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Небесная энциклопедия

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

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Мониторинг СМИ

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

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 7060. Отображено 100.
16-02-2012 дата публикации

Tetracyclic terpene series compounds, methods for preparing same, uses thereof as medicines and pharmaceutical compounds containing same

Номер: US20120040930A1
Автор: Catherine Guillou, Daniel Guenard, Denyse Herlem, Françoise Khuong-Huu, Jean-Yves Lallemand, Jordi Molgo, Thibault SAUVAÎTRE
Принадлежит: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

The invention concerns a triterpene alkaloid of general formula (I). The invention also concerns a method for making same and use thereof as medicine.

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Номер записи: 1
10-05-2012 дата публикации

TGR5 Modulators and Methods of Use Thereof

Номер: US20120115832A1
Автор: Roberto Pellicciari
Принадлежит: Intercept Pharmaceuticals Inc

The invention relates to compounds of Formula A: or a salt, solvate, hydrate, or prodrug thereof. The compounds of Formula A are TGR5 modulators useful for the treatment of various diseases, including metabolic disease, inflammatory disease, liver disease, autoimmune disease, cardiac disease, kidney disease, cancer, and gastrointestinal disease.

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Номер записи: 2
26-07-2012 дата публикации

Angiogenesis inhibitors

Номер: US20120190659A1
Автор: Akiko Mammoto, Barbara Czako, Donald E. Ingber, Elias James Corey, László KÜRTI
Принадлежит: Childrens Medical Center Corp, Harvard College

Compounds of Structural Formula I or pharmaceutically acceptable salts thereof, are effective inhibitors of angiogenesis:

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Номер записи: 3
23-08-2012 дата публикации

Bile acid or bile salt fatty acid conjugates

Номер: US20120214872A1
Автор: Beatrice Gilat, Tuvia Gilat
Принадлежит: Galmed International Ltd

A method for treating a disease or disorder associated with altered glucose metabolism or insulin action in a subject in need thereof. The method includes administering to the subject a BAFAC (bile acid or bile salt fatty acid conjugate) of general formula II: W-X-G in which G is a bile acid or bile salt radical, which is optionally conjugated in position 24 with a suitable amino acid, W stands for one or two fatty acid radicals, each having from 14-22 carbon atoms, and X is a suitable bonding member or a direct C═C bond between G and each W, said suitable bonding member being selected from the group consisting of NH, O, P and S. The disease or disorder associated with altered glucose metabolism is selected from the group consisting of hyperglycemia, diabetes, insulin resistance and obesity.

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Номер записи: 4
21-03-2013 дата публикации

PROGESTERONE RECEPTOR ANTAGONISTS

Номер: US20130072464A1
Автор: Bone Wilhelm, Huwe Christoph, Klar Ulrich, Möller Carsten, Rotgeri Andrea, Schwede Wolfgang
Принадлежит: Bayer Intellectual Property GmbH

The invention relates to 17-hydroxy-17-pentafluoroethyl-estra-4,9(10)-dien-11-aryl derivatives of formula I with progesterone-antagonizing action and methods of production thereof, use thereof for the treatment and/or prevention of diseases and use thereof for producing medicinal products for the treatment and/or prevention of diseases, in particular uterine fibroids (myomata, uterine leiomyomata), endometriosis, heavy menstrual bleeding, meningiomata, hormone-dependent breast cancers and menopause-associated complaints or for fertility control and emergency contraception. 6. Compound according to in which{'sup': '9', 'Rdenotes hydrogen, methyl or ethyl and'}{'sup': '10', 'sub': 3', '2', '2', '3', '2', '2', '2', '3, 'Rdenotes —O—CH, —Cl, —COH, —COCH, —CO—NH, —SO—NH; —NH—CO—CHor —CO—NH-phenyl.'}7. A compound selected from4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzamide4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]-N,N-dimethylbenzamide(11β,17β)-17-hydroxy-11-{4-[(4-methylpiperazin-1-yl)carbonyl]phenyl}-17-(pentafluoroethyl)estra-4,9-dien-3-onetert-butyl-4-{4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzoyl}piperazine-1-carboxylate(11β,17β)-17-hydroxy-17-(pentafluoroethyl)-11-[4-(piperidin-1-ylcarbonyl)phenyl]estra-4,9-dien-3-onemethyl-1-{4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzoyl}piperidine-4-carboxylateN-[2-(dimethylamino)ethyl]-4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzamideN-[3-(dimethylamino)propyl]-4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzamideN-[2-(dimethylamino)ethyl]-4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]-N-methylbenzamidemethyl-2-({4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]benzoyl}amino)benzoate4-[(11β,17β)-17-hydroxy-3-oxo-17-(pentafluoroethyl)estra-4,9-dien-11-yl]-N-(pyridin-2-yl)benzamide4-[(11β,17β)- ...

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Номер записи: 5
25-04-2013 дата публикации

SHIP INHIBITORS AND USES THEREOF

Номер: US20130102577A1
Автор: Chisholm John D., KERR William G.
Принадлежит: The Research Foundation of the State University of New York

The present invention relates to SHIP inhibitor compounds and methods for using these compounds. In particular, the present invention discloses the following methods: (i) a method of treating graft versus host disease in a subject; (ii) a method of inhibiting a SHIP1 protein in a cell; (iii) a method of selectively inhibiting a SHIP1 protein in a cell; (iv) a method for treating or preventing graft-versus-host disease (GVHD) in a recipient of an organ or tissue transplant; (v) a method of modulating SHIP activity in a cell expressing SHIP1 or SHIP2; (vi) a method of ex vivo or in vitro treatment of transplants; (vii) a method of inhibiting tumor growth and metastasis in a subject; (viii) a method of treating a hematologic malignancy in a subject; (ix) a method of inducing apoptosis of multiple myeloma cells; (x) a method of treating multiple myeloma in a subject; (xi) a method of inhibiting the proliferation of a human breast cancer cell; and (xii) a method of treating breast cancer in a subject. 215-. (canceled)16. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a compound according to ; and'}a pharmaceutically acceptable carrier.1733-. (canceled)35. A method according to claim 34 , wherein Rand Rare each methyl claim 34 , and Rand Rare each hydrogen.36. A method according to claim 34 , wherein Rrepresents one hydrogen atom together with a 1 claim 34 ,5-dimethylhexyl group.37. A method according to claim 34 , wherein Rand Rare each hydrogen.38. A method according to claim 34 , wherein Xis selected from the group consisting of hydroxy claim 34 , mercapto claim 34 , alkoxy claim 34 , aryloxy claim 34 , alkylthio claim 34 , and arylthio.39. A method according to claim 34 , wherein Xis selected from the group consisting of alkylcarbonamido claim 34 , alkoxycarbonamido claim 34 , arylcarbonamido claim 34 , aryloxycarbonamido claim 34 , aminocarbonamido claim 34 , and hydrazinocarbonamido.40. A method according to claim 39 , ...

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Номер записи: 6
25-04-2013 дата публикации

New Steroids Having Increased Water Solubility and Resistance Against Metabolism and Methods For Their Production

Номер: US20130102578A1
Автор: Gianna Ragagnin, Torbjorn Backstrom
Принадлежит: UMECRINE AB

Steroid compounds having increased resistance against metabolism and increased water solubility are disclosed, together with methods for their production. These substances are suitable for the manufacture of pharmaceuticals for the treatment of steroid related or steroid induced CNS disorders and for use in methods of prevention, alleviation or treatment of such disorders.

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Номер записи: 7
09-05-2013 дата публикации

TANDEM FACIAL AMPHIPHILES

Номер: US20130115251A1
Автор: Chae Pil Seok, GELLMAN Samuel Helmer
Принадлежит: WISCONSIN ALUMNI RESEARCH FOUNDATION

The invention provides tandem facial amphiphiles for biochemical manipulations and characterization of membrane proteins, such as intrinsic membrane proteins. Members of this new family display favorable behavior with several membrane proteins. These amphiphiles can form relatively small micelles, and small changes in amphiphile chemical structures can result in large changes in their physical properties. The tandem facial amphiphiles can be used to aid the solubilization, isolation, purification, stabilization, crystallization, and/or structural determination of membrane proteins. 2. The compound of wherein each Ris (C-C)alkyl.3. The compound of wherein Y is a direct bond.4. The compound of wherein at least two of R claim 1 , Rand Rare O-Sac and each Sac is a disaccharide.15. The compound of wherein a plurality of the compounds form a micelle in water comprising about 6 to about 15 molecules of the compound.16. A composition comprising a plurality of compounds of and an isolated membrane protein.17. A micelle formed from a plurality of compounds of claim 1 , optionally comprising one or more drugs claim 1 , therapeutic molecules claim 1 , bioactive molecules claim 1 , polypeptides claim 1 , proteins claim 1 , genes claim 1 , or a combination thereof claim 1 , within the micelle.18. A method of solubilizing or stabilizing a membrane protein comprising contacting a membrane protein with an effective amount of a plurality of compounds as described by claim 1 , in an aqueous solution claim 1 , and optionally heating the protein and the compounds claim 1 , thereby forming a solubilized or stabilized aggregation of the compounds and the membrane protein.19. The method of wherein the aggregation of the compounds is in the form of a micelle.20. A method of extracting a protein from a lipid bilayer comprising contacting the lipid bilayer with an effective amount a plurality of compounds as described by in an aqueous solution to form a mixture claim 1 , optionally in the ...

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Номер записи: 8
16-05-2013 дата публикации

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Номер: US20130123224A1
Автор: Qian Xiangping
Принадлежит: SUZHOU NEUPHARMA CO., LTD.

Chemical entities that are bufalin derivatives, pharmaceutical compositions and methods of treatment of cancer are described. 18.-. (canceled)10. At least one chemical entity of wherein Rand Rare each independently chosen from hydrogen and optionally substituted lower alkyl.11. At least one chemical entity of wherein Rand Rare both hydrogen.12. At least one chemical entity of wherein Rand Rare joined together to form a 5- to 7-membered heterocycloalkyl ring.13. At least one chemical entity of wherein Rand Rare each independently chosen from hydrogen and optionally substituted lower alkyl.14. At least one chemical entity of wherein n is chosen from 1 claim 9 , 2 claim 9 , and 3.15. At least one chemical entity of wherein n is 1 claim 9 , and Rand Rare joined together to form a 5- to 7-membered heterocycloalkyl ring.1727.-. (canceled)28. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one chemical entity of .29. A pharmaceutical composition of wherein the composition is formulated in a form chosen from tablets claim 28 , capsules claim 28 , powders claim 28 , liquids claim 28 , suspensions claim 28 , suppositories claim 28 , and aerosols.30. (canceled)31. (canceled) This application is a divisional of U.S. application Ser. No. 13/007,516 filed Jan. 14, 2011, which claims the benefit of priority to U.S. Provisional Application No. 61/295,177, filed Jan. 15, 2010, which are incorporated herein by reference in their entirety.Provided are certain chemical entities and compositions thereof that may be useful in the treatment of cancer.Cancer can be viewed as a breakdown in the communication between tumor cells and their environment, including their normal neighboring cells. Signals, both growth-stimulatory and growth-inhibitory, are routinely exchanged between cells within a tissue. Normally, cells do not divide in the absence of stimulatory signals, and likewise, will cease dividing in the presence of inhibitory signals. In a ...

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Номер записи: 9
27-06-2013 дата публикации

4-[17BETA-METHOXY-17ALPHA-METHOXYMETHYL-3-OXOESTRA-4,9-DIEN-11-BETA-YL]BENZALDEHYDE (E)-OXIME (ASOPRISNIL)

Номер: US20130165421A1
Автор: BAHL Klaus, BOHLMANN Ulf, EILERS Robert, ERHART Bernd, GERECKE Hagen, GLIESING Sabine, GRAWE Detlef, HOESEL Peter, JACKE Jurgen, KNABE Uwe, MICHEL Thomas, MOSEBACH Michael, MUELLER Uwe, Sander Michael, TILSTAM Ulf, VOIGTLAENDER David, WEHMEIER Dieter
Принадлежит: Bayer Pharma AG

The present invention relates to a method for the reliable and reproducible preparation of 4-[17β-methoxy-17α-methoxymethyl-3-oxoestra-4,9-dien-11β-yl]benzaldehyde (E)-oxime (asoprisnil) on the pilot and manufacturing scale. Asoprisnil, which is prepared by this method, is distinguished by a very good physical stability and is therefore particularly suitable for the manufacture of solid pharmaceutical forms (tablets, coated tablets, etc.). 2. The microparticles according to claim 1 , where in the process hydroxyestradienone is converted into nordienedione ketal by ketalization with Lewis acids and either by chromic acid oxidation or Oppenauer oxidation.3. The microparticles according to claim 2 , where in the process either the hydroxyestradienone is first oxidized and then ketalized or is first ketalized and then oxidized.4. The microparticles according to claim 3 , where the process comprises carrying out the chromic acid oxidation first and a selective ketalization subsequently or the ketalization first and an Oppenauer oxidation subsequently.5. The microparticles according to claim 3 , where in the process the chromic acid oxidation is carried out as two-phase reaction between two liquid phases.6. The microparticles according to claim 5 , where in the process water claim 5 , is added to a solution of hydroxyestradienone in acetone in such a way that a defined systemic water concentration claim 5 , preferably of 10-15% by weight claim 5 , is set up claim 5 , with the steroid concentration not exceeding 8 g/l of acetone.7. The microparticles according to and claim 5 , where the ketalization is carried out first.8. The microparticles according to claim 7 , where in the process the ketalization takes place in a bypass method.9. The microparticles according to claim 3 , where in the process the Oppenauer oxidation takes place with catalysis by aluminium diisopropoxide trifluoroacetate (DIPAT).10. The microparticles according to claim 1 , where in the process ...

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Номер записи: 10
25-07-2013 дата публикации

Anti-Diabetic Compounds

Номер: US20130190280A1
Автор: John Soong
Принадлежит: SEN CAPITAL LLC

The preset invention relates to a new oral anti-diabetic compound prepared by synthesizing a steroid and a guanide or biguanide, which is eliminated via the hepatic route, instead of the renal route, to avoid adverse effects of Metformin, such as renal dysfunction. A pharmaceutical composition comprising the compound of the invention and the method for treating diabetes using the compound are also provided.

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Номер записи: 11
15-08-2013 дата публикации

PROGESTERONE ANALOGS AND USES RELATED THERETO

Номер: US20130210785A1
Автор: Guthrie David B., Liotta Dennis C., Lockwood Mark A., Natchus Michael G., Sayeed Iqbal, Stein Donald G.
Принадлежит: EMORY UNIVERSITY

This disclosure relates to progesterone derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation resulting from traumatic brain injury or stroke. 3. The compound of claim 1 , wherein Ris alkyl substituted with a heterocyclyl further optionally substituted with one or more claim 1 , the same or different R.5. The compound of claim 4 , wherein Ris heterocyclyl or alkyl substituted with a group selected from amino and heterocyclyl claim 4 , wherein Ris optionally substituted with one or more claim 4 , the same or different claim 4 , R.7. The compound of claim 6 , wherein Rand Ris morpholinyl claim 6 , pyrrolidinyl claim 6 , piperidinyl claim 6 , or piperazinyl ring optionally substituted with one or more claim 6 , the same or different claim 6 , R.10. The compound of wherein claim 9 , Rand Ris morpholinyl claim 9 , pyrrolidinyl claim 9 , piperidinyl claim 9 , or piperazinyl ring optionally substituted with one or more claim 9 , the same or different claim 9 , R.11. The compound of selected from:17-(1-(hydroxyimino)ethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;17-(1-(methoxyimino)ethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;10,13-dimethyl-17-(1-((2-morpholinoethoxy)imino)ethyl)-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;17-(1-(acetoxyimino)ethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;17-(1-(((2-amino-3-methylbutanoyl)oxy)imino)ethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;10,13-dimethyl-17-(1-(((pyrrolidine-2-carbonyl)oxy)imino)ethyl)-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one;2-((((1-(10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a] ...

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Номер записи: 12
22-08-2013 дата публикации

Zwitterionic lipids

Номер: US20130216607A1
Автор: Colin Walsh, Emily Perttu, Francis C. Szoka, Jr., Juliane Nguyen, Vincent Venditto
Принадлежит: UNIVERSITY OF CALIFORNIA

In various embodiments, the present invention provides zwitterionic lipids, encapsulants incorporating these zwitterionic lipids and such encapsulants encapsulating one or more bioactive agent. An exemplary bioactive agent is a nucleic acid. Also provided are pharmaceutical formulations of the encapsulants and methods of using such formulations to deliver a bioactive agent to a subject in treating or diagnosing disease in that subject.

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Номер записи: 13
05-09-2013 дата публикации

Modified drugs for use in liposomal nanoparticles

Номер: US20130230582A1
Автор: Igor Jigaltsev, Marcel Bally, Marco Ciufolini, Norbert Maurer, Pieter Cullis
Принадлежит: The University of British Columbia

Drug derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drug derivatized with a weak-base moiety that facilitates active loading of the drug through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drug to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drug derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drugs.

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Номер записи: 14
03-10-2013 дата публикации

METHODS FOR PREPARING SYNTHETIC BILE ACIDS AND COMPOSITIONS COMPRISING THE SAME

Номер: US20130261317A1
Автор: Moriarty Robert M., Rao Photon
Принадлежит: Kythera Biopharmaceuticals, Inc.

This invention relates generally to methods for preparing certain bile acids from non-mammalian sourced starting materials as well as to synthetic bile acids and compositions comprising such acids wherein the acids are characterized by a different Cpopulation than naturally occurring bile acids as well as being free from any mammalian pathogens. This invention is also directed to the synthesis of intermediates useful in the synthesis of such bile acids. Accordingly, the C ring of the steroidal scaffold is oxidized to provide a synthetic route and intermediates to DCA. This invention also provides synthetic methods for preparing deoxycholic acid or a salt thereof starting from aromatic steroids such as estrogen, equilenin, and derivatives thereof. This invention is also directed to intermediates such as 12-oxo or delta-9,11-ene steroids as well as novel processes for their preparation. In preferred embodiments, bile acids are provided herein which have substituents on the B-ring and/or D-ring side chain and optionally on the hydroxy group of the A-ring. 8. (canceled)10. (canceled)1321-. (canceled)2644-. (canceled) This invention relates generally to methods for preparing certain bile acids from non-mammalian sourced starting materials as well as to synthetic bile acids and compositions comprising such acids. In some cases, the acids are characterized by a different Cpopulation than naturally occurring bile acids. Importantly, the bile acids of the present invention are not isolated from mammals and microbial organisms naturally producing these acids and thus are free of any toxins and contaminants associated with such organisms. This invention is also directed to novel intermediates of bile acids and methods of making them. Accordingly, the C ring of a steroidal scaffold, preferably that of an aromatic or an A,B-trans steroid, is oxidized to provide synthetic routes and intermediates to bile acids. Thus, e.g., this invention provides synthetic methods for preparing a ...

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Номер записи: 15
10-10-2013 дата публикации

Derivatives of steroid benzylamines, having an antiparasitic antibacterial, antimycotic and/or antiviral action

Номер: US20130266645A1
Автор: Bruno SCHÖNECKER, Katja Becker, Reimar Krieg
Принадлежит: Justus Liebig Universitaet Giessen

The present invention relates to compounds derived from steroids of the general formula (I) wherein L represents a linker and R # represents a steroid residue, the use of compounds of the general formula (I) in medicine and for the prophylaxis and/or the treatment of infectious diseases. Furthermore described are pharmaceutical compositions containing at least one compound of the general formula (I). A further aspect of the invention relates to the synthesis of said compounds of the general formula (I).

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Номер записи: 16
10-10-2013 дата публикации

AMPHIPHILIC COMPOUNDS

Номер: US20130266656A1
Автор: Chae Pil Seok, GELLMAN Samuel Helmer, Kobilka Brian, Rasmussen Søren
Принадлежит: WISCONSIN ALUMNI RESEARCH FOUNDATION

Bringing membrane proteins into aqueous solution generally requires the use of detergents or other amphiphilic agents. The invention provides a new class of amphiphiles, each of which includes a multi-fused ring system as a lipophilic group. These new amphiphiles confer enhanced stability to a range of membrane proteins in solution relative to conventional detergents, leading to improved structural and functional stability of membrane proteins, including integral membrane proteins. Accordingly, the invention provides new amphiphiles for biochemical manipulations and characterization of membrane proteins. These amphiphiles display favorable behavior with membrane proteins and can be used to aid the solubilization, isolation, purification, stabilization, crystallization, and/or structural determination of membrane proteins. 2. The compound of wherein Ris methyl.3. The compound of wherein each Sac is an oxygen-linked monosaccharide.4. The compound of wherein each Sac is an oxygen-linked disaccharide.5. The compound of wherein each Sac is an oxygen-linked trisaccharide.6. The compound of wherein X is NH claim 1 , Y is O claim 1 , Z is H claim 1 , and L is a direct bond.7. The compound of wherein L is —CH— claim 1 , X is O claim 1 , Y is absent claim 1 , and Z is Me.8. The compound of wherein L is a direct bond claim 1 , X is a direct bond claim 1 , Y is absent claim 1 , and Z is H.12. The compound of wherein the optional double bond is present.13. The compound of wherein each Sac is an oxygen-linked monosaccharide.14. The compound of wherein each Sac is an oxygen-linked disaccharide.15. The compound of wherein each Sac is an oxygen-linked trisaccharide.16. The compound of wherein X is NH claim 11 , Y is O claim 11 , Z is H claim 11 , and L is a direct bond.17. The compound of wherein L is —CH— claim 11 , X is O claim 11 , Y is absent claim 11 , and Z is Me.18. The compound of wherein L is a direct bond claim 11 , X is a direct bond claim 11 , Y is absent claim 11 , and ...

