ac claim 1 , In or Zr.6. The method of claim 1 , further comprising reacting an electrophile on a side chain with a sulfhydryl group covalently linked to the first click reaction partner to obtain the modified polypeptide.7. The method of claim 1 , wherein the modified polypeptide is a modified antibody or antigen binding fragment thereof obtained by a site-specific incorporation of the first click reaction partner.8. The method of claim 7 , wherein the modified antibody or antigen binding fragment thereof is obtained by a method comprising trimming an antibody or ...

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Номер записи: 92
16-01-2020 дата публикации

USE OF FLUORINATED DERIVATIVES OF 4-AMINOPYRIDINE IN THERAPEUTICS AND MEDICAL IMAGING

Номер: US20200017445A1
Автор: Appelbaum Daniel, Brugarolas Pedro, Chen Chin-Tu, Popko Brian
Принадлежит:

The present disclosure provides novel compounds, including compounds that bind to potassium channels, methods for their manufacture, and methods for their use, including their use to diagnose and/or assess traumatic brain injury and use to treat dymeylinating diseases, and/or in vivo imaging of the central neverous system, and to diagnose and/or assess the progression of MS or other diseases. 3. The method of claim 2 , wherein a dose is from about 0.005 to 50 mCi.4. The method of claim 2 , further comprising quantifying an amount of the compound in the subject.5. The method of claim 2 , wherein the demyelinating disease is multiple sclerosis claim 2 , spinal cord compression claim 2 , ischemia claim 2 , acute disseminated encephalomyelitis claim 2 , optic neuromyelitis claim 2 , leukodystrophy claim 2 , progressive multifocal leukoencephalopathy claim 2 , metabolic disorders claim 2 , toxic exposure claim 2 , congenital demyelinating disease claim 2 , peripheral neuropathy claim 2 , encephalomyelitis claim 2 , central pontine myelolysis claim 2 , Anti-MAG Disease claim 2 , Guillain-Barre syndrome claim 2 , chronic inflammatory demyelinating polyneuropathy claim 2 , or multifocal motor neuropathy (MMN).6. The method of claim 2 , wherein the radiodiagnostic method is Positron Emission Tomography (PET) claim 2 , PET-Time-Activity Curve (TAC) claim 2 , PET-Magnetic Resonance Imaging (MRI) claim 2 , or PET/CT.7. The method of claim 2 , wherein a demyelinated region in the subject is detected by detecting the compound.8. The method of claim 2 , wherein the compound binds to potassium channels located at a demyelinated region in an axon in the subject.10. The method of claim 9 , wherein the subject is at risk for traumatic brain injury or a concussion.11. The method of claim 9 , wherein the imaging is affected by a radiodiagnostic method.12. The method of claim 11 , wherein the radiodiagnostic method is Positron Emission Tomography (PET) claim 11 , PET-Time-Activity Curve ...

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Номер записи: 93
21-01-2021 дата публикации

USE OF FLUORINATED DERIVATIVES OF 4-AMINOPYRIDINE IN THERAPEUTICS AND MEDICAL IMAGING

Номер: US20210017133A1
Автор: Appelbaum Daniel, Brugarolas Pedro, Chen Chin-Tu, Popko Brian
Принадлежит:

The present disclosure provides novel compounds, including compounds that bind to potassium channels, methods for their manufacture, and methods for their use, including their use to diagnose and/or assess traumatic brain injury and use to treat dymeylinating diseases, and/or in vivo imaging of the central neverous system, and to diagnose and/or assess the progression of MS or other diseases. 115-. (canceled)17. The compound of claim 16 , wherein at least one hydrogen atom is a deuterium isotope.18. The compound of claim 16 , wherein the compound is [F]3-fluoro-4-aminopyridine.19. The compound of claim 16 , wherein the compound 3-[F]fluoromethyl-4-aminopyridine.20. The compound of claim 16 , wherein the compound 3-[F]fluoroethyl-4-aminopyridine.21. The compound of claim 16 , wherein the compound 3-[F]trifluoromethyl-4-aminopyridine.22. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier. This application is is a continuation of U.S. patent application Ser. No. 16/584,071 filed Sep. 26, 2019, which is a continuation of U.S. patent application Ser. No. 15/452,179 filed Mar. 7, 2017, which is a continuation of U.S. patent application Ser. No. 14/329,597 filed Jul. 11, 2014, which is a continuation-in-part of U.S. patent application Ser. No. 13/897,035 filed May 17, 2013 and PCT Application PCT/US2013/041638 filed May 17, 2013, both of which claim priority to U.S. Provisional Patent Application Ser. No. 61/648,214 filed May 17, 2012. U.S. patent application Ser. No. 14/329,597 also claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 61/845,878 filed Jul. 12, 2013. The entire contents of each of the above-referenced disclosures are specifically incorporated herein by reference without disclaimer.The present invention relates generally to the fields of biology, chemistry and medicine. More particularly, it concerns derivatives of potassium channel inhibitors, including derivatives of 4-aminopyridine, ...