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Номер записи: 17
24-10-2013 дата публикации

STEROIDS HAVING INCREASED WATER SOLUBILITY AND RESISTANCE AGAINST METABOLISM AND METHODS FOR THEIR PRODUCTION

Номер: US20130281421A1
Автор: Bäckström Torbjörn, Ragagnin Gianna
Принадлежит:

Steroid compounds having increased resistance against metabolism and increased water solubility are disclosed, together with methods for their production. These substances are suitable for the manufacture of pharmaceuticals for the treatment of steroid related or steroid induced CNS disorders and for use in methods of prevention, alleviation or treatment of such disorders. 18-. (canceled)9. A compound which is 3α-ethynyl , 3β-hydroxyl , androstan-17-one oximeor a pharmaceutically acceptable salt, prodrug or solvate thereof.1016-. (canceled)17. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to and a pharmaceutically acceptable carrier.1820-. (canceled)21. A method for the treatment of a CNS disorder claim 9 , wherein a compound according to is administered to a patient in need thereof.2025-. (canceled) This application claims priority to U.S. Provisional Application Ser. No. 60/860,658 filed Nov. 21, 2006, which is hereby incorporated by reference in its entirety.The present invention concerns novel steroid compounds that act on the gamma-aminobutyric acid receptor-chloride ionophore (GABA-R) complex, and which can be used in the treatment of GABA and GABA-steroid related and/or steroid induced disorders of the central nervous system (CNS).The metabolites of progesterone, desoxycorticosterone, testosterone, androstenedione cortisone and cortisol known as androstanolones and pregnanolones have been the subject of various studies, at least partially elucidating their role in the neurological signal system in mammals. The nomenclature differs in the field and therefore the IUPAC nomenclature will be used throughout this application. The steroids inducing CNS symptoms and disorders of interest in the present application all share a common feature in comprising a 3α-hydroxy group, a 5α or 5β pregnane steroid body, and a ketone on position 20. Examples of such steroids are given in table 1:To the best knowledge of the ...

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Номер записи: 18
14-11-2013 дата публикации

Compounds and methods for treating neoplasia

Номер: US20130303500A1
Автор: Konstantinos Alevizopoulos, Theodora Calogeropoulou
Принадлежит: Medexis SA

The invention features compounds, pharmaceutical compositions and methods useful for the treatment of neoplasia. In particular embodiments, the compounds of the invention are useful for the treatment of multidrug resistant neoplasia.

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Номер записи: 19
19-12-2013 дата публикации

PREGNANOLONE DERIVATIVES SUBSTITUTED IN 3ALPHA-POSITION WITH THE CATIONIC GROUP, METHOD OF THEIR PRODUCTION, USAGE AND PHARMACEUTICAL PREPARATION INVOLVING THEM

Номер: US20130338383A1
Автор: Borovska Jirina, Chodounska Hana, Kapras Vojtech, Rambousek Lukas, Stuchlik Ales, Vales Karel, Vyklicky Ladislav, Vyklicky Vojtech
Принадлежит:

Pregnanolone derivatives, substituted in 3 alpha-position with the cationic group, of general formula I, and a method of the production of these compounds and their utilization for treatment of neuropsychiatric disorders related to imbalance of glutamatergic neurotransmitter system, such as ischemic damage of CNS, neurodegenerative changes and disorders of CNS, affective disorders, depression, post traumatic stress disorder, and other diseases related to stress, anxiety, schizophrenia, and psychotic disorders, pain, addictions, multiple sclerosis, epilepsy, and gliomas. The compounds are also used for production of veterinary and human pharmaceutical preparation for treatment of above mentioned diseases and for production of pharmaceutical preparations containing these compounds. 3. Method of production according to claim 2 , wherein the reaction mixture is mixed from 10 to 12 h claim 2 , acetonitrile is used as organic solvent claim 2 , the product is purified by crystallization claim 2 , or by chromatography on the silica gel column and in case of removing a protecting group preferably the mixture of acetic acid and methanol is used and the time of hydrogenation is preferably 72 hours.4. Method of production according to claim 2 , wherein the protecting group of arginine structure of the compound of general formula I claim 2 , being benzyloxycarbonyl group or (2 claim 2 ,2 claim 2 ,4 claim 2 ,6 claim 2 ,7-pentamethyl-dihydrobenzofuran-5-sulfonyl) group claim 2 , is removed by trifluoroacetic acid treatment of the protected derivative; the reaction mixture is allowed to react from 16 to 72 hours at temperatures from 0° to 50° C. claim 2 , then the mixture is poured into saturated solution of sodium or potassium bicarbonate and the product is extracted with an organic solvent in which is well soluble claim 2 , chosen from a group claim 2 , including chloroform claim 2 , dichloromethane or dichloroethane; collected organic phases are washed with 5% aqueous ...

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Номер записи: 20
02-01-2014 дата публикации

BIOSURFACE ENGINEERING

Номер: US20140004499A1
Автор: Bovin Nicolai Vladimirovich, Formanovsky Andrey Alfredovich, Henry Stephen Micheal, PARKER Stephen Robert, Popova Inna Stanislavovna
Принадлежит:

The invention relates to methods of localizing biofunctional moieties (F) to surfaces and synthetic constructs of the general structure F-S-S′ for use in such methods. F is the biofunctional moiety, S is a spacer covalently linking F to S′, and S′ is sterol. In particular, the invention relates to the preparation of biofunctional surfaces and surface modified biological structures including cells (kodecytes), enveloped viruses (kodevirions) and liposomes or virosomes (kodesomes). 138-. (canceled)39. A method of localizing a hydrophilic biofunctional moiety (F) to a surface comprising the step of contacting the surface with an aqueous solution of a water dispersible construct of the structure F-S-S′ where F is the biofunctional moiety , S is a spacer covalently linking F to S′ , and S′ is steryl.40. The method of where the biofunctional moiety (F) is selected from the group consisting of: biotin and O-linked oligosaccharides.41. The method of where the biofunctional moiety (F) is an oligosaccharide selected from the group consisting of: GalNAcα3 (Fucα2) Galβ-; Galα3 (Fucα2) Galβ-; GalNα3 (Fucα2) Galβ-; Fucα2Galβ-; Galβ4GlcNAcβ3 (Galβ4GlcNAcβ6) Galβ-; Galβ4GlcNAcβ3-; Galβ4Glcβ-; Galβ3GlcNAcβ-; Galβ3 (Fucα4) GlcNAcβ-; Fucα2Galβ3(Fucα4)GlcNAcβ-; GalNAcα3 (Fucα2)Galβ3 (Fucα4) GlcNAcβ-; Galα3 (Fucα2) Cairn (Fucα4) GlcNAcβ-; Galβ4 (Fucα3) GlcNAcβ-; Fucα2Galβ4 (Fucα3) GlcNAcβ-; NeuAca2-3Galβ3 (Fucα4) GlcNAcβ-; NeuAcα2-3Galβ4 (Fucα3) GlcNAcβ-; GalNAcβ4 (NeuAcα2-3) Galβ4-; Galβ3GalNAcα-; NeuAcα2-3Galβ4-; NeuAcα2-6Gal8β-; Galα4Galβ4-; GalNAcβ3Galα4Galβ4-; Galα4Galβ4GlcNAcβ3-; Galβ3GalNAcβ3Galα4-; NeuAcα2-3Galβ3GalNAcβ3Galα4-; Galα3Galβ-; GalNAcα3GalNAcβ3Galα4-; GalNAcβ3GalNAcβ3Galα4-; Galβ1-4GlcNAc; Galβ1-3GlcNAc; SAα2-6Galβ1-4Glc; SAα2-3Galβ1-4Glc; SAα2-6Galβ1-4GlcNAc; SAα2-3Galβ1-4GlcNAc; SAα2-3Galβ1-3GlcNAc; Galβ1-4 (Fucα1-3) GlcNAc; Galβ1-3 (Fucα1-3) GlcNAc; SAα2-3Galβ1-3 (Fucα1-4) GlcNAc; SAα2-3Galβ1-4 (Fucα1-3) GlcNAc; Galβ1-4GlcNAcβ1-4GlcNAc; Galβ1-3GlcNAcβ1-4GlcNAc; SA ...

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Номер записи: 21
02-01-2014 дата публикации

AMINOALKYLSTEROL COMPOUNDS WITH ANTITUMORAL AND NEUROPROTECTIVE ACTIVITY

Номер: US20140005156A1
Автор: de Medina Philippe, Poirot Marc, Poirot Sandrine
Принадлежит: Institut National de la Sante et de la Recherche Medicale (INSERM)

Sterol derivatives of formula (I) and a method for the production of the compounds, a medicament using one of the compounds and a pharmaceutical composition comprising the medicament. 2. The sterol-based compound of formula (I) as claimed in wherein:Z is in position 5 and represents OH; andR is in position 6 and represents the substituent{'sub': 0', '1, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'of formula -QQas defined in .'}3. The sterol-based compound of formula (I) as claimed in claim 1 , wherein the bond between carbons Cand Cis a double bond claim 1 , R═NH—(CH)—NH—(CH)—NHand T=T=T=H.4. The sterol-based compound of formula (I) as claimed in wherein the bond between carbons Cand Cis a double bond claim 1 , T=T=T=H and R═NH—(CH)—NH—(CH)—NH—(CH)—NH.6. The sterol-based compound of formula (I) as claimed in wherein the bond between carbons Cand Cis a double bond claim 1 , T=T=T=H and R═—NH—(CH)—NH.7. The sterol-based compound of formula (I) as claimed in wherein the bond C-Cis a double bond claim 1 , T=T=T=H and R═—NH—(CH)—O—(CH)—O—(CH)—NH.8. The sterol-based compound of formula (I) as claimed in wherein the bond C-Cis a single bond claim 1 , Z represents OH in position 5 claim 1 , T=T=T=H and R is in position 6 and R═—NH—(CH)—NH—(CH)—NH—(CH)—NH.12. The sterol-based compound of formula (I) as claimed in wherein the bond C-Cis a single bond claim 1 , Z represents OH in position 5 claim 1 , T=T=T=H and R is in position 6 and represents R═NH—(CH)—NH—(CH)—NH.13. The sterol-based compound of formula (I) as claimed in selected from the group consisting of:cholestane-3β,5α diol-6β-N-[1-N1-(3-aminopropyl)butane-1,4-diamine];cholestane-3β,5α diol-6β-N-[N,N′-bis(3-aminopropyl)butane-1,4-diamine];cholest-7-ene-3β,5α diol-6β-N-[1-N-1-(3-aminopropyl)butane-1,4-diamine];cholest-7-ene-3β,5α diol-6β-N-[N,N′-bis(3-aminopropyl)butane-1,4-diamine];cholest-7-ene-3β,5α diol-6β-N-[2-ethylamino-(1H-imidazol-4-yl)];cholestane-3β,5α diol-6β-N-[2-ethylamino(1H-imidazol-4-yl)];cholest- ...

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Номер записи: 22
09-01-2014 дата публикации

LOCALLY ACTIVE "SOFT" ANTIANDROGENS

Номер: US20140011785A1
Автор: Hochberg Richard
Принадлежит: YALE UNIVERSITY

The present invention relates to antiandrogenic compounds which may be administered for the treatment of androgen excess in the skin and by way of consequence, the treatment of acne, baldness or hirsuitism in subject or patient. These compounds have the general chemical structure I, II, III or IV: 3. The compound according to claim 1 , wherein n is 1 or 2.4. The compound according to having the chemical structure I claim 1 , wherein R is a C-Calkyl group.5. The compound according to having the chemical structure II claim 1 , wherein R′ is a C-Calkyl group.6. The compound according to having the chemical structure III claim 1 , wherein j is 2 or 3.7. The compound according to having the chemical structure IV claim 1 , wherein Ris an optionally substituted Cor Calkyl group.8. The compound according to having the chemical structure II claim 1 , wherein R′ is an ethyl group.9. The compound according to having the chemical structure III claim 1 , wherein n is 1 or 2 and j is 2 or 3.17. The compound according to wherein Rand Rare independently H or a C-Calkyl group.18. The compound according to wherein Rand Rare each independently H or CH.19. A pharmaceutical composition comprising an effective amount of a compound according to in combination with a pharmaceutically acceptable carrier claim 1 , additive or excipient.20. The composition according to in topical dosage form.21. A method of treating acne in a patient in need thereof comprising administering an effective amount of a composition according to to said patient.22. A method of treating baldness in a patient in need thereof comprising administering an effective amount of a composition according to to said patient.23. The method according to wherein said baldness is female pattern baldness.24. The method according to wherein said baldness is male pattern baldness.25. A method of treating hirsutism in a patient in need thereof comprising administering an effective amount of a composition according to to said patient. ...

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Номер записи: 23
09-01-2014 дата публикации

STEROIDS HAVING INCREASED WATER SOLUBILITY AND RESISTANCE AGAINST METABOLISM AND METHODS FOR THEIR PRODUCTION

Номер: US20140011792A1
Автор: Bäckström Torbjörn, Ragagnin Gianna
Принадлежит: UMECRINE AB

Steroid compounds having increased resistance against metabolism and increased water solubility are disclosed, together with methods for their production. These substances are suitable for the manufacture of pharmaceuticals for the treatment of steroid related or steroid induced CNS disorders and for use in methods of prevention, alleviation or treatment of such disorders. 1. A compound which is 3β-ethynyl , 3α-hydroxyl , 5α-pregnan-20-one oximeor a pharmaceutically acceptable salt, prodrug or solvate thereof214-. (canceled)15. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to and a pharmaceutically acceptable carrier.1618-. (canceled)19. A method for the treatment of a CNS disorder claim 1 , wherein a compound according to is administered to the patient in need thereof.2025-. (canceled) This application claims priority to U.S. Provisional Application Ser. No. 60/860,658 filed Nov. 21, 2006, which is hereby incorporated by reference in its entirety.The present invention concerns novel steroid compounds that act on the gamma-aminobutyric acid receptor-chloride ionophore (GABA-R) complex, and which can be used in the treatment of GABA and GABA-steroid related and/or steroid induced disorders of the central nervous system (CNS).The metabolites of progesterone, desoxycorticosterone, testosterone, androstenedione cortisone and cortisol known as androstanolones and pregnanolones have been the subject of various studies, at least partially elucidating their role in the neurological signal system in mammals. The nomenclature differs in the field and therefore the IUPAC nomenclature will be used throughout this application. The steroids inducing CNS symptoms and disorders of interest in the present application all share a common feature in comprising a 3α-hydroxy group, a 5α or 5β pregnane steroid body, and a ketone on position 20. Examples of such steroids are given in table 1:To the best knowledge of the inventors, all ...

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Номер записи: 24
09-01-2014 дата публикации

NEW STEROIDS HAVING INCREASED WATER SOLUBILITY AND RESISTANCE AGAINST METABOLISM, AND METHODS FOR THEIR PRODUCTION

Номер: US20140011793A1
Автор: Bäckström Torbjörn, Ragagnin Gianna
Принадлежит: UMECRINE AB

Steroid compounds having increased resistance against metabolism and increased water solubility are disclosed, together with methods for their production. These substances are suitable for the manufacture of pharmaceuticals for the treatment of steroid related or steroid induced CNS disorders and for use in methods of prevention, alleviation or treatment of such disorders. 214-. (canceled)15. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to and a pharmaceutically acceptable carrier.1618-. (canceled)19. A method for the treatment of a CNS disorder claim 1 , wherein a compound according to is administered to a patient in need thereof.2025-. (canceled) This application claims priority to U.S. Provisional Application Ser. No. 60/860,658 filed Nov. 21, 2006, which is hereby incorporated by reference in its entirety.The present invention concerns novel steroid compounds that act on the gamma-aminobutyric acid receptor-chloride ionophore (GABA-R) complex, and which can be used in the treatment of GABA and GABA-steroid related and/or steroid induced disorders of the central nervous system (CNS).The metabolites of progesterone, desoxycorticosterone, testosterone, androstenedione cortisone and cortisol known as androstanolones and pregnanolones have been the subject of various studies, at least partially elucidating their role in the neurological signal system in mammals. The nomenclature differs in the field and therefore the IUPAC nomenclature will be used throughout this application. The steroids inducing CNS symptoms and disorders of interest in the present application all share a common feature in comprising a 3α-hydroxy group, a 5α or 5β pregnane steroid body, and a ketone on position 20. Examples of such steroids are given in table 1:To the best knowledge of the inventors, all compounds described as novel in the description and examples are previously non-disclosed. Other steroids for the treatment of CNS disorders ...

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Номер записи: 25
09-01-2014 дата публикации

SYNTHESIS OF ABIRATERONE AND RELATED COMPOUNDS

Номер: US20140011992A1
Автор: Gallo Nieto Francisco Javier, Lorente Bonde-Larsen Antonio, Perez Encabo Alfonso, Sandoval Rodriguez Celso Miguel, Turiel Hernandez Jose Angel
Принадлежит: CRYSTAL PHARMA, S.A.U.

The present invention relates to processes for obtaining abiraterone and derivatives thereof, such as abiraterone acetate, by means of a Suzuki coupling through a steroid borate of general formula (IV) or a C—C coupling through a steroid hydrazone of general formula (II), as well as to intermediates useful in said processes. 2. The process according to claim 1 , wherein the palladium catalyst is selected from Pd(PPh) claim 1 , Pd(dba) claim 1 , Pd(OAc) claim 1 , Pd(PPh)Cl claim 1 , Pd(dppe)Cl claim 1 , Pd(dppf)Cl claim 1 , Pd(dppf)Cl.CHCl claim 1 , Pd(dcypp)Cl claim 1 , Pd(PhCN)Cland Pd(CHCN)Cl.3. The process according to any claim 1 , wherein the base is selected from alkaline and alkaline earth metal carbonates claim 1 , bicarbonates claim 1 , phosphates claim 1 , acetates claim 1 , alkoxides claim 1 , hydroxides and halides.4. The process according to claim 1 , wherein the process is performed in the presence of a solvent or mixture of solvents selected from THF claim 1 , toluene and water; or THF and water; or water.7. The process according to claim 6 , wherein the palladium catalyst is selected from Pd(dba) claim 6 , Pd(PPh) claim 6 , Pd(dppf)Cl.CHCl claim 6 , Pd(dcypp)Cl claim 6 , PdCl(CNMe) claim 6 , Pd(OH)and Pd(OAc).8. The process according to claim 7 , further comprising the addition of a ligand to the reaction media claim 7 , said ligand being preferably selected from X-phos (2-dicyclohexylphosphino-2′ claim 7 ,4′ claim 7 ,6′-triisopropylbiphenyl) claim 7 , dppp (1 claim 7 ,4-bis(diphenylphosphino)butane) claim 7 , S-phos (2-dicyclohexylphosphino-2′ claim 7 ,6′-dimethoxybiphenyl) claim 7 , dppm (1 claim 7 ,1-bis(diphenylphosphino)-methane) claim 7 , dippe (1 claim 7 ,2-bis(diisopropylphosphino)ethane claim 7 , dmpe (1 claim 7 ,2-Bis(dimethylphosphino)ethane and dppe (1 claim 7 ,2-bis(diphenylphosphino)ethane.9. The process according to claim 6 , wherein the base is selected from alkoxides and carbonates of alkaline and alkaline earth metals claim 6 , ...

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Номер записи: 26
23-01-2014 дата публикации

Steroids as Agonists for FXR

Номер: US20140024631A1
Автор: Pellicciari Roberto
Принадлежит: Intercept Pharmaceuticals, Inc.

The invention relates to compounds of formula (I): 2. 3α ,7α-Dihydroxy-6α-ethyl-5β-cholan-24-oic acid or a pharmaceutically acceptable salt , solvate or amino acid conjugate thereof.5. A compound according to claim 1 , wherein said compound is an FXR agonist.6. A pharmaceutical formulation comprising a compound according to and a pharmaceutically acceptable carrier or diluent.7. A method for the prevention or treatment of an FXR mediated disease or condition in a mammal comprising administering to a mammal suffering from an FXR mediated disease or condition a therapeutically effective amount of a compound according to .8. A method for the prevention or treatment of cardiovascular disease in a mammal comprising administering to a mammal suffering from a cardiovascular disease a therapeutically effective amount of a compound according to .9. The method according to claim 8 , wherein said cardiovascular disease is atherosclerosis.10. A method for increasing HDL cholesterol in a mammal claim 1 , said method comprising administering to a mammal whose HDL cholesterol is to be increased a therapeutically effective amount of a compound according to .11. A method for lower triglycerides in a mammal claim 1 , said method comprising administering to a mammal whose triglycerides are to be increased a therapeutically effective amount of a compound according to .12. A method for the prevention or treatment of cholestatic liver disease in a mammal comprising administering to a mammal suffering from cholestatic liver disease a therapeutically effective amount of a compound according to .13. A radiolabeled compound according to .14. The compound of claim 13 , wherein said compound is tritiated.15. A pharmaceutical formulation claim 1 , comprising a compound according to and a pharmaceutically acceptable carrier or diluent claim 1 , for the prevention or treatment of an FXR mediated disease or condition.16. A pharmaceutical formulation claim 1 , comprising a compound according to and ...

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Номер записи: 27
13-02-2014 дата публикации

Reducing Risk of Contracting Clostridium-Difficile Associated Disease

Номер: US20140045808A1
Автор: Abel-Santos Ernesto, Howerton Amber
Принадлежит:

A method of treating a patient to reduce risk of developing -associated disease or reducing existing -associated disease in a mammalian subject involves administering to a mammalian subject an effective amount of a germination-inhibiting compound derived from taurocholate. Novel compounds of this class are also provided. 1Clostridium difficileClostridium difficile. A method of treating a patient to reduce risk of developing -associated disease or reducing existing -associated disease in a mammalian subject comprising administering to a mammalian subject an effective amount of a germination-inhibiting compound derived from taurocholate.4. The method of wherein the compound derived from taurocholate consists of a compound selected from the group consisting of:2-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino]ethanesulfonic acid1-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino]methanesulfonic acid3-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino]propanesulfonic acid4-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino]benzenesulfonic acid1-[(3α,7α,12α-Trihydroxy-24-oxo-5β-cholan-24-yl)amino]benzenesulfonic acid3-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino]benzenesulfonic acid2-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino]ethanesulfinic acid3α,7α,12α-Trihydroxy-5β-cholan-24-oic acid N-(carboxymethyl)amide1-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino]methanecarboxylic acid2-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino]ethanecarboxylic acid6-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino]-(4-amido)hexanecarboxylic acid3-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino]propanecarboxylic acid8-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino]-(5-amido)octanecarboxylic acid; and2-[(3α,7α,12α-trihydroxy-5β-cholan-24-oyl)oxy]ethanesulfonic acid7. The compound of wherein the compound derived from taurocholate consists of a compound selected from the group consisting of:2-[(3α,7α,12α-trihydroxy-24-oxo-5β-cholan-24-yl)amino] ...

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Номер записи: 28
27-03-2014 дата публикации

INHIBITORS OF 17Beta-HSD1, 17Beta-HSD3 AND 17Beta-HSD10

Номер: US20140088053A1
Автор: Donald Poirier, Jenny Roy, Rene Maltais
Принадлежит: UNIVERSITE LAVAL

The present application discloses 17β hydroxy steroid dehydrogenase (17β HSD) type 1, 3, 10 inhibitors and use thereof (alone and in combination) in the treatment of cancer and other afflictions. 17β HSD1 inhibitors include estradiol derivatives with a nieta-carbamoylbenzyl substituent at C 16. 17β HSD3/HSD10 inhibitors include androsterone derivatives substituted at the C3 position with a sulfonamide piperazine. Also disclosed are compounds that are inhibitors of both 17β HSD1 and 17β HSD3 that have a spiro-morpholine substituent at C20.

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Номер записи: 29
27-03-2014 дата публикации

METHOD OF TREATING DISORDER RELATED TO HIGH CHOLESTERAL CONCENTRATION

Номер: US20140088060A1
Автор: DAI QING, Liao Shutsung, Song Ching
Принадлежит: University of Chicago

A method of treating a disorder related to a high cholesterol concentration, comprising administering to a subject in need thereof a compound of formula (I): 2. The method of claim 1 , whereinX, Y, and Z are independently haloalkyl or —OR′.3. The method of claim 1 , wherein{'sub': 1', '2', '3', '4', '5', '6', '7', '11', '12', '15', '16', '20, 'R, R, R, R, R, R, R, R, R, R, R, and Rare independently hydrogen, alkyl, or hydroxy;'}{'sub': 8', '9', '10', '13', '14, 'R, R, R, R, and Rare independently hydrogen, alkyl, or hydroxyl; and'}X, Y, and Z are independently alkyl, haloalkyl, or hydroxyl.4. The method of claim 3 , wherein{'sub': 1', '2', '4', '5', '7', '11', '12', '15', '16, 'R, R, R, R, R, R, R, R, and R, are each hydrogen;'}{'sub': 3', '6', '20, 'R, R, and Rare independently alkyl or hydroxyl;'}{'sub': 8', '9', '10', '13', '14, 'R, R, R, R, and Rare independently hydrogen or alkyl; and'}X, Y, and Z are independently haloalkyl or hydroxyl.5. The method of claim 4 , wherein{'sub': 3', '6', '20, 'R, R, and Rare independently methyl or hydroxyl;'}{'sub': 8', '9', '10', '13', '14, 'R, R, R, R, and Rare independently hydrogen or methyl; and'}X, Y, and Z are independently trifluoromethyl or hydroxyl.6. The method of claim 5 , wherein A is ethenylene.7. The method of claim 5 , wherein n is 0.9. The method of claim 8 , whereinX, Y, and Z are independently haloalkyl or —OR′.10. The method of claim 8 , wherein{'sub': 1', '2', '3', '4', '5', '6', '7', '11', '12', '15', '16', '20, 'R, R, R, R, R, R, R, R, R, R, R, and Rare independently hydrogen, alkyl, or hydroxy;'}{'sub': 8', '9', '10', '13', '14, 'R, R, R, R, and Rare independently hydrogen, alkyl, or hydroxyl; and'}X, Y, and Z are independently alkyl, haloalkyl, or hydroxyl.11. The method of claim 10 , wherein{'sub': 1', '2', '4', '5', '7', '11', '12', '15', '16, 'R, R, R, R, R, R, R, R, and R, are each hydrogen;'}{'sub': 3', '6', '20, 'R, R, and Rare independently alkyl or hydroxyl;'}{'sub': 8', '9', '10', '13', '14, 'R ...

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Номер записи: 30
03-04-2014 дата публикации

ANDROSTANE AND PREGNANE STEROIDS WITH POTENT ALLOSTERIC GABA RECEPTOR CHLORIDE IONOPHORE MODULATING PROPERTIES

Номер: US20140094619A1
Автор: COOK Edgar, KAMINSKI Rafal, KEPLER John, NAVARRO Hernan, Orr Matthew, ROGAWSKI Michael, RUNYON Scott P.
Принадлежит:

This invention describes compounds of Structures 1, 2, and 3 and their use as allosteric modulators of the GABA receptor chloride ionophore complex to alleviate stress, anxiety, mood disorders, seizures, depression, treatment of drug and alcohol abuse, memory, premenstrual disorders, and neural system damage. 6. The use of a compound of as an intermediate for synthesis of biologically active compounds.7. The use of a compound of as an intermediate for synthesis of biologically active compounds.8. The use of a compound of as an intermediate for synthesis of biologically active compounds.9. The use of a compound of for treatment of convulsions claim 1 , epilepsy claim 1 , depression claim 1 , drug and alcohol abuse claim 1 , anxiety claim 1 , memory problems claim 1 , and neural system damage in humans or animals.10. The use of a compound of for treatment of convulsions claim 2 , epilepsy claim 2 , depression claim 2 , drug and alcohol abuse claim 2 , anxiety claim 2 , memory problems claim 2 , and neural system damage in humans or animals.11. The use of a compound of for treatment of convulsions claim 3 , epilepsy claim 3 , depression claim 3 , drug and alcohol abuse claim 3 , anxiety claim 3 , memory problems claim 3 , and neural system damage in humans or animals. The present application is a divisional of U.S. Ser. No. 12/664,470, filed May 5, 2010, now allowed, which was a 371 application of PCT/US08/67059, filed Jun. 16, 2008, and claims priority to U.S. Provisional Ser. No. 60/944,257, filed Jun. 15, 2007.1. Field of InventionThe present invention relates to androstane and pregnane steroid compounds and their use as allosteric modulators of the GABA receptor chloride ionophore complex and their use to alleviate stress, anxiety, mood disorders, seizures, depression, treatment of drug and alcohol abuse, memory, premenstrual disorders, and neural system damage.2. Discussion of the BackgroundThe present invention encompasses methods and compounds related to ...

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Номер записи: 31
05-01-2017 дата публикации

PEGYLATED 7-DEHYDROCHOLESTEROL DERIVATIVES

Номер: US20170000715A1
Автор: BANG Sung Sik, CHUNG Bong Youl, JEONG In Wha, JEONG Min Wook, KIM Myung Su, Kim Yong Soo, YOO Min Ji
Принадлежит: HUMEDIX CO., LTD.

The present invention relates to pegylated 7-dehydrocholesterol derivatives, and a composition for wrinkle alleviation and anti-aging comprising the same. The pegylated 7-dehydrocholesterol derivatives according to the present invention have improved stability and solubility in water, and thus can be effectively used as a good source for supplying vitamin D in a cosmetic composition, a pharmaceutical composition and a functional food for wrinkle alleviation and anti-aging. 11. The pegylated 7-dehydrocholesterol derivative of claim 1 , wherein n is an integer of 3 to 200.12. The pegylated 7-dehydrocholesterol derivative of claim 1 , wherein m and m′ are 1.13. The pegylated 7-dehydrocholesterol derivative of claim 2 , wherein m is 1.14. A cosmetic composition for wrinkle alleviation and anti-aging claim 1 , comprising the pegylated 7-dehydrocholesterol derivative of .15. A pharmaceutical composition for wrinkle alleviation and anti-aging claim 1 , comprising the pegylated 7-dehydrocholesterol derivative of .16. A functional food for wrinkle alleviation and anti-aging claim 1 , comprising the pegylated 7-dehydrocholesterol derivative of . The present invention relates to pegylated 7-dehydrocholesterol derivatives. More particularly, the present invention relates to pegylated 7-dehydrocholesterol derivatives which have improved stability and solubility and are hydrolyzed in vivo to supply vitamin D, and a composition for wrinkle alleviation and anti-aging comprising the same.Vitamin D has two types of vitamin D(ergocalciferol) and vitamin D(cholecalciferol, Compound B), and these two substances are subject to metabolism in liver and kidney to be converted into their active form (calcitriol, Compound C). 7-dehydrocholesterol (7-DHC, Compound A) is a provitamin form of vitamin Dand thus is converted into vitamin Dby sunlight.Vitamin Dgenerally promotes calcium absorption to strengthen the density of bone, so it is used as a therapeutic agent of osteoporosis and as a ...

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Номер записи: 32
06-01-2022 дата публикации

FLUORINATED AND ALKYLATED BILE ACIDS

Номер: US20220002339A1
Автор: Dias Lucas de Oliveira Susana, Finch Michael, Munshi Cyrus B., Rodrigues Cecilia M.P.
Принадлежит:

The present invention relates to fluorinated and alkylated bile acids. 3. The compound according to wherein X claim 2 , X claim 2 , Xand Xare all —F.4. The compound according to wherein any three of X claim 2 , X claim 2 , Xand Xare —F.5. The compound according to wherein any two of X claim 2 , X claim 2 , Xand Xare —F.6. The compound according to wherein one of X claim 2 , X claim 2 , Xand Xis —F.10. The compound according to claim 9 , wherein Xand Xare all alkylated.11. The compounds according to claim 9 , wherein any one of Xand Xare alkylated.13. A method of treating or preventing a disease that is selected from the group consisting of neurological disease claims 1 , diabetes claims 1 , ocular disorders claims 1 , spinal cord injury claims 1 , kidney injury or metabolic syndrome in a subject claims 1 , said method comprising administering to said subject a therapeutically effective amount of a compound according to claims 1 ,14. The method according to claim 13 , wherein the disease is a neurological disease selected from the group consisting of Alzheimer's claim 13 , Parkinson's claim 13 , Huntington's claim 13 , and amyotrophic lateral sclerosis (ALS).15. The method according to claim 13 , wherein the disease is type 2 diabetes.16. The method according to claim 13 , wherein the disease is acute kidney injury.17. The method according to claim 13 , wherein the disease is an ocular disorder selected from macular degeneration (MD) and diabetic retinopathy. This application is a divisional of U.S. patent application Ser. No. 15/556768, filed Sep. 8, 2017, which is a U.S. National Stage Application filed under 35 U.S.C. § 371 from International Application Serial No. PCT/US2016/021809, filed on Mar. 10, 2016, and published as WO 2016/145216 on Sep. 15, 2016, which claims the benefit of priority to U.S. Provisional Application Ser. No. 62/130,931, filed on Mar. 10, 2015 and U.S. Provisional Application Ser. No. 62/141,506, filed on Apr. 1, 2015, which applications ...

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Номер записи: 33
06-01-2022 дата публикации

C7, c12, and c16 substituted neuroactive steroids and their methods of use

Номер: US20220002340A1
Автор: Albert Jean Robichaud, Andrew Griffin, Boyd L. Harrison, Francesco G. Salituro, Gabriel Martinez Botella, Maria Jesus Blanco-Pillado
Принадлежит: Sage Therapeutics Inc

Described herein are neuroactive steroids of Formula (I), Formula (V), or Formula (IX) or a pharmaceutically acceptable salt thereof; wherein each instance of R2, R3, R4, R5, R6, R7, R11a, R11b, R12, R16, R17, R19, and are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. Also provided are pharmaceutical compositions comprising a compound described herein and methods of use and treatment, e.g., such as for inducing sedation and/or anesthesia.

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Номер записи: 34
03-01-2019 дата публикации

LIPID-BASED PLATINUM COMPOUNDS AND NANOPARTICLES

Номер: US20190002489A1
Автор: ANSARI Aasif, DUTTA Pradip Kumar, Hossain Sk Samad, ROY Monideepa, SARKAR Arindam, Sengupta Aniruddha, Sengupta Shiladitya
Принадлежит:

The present disclosure is in relation to the field of nanotechnology and cancer therapeutics. In particular, the present disclosure relates to platinum based compounds comprising platinum moiety, linker moiety and lipid moiety and corresponding nanoparticles thereof. The disclosure further relates to synthesis of said platinum based compounds, nanoparticles and compositions comprising said platinum based compounds/nanoparticles. The disclosure also relates to methods of managing cancer by employing aforesaid carbene compounds, platinum based compounds, nanoparticles and compositions thereof. 1. A compound comprising:(a) a platinum moiety; and(b) a lipid connected to said platinum moiety.2. The compound of claim 1 , wherein the compound comprises a carbonyl moiety.3. The compound of claim 2 , wherein the carbonyl moiety is a carboxylic acid that is succinic acid claim 2 , malonic acid claim 2 , oxalic acid claim 2 , keto acid claim 2 , or a combination thereof4. The compound of claim 1 , wherein the platinum moiety comprises a platinum atom that is conjugated to said lipid via covalent bond claim 1 , coordinate bond or a combination thereof.5. The compound of claim 1 , further comprising at least one linker between the platinum moiety and the lipid.7. The compound of claim 1 , wherein the linker is:{'sub': 2', '2', '1, 'claim-text': X is NH;', {'sub': 1', '2, 'Xis C(O)O, C(O)NH, O(CH)—O, NH, or O;'}, {'sub': 2', '2', 'n, 'Xis (CH)or C(O); and'}, 'n is 0, 1, 2, 3, 4, or 5;, '(i) —X—CH—X—X—, wherein{'sub': 2', 'n', '2', 'n', '2', 'n', '2', 'n', '2', 'm', '2', 'n', '2', 'm', '2', 'n', '2', 'n', '2', 'm', '2', 'n, 'claim-text': 'wherein, n and m are, independently, 0, 1, 2, 3, 4, or 5;', '(ii) —(CH)O—, —(CH)NHC(O)O—, —(CH)OC(O)NH—, —(CH)C(O)NH(CH)O—, —(CH)O(CH)O—, —(CH)OC(O)—, (CH)NHC(O)(CH)O—, or —(CH)C(O)O—;'}{'sub': 3', '4', '5', '6, 'claim-text': [{'sub': 3', '2, 'Xis CH, CH, or O; and'}, {'sub': 4', '5', '6', '2, 'X, Xand Xare, independently, —CHO— or O; or'}], '( ...

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Номер записи: 35
07-01-2021 дата публикации

METHOD OF SYNTHESIS OF AN IONIZABLE CATIONIC LIPID

Номер: US20210002217A1
Автор: Chivukula Padmanabh, Payne Joseph E.
Принадлежит:

What is described is a method of synthesis of the compound of formula 1A, 2. The method of claim 1 , wherein the nucleic acid is an RNA.3. The method of claim 2 , wherein the RNA is siRNA claim 2 , mRNA claim 2 , or miRNA.4. The method of claim 1 , wherein the target cell is a lung epithelial cell.5. The method of claim 1 , wherein the target cell is a hepatocyte.6. The method of claim 1 , wherein the lipid formulation is a lipid nanoparticle or a liposome.7. The method of claim 6 , wherein 30-70% of the lipids in the lipid formulation are a compound having Formula IA.8. The method of claim 7 , wherein 5-30% of the lipids in the lipid formulation are a helper lipid.9. The method of claim 7 , wherein 20-40% of the lipids in the lipid formulation are cholesterol.10. The method of claim 1 , wherein the composition is administered in an aqueous solution to a subject via inhalation.11. The method of claim 10 , wherein the composition is administered to the subject via pulmonary inhalation.12. The method of claim 10 , wherein the aqueous solution is aerosolized claim 10 , atomized claim 10 , or nebulized.16. The method of claim 1 , wherein the nucleic acid is a mRNA and delivery of the mRNA into the target cell results in expression of the mRNA into a protein of interest.17. The method of claim 16 , wherein the protein of interest is an enzyme.18. The method of claim 16 , wherein the protein of interest is an antigen.19. The method of claim 1 , wherein the nucleic acid is an siRNA and delivery of the siRNA into the target cell results in reduced expression of a gene of interest.20. The method of claim 1 , wherein the nucleic acid comprises one or more modified nucleotides selected from phosphorothioates claim 1 , phosphoramidates claim 1 , methyl phosphonates claim 1 , 2′-O-methyl ribonucleotides claim 1 , and peptide-nucleic acids. This application is a continuation of U.S. patent application Ser. No. 15/925,670, filed Mar. 19, 2018, which is a continuation of U.S. ...

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Номер записи: 36
04-01-2018 дата публикации

METHODS OF TREATING AND/OR PREVENTING AFFECTIVE DISORDERS OF THE NERVOUS SYSTEM (DEPRESSION) USING AMINOSTEROLS

Номер: US20180002370A1
Автор: Zasloff Michael
Принадлежит: Enterin Laboratories, Inc.

This invention relates to methods of stimulating the activity of the human and animal enteric nervous system. The method comprises orally administering an aminoserol, such as squalamine, a naturally occurring aminosterol isolated from , or derivatives thereof, to a subject in need. 1. A method of treating or preventing depression in a subject , comprising orally administering to the subject a composition comprising a pharmaceutically acceptable grade of at least one aminosterol , or a pharmaceutically acceptable salt or derivative thereof , in an amount sufficient to produce a beneficial effect.2. The method of claim 1 , wherein administration of the aminosterol induces production of neuro-protective hormones which provide a preventative or therapeutic benefit.3. The method of claim 1 , wherein the beneficial effect results from the effects of the aminosterol on enteric neurons.4. The method of claim 1 , wherein the beneficial effect is the result of the aminosterol triggering the stimulation of electrical signals flowing through the afferent arm of the vagus.510.-. (canceled)13. The method of claim 1 , wherein the aminosterol is Aminosterol 1436 (Compound 7).14. The method of claim 1 , wherein the aminosterol is a squalamine isomer.15. The method of claim 1 , wherein the aminosterol comprises a sterol nucleus and a polyamine claim 1 , attached at any position on the sterol claim 1 , such that the molecule exhibits a net charge of at least +1 claim 1 , the charge being contributed by the polyamine.16. The method of claim 1 , wherein the aminosterol comprises a bile acid nucleus and a polyamine claim 1 , attached at any position on the bile acid claim 1 , such that the molecule exhibits a net charge of at least +1 claim 1 , the charge being contributed by the polyamine.17. The method of claim 1 , wherein the aminosterol is modified to include one or more of the following: (1) substitutions of the sulfate by a sulfonate claim 1 , phosphate claim 1 , carboxylate claim ...

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Номер записи: 37
07-01-2021 дата публикации

INHIBITORS OF GLUCOCORTICOID RECEPTOR

Номер: US20210002324A1
Автор: BALBAS Minna Delarae, Du Xiaohui, EKSTEROWICZ John, FANTIN Valeria R., McGee Lawrence R., MEDINA Julio C., REW Yosup, SUN Daqing, YAN Xuelei, ZHOU Haiying, ZHU Liusheng
Принадлежит:

The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism. 2. The compound of or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris hydrogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , hydroxy claim 1 , halo claim 1 , carbocyclyl claim 1 , or heteroalkyl.3. The compound of either of or or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris Calkyl or hydrogen.4. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris methyl.5. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris methyl and Rand Rare H.6. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris H.7. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein R claim 1 , R claim 1 , and Rare H.8. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is monocyclic heteroaryl or monocyclic aryl.9. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is phenyl claim 1 , pyridinyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , or pyridazinyl.10. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or ...

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Номер записи: 38
07-01-2021 дата публикации

CHEMILUMINESCENT ANDROSTENEDIONE CONJUGATES

Номер: US20210003596A1
Автор: DONOVAN Patrick, Driscoll John, PARKER Lauren, Zhao Zhijian, Zheng Yi Feng
Принадлежит: SIEMENS HEALTHCARE DIAGNOSTICS INC.

Chemiluminescent androstenedione conjugates are disclosed. These chemiluminescent androstenedione conjugates may be used as chemiluminescent tracers in immunoassays for the quantification and identification of certain analytes.