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Номер записи: 94
16-01-2020 дата публикации

PET Imaging Agents

Номер: US20200017474A1
Автор: Berndt Oberhauser, Darren Le Grand, Emmanuelle Briard, Yves Auberson
Принадлежит: NOVARTIS AG

Preparation of novel 2-benzyl-5-methyl-2H-tetrazole derivatives of the formula (I) for use as PET imaging agents. The present invention relates to novel compounds of formula (I) their preparation and use as PET imaging agents for imaging techniques and diagnostics in the field of diseases and disorders mediated by or related to the enzyme autotaxin.

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Номер записи: 95
16-01-2020 дата публикации

METHODS AND REAGENTS FOR RADIOLABELING

Номер: US20200017502A1
Автор: Chiosis Gabriela, Ochiana Stefan O., Pillarsetty NagaVaraKishore, Taldone Tony
Принадлежит:

The present invention provides methods for radiolabeling compounds useful as Hsp90 inhibitors. The present invention also provides intermediates useful in such methods, and compositions of radiolabeled compounds. The present invention provides, among other things novel methods for the synthesis of radiolabeled compounds. In certain embodiments, the present invention provides compounds of formula I. 190-. (canceled)93. The method of claim 92 , wherein Z claim 92 , Z claim 92 , and Zare —N—.94. The method of claim 93 , wherein Yis —CR—.95. The method of claim 94 , wherein Yis —CR—.96. The method of claim 95 , wherein each of Ris hydrogen.97. The method of claim 96 , wherein X is —CH— or —S—.98. The method of claim 97 , wherein X is —CH—.99. The method of claim 97 , wherein X is —S—.100. The method of claim 97 , wherein Ris hydrogen.101. The method of claim 97 , wherein Ris halogen.102. The method of claim 101 , wherein Ris fluoro.103. The method of claim 96 , wherein -L-Rcomprises a methylene that is replaced with —NH— to form a secondary amine.104. The method of claim 97 , wherein L is a Caliphatic group claim 97 , wherein a methylene of the aliphatic group is replaced with —NH— to form a secondary amine.105. The method of claim 104 , wherein L is a Caliphatic group claim 104 , wherein a methylene of the aliphatic group is replaced with —NH— to form a secondary amine.108. The method of claim 96 , wherein two Rgroups are taken together with their intervening atoms to form Ring A claim 96 , wherein Ring A is a 5- to 6-membered partially unsaturated monocyclic heterocyclyl having 1-2 heteroatoms selected from oxygen claim 96 , nitrogen claim 96 , or sulfur claim 96 , 5- to 6-membered heteroaryl having 1-4 heteroatoms selected from oxygen claim 96 , nitrogen claim 96 , or sulfur claim 96 , or 6-membered aryl.109. The method of claim 108 , wherein Ring A is a 5-membered partially unsaturated monocyclic heterocyclyl having 2 heteroatoms selected from oxygen.110. The method ...

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Номер записи: 96
22-01-2015 дата публикации

Novel Aspartylamide Inhibitors of Excitatory Amino Acid Transporters

Номер: US20150023878A1
Автор: Ahmed Syed K., Bridges Richard J., Gerdes John M., PATEL Sarjubhai
Принадлежит:

The compounds of the invention are inhibitors of excitatory amino acid transporters (EAAT) that penetrate the blood-brain barrier to access the central nervous system. The compounds of the invention follow the structural formula: 2. The compound of claim 1 , wherein said halogen is fluorine.3. The compound of claim 1 , wherein said halogen or radionuclide is fluorine-18.4. The compound of claim 1 , wherein said radionuclide is selected from the group consisting of carbon-11 claim 1 , nitrogen-13 claim 1 , oxygen-15 claim 1 , fluorine-18 claim 1 , zinc-62 claim 1 , copper-62 claim 1 , gallium-68 claim 1 , germanium-68 claim 1 , strontium-82 claim 1 , technicium-94m claim 1 , iodine 124 claim 1 , or rubidium-82.5. The compound of claim 3 , wherein said fluorine-18 has a specific activity of at least 1.0 Ci/mmol.6. The compound of claim 3 , wherein said fluorine-18 has a specific activity of at least 2.0 Ci/mmol.7. The compound of in combination with a pharmaceutically acceptable excipient.11. The method of claim 10 , wherein said neuronal disorder is caused by amyotrophic lateral sclerosis claim 10 , Alzheimer's disease claim 10 , Huntington's disease claim 10 , or ALS-parkinsonism dementia complex.12. The method of claim 10 , wherein said neuronal disorder is caused by ischemia claim 10 , hypoglycemia claim 10 , spinal cord injury or traumatic brain injury.13. The method of claim 10 , wherein said halogen or radionuclide is fluorine or fluorine-18.14. The method of claim 10 , wherein said radionuclide is selected from the group consisting of carbon-11 claim 10 , nitrogen-13 claim 10 , oxygen-15 claim 10 , fluorine-18 claim 10 , zinc-62 claim 10 , copper-62 claim 10 , gallium-68 claim 10 , germanium-68 claim 10 , strontium-82 claim 10 , technicium-94m claim 10 , iodine 124 claim 10 , or rubidium-82.16. The method of claim 15 , wherein said radiographic scanner is a positron emission tomography scanner.17. The method of claim 15 , wherein said excitatory amino acid ...