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Номер записи: 39
20-01-2022 дата публикации

STEROID DERIVATIVE REGULATORS, METHOD FOR PREPARING THE SAME, AND USES THEREOF

Номер: US20220017565A1
Автор: Bao Rudi, CHEN Xiaopo, SU Yidong, Wang Jun
Принадлежит:

Steroid derivative regulators, a method for preparing the same, and uses thereof are described. Specifically, a compound as shown in formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and uses thereof as a regulator of GABA A receptor for treating depression, convulsion, Parkinson's disease, and nervous system diseases are described, wherein the substituents of the formula (I) are as defined in the description. 16. The compound of formula (I) claim 5 , the stereoisomer thereof claim 5 , or the pharmaceutically acceptable salt thereof according to claim 5 , wherein Rselected from the group consisting of hydrogen atom claim 5 , cyano claim 5 , halogen claim 5 , nitro claim 5 , Calkyl claim 5 , Calkynyl claim 5 , Calkoxy claim 5 , Chaloalkyl claim 5 , Ccycloalkyl claim 5 , Chydroxyalkyl claim 5 , 5 to 10 membered heterocyclyl claim 5 , 5 to 10 membered heteroaryl claim 5 , —(CH) claim 5 ,10R claim 5 , —(CH)SR claim 5 , —(CH)C(O)R claim 5 , —(CH)C(O)NRR claim 5 , —(CH)C(O)ORand —(CH)S(O)R claim 5 , wherein the Calkyl claim 5 , Calkoxy claim 5 , Chaloalkyl claim 5 , Ccycloalkyl claim 5 , Chydroxyalkyl claim 5 , wherein the 5 to 10 membered heterocyclyl and 5 to 10 membered heteroaryl are each optionally substituted by one or more substituents selected from the group consisting of hydrogen atom claim 5 , Calkyl claim 5 , halogen claim 5 , cyano claim 5 , hydroxy claim 5 , Ccycloalkyl claim 5 , Chydroxyalkyl claim 5 , 5 to 10 membered heterocyclyl and 5 to 10 membered heteroaryl;{'sub': 23', '24', '1-6, 'Rand Rare each independently selected from the group consisting of hydrogen atom, Calkyl and 3 to 8 membered heterocyclyl.'}17. The compound of formula (I) claim 5 , the stereoisomer thereof claim 5 , or the pharmaceutically acceptable salt thereof according to claim 5 ,wherein:{'sub': 2', '2', '2', '2', '2, 'Z is selected from the group consisting of —CH—, —CHNH—, —CHO—, —CH—, —NH— and —NHSO—;'}{'sub': 3a', '1-6', '1-6', '1-6 ...

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Номер записи: 40
11-01-2018 дата публикации

Cleavable Lipids

Номер: US20180008543A1
Автор: DeRosa Frank, GUILD Braydon Charles, Heartlein Michael, Zhang Jerry Chi
Принадлежит:

Disclosed herein are novel compounds, pharmaceutical compositions comprising such compounds and related methods of their use. The compounds described herein are useful, e.g., as liposomal delivery vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and subsequent iransfection of said target cells, and in certain embodiments are characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids. 2. (canceled)3. The nanoparticle of claim 1 , wherein Ris imidazole.4. The nanoparticle of claim 1 , wherein{'sub': '1', 'Ris imidazole;'}andn is 1.5. The nanoparticle of claim 1 , wherein Ris guanidinium.6. The nanoparticle-of claim 1 , wherein{'sub': '1', 'Ris guanidinium;'}andn is 1.723.-. (canceled)2629.-. (canceled)30. The nanoparticle of claim 1 , further comprising one or more compounds selected from the group consisting of a cationic lipid claim 1 , a PEG-modified lipid claim 1 , a non-cationic lipid and a helper lipid.31. (canceled)32. The nanoparticle of claim 1 , wherein one or more of the polynucleotides comprises a chemical modification.33. The nanoparticle of claim 1 , wherein the one or more polynucleotides is selected from the group consisting of an antisense oligonucleotide claim 1 , siRNA claim 1 , miRNA claim 1 , snRNA claim 1 , snoRNA and combinations thereof.34. (canceled)35. The nanoparticle of claim 1 , wherein the one or more polynucleotides comprise DNA.36. The nanoparticle of claim 1 , wherein the one or more polynucleotides comprise RNA.37. (canceled)38. The nanoparticle of claim 36 , wherein the RNA encodes an enzyme.39. The nanoparticle of claim 38 , wherein the enzyme is selected from the group consisting of agalsidase alfa claim 38 , alpha-L-iduronidase claim 38 , iduronate-2-sulfatase claim 38 , N-acetylglucosamine-1-phosphate transferase claim 38 , N-acetylglucosaminidase claim 38 , alpha-glucosaminide acetyltransferase claim 38 , N- ...

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Номер записи: 41
10-01-2019 дата публикации

Steroid alkaloids and compositions and kits thereof

Номер: US20190008875A1
Автор: Eric Marsault, Felix Chagnon, Francois Malouin, Isabelle GUAY, Simon BOULANGER
Принадлежит: SOCPRA Sciences et Genie SEC

The present invention provides bacterial ATP synthase inhibitors such as a compound of formula (I): There are provided compositions and kits using such compounds and inhibitors.

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Номер записи: 42
10-01-2019 дата публикации

COMPOUNDS AND METHODS FOR TRANS-MEMBRANE DELIVERY OF MOLECULES

Номер: US20190008976A1
Автор: DUBROVSKY Joseph, Grimberg Hagit, ZIV Ilan
Принадлежит: Aposense Ltd.

A conjugate for delivery of drugs, such as genetic drugs, [e.g., siRNA, dsiRNA, or antisense oligonucleotides (ASO)]across biological membranes is provided. The conjugates of the Invention are capable of delivering drugs in both presence and absence of plasma proteins. 2. The conjugate according to claim 1 , wherein in E claim 1 , E′ claim 1 , or E″ moiety claim 1 , W is a nucleoside claim 1 , selected from natural or modified adenine claim 1 , cytosine claim 1 , thymine and uracil claim 1 , and the sugar moiety is ribose or 2′-deoxyribose.3. The conjugate according to claim 2 , wherein in E claim 2 , E′ claim 2 , or E″ moiety claim 2 , W is 2′-deoxyuridine.4. The conjugate according to claim 1 , wherein in E claim 1 , E′ claim 1 , or E″ moiety claim 1 , W has the structure set forth in Formula (II′) claim 1 , wherein J is —CH—.24. The conjugate according to claim 1 , comprising E claim 1 , E′ or E″ moiety according to any of Formulae (II) claim 1 , (III) claim 1 , (IVa) claim 1 , (IVb) claim 1 , (IVc) claim 1 , (Va′) claim 1 , (Va″) claim 1 , (Va′″) claim 1 , (Vb′) claim 1 , (Vb″) claim 1 , (Vb′″) claim 1 , (Vc′) claim 1 , (Vc″) or (Vc′″) claim 1 , linked to a drug.25. The conjugate according to claim 24 , wherein the drug is a macromolecule drug.26. The conjugate according to claim 25 , wherein the macromolecule drug is an oligonucleotide drug (OD) claim 25 , comprising natural or modified oligonucleotide chains claim 25 , and selected from siRNA claim 25 , dsiRNA claim 25 , mRNA claim 25 , microRNA claim 25 , and antisense oligonucleotide (ASO).27. A pharmaceutical composition claim 24 , comprising the conjugate according to claim 24 , and a pharmaceutically-acceptable salt or carrier.28. The conjugate according to claim 26 , wherein the OD is linked to either one claim 26 , two claim 26 , three claim 26 , or more than three of E claim 26 , E′ claim 26 , or E″ moieties.29. The conjugate according to claim 26 , wherein the OD is a Dicer substrate claim 26 , being ...

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Номер записи: 43
14-01-2016 дата публикации

PREGNANE-OXIMINO-AMINOALKYLETHERS AND PROCESS FOR PREPARATION THEREOF, USEFUL AS ANTIDIABETIC AND ANTIDYSLIPIDEMIC AGENTS

Номер: US20160009752A1
Автор: DWIVEDI Anil Kumar, GUPTA Jyoti, Gupta Varsha, Jaiswal Natasha, KHANNA Ashok Kumar, KUSHWAHA Hari Narayan, MISRA Anamika, PRATAP Ram, Rahuja Neha, SINGH Dharmendra Pratap, SINGH Shio Kumar, Srivastava Arvind Kumar, Srivastava Rohit, Tamrakar Akhilesh Kumar, VERMA Prem Chandra
Принадлежит:

The present invention relates to the synthesis of pregnane-oximino-aminoalkyl-ethers and their antidiabetic and antidyslipidemic activities. More particularly, the invention relates to the synthesis of compounds of formula 3 and biological profile thereof. Further the invention relates to compounds of formula 3 and pharmaceutically acceptable salts thereof. 2. The compound as claimed in claim 1 , selected from the group consisting of:3β-Hydroxy-pregna-5,16-dien-20-one-O-n-butyl-oxime (10a),3β-Hydroxy-pregna-5,16-dien-20-one-O-benzyl-oxime (10b),3β-Hydroxypregna-5,16-dien-20-one-O-(2-piperidinyl-ethyl)-oxime (11a),3β-Hydroxypregna-5,16-dien-20-one-O-(2-azepan-1-yl-ethyl)-oxime (11b),3β-Hydroxypregna-5,16-dien-20-one-O-(2-morpholin-4-yl-ethyl)-oxime (11c),3β-Hydroxypregna-5,16-dien-20-one-O-(2-diethylamino-ethyl)-oxime (11d),3β-Hydroxy-pregna-5,16-dien-20-one-O-[3-{2-hydroxy-3-(4-(2-methoxy-phenyl-piperazinyl)-propyl)}]-oxime (13a),3β-Hydroxy-pregna-5,16-dien-20-one-O[3-(2-hydroxy-3-(4-phenyl-piperazinyl)-propyl)]-oxime (13b),3β-Hydroxy-pregna-5-en-20-one-O-(2-pyrrolidin-1-yl-ethyl)-oxime (14a),3β-Hydroxy-pregna-5-en-20-one-O-(2-piperidin-1-yl-ethyl)-oxime (14b),3β-Hydroxy-pregna-5-en-20-one-O[2-hydroxy-3-iso-propylamino-propyl)-oxime (16a),3β-Hydroxy-pregna-5-en-20-one-O-[2-hydroxy-3-tert.-butylamino-propyl]-oxime (16b),3β-Hydroxy-pregna-5-en-20-one-O-[2-hydroxy-3-(4-phenyl-piperazin-1-yl)-propyl]-oxime (16c),3β-Hydroxy-pregna-5-en-20-one-O-{2-hydroxy-3-[4-(2-methoxyphenyl)-piperzin-1-yl]-propyl}-oxime (16d),3β-Hydroxy-pregna-5-en-20-one-O[2-hydroxy-3-(2-pyridyl-piperazin-1-yl)-propyl]-oxime (16f),3β-Hydroxy-pregna-5-en-2-one-O-[2-hydroxy-3-pipridinyl-propyl)-oxime (16g),3β-Hydroxy-pregna-5-en-20-one-O-[2-hydroxy-3-(4-methyl-piperazin-1-yl)-propyl]-oxime (16h),3β-Hydroxy-pregna-5-en-20-one-O-[2-hydroxy-3-diisopropylamino-propyl)-oxime (16i), and3β-Hydroxy-pregna-5-en-20-one-O-[2-hydroxy-3-diethylamino-propyl)-oxime (16j).3. The compound as claimed in claim 1 , ...

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Номер записи: 44
14-01-2016 дата публикации

Reducing Risk of Contracting Clostridium-Difficile Associated Disease

Номер: US20160009753A1
Автор: Abel-Santos Ernesto, Howerton Amber
Принадлежит:

A method of treating a patient to reduce risk of developing -associated disease or reducing existing -associated disease in a mammalian subject involves administering to a mammalian subject an effective amount of a germination-inhibiting compound derived from taurocholate. Novel compounds of this class are also provided. 24-. (canceled)68-. (canceled)9. The method of claim 1 , wherein each of Rand Ris —OH.10. The method of claim 1 , wherein Ris hydrogen.11. The method of claim 1 , wherein Ris O.12. The method of claim 1 , wherein Ris selected from —NH(o-Ph)SOH claim 1 , —NH(m-Ph)SOH claim 1 , —NH(p-Ph)SOH claim 1 , —NH(CH)SOH claim 1 , —NH(CH)CONH(CH)COH claim 1 , and —NH(CH)CONH(CH)COH.13. The method of claim 1 , wherein Ris selected from —NH(o-Ph)SOH claim 1 , NH(p-Ph)SOH claim 1 , —NH(CH)SOH claim 1 , —NH(CH)CONH(CH)COH claim 1 , and —NH(CH)CONH(CH)COH.14. The method of claim 1 , wherein Ris selected from —NH(CH)SOH claim 1 , —NH(CH)CONH(CH)COH claim 1 , and —NH(CH)CONH(CH)COH.18. The compound of claim 5 , wherein each of Rand Ris —OH.19. The compound of claim 5 , wherein Ris hydrogen.20. The compound of claim 5 , wherein Ris O.21. The compound of claim 5 , wherein Ris selected from —NH(o-Ph)SOH claim 5 , —NH(m-Ph)SOH claim 5 , —NH(CH)SOH claim 5 , —NH(CH)CONH(CH)COH claim 5 , and —NH(CH)CONH(CH)COH.22. The compound of claim 5 , wherein Ris selected from —NH(CH)SOH claim 5 , —NH(CH)CONH(CH)COH claim 5 , and —NH(CH)CONH(CH)COH. This application claims priority from U.S. provisional Patent Application Ser. No. 61/682,505, filed 13 Aug. 2012,having the same title, inventors and assignee as the present application.This invention was made with government support under CHE0957400 awarded by the National Science Foundation. The government has certain rights in the invention.1. Field of the InventionThe present invention relates to compounds which are of use in the treatment of bacterial diseases and infections, to compositions containing those compounds and to methods ...

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Номер записи: 45
08-01-2015 дата публикации

TANDEM FACIAL AMPHIPHILES

Номер: US20150011739A1
Автор: Chae Pil Seok, GELLMAN Samuel Helmer
Принадлежит: WISCONSIN ALUMNI RESEARCH FOUNDATION

The invention provides tandem facial amphiphiles for biochemical manipulations and characterization of membrane proteins, such as intrinsic membrane proteins. Members of this new family display favorable behavior with several membrane proteins. These amphiphiles can form relatively small micelles, and small changes in amphiphile chemical structures can result in large changes in their physical properties. The tandem facial amphiphiles can be used to aid the solubilization, isolation, purification, stabilization, crystallization, and/or structural determination of membrane proteins. 2. The compound of wherein each Ris (C-C)alkyl.3. The compound of wherein Y is a direct bond.4. The compound of wherein at least two of R claim 1 , Rand Rare O-Sac and each Sac is a disaccharide.15. The compound of wherein a plurality of the compounds form a micelle in water comprising about 6 to about 15 molecules of the compound.1620-. (canceled) This application is a continuation of U.S. patent application Ser. No. 13/669,198, filed Nov. 5, 2012, which claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 61/556,625, filed Nov. 7, 2011, all of which are incorporated herein by reference.This invention was made with government support under GM075913 awarded by the National Institutes of Health. The government has certain rights in the invention.Membrane proteins (MPs) play crucial roles in biology, but these proteins are difficult to handle and analyze because of their physical properties. The native conformations of MPs display extensive nonpolar surfaces. The display of these nonpolar surfaces is necessary for residence in a lipid bilayer but leads to denaturation and/or aggregation in an aqueous medium. Detergents such as dodecyl-β--maltoside (DDM) are typically employed to render MPs soluble by coating the nonpolar protein surfaces. However, only some MPs can be maintained in native-like conformations when solubilized with conventional detergents (Serrano ...

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Номер записи: 46
10-01-2019 дата публикации

METHODS FOR PREPARATION OF BILE ACIDS AND DERIVATIVES THEREOF

Номер: US20190010184A1
Автор: Gioiello Antimo, Pellicciari Roberto
Принадлежит:

The present application relates to a method of preparing compounds of Formula (I) or a pharmaceutically acceptable salt, solvate, or amino acid conjugate thereof, Ris H, α-OH, β-OH, or an oxo group. 3. The method of claim 2 , wherein the deprotecting in step 2 and the hydrolyzing in step 3 occur in a single step.6. The method of or claim 2 , wherein the deprotecting in step 4 and the hydrolyzing in step 5 occur in a single step.8. The method of claim 7 , wherein the stereoselective reduction comprises hydrogenation.9. The method of claim 8 , wherein the hydrogenation is conducted with a catalyst and hydrogen gas.11. The method of claim 10 , wherein the stereoselective reduction comprises hydrogenation.12. The method of claim 11 , wherein the hydrogenation is conducted with a catalyst and hydrogen gas.14. The method of claim 13 , wherein the stereoselective reduction comprises hydrogenation.15. The method of claim 14 , wherein the hydrogenation is conducted with a catalyst and hydrogen gas.19. The method of claim 18 , wherein the stereoselective reduction of 15 to 16A comprises reacting 15 with K-Selectride.20. The method of claim 18 , wherein the stereoselective reduction of 16A to 17 comprises hydrogenation.21. The method of claim 20 , wherein the hydrogenation comprises reacting 16A with a catalyst and hydrogen gas.23. The method of claim 22 , wherein stereoselective reduction of 15 to 16B comprises reacting 15 with NaBHand CeCl.7HO.24. The method of claim 22 , wherein the stereoselective reduction of 16B to 18 comprises hydrogenation.25. The method of claim 24 , wherein the hydrogenation comprises reacting 16B with a catalyst and hydrogen gas. Bile acids and bile acid derivatives are useful in the treatment and prevention of diseases. Bile acids have been shown to induce internalization of the TGR5 fusion protein from the cell membrane to the cytoplasm (Kawamata et al., 2003, J. Biol. Chem. 278, 9435). TGR5 is associated with the intracellular accumulation of ...

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Номер записи: 47
15-01-2015 дата публикации

RADIOLABELED BILE ACIDS AND BILE ACID DERIVATIVES

Номер: US20150017093A1
Автор: Frisch Kim, Hofmann Alan, Keiding Susanne, Ott Peter, Sorensen Michael
Принадлежит:

The present invention relates in one aspect to radiolabeled compounds comprising the structure of Formula 1. The radiolabeled compounds are preferably bile acids or bile acid derivatives. Further aspects of the invention relates to use of the compounds comprising the structure of Formula 1 in imaging methods such as for example PET, imaging method using a compound comprising the structure of Formula 1, administering said compound to an individual and making a radiographic image of a region of interest from said individual. 2. The compound according to claim 1 , wherein said steroid structure (ABCD) comprises one or more double bonds.3. The compound according to any of and claim 1 , wherein R claim 1 , Rand Ris H or OH.4. The compound according to claim 3 , wherein Ris OH.5. The compound according to claim 4 , wherein R claim 4 , Rand Ris OH.6. The compound according to claim 5 , wherein R claim 5 , Rand Ris OH in an α-position.7. The compound according to any of the preceding claims claim 5 , wherein n=1.8. The compound according to any of the preceding claims claim 5 , wherein R claim 5 , R claim 5 , Rand Ris H.9. The compound according to any of the preceding claims claim 5 , wherein Y is OH.10. The compound according to any of the preceding claims claim 5 , wherein Y is NRR.11. The compound according to claim 10 , wherein Ris CHCOOH.13. The compound according to claim 12 , wherein Ris OH.14. The compound according to claim 12 , wherein Rand Rare OH.15. The compound according to claim 12 , wherein R claim 12 , Rand Rare OH and Ris H.17. The compound according to claim 16 , wherein R claim 16 , Rand Rare OH and Ris H.18. The compound according to claim 17 , wherein R claim 17 , Rand Rare OH in α-position.1918. The compound according to any of - claim 16 , wherein Ris —CHCOOH and Ris CH.2018. The compound according to any of - claim 16 , wherein Ris —CHCOOH and Ris CHF.2118. The compound according to any of - claim 16 , wherein Ris —CHCHSOOH and Ris CH.2218. The ...

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Номер записи: 48
18-01-2018 дата публикации

TGR5 Modulators and Methods of Use Thereof

Номер: US20180016295A1
Автор: Pellicciari Roberto
Принадлежит:

The invention relates to compounds of Formula A: 4. The compound according to claim 3 , wherein Rand Rtaken together with the carbon to which they are attached form a carbonyl.5. The compound according to claim 4 , wherein Ris R.6. The compound according to claim 5 , wherein Ris selected from hydroxyl claim 5 , NH(CH)SOH claim 5 , and NHCHCOH.7. The compound according to claim 6 , wherein Ris hydrogen.8. The compound according to claim 7 , wherein Ris in the S-configuration.9. The compound according to claim 8 , wherein Ris unsubstituted alkyl.10. The compound according to claim 9 , wherein Ris methyl.12. The compound according to claim 3 , wherein the compound is selected from Compounds Ig3e claim 3 , Ih3e claim 3 , Ii3e claim 3 , Ig4e claim 3 , Ih4e claim 3 , Ii4e claim 3 , Ig5e claim 3 , Ih5e claim 3 , and Ii5e.13. The compound according to selected from Compounds Ib3e claim 2 , Ic3e claim 2 , Id3e claim 2 , Ie3e claim 2 , If3e claim 2 , Ig3e claim 2 , Ih3e claim 2 , Ii3e claim 2 , Il3e claim 2 , Im3e claim 2 , In3e claim 2 , Ia4e claim 2 , Ib4e claim 2 , Ic4e claim 2 , Id4e claim 2 , Ie4e claim 2 , If4e claim 2 , Ig4e claim 2 , Ih4e claim 2 , Ii4e claim 2 , Il4e claim 2 , Im4e claim 2 , In4e claim 2 , Ia5e claim 2 , Ib5e claim 2 , Ic5e claim 2 , Id5e claim 2 , Ie5e claim 2 , If5e claim 2 , Ig5e claim 2 , Ih5e claim 2 , Ii5e claim 2 , Il5e claim 2 , Im5e claim 2 , In5e claim 2 , Ia9e claim 2 , Ib9e claim 2 , Ic9e claim 2 , Id9e claim 2 , Ie9e claim 2 , If9e claim 2 , Ig9e claim 2 , Ih9e claim 2 , Ii9e claim 2 , Il9e claim 2 , Im9e claim 2 , In9e claim 2 , Ia10e claim 2 , Ib10e claim 2 , Ic10e claim 2 , Id10e claim 2 , Ie10e claim 2 , If10e claim 2 , Ig10e claim 2 , Ih10e claim 2 , Ii10e claim 2 , Il10e claim 2 , Im10e claim 2 , In10e claim 2 , Ia11e claim 2 , Ib11e claim 2 , Ic11e claim 2 , Id11e claim 2 , Ie11e claim 2 , If11e claim 2 , Ig11e claim 2 , Ih11e claim 2 , Ii11e claim 2 , Il11e claim 2 , Im11e claim 2 , In11e claim 2 , Ia15e claim 2 , Ib15e claim 2 , ...

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Номер записи: 49
15-01-2015 дата публикации

PRO-DRUG FORMING COMPOUNDS

Номер: US20150018322A1
Автор: Ahmed Gulzar, Elger Walter, Meece Frederick, Nair Hareesh, Nickisch Klaus, Santhamma Bindu, WYRWA Ralf
Принадлежит:

Various prodrug compounds having the general structure: Active agent-(acid)-(linker)-SONRRare described herein. Compounds having this general structure were shown to be more orally active than the unmodified parent molecule. 2. The compound of claim 1 , wherein the active agent is an androgen.3. The compound of claim 1 , wherein the active agent is testosterone.4. The compound of claim 1 , wherein the active agent is 7α claim 1 ,11β-dimethyl-estra-4 claim 1 ,9-dien-17β-ol5. The compound of claim 1 , wherein the active agent is an estrogen.6. The compound of claim 1 , wherein the active agent is estradiol.7. The compound of claim 1 , wherein the active agent is estriol.8. The compound of claim 1 , wherein the active agent is a progestin.9. The compound of claim 1 , wherein the active ingredient is trimesgestone.10. The compound of claim 1 , wherein Rand Rare linked together to form a cycloalkyl or a 3-7 membered ring with up to one heteroatom.11. The compound of claim 10 , wherein n is 1; m is 0; L is 1; hAr is aryl; Rand Rare H claim 10 , and Y and X are H.12. The compound of claim 10 , wherein n is 1; m is 1; L is 0; hAr is aryl; Rand Rare H claim 10 , and Y and X are H.13. The compound of claim 1 , wherein Ris alkyl.14. The compound of claim 13 , wherein n is 1; Ris H; m is 0; L is 1; hAr is aryl; Y and X are H; and Rand Rare H.15. The compound of claim 13 , wherein Ris isopropyl.14. The compound of claim 13 , wherein Ris methyl.15. A pharmaceutical composition comprising a compound as described in and one or more pharmaceutically acceptable carriers.17. The compound of claim 16 , wherein the active agent is an androgen.18. The compound of claim 16 , wherein the active agent is testosterone.19. The compound of claim 16 , wherein the active agent is 7α claim 16 ,11β-dimethyl-estra-4 claim 16 ,9-dien-17β-ol20. The compound of claim 16 , wherein the active agent is an estrogen.21. The compound of claim 16 , wherein the active agent is estradiol.22. The compound of ...

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Номер записи: 50
15-01-2015 дата публикации

COMPOSITIONS AND METHODS FOR INHIBITING NOROVIRUS INFECTION

Номер: US20150018326A1
Автор: Jiang Xi, Tan Ming, Zhang Xufu
Принадлежит: CHILDREN'S HOSPITAL MEDICAL CENTER

A composition for use in inhibiting the binding of a Norovirus to the histo-blood group antigen on the surface of epithelia is disclosed. The composition may contain a therapeutically effective amount of a binding-inhibiting compound and a carrier and/or excipient. The compounds may competitively bind a Norovirus that has the capability of binding with the histo-blood group antigens of secretor blood type, including A, B, AB, and O blood types. The compositions may be administered to a human prior to or after infection by a Norovirus, to prevent, ameliorate, or reduce the effects of an infection. 2. A composition for use in inhibiting the binding of a Norovirus to the histo-blood group antigen on the surface of epithelia , the composition comprising a therapeutically effective amount of a binding-inhibiting compound selected from any one of Compound 1 through 21 and combinations thereof , or a pharmaceutically acceptable salt thereof , and a carrier and/or excipient.8. The composition according to claim 1 , wherein the binding-inhibiting compound competitively binds to the Norovirus.9. The composition of claim 1 , wherein said compound selectively binds to the oligosaccharide-PAA conjugated A and B.10. The composition according to comprising from about 1 claim 1 ,000 to about 100 claim 1 ,000 units per dose claim 1 , where a unit defines the amount of the binding-inhibiting compound to bind with a single virus particle.11. A method for treating claim 1 , preventing or reducing the likelihood of occurrence of an infection of a mammal by a Norovirus claim 1 , comprising the step of administering to a mammal a therapeutically effective amount of a compound that inhibits binding of at least one Norovirus to a native histo blood group antigen of the mammal.13. The method of wherein said compound is selected from any one of Compound 1 through 21 claim 11 , pharmaceutically acceptable salts of Compounds 1 through 21 claim 11 , or a combination thereof. This application ...

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Номер записи: 51
15-01-2015 дата публикации

Lipopolyamines of spermine type for construction of liposomal transfection systems

Номер: US20150018436A1
Автор: Jaroslav Turanek, Lukas Drasar, Miroslav Ledvina, Zina Korvasova
Принадлежит: Institute of Organic Chemistry and Biochemistry CAS, Vyzkumny USTAV Veterinarniho Lekarstvi VVI

The invention provides new lipopolyamines of spermine type of the general formula I, wherein X is C—N bond or aminopolyethyleneglycolcarboxamide linker or o-hydroxy-alkylcarboxamide linker or ω-hydroxyalkylcarboxamidopolyethyleneglycol-carboxamide linker, and wherein a hydrophobic domain Y is an acyl symmetrically branched in the position C(2) or cholesteryl. The invention further provides a method of preparation of said lipopolyamines and their use for construction of polycationic liposomal drug carriers.

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Номер записи: 52
16-01-2020 дата публикации

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Номер: US20200017542A1
Автор: Harrison Boyd L., Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Described herein are neuroactive steroids of the Formula (I): 17-. (canceled)10. The compound of claim 8 , wherein Rand Rare taken together with the carbon to which they are attached to form C(═O).11. The compound of claim 8 , wherein Ror Ris hydroxy claim 8 , alkyl claim 8 , or alkoxy.12. The compound of claim 8 , wherein Rand Rare taken together with the carbon to which they are attached to form C(═O) and Ror Ris hydroxy claim 8 , alkyl claim 8 , or alkoxy.13. The compound of claim 8 , wherein Ror Ris hydroxy claim 8 , alkyl claim 8 , or alkoxy.14. The compound of claim 13 , wherein Ris hydroxy.15. The compound of claim 13 , wherein Ris alkoxy.16. The compound of claim 8 , wherein Ror Ris hydroxy claim 8 , alkyl claim 8 , or alkoxy and Ror Ris hydroxy claim 8 , alkyl claim 8 , or alkoxy.17. The compound of claim 11 , wherein Ris alkyl.18. The compound of claim 11 , wherein Ris alkoxy.19. The compound of claim 8 , wherein Ris C-Calkyl.2133-. (canceled)34. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable excipient.3546-. (canceled) This application is a divisional of U.S. Ser. No. 15/698,151 filed Sep. 7, 2017, which is a continuation of U.S. Ser. No. 14/906,043 filed Jan. 19, 2016, which is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/US2014/047246 filed Jul. 18, 2014, which claims priority under 35 U.S.C. § 119(e) to U.S. provisional patent application, U.S. Ser. No. 61/856,592, filed Jul. 19, 2013, the contents of each of which are incorporated herein by reference.Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately −70 mV, the cell interior being negative with respect to ...

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Номер записи: 53
21-01-2021 дата публикации

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Номер: US20210017218A1
Автор: Beresis Richard Thomas, Harrison Boyd L., Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Described herein are neuroactive steroids of the Formula (II): or a pharmaceutically acceptable salt thereof; wherein A, R, R, R, R, R, R, R, R, Rand are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e. g., such for inducing sedation and/or anesthesia. 164-. (canceled)74. The method of claim 66 , wherein A is a 5-10-membered ring.75. The compound of claim 74 , wherein A is phenyl claim 74 , naphthyl claim 74 , furan claim 74 , thiophene claim 74 , thiazole claim 74 , pyrrole claim 74 , imidazole claim 74 , pyrazole claim 74 , or triazole.77. The method of claim 65 , wherein the CNS-related disorder is a sleep disorder claim 65 , a mood disorder claim 65 , a schizophrenia spectrum disorder claim 65 , a convulsive disorder claim 65 , a disorder of memory claim 65 , a disorder of cognition claim 65 , a movement disorder claim 65 , a personality disorder claim 65 , autism spectrum disorder claim 65 , pain claim 65 , traumatic brain injury claim 65 , a vascular disease claim 65 , a substance abuse disorder claim 65 , a substance abuse withdrawal syndrome claim 65 , a neurodegenerative disorder claim 65 , or tinnitus.78. The method of claim 77 , wherein the CNS-related disorder is tremor.79. The method of claim 78 , wherein the tremor is essential tremor.80. The method of claim 66 , wherein the CNS-related disorder is a sleep disorder claim 66 , a mood disorder claim 66 , a schizophrenia spectrum disorder claim 66 , a convulsive disorder claim 66 , a disorder of memory claim 66 , a disorder of cognition claim 66 , a movement disorder claim 66 , a personality disorder claim 66 , autism spectrum disorder claim 66 , pain claim 66 , traumatic brain injury claim 66 , a vascular disease claim 66 , a substance abuse disorder claim 66 , a substance abuse withdrawal syndrome claim ...

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Номер записи: 54
21-01-2021 дата публикации

INHIBITORS OF GLUCOCORTICOID RECEPTOR

Номер: US20210017219A1
Автор: BALBAS Minna Delarae, Du Xiaohui, EKSTEROWICZ John, FANTIN Valeria R., McGee Lawrence R., MEDINA Julio C., REW Yosup, SUN Daqing, YAN Xuelei, ZHOU Haiying, ZHU Liusheng
Принадлежит:

The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer. 2. The compound of or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein R is hydrogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , hydroxy claim 1 , halo claim 1 , carbocyclyl claim 1 , or heteroalkyl.3. The compound of or or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris Calkyl or hydrogen.4. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris methyl.5. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris H.6. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is monocyclic heteroaryl or monocyclic aryl.7. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is phenyl claim 1 , pyridinyl claim 1 , pyrimidinyl claim 1 , pyrazinyl claim 1 , or pyridazinyl.8. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein ring A is phenyl.9. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris Calkyl.10. The compound of any one of - or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris Calkyl.11. The compound of any ...

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Номер записи: 55
21-01-2021 дата публикации

INHIBITORS OF GLUCOCORTICOID RECEPTOR

Номер: US20210017220A1
Автор: BALBAS Minna Delarae, Du Xiaohui, EKSTEROWICZ John, FANTIN Valeria R., McGee Lawrence R., MEDINA Julio C., REW Yosup, SUN Daqing, YAN Xuelei, ZHOU Haiying, ZHU Liusheng
Принадлежит:

The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism. 25.-. (canceled)6. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein each Ris independently —NRR claim 1 , halo claim 1 , alkyl claim 1 , carbocyclyl claim 1 , alkoxy claim 1 , or —CN.7. (canceled)8. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Rand Rare each independently —H claim 1 , alkyl claim 1 , or —S(O)R.9. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein{'sup': 4', '5', '6, 'sub': '2', 'Rand Rattached to the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted 4-, 5-, or 6-membered ring heterocycle additionally containing 0-3 heteroatoms selected from the group consisting of —O—, —NH—, —NR—, —S—, and —S(O)—; and'}{'sup': '6', 'Ris alkyl.'}10. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris alkyl claim 1 , carbocyclyl claim 1 , or fluoroalkyl.11. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein Ris alkyl claim 1 , carbocyclyl claim 1 , optionally substituted aryl claim 1 , optionally substituted aralkyl claim 1 , or optionally substituted heterocyclyl.1213.-. (canceled)14. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or ...

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Номер записи: 56
26-01-2017 дата публикации

BONE-SELECTIVE OSTEOGENIC OXYSTEROL BISPHOSPHONATE ANALOGS

Номер: US20170022244A1
Автор: Chamberlain Brian T., Parhami Farhad, Stappenbeck Frank
Принадлежит:

Oxysterol-bisphosphonate and oxysterol-alendronic acid compounds, compositions including them, and methods using them for the treatment of bone disorders. 15. The compound of claim 14 , wherein the compound is a sodium salt.17. The compound of claim 16 , wherein the compound is a sodium salt.19. The compound of claim 18 , wherein the compound is a sodium salt.21. The compound of claim 20 , wherein the compound is a sodium salt.23. The compound of claim 22 , wherein the compound is a sodium salt.25. The compound of claim 24 , wherein the compound is a sodium salt.27. The compound of claim 26 , wherein the compound is a sodium salt.29. The compound of claim 28 , wherein the compound is a sodium salt.31. The compound of claim 30 , wherein the compound is a sodium salt.32. A pharmaceutical composition comprising a compound of any one of through and a pharmaceutically acceptable carrier or diluent.33. A method for treating a human or an animal subject suffering from a bone disorder claim 30 , comprising administering to the subject an effective amount of the compound of any one of through .34. The method of claim 33 , wherein the compound is administered to effect localized delivery to the subject.35. The method of claim 33 , wherein the compound is administered to effect systemic delivery to the subject.36. The method of claim 33 , wherein the bone disorder is selected from the group consisting of a bone fracture claim 33 , osteoporosis claim 33 , and osteopenia.37. A method for treating a human or an animal subject suffering from a bone disorder claim 33 , comprising contacting an osteoblast progenitor cell with an effective amount of the compound of any one of through .38. The method of claim 37 , wherein the osteoblast progenitor cell is contacted with the compound in vitro.39. The method of claim 37 , wherein the bone disorder is selected from the group consisting of a bone fracture claim 37 , osteoporosis claim 37 , and osteopenia.40. A method for treating a human ...

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Номер записи: 57
26-01-2017 дата публикации

GANAXOLONE DERIVATIVES FOR TREATMENT OF CENTRAL NERVOUS SYSTEMS DISORDERS

Номер: US20170022245A1
Автор: Marfat Anthony, Volkmann Robert A
Принадлежит: BioPharma Works

The present invention is directed to Ganaxolone prodrugs with increased aqueous solubility and oral bioavailability relative to Ganaxolone and that enable development of stable extended release formulations which offer a significant therapeutic advantage and improved patience compliance by enabling treatments with lower doses over prolonged periods of time. 223-. (canceled)25. A compound according to claim 24 , wherein Xis selected from the group consisting of:{'sup': 2', '1', '2', '1', '2', '−', '+', '2', '2', '1', '2', '2', '2, 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, '(C═O)—OC(R)O(C═O)R, (C═O)—OC(R)O(C═O)OR, (C═O)—OC(R)O(P═O)—(OM), (C═O)—OC(R)O(P═O)—(OC(R)O(C═O)YR), (C═O)—OC(R)O(C═O)(CHR)N(R), (C═O)—OC(R)O(C═O)N(R), and (C═O)—OC(R)O(C═O)N(CHCOR).'}26. A compound according to claim 24 , wherein Xis selected from the group consisting of:{'sup': 1', '−', '+', '−', '+', '4', '+', '−', '1', '−', '+', '2', '1, 'sub': 2', 'n', '2', '2', 'n', '2', '2', 'm', '2', 'n', '2', '2', '2', 'n', '2', '2', 'n', '2', '2', 'p', '2', '2', '3', '2', '2', '2', '2', '2', '2, '(C═O)R, (C═O)—(CH)COM, (C═O)—(CH)COR, (C═O)—(CH)O(C═O)R, (C═O)—(CH)OR, (C═O)—CH═CH—COR, (C═O)—CH═CH—COM, (C═O)—(CH)N(R), (C═O)—(CH)(C═O)N(R), (C═O)—(CH)N(C═O)R, (C═O)—(CHR)N(R), (C═O)—(CH)NRA, (C═O)OR, (P═O)—(OM), (P═O)—(OC(R)O(C═O)YR), and (C═O)—N(CHCOR).'}27. A compound according to claim 24 , wherein Xis selected from the group consisting of:{'sup': 2', '1', '2', '1', '2', '−', '+', '2', '2', '1', '2', '2', '2, 'sub': 2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2', '2, 'C(R)O(C═O)R, C(R)O(C═O)OR, C(R)O(P═O)—(OM), C(R)O(P═O)—(OC(R)O(C═O)YR), C(R)O(C═O)(CHR)N(R), C(R)O(C═O)N(R), and C(R)O(C═O)N(CHCOR).'}28. A compound according to wherein R is hydrogen.29. A compound according to wherein R is methyl.30. (canceled)31. A compound according to wherein Ris alkyl.32. (canceled)33. (canceled)34. (canceled)35. A compound according to wherein Ris hydrogen36. A ...

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Номер записи: 58
17-04-2014 дата публикации

STRUCTURAL MODIFICATION OF 19-NORPROGESTERONE I: 17-ALPHA-SUBSTITUTED-11-BETA-SUBSTITUTED-4-ARYL AND 21-SUBSTITUTED 19-NORPREGNADIENEDIONE AS NEW ANTIPROGESTATIONAL AGENTS

Номер: US20140107089A1
Автор: Acosta Carmie K., Blye Richard P., Cessac James W., Kim Hyun K., Rao Pemmaraju N., Simmons Anne Marie
Принадлежит: The United States of America, as represented by the Secretary, Department of Health and Human Serv

Disclosed are compounds having the general formula: 160-. (canceled)62. The compound in accordance with claim 61 , wherein Ris a member selected from the group consisting of —N(CH) claim 61 , —NCH claim 61 , —NCHO claim 61 , —C(O)CH claim 61 , —O(CH)N(CH) claim 61 , —O(CH)NCH claim 61 , and —O(CH)NCH.63. The compound in accordance with claim 61 , wherein Ris a member selected from the group consisting of hydrogen claim 61 , alkyloxy claim 61 , alkoxy claim 61 , —SAc claim 61 , —SCN claim 61 , —OC(O)CHN(CH) claim 61 , and —OC(O)R claim 61 , wherein Ris a member selected from the group consisting of alky claim 61 , alkoxy ester and alkoxy.64. The compound in accordance with claim 63 , wherein Ris —OC(O)Rand Ris a member selected from the group consisting of-CHCH claim 63 , —CHOCH claim 63 , and —OCH.65. The compound in accordance with claim 61 , wherein Ris an alkoxy selected from the group consisting of methoxy claim 61 , ethoxy claim 61 , vinyloxy claim 61 , ethynyloxy and cyclopropyloxy.66. The compound in accordance with claim 61 , wherein Ris a member selected from the group consisting of alkyl claim 61 , alkoxy claim 61 , acyloxy and hydroxy.67. The compound in accordance with claim 61 , wherein Ris alkyl.68. The compound in accordance with claim 61 , wherein X is ═O.69. The compound in accordance with claim 61 , wherein X is ═N—OR.70. The compound in accordance with claim 61 , wherein Ris acyloxy selected from the group consisting of —OC(O)H claim 61 , —OC(O)CHCHand —OC(O)CH.71. The compound in accordance with claim 61 , wherein the compound is:{'sup': '1', 'sub': 3', '2, 'Ris —N(CH);'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3', 'Ris methoxymethyl;'}{'sup': '4', 'Ris methyl; and'}X is ═O;{'sup': '1', 'sub': 4', '8, 'Ris —NCH;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3', 'Ris acetoxy;'}{'sup': '4', 'Ris methyl; and'}X is ═O;{'sup': '1', 'sub': 5', '10, 'Ris —NCH;'}{'sup': '2', 'Ris hydrogen;'}{'sup': '3', 'Ris acetoxy;'}{'sup': '4', 'Ris methyl; and'}X is ═O;{'sup': ...