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Номер записи: 97
25-01-2018 дата публикации

Disconnector Device

Номер: US20180021750A1
Автор: Dumont Philippe
Принадлежит: GE HEALTHCARE LIMITED

The present invention relates to an automated radiosynthesis device adapted for enhanced automatic disconnection of a disposable kit once a radiosynthesis has been carried out. The automated radiosynthesis device of the invention therefore reduces the time to remove the disposable kit from the radiosynthesis device and reduces radiation exposure to the operator. 21. The automated radiosynthesis device as defined in claim , wherein said plurality of connectors is selected from the group comprising fasteners , and fluidic connectors.3. The automated radiosynthesis device as defined in claim 2 , wherein said fluidic connectors are selected from the group comprising push-on type connectors luer slip connectors and luer screw connectors.41. The automated radiosynthesis device as defined in claim claim 2 , wherein said disposable kit is suitable for the synthesis of a radiotracer compound.5. The automated radiosynthesis device as defined in claim 4 , wherein said radiotracer compound is a positron-emission tomography (PET) tracer.6. The automated radiosynthesis device as defined in claim 5 , wherein said radiotracer compound is an F-labelled PET tracer.71. The automated radiosynthesis device as defined in claim claim 5 , wherein said disposable kit is a single-use cassette.81. The automated radiosynthesis device as defined in claim claim 5 , wherein said plurality of actuators is selected from the group comprising rotatable arms for stopcocks of valves claim 5 , linear actuators claim 5 , arms that press onto reagent vials and pinch valves.91. The automated radiosynthesis device as defined in claim claim 5 , wherein said moving parts of said disposable kit are selected from the group comprising reagent vials claim 5 , syringes and valves.101. The automated radiosynthesis device as defined in claim claim 5 , wherein said control unit includes software comprising instructions for a particular radiosynthesis method to be carried out on said disposable kit attached to said ...

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Номер записи: 98
10-02-2022 дата публикации

RADIOLABELED PABA AND DERIVATIVES THEREOF FOR USE AS FUNCTIONAL RENAL IMAGING AGENTS

Номер: US20220040335A1
Автор: Jain Sanjay K., Ordonez Alvaro A., Ruiz-Bedoya Camilo A.
Принадлежит:

The present invention provides positron emitter radiolabeled versions of PABA, metabolites and derivatives, with good radiochemical yield, high specific activity, high chemical and radiochemical purity and having excellent characteristics for PET imaging. The inventive composition and methods provide high quality dynamic images of the kidneys while reducing the radiation exposure. The short biological half-life of PABA, added to the short physical half-life of positron emitters such as C will also benefit patients that require multiple renography assessments in a short period of time. 1. An imaging agent for use in functional renal imaging of one or both kidneys in a subject in need thereof , characterized in that the imaging agent comprises para-amino benzoic acid (PABA) or a metabolite or derivative thereof , labeled with a positron emitting radionuclide , and wherein the imaging agent is administered to the subject in conjunction with obtaining a series of images at regular intervals of at least one or more regions of interest of the kidney of the subject for a period of time , and quantifying the amount of radioactivity in each interval during said time period.2. An imaging agent for use as in claim 1 , wherein the a positron emitting radionuclide is selected from the group consisting of C claim 1 , N claim 1 , O claim 1 , F claim 1 , K claim 1 , Ti claim 1 , Mn claim 1 , Mn claim 1 , Fe claim 1 , Co claim 1 , Cu claim 1 , Cu claim 1 , Cu claim 1 , Ga claim 1 , As claim 1 , Rb claim 1 , Sr claim 1 , Y claim 1 , and Zr.3. An imaging agent for use as in or claim 1 , wherein the PABA metabolite is selected from the group consisting of N-acetyl-PABA claim 1 , p-aminohippuric acid claim 1 , and p-acetylaminohippuric acid.5. An imaging agent for use in functional renal imaging of one or both kidneys in a subject in need thereof claim 1 , characterized in that the imaging agent comprises para-amino benzoic acid (PABA) or a metabolite or derivative thereof claim 1 , ...

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Номер записи: 99
26-01-2017 дата публикации

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

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

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

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Номер записи: 100