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Номер записи: 59
10-02-2022 дата публикации

ESTRA-1,3,5(10)-TRIENE COMPOUNDS CONDENSED IN POSITION 16(17) WITH A PYRAZOLE RING AS INHIBITORS OF 17-HSD1

Номер: US20220041647A1
Автор: HAKOLA Marjo, HIRVELÄ Leena, KOSKIMIES Pasi, Linnanen Tero, STJERNSCHANTZ Camilla
Принадлежит:

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof 3. The compound according to claim 1 , whereinR1 is selected from the group consisting of H, F and Cl,R2 is selected from the group consisting of H, F and Cl, and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R3, R4 and R5 are as defined in ,'}or a pharmaceutically acceptable salt thereof.4. The compound according to claim 1 , whereinR1 is selected from the group consisting of H, F and Cl,R2 is H or F, and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R3, R4 and R5 are as defined in ,'}or a pharmaceutically acceptable salt thereof.5. The compound according to claim 1 , whereinR1 is HR2 is F, and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'R3, R4 and R5 are as defined in ,'}or a pharmaceutically acceptable salt thereof.7. The compound according to claim 1 , whereinthe 1 to 3 heteroatoms of the 5 membered unsubstituted unsaturated or aromatic heterocycle are independently selected from nitrogen and oxygen,the 1 to 3 heteroatoms of the 5 membered unsubstituted unsaturated or aromatic heterocycle are independently selected from 2 nitrogens and 1 sulphur, orthe 1 to 3 heteroatoms of the 5 membered unsubstituted unsaturated or aromatic heterocycle are independently selected from 2 nitrogens and 1 oxygen,or a pharmaceutically acceptable salt thereof.8. The compound according to claim 1 , whereinR3 is H,{'sub': '2', 'R4 is a 5 membered unsaturated or aromatic heterocycle with 1 to 3 heteroatoms selected from the group consisting of nitrogen, and oxygen, optionally substituted with one or two substituent(s) selected from the group consisting of CN, C1-4-alkyl, C1-3-alkoxy, halogen and C(O)N(C1-3-alkyl),'}or a pharmaceutically acceptable salt thereof.11. The compound according to claim 1 , whereinR1 is H,R2 is H or F,R3 is H,{'sub': '2', 'R4 is a 6 membered aromatic heterocycle with 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, ...

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Номер записи: 60
23-01-2020 дата публикации

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Номер: US20200024303A1
Автор: Qian Xiangping
Принадлежит:

Chemical entities that are novel compounds, pharmaceutical compositions and methods of treatment of cancer are described. 2. (canceled)3. (canceled)4. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare independently chosen from hydrogen claim 1 , hydroxy claim 1 , and methyl.5. The compound of claim 1 , wherein Ris hydroxy.6. (canceled)7. The compound of claim 1 , wherein Rand Rare joined together with any intervening atoms to form an oxirane ring.8. (canceled)9. (canceled)10. The compound of claim 1 , wherein Ris chosen from hydrogen and —OCOCH.11. The compound of claim 1 , wherein Rand Ware independently chosen from hydrogen and optionally substituted alkyl.12. (canceled)13. The compound of claim 1 , wherein Ris chosen from hydrogen claim 1 , methyl claim 1 , and hydroxymethyl.1417.-. (canceled)18. The compound of claim 1 , wherein represents a single bond.19. The compound of claim 1 , wherein represents a double bond.2931.-. (canceled)32. The compound of claim 1 , wherein Ris chosen from 2-morpholinoethyl claim 1 , 2-(pyrrolidin-1-yl)ethyl claim 1 , and 2-(3-oxopiperazin-1-yl)ethyl.3340.-. (canceled)41. The compound of claim 1 , wherein the compound is selected from:(1R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl (2-(pyrrolidin-1-yl)ethyl) carbonate,(1R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-7-yl (2-morpholinoethyl) carbonate,(1R,2R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-1-(2-oxo-2H-pyran-5-yl)-7-(((2-(pyrrolidin-1-yl)ethoxy)carbonyl)oxy)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-2-yl acetate,(1R,2R,2aR,3aS,3bR,5aR,7S,9aS,9bS,11aR)-9a,11a-dimethyl-7-(((2-morpholinoethoxy)carbonyl)oxy)-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7]indeno[1,7a-b]oxiren-2-yl acetate,(1R,2R,2aR,3aS,3bR,5aS,7S,9aR, ...

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Номер записи: 61
28-01-2021 дата публикации

HYDROXYSTEROID COMPOUNDS, THEIR INTERMEDIATES, PROCESS OF PREPARATION, COMPOSITION AND USES THEREOF

Номер: US20210024572A1
Автор: DUGAR Sundeep, Mahajan Dinesh, SCHREINER George Frederic
Принадлежит:

The present invention relates to novel steroidal compounds of formula (I), process for preparation of the same and composition comprising these compounds. 4. (canceled)5. The compound of claim 3 , wherein the compound is selected from the group consisting of:xiii. (10R,11S,13S,17S)-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid;xiv. (10R,11S,13S,17S)-11-hydroxy-N,N,10,13-tetramethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxamide;xv. (10R,11S,13S,17S)-17-acetyl-1-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;xvi. (10R,11S,13S,17S)-11-hydroxy-17-((R)-1-hydroxyethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;xxxiii. (10R,11S,13S,17S)-11,17-dihydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;xxxiv. (10R,11S,13S)-11-hydroxy-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione;xli. (10R,11S,13S,17S)-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxamide;xlii. (10R,11S,13S,17S)-11-hydroxy-17-(hydroxymethyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;xliii. (10R,11S,13S,17S)-17-((dimethylamino)methyl)-11-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;lvi. (8S,9S,10R,11S,13S,14S,Z)-11-hydroxy-17-(hydroxyimino)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;lvii. (8S,9S,10R,11S,13S,14S)-17-amino-11-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;lviii. (8S,9S,10R,11S,13S,14S)-11-hydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one; andlix. (8S,9S, ...

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Номер записи: 62
29-01-2015 дата публикации

NANOPARTICLE PEG MODIFICATION WITH H-PHOSPHONATES

Номер: US20150030541A1
Автор: Rogers Thomas E.
Принадлежит:

The present invention provides phosphonate conjugates and methods of preparing the phosphonate conjugates so as to allow, for example, improved methods and compounds for modifying the surface of a nanoparticle to increase in vivo circulation times and targeted delivery performance. 120-. (canceled)22. The method of claim 21 , wherein the primary amine compound claim 21 , the carbonyl compound claim 21 , and the H-phosphonate compound are combined at a molar ratio of 1:2:2 claim 21 , respectively.23. The method of claim 21 , wherein the primary amine compound and the carbonyl compound are combined before being combined with the H-phosphonate compound.24. The method of claim 21 , wherein the H-phosphonate compound and the carbonyl compound are combined before being combined with the primary amine compound.25. The method of claim 21 , wherein two of the H-phosphonate compounds are adjacently associated with a bilayer of a liposome before being combined with the primary amine compound and the carbonyl compound claim 21 , wherein each of Rand Ris independently selected from the group consisting of a lipid and cholesterol.27. The compound of claim 26 , wherein each of Rand Ris independently selected from the group consisting of a lipid and cholesterol; and each of Land Lis a bond.28. The compound of claim 27 , wherein the lipid is saturated or unsaturated C-Calkyl.29. The compound of claim 26 , wherein Ris a stealth agent.30. The compound of claim 29 , wherein the stealth agent is selected from the group consisting of PEG claim 29 , PEG claim 29 , PEG claim 29 , PEG claim 29 , PEGand PEG.31. The compound of claim 26 , wherein Ris C-Calkyl and Lis a bond.33. (canceled)34. The targeted delivery composition of claim 41 , wherein the nanoparticle is a liposome and each of Rand Ris associated with a bilayer of the liposome and independently selected from the group consisting of a lipid and cholesterol.35. (canceled)36. The targeted delivery composition of claim 42 , wherein ...

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Номер записи: 63
01-02-2018 дата публикации

DEUTERATED BILE ACIDS

Номер: US20180030084A1
Автор: Dias Lucas de Oliveira Susana, FINCH Michael D., Low Walter, Munshi Cyrus B., Rodrigues Cecilia M.P., STEER Clifford
Принадлежит:

This disclosure relates to deuterated bile acid compositions. A deuterated compound is selected from the disclosed groups of bile acids and their derivatives, analogs and salts. At least one of the hydrogen atoms in the compound is replaced with deuterium. 117.-. (canceled)21. A pharmaceutical composition comprising the composition according to and a carrier.22. A pharmaceutical composition comprising the composition according to and a carrier.23. A pharmaceutical composition comprising the composition according to and a carrier.24. A method for treating a patient suffering from a neurodegenerative disorder or acute kidney injury claim 18 , comprising administering to the patient a therapeutically effective amount of a composition according to .25. The method according to claim 24 , wherein the patient suffers from a neurodegenerative disorder selected from Alzheimer's disease and Parkinson's disease. This application is a continuation of U.S. application Ser. No. 14/520,889, filed Oct. 22, 2014, and entitled “DEUTERATED BILE ACIDS”, which claims priority from U.S. Provisional Application Ser. No. 61/894,012, filed Oct. 22, 2013, and entitled “DEUTERATED BILE ACIDS”.Ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA) are anti-apoptotic molecules with protective effects against several neurodegenerative disorders such as Alzheimer's and Parkinson's diseases as well as against acute kidney injury. Both UDCA and TUDCA block the initiating event of the apoptotic process, in part, through stabilizing the mitochondrial membrane potential, a mechanism that enhances the integrity of the mitochondria. Enhanced mitochondrial integrity abolishes the release of several mitochondrial proteins such as cytochrome C into the cytosol, thereby preventing the onset of apoptosis. Further, UDCA and TUDCA upregulate several pathways that function synergistically with their anti-apoptotic properties.The kinetic deuterium isotope effect (KDIE) is a function of enhanced carbon ...

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Номер записи: 64
17-02-2022 дата публикации

OXYSTEROLS AND METHODS OF USE THEREOF

Номер: US20220048943A1
Автор: Harrison Boyd L., Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R, R, and Rare as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions. 2. (canceled)3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris substituted Calkyl.4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris unsubstituted Calkyl.5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CH claim 1 , —CF claim 1 , —CHOCH claim 1 , —CH(CH)(CF) claim 1 , —CHCH claim 1 , or —CH(CH).6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris —CHor —CHCH.7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris unsubstituted Calkyl.8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris substituted or unsubstituted ethyl claim 1 , substituted or unsubstituted isopropyl claim 1 , or substituted or unsubstituted tert-butyl.911-. (canceled)12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein represents a single bond.1617-. (canceled)2021-. (canceled)23. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.24. A method of inducing sedation or anesthesia comprising administering to a subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a pharmaceutical composition thereof.25. A method for treating a disorder claim 1 , comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , or a pharmaceutical composition thereof; wherein the disorder is a gastrointestinal (GI) disorder ...

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Номер записи: 65
11-02-2016 дата публикации

16- AND 17- DEUTERATED ESTROGEN-3-SULFAMATES AS ESTROGENIC AGENTS

Номер: US20160039866A1
Автор: Potter Barry Victor Lloyd
Принадлежит:

The present invention relates to novel derivatives of estradiol, in particular to deuterated derivatives of estradiol sulfamates. The present invention also relates to compositions comprising said novel derivatives, as well as to uses of said novel derivatives and compositions comprising said derivatives. 2. The compound of claim 1 , wherein Ris deuterium and Rand Rare each H.3. The compound of claim 1 , wherein Ris deuterium and Rand Rare each H.4. The compound of claim 1 , wherein Ris deuterium and Rand Rare each H.5. The compound of claim 1 , wherein at least two of R claim 1 , Ror Rare deuterium.6. The compound of claim 5 , wherein Ris H and Rand Rare each deuterium.7. The compound of claim 5 , wherein Ris H and Rand Rare each deuterium.8. The compound of claim 5 , wherein Ris H and Rand Rare each deuterium.9. The compound of claim 1 , wherein each of R claim 1 , Ror Rare simultaneously deuterium.10. The compound according to claim 1 , wherein Rand Rare each simultaneously H.11. The compound according to claim 1 , wherein Rand Rare each simultaneously deuterium.13. A The compound according to claim 1 , wherein any atom not designated as deuterium is present at its natural abundance.14. A composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and at least one pharmaceutically acceptable carrier.15. A medicament comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof.16. A method of hormone replacement therapy comprising administering to a patient in need thereof the compound of claim 1 , or a pharmaceutically acceptable salt thereof.17. A method of contraception comprising administering to a patient in need thereof the compound of claim 1 , or a pharmaceutically acceptable salt thereof.18. (canceled)19. (canceled) The present invention relates to novel derivatives of estradiol, in particular to deuterated derivatives of estradiol. The present invention also relates to compositions ...

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Номер записи: 66
24-02-2022 дата публикации

NOVEL DRUG DELIVERY CONJUGATED MOIETY FOR ORAL ADMINISTRATION OF DRUG UNSUITABLE FOR ORAL ADMINISTRATION AND PREPARATION METHOD THEREOF

Номер: US20220054644A1
Автор: JEON Ok-cheol, JUNG Hyukjun, Kim Kyungjin, LEE Myungyun, NAM Hwajung, YUN Jisuk
Принадлежит:

The present invention provides a novel drug delivery conjugated moiety for oral administration of a drug that is not suitable for oral administration or a pharmaceutically acceptable salt thereof. When the drug delivery conjugated moiety of the present invention or a pharmaceutically acceptable salt thereof is combined with a drug, which is not suitable for oral administration, and is administered orally, it exhibits an excellent absorption rate without decreasing the biological activities of the drug. Moreover, the drug delivery conjugated moiety of the present invention or a pharmaceutically acceptable salt thereof can be easily prepared in a few steps, which is very advantageous in terms of mass production. 121-. (canceled)23. The method of claim 22 , wherein B is a bile acid residue selected from the group consisting of cholic acid claim 22 , deoxycholic acid claim 22 , chenodeoxycholic acid claim 22 , lithocholic acid claim 22 , ursocholic acid claim 22 , ursodeoxycholic acid claim 22 , isoursodeoxycholic acid claim 22 , lagodeoxycholic acid claim 22 , glycocholic acid claim 22 , taurocholic acid claim 22 , glycodeoxycholic acid claim 22 , glycochenodeoxycholic acid claim 22 , dehydrocholic acid claim 22 , hyocholic acid claim 22 , and hyodeoxycholic acid residues.24. The method of claim 22 , wherein P1 is C-Calkyl or benzyl.25. The method of claim 22 , wherein P2 is tert-butyloxycarbonyl (Boc) claim 22 , benzyloxycarbonyl (Cbz) claim 22 , p-methoxybenzylcarbonyl (Moz) claim 22 , or fluorenylmethyloxycarbonyl (FMoc).26. The method of claim 22 , wherein the lysine in (S1) is -lysine.27. The method of claim 22 , wherein the reaction in (S2) is performed under peptide coupling reaction conditions.28. The method of claim 22 , wherein the reaction in (S4) is performed under peptide coupling reaction conditions.29. The method of claim 22 , wherein the connecting in (S5) is performed under conditions for amidation of an ester.30. The method of claim 22 , wherein the ...

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Номер записи: 67
24-02-2022 дата публикации

METHODS OF MAKING CHOLIC ACID DERIVATIVES AND STARTING MATERIALS THEREFOR

Номер: US20220056070A1
Автор: Hossain Sk Samad, Paul Bernhard J., Reddy Jayachandra P, Reid J. Gregory
Принадлежит:

Methods of making cholic acid derivatives, particularly ursodeoxycholic acid, tauroursodeoxycholic acid, 7-ketolithocholic acid, obeticholic acid, their carboxylate salts and carboxylate esters, and starting materials and intermediates therefor. 2) The compound of claim 1 , wherein X is oxy and Y is oxy.3) The compound of claim 1 , wherein X is oxy claim 1 , Y is oxy claim 1 , and Rand Rare joined to form with X and Y a spirofused heterocyclic ring at the 3-position of Formula I.5) The compound of claim 4 , of Formula Ia claim 4 , wherein Ris methyl.6) The compound of claim 4 , of Formula Ia claim 4 , wherein Ris ethyl.7) The compound of claim 4 , of Formula Ib claim 4 , wherein Ris methyl.8) The compound of claim 4 , of Formula Ib claim 4 , wherein Ris ethyl.9) (canceled)10) (canceled)11) (canceled)12) (canceled)13) (canceled)14) (canceled)15) (canceled)16) (canceled)18) The compound of claim 17 , wherein X is oxy and Y is oxy.19) The compound of claim 17 , wherein X is oxy claim 17 , Y is oxy claim 17 , and Rand Rare joined to form with X and Y a spirofused heterocyclic ring at the 3-position of Formula III.21) The compound of claim 20 , of Formula IIIa claim 20 , wherein Ris methyl.22) The compound of claim 20 , of Formula IIIa claim 20 , wherein Ris ethyl.23) The compound of claim 20 , of Formula IIIb claim 20 , wherein Ris methyl.24) The compound of claim 20 , of Formula IIIb claim 20 , wherein Ris ethyl.25) A method of converting the compound of to ursodeoxycholic acid or a carboxylate salt at the 24-position thereof claim 1 , comprising:a) reducing the 5,6-alkene double bond to a dihydro product with 5β stereochemistry;b) hydrolyzing the electronegative groups at the 3-position to produce a 3-ketone;c) reducing the 3-ketone to 3α-hydroxyl;d) reducing the 7-ketone to 7β-hydroxyl; and{'sub': 1', '2', '1, 'e) when Ris alkyl or aryl, hydrolyzing the —CORester to a carboxylic acid;'}wherein steps (a)-(e) may be carried out sequentially, simultaneously, or in any ...

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Номер записи: 68
15-02-2018 дата публикации

Compounds that are Analogs of Squalamine, Used as Antibacterial Agents

Номер: US20180042942A1
Автор: Jean-Michel Brunel, Jean-Pascal MARC
Принадлежит: VIRBAC SA

The invention relates to compounds of formula (I), to the pharmaceutical compositions comprising same, and to the use thereof in the treatment of bacterial, fungal, viral and parasitic infections or in the treatment of cancer in humans or animals. In formula (I), R1 and R2 are as defined in claim 1.

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Номер записи: 69
16-02-2017 дата публикации

SELECTIVE GLUCOCORTICOID RECEPTOR LIGANDS

Номер: US20170044208A1
Автор: Dawson William, Payne Jane Helen, Ray William David
Принадлежит:

Described herein are certain steroid derivative compounds, for example of formula (I): wherein X, X, XL, and Ar are as defined herein, pharmaceutical compositions comprising such compounds, the use of such compounds and compositions to specifically target glucocorticoid action, and the use of such compounds and compositions in the treatment of acute and chronic inflammatory conditions, in particular rheumatoid arthritis, haematological and other malignancies, and for causing immunosuppression in the prevention or treatment of transplant rejection, as well as methods of preparing such compounds. 3. The compound of claim 1 , wherein Ar is independently selected from phenyl claim 1 , pyridinyl claim 1 , thiazolyl claim 1 , pyrrolyl claim 1 , furanyl claim 1 , benzothiazolyl claim 1 , and benzoxazolyl claim 1 , optionally substituted with one or more substituents R.4. The compound of claim 1 , wherein Ar is independently phenyl or pyridinyl claim 1 , optionally substituted with one or more substituents R.5. The compound of claim 1 , wherein Ris independently selected from —F claim 1 , —OMe claim 1 , and —COMe.6. The compound of claim 1 , wherein L is L.7. The compound of claim 1 , wherein Lis -L-O— claim 1 , wherein -L- is independently saturated Calkylene.8. The compound of claim 1 , wherein Lis —CHCH— or —CHCHCH—.9. The compound of wherein Ris —H.1112.-. (canceled)13. A method of treating a medical condition selected from an inflammatory condition claim 1 , a rheumatoid disease claim 1 , a malignancy claim 1 , a vascular disease or a lung disease claim 1 , comprising administering to a subject in need thereof a therapeutically effective amount of the compound of .14. The method of wherein treating the medical condition comprises one or more of (i) inducing apoptosis in target cells in the subject (ii) causing immunosuppression in the subject and (iii) preventing or treating transplant rejection in the subject.15. The method of wherein the medical condition is selected ...

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Номер записи: 70
25-02-2021 дата публикации

COMPOUNDS AND METHODS FOR TRANS-MEMBRANE DELIVERY OF MOLECULES

Номер: US20210052736A1
Автор: DUBROVSKY Joseph, Grimberg Hagit, ZIV llan
Принадлежит: APOSENSE LTD

The Invention provides a novel delivery system for delivery of drugs across biological membranes. It provides novel chemical conjugates that comprise said delivery system, methods for synthesis of said compounds, and methods for utilization of said delivery system, among others, for delivery of genetic drugs into tissues and cells, in vitro, ex vivo, and in vivo, for the treatment of various medical disorders. 168.-. (canceled)70. A Conjugate according to claim 69 , wherein g is an integer of 0 claim 69 , 1 claim 69 , or 2.71. A Conjugate according to claim 69 , wherein c and d each stands independently for an integer of 1 claim 69 , 2 or 3; c and d can be the same or different.72. A Conjugate according to claim 69 , wherein L is difluorobenzylamine.73. A Conjugate according to claim 69 , wherein G claim 69 , G claim 69 , G claim 69 , Gare all hydrogen atoms.74. A Conjugate according to claim 69 , wherein X is TEOC [2-(trimethylsilyl)ethyl carbamate] claim 69 , or Fmoc.76. A Conjugate according to claim 69 , comprising E claim 69 , E′ claim 69 , or E″ moieties according to any of Formulae (II) claim 69 , (III) claim 69 , (V) claim 69 , (V) claim 69 , (VI) claim 69 , (VII) claim 69 , (VIII) claim 69 , (VIII-H) claim 69 , (VIII-M) claim 69 , (IX) claim 69 , (X) claim 69 , (XI) claim 69 , (XII) claim 69 , (XIIa) claim 69 , (XIII) claim 69 , (XIIIa) claim 69 , (XV) claim 69 , (XIV-H) claim 69 , (XIV-M) claim 69 , (XV) claim 69 , (XV-H) claim 69 , (XV-M) claim 69 , (XVI) claim 69 , (XVI-H) claim 69 , (XVI-M) claim 69 , linked to a drug.77. A pharmaceutical composition claim 69 , comprising a Conjugate according to claim 69 , and a pharmaceutically-acceptable salt or carrier.78. A Conjugate according to claim 69 , wherein D is an Oligonucleotide Drug (OD) claim 69 , including pharmaceutically-acceptable salts claim 69 , hydrates claim 69 , solvates and metal chelates of the respective Conjugates.79. A Conjugate according to claim 69 , wherein the OD is a Dicer substrate ...

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Номер записи: 71
13-02-2020 дата публикации

Dihydroartemisinin-steroid conjugate and preparation method and application thereof

Номер: US20200046679A1
Автор: Jinghua Zhang, Zhengwu Shen
Принадлежит: Yunbaiyao Zhengwu Science And Technology (shanghai) Co Ltd

Described is a dihydroartemisinin-steroid conjugate of formula (I), or a pharmaceutically acceptable salt thereof, where position 10 of dihydroartemisinin is linked to the steroid through a linker X. This application further provides a preparation method of the dihydroartemisinin-steroid conjugate and an application of the dihydroartemisinin-steroid conjugate in the preparation of a drug for treating cancer. The dihydroartemisinin-steroid conjugate of the invention exhibits potent inhibitory activity against various tumor cells and low cytotoxicity, moreover, the conjugate is capable of penetrating the blood-brain barrier, having a broad application prospect.

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Номер записи: 72
25-02-2016 дата публикации

Progesterone analogs and uses related thereto

Номер: US20160052957A1
Автор: David B Guthrie, Dennis C. Liotta, Donald G. Stein, Iqbal Sayeed, Mark A Lockwood, Michael G Natchus
Принадлежит: EMORY UNIVERSITY

This disclosure relates to progesterone derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation resulting from traumatic brain injury or stroke.

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Номер записи: 73
25-02-2016 дата публикации

Radiolabeled cationic steroid antimicrobials and diagnostic methods

Номер: US20160052959A1
Автор: Paul B. Savage
Принадлежит: BRIGHAM YOUNG UNIVERSITY

The disclosure provides compounds, methods, and kits for diagnosis, detection, screening, and imaging of a disease condition (e.g., infection, cancer, tumor, neoplasia), in vitro, ex vivo, and/or in vivo. Certain embodiments include administering a cationic steroid antimicrobial “CSA” or “ceragenin”), the CSA including a steroidal backbone and a heterocyclic ring separated from the steroidal backbone by at least 4 atoms (and up to 24 atoms or more), to a subject having or at risk of having a disease condition in an amount effective to diagnose, detect, screen for or image the disease condition in the subject.

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Номер записи: 74
25-02-2021 дата публикации

CONDUCTING REACTIONS IN LEIDENFROST-LEVITATED DROPLETS

Номер: US20210053921A1
Автор: Bain Ryan M., Cooks Robert Graham, Pulliam Christopher
Принадлежит: PURDUE RESEARCH FOUNDATION

The invention generally relates to conducting reactions in Leidenfrost-levitated droplets. 1. A method for forming and collecting a reaction product , the method comprising conducting a reaction within a Leidenfrost-levitated droplet while maintaining a substantially constant volume of the Leidenfrost-levitated droplet , thereby forming a reaction product within the Leidenfrost-levitated droplet; andcollecting the reaction product in the Leidenfrost-levitated droplet without evaporating the Leidenfrost-levitated droplet.2. The method according to claim 1 , further comprising analyzing the reaction product.3. The method according to claim 2 , wherein analyzing is by a mass spectrometry technique.4. The method according to claim 1 , wherein maintaining the substantially constant volume comprises introducing droplets of pure solvent or the reaction mixture to the Leidenfrost-levitated droplet.5. The method according to claim 4 , wherein a rate at which the droplets of the pure solvent or reaction mixture are introduced to the Leidenfrost-levitated droplet is dependent on an evaporation rate of the Leidenfrost-levitated droplet.6. The method according to claim 1 , wherein the method further comprises conducting multiple reactions in multiple separate Leidenfrost-levitated droplets.7. The method according to claim 6 , wherein the multiple separate Leidenfrost-levitated droplets are merged with each other.8. The method according to claim 6 , wherein the multiple reactions are the same.9. The method according to claim 6 , wherein the multiple reactions are different.10. The method according to claim 1 , wherein the method is conducted without the use of surfactants.11. (canceled)12. A method for forming and collecting a reaction product claim 1 , the method comprising:introducing a first liquid droplet onto a heated surface that is at a temperate that is at or above a Leidenfrost point of the first liquid such that the first liquid droplet levitates on the heated surface, ...

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Номер записи: 75
25-02-2021 дата публикации

Panaxadiol glycoside derivative and preparation method and application thereof

Номер: US20210054019A1
Автор: Jun Zhang, Quanhai Liu
Принадлежит: Suzhou Ji Er Biological Medicine Co Ltd

The invention discloses a panaxadiol glycoside derivative and a preparation method and application thereof. Such compounds show strong anti-inflammatory effects in vitro and in animal model experiments, and thus can be used to prepare anti-inflammatory drugs, especially can be used for treating asthma and COPD. In the experiment, the above-mentioned compounds have obvious effects on asthma and COPD, and the efficacy of the high-dose group is superior than that of dexamethasone and budesonide. Even under the dose much exceeding the therapeutic dose, no obvious affect on blood routine and blood glucoseis observed. It has high industrial prospects in the field of anti-inflammatory drugs, especially in the field for treating asthma and COPD.

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Номер записи: 76
23-02-2017 дата публикации

SHIP INHIBITORS AND USES THEREOF

Номер: US20170051006A1
Автор: Chisholm John D., KERR William G.
Принадлежит: The Research Foundation for The State University of New York

The present invention relates to SHIP inhibitor compounds and methods for using these compounds. In particular, the present invention discloses the following methods: (i) a method of treating graft versus host disease in a subject; (ii) a method of inhibiting a SHIP1 protein in a cell; (iii) a method of selectively inhibiting a SHIP1 protein in a cell; (iv) a method for treating or preventing graft-versus-host disease (GVHD) in a recipient of an organ or tissue transplant; (v) a method of modulating SHIP activity in a cell expressing SHIP1 or SHIP2; (vi) a method of ex vivo or in vitro treatment of transplants; (vii) a method of inhibiting tumor growth and metastasis in a subject; (viii) a method of treating a hematologic malignancy in a subject; (ix) a method of inducing apoptosis of multiple myeloma cells; (x) a method of treating multiple myeloma in a subject; (xi) a method of inhibiting the proliferation of a human breast cancer cell; and (xii) a method of treating breast cancer in a subject. 2. A SHIP inhibitor compound according to claim 1 , wherein Ris hydrogen.7. A compound according to claim 1 , wherein Ris hydrogen.8. A compound according to claim 1 , wherein Xis hydroxy.9. A compound according to claim 7 , wherein Xis hydroxy.10. A SHIP inhibitor compound according to claim 1 , wherein Ris alkyl.12. A compound according to claim 10 , wherein claim 10 , wherein Rrepresents a 1 claim 10 , 5-dimethylhexyl group.13. A compound according to claim 10 , wherein Xis hydroxy.14. A compound according to claim 10 , wherein Ris substituted or unsubstituted amino.15. A compound according to claim 10 , wherein Ris methyl. This application is a divisional of U.S. application Ser. No. 13/640,162, filed Oct. 9, 2012, and published as 2013-0102577A1 on Apr. 25, 2013, which is a §371 U.S. National Phase application of PCT application PCT/US11/31930, filed Apr. 11, 2011, and published as WO 2011/127465 on Oct. 13, 2011, and claims priority benefit of U.S. Provisional Patent ...

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Номер записи: 77
23-02-2017 дата публикации

PHARMACEUTICAL COMPOSITIONS AND METHODS

Номер: US20170051007A1
Автор: "OBrien Rebecca", Altschul Randice Lisa, Arment Anthony R., Kesel Andreas J., Rapkin Myron, Theise Neil David
Принадлежит:

This invention relates the use of cortisol blockers (e.g., glucocorticoid receptor [GR] antagonists) for the treating or preventing viral infections, treating or preventing treatment resistant prostate cancer, treating or preventing neoplasia, and treating or preventing infection related to acute or chronic injury or disease. 3. The pharmaceutical composition of in a dosage form selected from the group consisting of a minicapsule claim 2 , a capsule claim 2 , a tablet claim 2 , an implant claim 2 , a troche claim 2 , a lozenge claim 2 , a minitablet claim 2 , a temporary or permanent suspension claim 2 , an injectable claim 2 , an ovule claim 2 , a suppository claim 2 , a wafer claim 2 , a chewable tablet claim 2 , a quick or fast dissolving tablet claim 2 , an effervescent tablet claim 2 , a buccal or sublingual solid claim 2 , a granule claim 2 , a film claim 2 , a sprinkle claim 2 , a pellet claim 2 , a topical formulation claim 2 , a patch claim 2 , a bead claim 2 , a pill claim 2 , a powder claim 2 , a triturate claim 2 , a smart pill claim 2 , a smart capsule claim 2 , a platelet claim 2 , a strip claim 2 , and a sachet.4. The pharmaceutical composition of in a dosage form for topical application claim 2 , and at least one pharmaceutically acceptable excipient.5. The pharmaceutical composition of in a dosage form for topical application wherein said formulation is in a form selected from the group consisting of: cream claim 2 , lotion claim 2 , gel claim 2 , oil claim 2 , ointment claim 2 , suppository claim 2 , spray claim 2 , foam claim 2 , liniment claim 2 , aerosol claim 2 , buccal and sublingual tablet or a transdermal device or patch for absorption through the skin or mucous membranes.632-. (canceled) This application claims benefit under 35 U.S.C. §119(e) of U.S. Provisional Patent Application No. 62/282,525, filed Aug. 3, 2015; U.S. Provisional Patent Application No. 62/220,583, filed Sep. 18, 2015; U.S. Provisional Patent Application No. 62/241,875, ...

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Номер записи: 78
23-02-2017 дата публикации

ANDROSTANE AND PREGNANE STEROIDS WITH POTENT ALLOSTERIC GABA RECEPTOR CHLORIDE IONOPHORE MODULATING PROPERTIES

Номер: US20170051008A1
Автор: COOK Edgar, KAMINSKI Rafal, KEPLER John, NAVARRO Herman, Orr Matthew, ROGAWSKI Michael, RUNYON Scott P.
Принадлежит:

This invention describes compounds of Structures 1, 2, and 3 and their use as allosteric modulators of the GABA receptor chloride ionophore complex to alleviate stress, anxiety, mood disorders, seizures, depression, treatment of drug and alcohol abuse, memory, premenstrual disorders, and neural system damage. 12-. (canceled)410-. (canceled)11. The method for treatment of a condition selected from the group consisting of convulsions , epilepsy , depression , drug and alcohol abuse , anxiety , memory problems , and neural system damage in humans or animals , comprising:{'claim-ref': {'@idref': 'CLM-00003', 'claim 3'}, 'administering, to a human or animal in need thereof, a pharmaceutical composition comprising an effective amount of the compound of and a pharmaceutically acceptable carrier.'}12. A pharmaceutical composition , comprising:{'claim-ref': {'@idref': 'CLM-00003', 'claim 3'}, 'the compound according to , and'}a pharmaceutically acceptable carrier. The present application is a continuation of U.S. Ser. No. 13/974,633, filed Aug. 23, 2013, now allowed, which is a divisional of U.S. Ser. No. 12/664,470, filed May 5, 2010, now U.S. Pat. No. 8,575,375, which is a 371 application of PCT/US08/67059, filed Jun. 16, 2008, and claims priority to U.S. Provisional Ser. No. 60/944,257, filed Jun. 15, 2007.Field of InventionThe present invention relates to androstane and pregnane steroid compounds and their use as allosteric modulators of the GABA receptor chloride ionophore complex and their use to alleviate stress, anxiety, mood disorders, seizures, depression, treatment of drug and alcohol abuse, memory, premenstrual disorders, and neural system damage.Discussion of the BackgroundThe present invention encompasses methods and compounds related to endogenous metabolites of androstane and pregnane steroids. Certain endogenous steroids including allopregnanolone (3α-hydroxy-5α-pregnane-20-one) and the A-ring reduced metabolite of progesterone are potent stereoselective ...

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Номер записи: 79
10-03-2022 дата публикации

OLIGOMER-CORTICOSTEROID CONJUGATES

Номер: US20220072010A1
Автор: Bentley Michael D., Harris J. Milton, Riggs-Sauthier Jennifer, Zhang Wen
Принадлежит:

The invention provides corticosteroids that are chemically modified by covalent attachment of a water-soluble oligomer. A compound of the invention, when administered by any of a number of administration routes, exhibits a reduced biological membrane crossing rate as compared to the biological membrane crossing rate of the corticosteroid not attached to the water-soluble oligomer. 1. A compound comprising a corticosteroid residue covalently attached via a linkage to a water-soluble , non-peptidic oligomer.2. The compound of claim 1 , wherein the linkage is a stable linkage.3. The compound of claim 1 , wherein the linkage is a degradable linkage.4. The compound of claim 1 , wherein the linkage is a hydrazone linkage.5. The compound of claim 1 , wherein the weight average molecular weight of the water-soluble claim 1 , non-peptidic oligomer is less than 400 Daltons.6. The compound of claim 1 , wherein the corticosteroid residue is covalently attached at a position other than through the 16 or 17 positions of the corticosteroid residue to the water-soluble claim 1 , non-peptidic oligomer.7. The compound of claim 1 , wherein the corticosteroid residue is covalently attached at a position other than through D-ring atom positions of the corticosteroid residue to the water-soluble claim 1 , non-peptidic oligomer.8. The compound of claim 1 , wherein the corticosteroid residue is covalently attached at a position selected from the consisting of A-ring atom positions claim 1 , B-ring atom positions claim 1 , and C-ring atom positions of the corticosteroid residue to the water-soluble claim 1 , non-peptidic oligomer.9. The compound of claim 8 , wherein the corticosteroid residue is covalently attached at A-ring atom positions of the corticosteroid residue to the water-soluble claim 8 , non-peptidic oligomer.10. The compound of claim 1 , wherein the corticosteroid residue is covalently attached at the 3 position of the corticosteroid residue to the water-soluble claim 1 , non- ...

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Номер записи: 80
03-03-2016 дата публикации

AMPHIPHILIC COMPOUNDS

Номер: US20160060290A1
Автор: Chae Pil Seok, GELLMAN Samuel Helmer, Kobilka Brian, Rasmussen Søren
Принадлежит:

Bringing membrane proteins into aqueous solution generally requires the use of detergents or other amphiphilic agents. The invention provides a new class of amphiphiles, each of which includes a multi-fused ring system as a lipophilic group. These new amphiphiles confer enhanced stability to a range of membrane proteins in solution relative to conventional detergents, leading to improved structural and functional stability of membrane proteins, including integral membrane proteins. Accordingly, the invention provides new amphiphiles for biochemical manipulations and characterization of membrane proteins. These amphiphiles display favorable behavior with membrane proteins and can be used to aid the solubilization, isolation, purification, stabilization, crystallization, and/or structural determination of membrane proteins. 2. The compound of claim 1 , wherein Ris methyl.3. The compound of claim 1 , wherein each Sac is an oxygen-linked monosaccharide.4. The compound of claim 1 , wherein each Sac is an oxygen-linked disaccharide.5. The compound of claim 1 , wherein each Sac is an oxygen-linked trisaccharide.6. The compound of claim 1 , wherein X is NH claim 1 , Y is O claim 1 , Z is H claim 1 , and L is a direct bond.7. The compound of claim 1 , wherein L is —CH— claim 1 , X is O claim 1 , Y is absent claim 1 , and Z is Me.8. The compound of claim 1 , wherein L is a direct bond claim 1 , X is a direct bond claim 1 , Y is absent claim 1 , and Z is H.11. The compound of claim 1 , wherein the critical micelle concentration (CMC) of the compound in water is about 5 nM to about 100 nM.12. The compound of claim 1 , wherein a plurality of the compounds form a micelle in water comprising about 5 to about 35 molecules of the compound.13. A composition comprising a compound of and an isolated membrane protein.14. A micelle comprising a compound of .15. The micelle of claim 14 , further comprising a polypeptide or a protein.16. A method of solubilizing or stabilizing a membrane ...

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Номер записи: 81
01-03-2018 дата публикации

AMINATION AND HYDROXYLATION OF ARYLMETAL COMPOUNDS

Номер: US20180057444A1
Автор: GAO HONGYIN, Kürti László, ZHOU Zhe
Принадлежит: William Marsh Rice University

In one aspect, the present disclosure provides methods of preparing a primary or secondary amine and hydroxylated aromatic compounds. In some embodiments, the aromatic compound may be unsubstituted, substituted, or contain one or more heteroatoms within the rings of the aromatic compound. The methods described herein may be carried out without the need for transition metal catalysts or harsh reaction conditions. 1. A method of preparing an aminoaromatic group or a hydroxyaromatic group comprising:(A) admixing a metal aromatic compound with an oxaziridine compound to form a first reaction mixture under conditions sufficient to cause a reaction to obtain an anionic intermediate;(B) admixing a weak acid with the anionic intermediate and the first reaction mixture to obtain a second reaction mixture under conditions sufficient to obtain an aminoaromatic group or a hydroxyaromatic group.2. The method of claim 1 , wherein the metal of the metal aromatic compound is attached to one of the carbon atoms of the aromatic ring.3. The method of claim 1 , wherein the metal of the metal aromatic compound is a magnesium halide or lithium.48-. (canceled)9. The method of claim 1 , wherein the metal aromatic compound is substituted.10. (canceled)11. The method of claim 9 , wherein the metal aromatic compound is substituted with a substituent wherein the substituent is amino claim 9 , aminosulfonyl claim 9 , carboxy claim 9 , cyano claim 9 , halo claim 9 , hydroxy claim 9 , hydroxyamino claim 9 , hydroxysulfonyl claim 9 , mercapto claim 9 , nitro claim 9 , oxo claim 9 , or thio; or acyl claim 9 , alkoxy claim 9 , cycloalkoxy claim 9 , alkenyloxy claim 9 , aryloxy claim 9 , aralkoxy claim 9 , acyloxy claim 9 , cycloalkylalkoxy claim 9 , heterocycloalkylalkoxy claim 9 , heterocycloalkoxy claim 9 , alkylthio claim 9 , cycloalkylthio claim 9 , amido claim 9 , alkylamino claim 9 , dialkylamino claim 9 , alkylsulfonyl claim 9 , arylsulfonyl claim 9 , or a substituted version of these groups ...

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Номер записи: 82
20-02-2020 дата публикации

INHIBITORS OF GLUCOCORTICOID RECEPTOR

Номер: US20200055892A1
Автор: BALBAS Minna Delarae, Du Xiaohui, EKSTEROWICZ John, FANTIN Valeria R., McGee Lawrence R., MEDINA Julio C., REW Yosup, SUN Daqing, YAN Xuelei, ZHOU Haiying, ZHU Liusheng
Принадлежит:

The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer. 155.-. (canceled)57. The method of claim 56 , wherein the cancer is breast cancer claim 56 , ovarian cancer claim 56 , or prostate cancer.58. The method of claim 56 , wherein the cancer is chemo-resistant.59. The method of claim 56 , wherein the cancer is castration resistant prostate cancer.60. The method of claim 56 , further comprising administering a second therapeutic agent to the subject selected from an androgen receptor inhibitor claim 56 , cisplatin claim 56 , carboplatin claim 56 , paclitaxel claim 56 , gemcitabine claim 56 , doxorubicin claim 56 , camptothecin claim 56 , topotecan claim 56 , an anti-PD-L1 agent or an anti-PD1 agent claim 56 , and any combinations thereof.61. The method of claim 56 , further comprising administering nab-paclitaxel or enzalutamide.63. The method of claim 62 , wherein the cancer is breast cancer claim 62 , ovarian cancer claim 62 , or prostate cancer.64. The method of claim 62 , wherein the cancer is chemo-resistant.65. The method of claim 62 , wherein the cancer is castration resistant prostate cancer.66. The method of claim 62 , further comprising administering a second therapeutic agent to the subject selected from an androgen receptor inhibitor claim 62 , cisplatin claim 62 , carboplatin claim 62 , paclitaxel claim 62 , gemcitabine claim 62 , doxorubicin claim 62 , camptothecin claim 62 , topotecan claim 62 , an anti-PD-L1 agent or an anti-PD1 agent claim 62 , and any combinations thereof.67. The method of claim 62 , further comprising administering nab-paclitaxel paclitaxel or enzalutamide.69. The method of ...

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Номер записи: 83
17-03-2022 дата публикации

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Номер: US20220079957A1
Автор: Qian Xiangping
Принадлежит:

Chemical entities that are bufalin derivatives, pharmaceutical compositions and methods of treatment of cancer are described. 2. At least one chemical entity of wherein Z is OR.3. At least one chemical entity of wherein Ris chosen from optionally substituted alkyl claim 2 , optionally substituted cycloalkyl claim 2 , and optionally substituted heterocycloalkyl.4. At least one chemical entity of wherein Z is NRR.5. At least one chemical entity of wherein Ris chosen from hydrogen claim 4 , optionally substituted alkyl claim 4 , optionally substituted cycloalkyl claim 4 , and optionally substituted heterocycloalkyl claim 4 , and Ris chosen from optionally substituted alkyl claim 4 , optionally substituted cycloalkyl claim 4 , and optionally substituted heterocycloalkyl.6. At least one chemical entity of wherein Ris hydrogen and Ris chosen from optionally substituted alkyl.7. At least one chemical entity of wherein Rand Rare joined together to form a 5- to 7-membered heterocycloalkyl ring.8. At least one chemical entity chosen from compounds I-a-I-f and pharmaceutically acceptable salts thereof.10. At least one chemical entity of wherein Rand Rare each independently chosen from hydrogen and optionally substituted lower alkyl.11. At least one chemical entity of wherein Rand Rare both hydrogen.12. At least one chemical entity of wherein Rand Rare joined together to form a 5- to 7-membered heterocycloalkyl ring.13. At least one chemical entity of any one of to wherein Rand Rare each independently chosen from hydrogen and optionally substituted lower alkyl.14. At least one chemical entity of any one of to wherein n is chosen from 1 claim 9 , 2 claim 9 , and 3.15. At least one chemical entity of wherein n is 1 claim 9 , and Rand Rare joined together to form a 5- to 7-membered heterocycloalkyl ring.16. At least one chemical entity chosen from compounds II-a-II-h and pharmaceutically acceptable salts thereof.18. At least one chemical entity of wherein Ris chosen from hydrogen ...

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Номер записи: 84
08-03-2018 дата публикации

Treatment of Pulmonary Disease

Номер: US20180064729A1
Автор: Adorini Luciano, Pruzanski Mark
Принадлежит:

The present invention relates to methods of treating, reducing the risk of, preventing, or alleviating a symptom of a pulmonary disease or condition, reducing or suppressing inflammation in the lung, and promoting lung repair, by using a compound of formula A: 2. The method of claim 1 , wherein Ris unsubstituted C-Calkyl.3. The method of claim 2 , wherein Ris methyl claim 2 , ethyl claim 2 , or propyl.4. The method of claim 3 , wherein Ris ethyl.5. The method of claim 1 , wherein Ris selected from methyl claim 1 , ethyl and propyl; Ris OH; Ris H; and Ris H.9. The method of claim 1 , wherein the compound is a pharmaceutically acceptable salt.10. The method of claim 9 , wherein the salt is sodium salt or a triethylammonium salt.11. The method of claim 1 , wherein the pulmonary disease or condition is selected from obstructive pulmonary disease (COPD) claim 1 , emphysema claim 1 , asthma claim 1 , idiopathic pulmonary fibrosis claim 1 , pneumonia claim 1 , tuberculosis claim 1 , cystic fibrosis claim 1 , bronchitis claim 1 , pulmonary hypertension (e.g. claim 1 , Idiopathic Pulmonary Arterial Hypertension (IPAH) (also known as Primary Pulmonary Hypertension (PPH)) and Secondary Pulmonary Hypertension (SPH)) claim 1 , interstitial lung disease claim 1 , and lung cancer.12. The method of claim 11 , wherein the pulmonary disease or condition is selected from COPD claim 11 , emphysema claim 11 , asthma claim 11 , cystic fibrosis claim 11 , and pulmonary hypertension.13. The method of claim 12 , wherein the pulmonary disease or condition is pulmonary hypertension.14. The method of claim 13 , wherein the pulmonary hypertension is IPAH or SPH.15. The method of claim 1 , wherein the pulmonary disease or condition is caused by inflammation claim 1 , autoimmune disease claim 1 , scleroderma claim 1 , rheumatoid arthritis claim 1 , Acute Lung Injury (ALI) claim 1 , Acute Respiratory Distress Syndrome (ARDS) claim 1 , birth defect of the heart claim 1 , blood clot in the lungs ( ...

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Номер записи: 85
11-03-2021 дата публикации

Compounds for treating neurodegenerative disorders

Номер: US20210070799A1
Автор: Cherif Rabhi, Christian Da Costa Noble, Geraldine Le Goff, Guillaume Arcile, Jamal Ouazzani, Leon Cariel
Принадлежит: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS, ETHNODYNE

The invention relates to compounds of formula (I), their method of synthesis as well as their use to treat neurodegenerative disorders.

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Номер записи: 86
29-05-2014 дата публикации

Treatment of Pulmonary Disease

Номер: US20140148428A1
Автор: Adorini Luciano, Pruzanski Mark
Принадлежит:

The present invention relates to methods of treating, reducing the risk of preventing, or alleviating a symptom of a pulmonary disease or condition, reducing or suppressing inflammation in the lung, and promoting lung repair, by using a compound of formula A: 2. The method of claim 1 , wherein Ris unsubstituted C-Calkyl.3. The method of claim 2 , wherein Ris methyl claim 2 , ethyl claim 2 , or propyl.4. The method of claim 3 , wherein Ris ethyl.5. The method of claim 1 , wherein Ris selected from methyl claim 1 , ethyl and propyl; Ris OH; Ris H; and Ris H.9. The method of claim 1 , wherein the compound is a pharmaceutically acceptable salt.10. The method of claim 9 , wherein the salt is sodium salt or a triethylammonium salt.11. The method of claim 1 , wherein the pulmonary disease or condition is selected from obstructive pulmonary disease (COPD) claim 1 , emphysema claim 1 , asthma claim 1 , idiopathic pulmonary fibrosis claim 1 , pneumonia claim 1 , tuberculosis claim 1 , cystic fibrosis claim 1 , bronchitis claim 1 , pulmonary hypertension (e.g. claim 1 , Idiopathic Pulmonary Arterial Hypertension (IPAH) (also known as Primary Pulmonary Hypertension (PPH)) and Secondary Pulmonary Hypertension (SPH)) claim 1 , interstitial lung disease claim 1 , and lung cancer.12. The method of claim 11 , wherein the pulmonary disease or condition is selected from COPD claim 11 , emphysema claim 11 , asthma claim 11 , cystic fibrosis claim 11 , and pulmonary hypertension.13. The method of claim 12 , wherein the pulmonary disease or condition is pulmonary hypertension.14. The method of claim 13 , wherein the pulmonary hypertension is IPAH or SPH.15. The method of claim 1 , wherein the pulmonary disease or condition is caused by inflammation claim 1 , autoimmune disease claim 1 , scleroderma claim 1 , rheumatoid arthritis claim 1 , Acute Lung Injury (ALI) claim 1 , Acute Respiratory Distress Syndrome (ARDS) claim 1 , birth defect of the heart claim 1 , blood clot in the lungs ( ...

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Номер записи: 87
29-05-2014 дата публикации

Process for preparing fluticasone propionate/furoate

Номер: US20140148593A1
Автор: Dhaval J Patel, Dhaval P Patel, Kirtipalsinh Solanki, Manoj Kumar Singh, Ruchir Z Bavadia, Tejash C Shah
Принадлежит: Cadila Healthcare Ltd

The present invention relates to an improved process for the preparation of substituted Fluticasone derivatives. The invention also reveals the processes for the purification of Fluticasones and related intermediates to provide the highly pure product.

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Номер записи: 88
07-03-2019 дата публикации

ANTAGONISTS OF CB1 RECEPTOR

Номер: US20190071465A1
Автор: Bellocchio Luigi, Cota Daniela, Felpin Francois-Xavier, Maldonado Rafael, Marsicano Giovanni, Piazza Pier Vincenzo, Revest Jean-Michel, Spampinato Umberto, Vallee Monique, Vitiello Sergio
Принадлежит:

The invention relates to an antagonist of CB1 receptor for use in the treatment of a pathologic condition or disorder selected from the group consisting of bladder and gastrointestinal disorders; inflammatory diseases; cardiovascular diseases; nephropathies; glaucoma; spasticity; cancer; osteoporosis; metabolic disorders; obesity; addiction, dependence, abuse and relapse related disorders; psychiatric and neurological disorders; neurodegenerative disorders; autoimmune hepatitis and encephalitis; pain; reproductive disorders and skin inflammatory and fibrotic diseases. 130-. (canceled)32. The method according to claim 31 , wherein said compound is not substantially converted into active pregnenolone down stream derivatives after administration to a subject.34. The pregnenolone derivative compound according to claim 33 , wherein said compound is 17α-Methylprogesterone or 17α-Benzylprogesterone.36. The method according to claim 35 , wherein said compound is 5-pregnen-3β-O-benzyl-20-one claim 35 , 3β-Aminopregnenolone or 5-pregnen-3β-azido-20-one.38. The method according to claim 37 , wherein said compound is 17α-Allyl-3β-methoxypregnenolone claim 37 , 17α-Benzyl-3β-fluoropregnenolone claim 37 , 3β-Fluoro-17α-methylpregnenolone claim 37 , 3β-Methoxy-17α-methylpregnenolone claim 37 , 17α-Benzyl-3β-methoxypregnenolone claim 37 , 3β-Benzyloxy-17α-methylpregnenolone or 17α-Benzyl-3β-benzyloxypregnenolone.40. The method according to claim 39 , wherein said compound is 17α-Benzylpregnenolone claim 39 , 17α-Ethylpregnenolone claim 39 , 17α-Methylpregnenolone or 17-Methoxypregnenolone.42. The method according to claim 41 , wherein said compound is 20-Deoxypregnenolone or 20-Methylamino-5-pregnen-3β-ol.44. The method according to wherein said compound is 5 claim 43 ,16-Pregnadien-20-one.45. The method according to wherein the bladder and gastrointestinal disorder is selected from the group consisting of liver fibrosis; liver steatosis; non-alcoholic steatohepatitis (NASH); liver ...

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Номер записи: 89
24-03-2016 дата публикации

19-nor c3, 3-disubstituted c21-c-bound heteroaryl steroids and methods of use thereof

Номер: US20160083417A1
Автор: Albert Jean Robichaud, Boyd L. Harrison, Francesco G. Salituro, Gabriel Martinez Botella, Richard Thomas Beresis
Принадлежит: Sage Therapeutics Inc

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein, , R 1 , R 2 , R 3a , R 3b , R 4a , and R 4b are as defined herein, and A is a carbon bound substituted or unsubstituted 5- to 6-membered heteroaryl ring as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.

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Номер записи: 90
26-03-2015 дата публикации

STEROL DERIVATIVES AND USE THEREOF FOR TREATING DISEASES INVOLVING TRANSFORMED ASTROCYTE CELLS OR FOR TREATING MALIGNANT HAEMOPATHIES

Номер: US20150086615A1
Автор: CLARION Ludovic, MERSEL Marcel, Petite Didier
Принадлежит: BETA INNOV

Novel sterol derivatives, the preparation method thereof, pharmaceutical compositions containing them and use thereof for treating diseases involving transformed astrocyte cells or for treating malignant haemopathies. The treatment of glioblastoma multiforme, as well as of other cancers, such as lymphomas, neuroblastomas and melanomas is also described. 122-. (canceled)25. Compound of formula (I) according to claim 23 , in which A represents a —C(O)—Rgroup in which Ris a 2 claim 23 ,2-dimethyl-1 claim 23 ,3-dioxolane group; or a linear or branched C-Calkyl group unsubstituted or substituted with a group selected from OR claim 23 , NHR and SR claim 23 , where R represents hydrogen claim 23 , a linear C-Calkyl or an unsubstituted C-Caryl; a C-Caryl group or a C-Cheteroaryl group claim 23 , which are unsubstituted or substituted with at least one linear or branched C-Calkyl claim 23 , or with at least one group selected from OR claim 23 , NHR and SR claim 23 , where R represents hydrogen claim 23 , a linear C-Calkyl or an unsubstituted C-Caryl; or else a sugar residue.26. Compound of formula (I) according to claim 23 , in which B represents an acyl group in which the alkyl group is C-C claim 23 , in particular acetyl claim 23 , or an alkoxycarbonyl group in which the alkyl group is C-C claim 23 , in particular a tert-butoxycarbonyl group.27. Compound of formula (I) according to claim 23 , in which B can also claim 23 , in particular claim 23 , represent a C-Calkyl group claim 23 , unsubstituted or substituted with at least one group selected from OR claim 23 , NHR and SR claim 23 , as defined above; or a C-Caryl group claim 23 , unsubstituted or substituted with at least one linear or branched C-Calkyl or with at least one group selected from OR claim 23 , NHR and SR claim 23 , where R represents hydrogen claim 23 , a linear C-Calkyl or an unsubstituted C-Caryl.28. Compound of formula (I) claim 23 , characterized in that it is selected from the following compounds:7-(( ...

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Номер записи: 91
12-03-2020 дата публикации

POLYHYDROXYLATED BILE ACIDS FOR TREATMENT OF BILIARY DISORDERS

Номер: US20200078374A1
Автор: Ling Victor, Sheps Jonathan Ahab, Wang Renxue
Принадлежит:

The invention provides, in part, polyhydroxylated bile adds for treating biliary disorders, for example, biliary disorders arising out of cholestasis of portal hypertension. The invention also provides, in part, polyhydroxylated bile acids for stimulating bile flow. New compounds 2α,3α,7α,12α-tetrahydroxy-5β-cholanoic acid and 3α,4α,7α,12α-tetrahydroxy-5β-cholanoic acid are disclosed, uses thereof and synthesis thereof. 2. The method of wherein said compound is selected from the group consisting of a tetrahydroxylated bile acid and a pentahydroxylated bile acid claim 1 , or a derivative thereof.3. The method of wherein said tetrahydroxylated bile acid is selected from the group consisting of:a 3,6,7,12-tetrahydroxycholanoic acid,a 3,4,7,12-tetrahydroxycholanoic acid,a 1,3,7,12-tetrahydroxycholanoic acid,a 2,3,7,12-tetrahydroxycholanoic acid,a 3,7,16,24-tetrahydroxycholanoic acid, anda 3,7,15,24-tetrahydroxycholanoic acid,or a derivative thereof.4. The method of wherein said 3 claim 3 ,6 claim 3 ,7 claim 3 ,12-tetrahydroxycholanoic acid is selected from the group consisting of:a 3α,6α,7α,12α-tetrahydroxy-5β-cholan-24-oic acid,a 3α,6β,7α,12α-tetrahydroxy-5β-cholan-24-oic acid,a 3α,6α,7β,12α-tetrahydroxy-5β-cholan-24-oic acid,a 3α,6β,7β,12α-tetrahydroxy-5β-cholan-24-oic acid,a 3α,6α,7α,12β-tetrahydroxy-5β-cholan-24-oic acid,a 3α,6β,7α,12β-tetrahydroxy-5β-cholan-24-oic acid, anda 3α,6β,7β,12β-tetrahydroxy-5β-cholan-24-oic acid,or wherein said 2,3,7,12-tetrahydroxycholanic acid is a 2α,3α,7α,12α-tetrahydroxy-5β-cholanic acid,or wherein said a 3,4,7,12-tetrahydroxycholanic acid is a 3α,4α,7α,12α-tetrahydroxy-5β-cholanic acid,or a derivative thereof.5. The method of wherein said compound has a hydrophilicity greater than that of cholate claim 1 , or has a preferential affinity for MDRI when compared to BSEP claim 1 , or wherein said compound has a high affinity for MDR1 claim 1 , or wherein said compound is selected from the group consisting of a tauryl or glycyl conjugate ...

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Номер записи: 92
12-06-2014 дата публикации

NANOPARTICLES FOR DELIVERY OF LIGANDS

Номер: US20140162966A1
Автор: Chen Xiaoyuan, Choi Ki Young, Lee Seulki, Liu Gang
Принадлежит:

Disclosed is a nanoparticulate complex comprising an artificial phosphate receptor of formula (I): P-[L-[-N(CH-2-pyridyl)]].pZN (I) wherein P represents a nanoparticulate substrate, L represents a linking group, and p is an integer of ≧1. Also disclosed are a method for silencing a gene in a cancer patient in need thereof, a method for treating or preventing cancer in a patient in need thereof, and a method for targeting a cell in cancer treatment comprising use of the nanoparticulate complex, for example, a DPA/Zn-functionalized nanoparticulate complex. 1. A nanoparticulate complex comprising an artificial phosphate receptor of formula (I):{'br': None, 'sub': 2', '2', 'p, 'i': '.p', 'sup': '2+', 'P-[L-[-N(CH-2-pyridyl)]]Zn\u2003\u2003(I)'}wherein P represents a nanoparticulate substrate,L represents a linking group, andp is an integer of ≧1,in combination with an anion or anions.2. The complex of claim 1 , wherein the nanoparticulate substrate is a synthetic organic polymeric substrate claim 1 , a biopolymeric substrate claim 1 , or an inorganic substrate.3. The complex of claim 1 , wherein the nanoparticulate substrate comprises a polysaccharide.4. The complex of claim 2 , wherein the nanoparticulate substrate comprises hyaluronic acid.6. The complex of claim 1 , wherein L comprises a substituted or unsubstituted aryl group.7. The complex of claim 6 , wherein L comprises an Ω-(3 claim 6 ,5-disubstituted aryl)alkylamino group.11. The complex of claim 10 , wherein the ratio of n to (1+m) is from 0.01 to about 1.0.12. The complex of claim 11 , wherein the ratio of n to (1+m) is from 0.1 to about 0.5.13. A phosphate anion ligand complex comprising at least one phosphate anion ligand complexed with the nanoparticulate complex of .14. The phosphate anion ligand complex of claim 13 , wherein the phosphate anion ligand is selected from siRNA claim 13 , miRNA claim 13 , oligonucleotides claim 13 , RNA claim 13 , and DNA.15. The phosphate anion ligand complex of claim 13 , ...

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Номер записи: 93
25-03-2021 дата публикации

COMPOUNDS FOR TREATING NEURODEGENERATIVE DISORDERS

Номер: US20210087222A1
Автор: Arcile Guillaume, Cariel Léon, Da Costa Noble Christian, Le Goff Géraldine, Ouazzani Jamal, Rabhi Chérif
Принадлежит:

The invention relates to compounds of formula (I), their method of synthesis as well as their use to treat neurodegenerative disorders. 2. Compound according to in whichR2 is H, OH or a heteroatom:{'sub': '2', 'R3 is H, OH or CHOH;'}{'sub': 3', '2, 'R4 is H, OH, CH, CHOH;'}{'sub': 'X1', 'Ris H or an aminoacid chosen among tryptophane, lysine, methionine, phenylalanine, threonine, valine, leucine, isoleucine, arginine or histidine;'}3. Compound according to in whichR2 is OHR3 is H{'sub': '2', 'R4 is CHOH'}{'sub': 'X1', 'Ris H;'}5. Method of synthesis according to claim 4 , in which the method is made in the presence of a solvent.6. Method of synthesis according to claim 4 , in which the solvent is tetrahydrofurane and/or water.7. Compound according to claim 1 , for its use as medicament.8. Compound according to for its use to treat or limit development of demyelinating diseases in a mammal.9. Compound for use according to claim 8 , in which the demyelinating diseases are chosen among multiple sclerosis claim 8 , acute disseminated encephalomyelitis claim 8 , adrenoleukodystrophy claim 8 , adrenomyeloneuropathy claim 8 , Leber's Hereditary Optic Atrophy and related mitochondrial disorders claim 8 , HTLV-associated Myelopathy and diseases linked to demyelination of PNS nerves.10. Compound according to for its use to treat or limit development of neuromuscular diseases in a mammal.11. Compound for use according to claim 10 , in which the neuromuscular diseases are chosen among MN diseases claim 10 , ALS claim 10 , PBP claim 10 , PMA claim 10 , PLS claim 10 , SMA claim 10 , Kennedy's disease claim 10 , PPS claim 10 , PPMA claim 10 , MMN claim 10 , MMA claim 10 , paraneoplastic motor neuron disease claim 10 , LEMS claim 10 , MG and botulism.12. A method of treating or limiting development of a demyelinating disease in a subject claim 1 , comprising administering to a subject a therapeutic amount of a compound according to .13. The method of claim 12 , wherein said ...

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Номер записи: 94
21-03-2019 дата публикации

Plant steroids and uses thereof

Номер: US20190083632A1
Автор: John F. ARNETT, Michael Davidson, Roelof Rongen, Sadik Elshani
Принадлежит: DAVIDSON LOPEZ LLC

The invention relates to a drug conjugate including a drug and a plant steroid. The drug conjugate may target the drug for intestinal cell delivery, and thus may be used to treat diseases, including intestinal diseases, or to affect intestinal metabolism. The invention therefore also relates to treating intestinal diseases and affecting intestinal metabolism with the drug conjugate.

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Номер записи: 95
29-03-2018 дата публикации

ESTROGEN RECEPTOR MODULATORS

Номер: US20180086787A1
Автор: Deng Gang, Jung Michael E., Marquez-Garban Diana C., Pietras Richard J.
Принадлежит:

Described herein, inter alia, are compositions and methods for treating or preventing hyperproliferative disorders, including cancer. 3. The compound of claim 2 , wherein Ris independently a hydrogen claim 2 , halogen claim 2 , —CX claim 2 , or unsubstituted alkyl.4. The compound of claim 2 , wherein Ris independently a hydrogen claim 2 , —F claim 2 , —CF claim 2 , or unsubstituted methyl.8. The compound of claim 7 , wherein Ris independently a hydrogen claim 7 , halogen claim 7 , —CX claim 7 , or unsubstituted alkyl.9. The compound of claim 7 , wherein Ris independently a hydrogen claim 7 , —F claim 7 , —CF claim 7 , or unsubstituted methyl.11. The compound of claim 1 , wherein L is a bond.12. The compound of claim 1 , wherein L is a heteroalkylene.13. The compound of claim 1 , wherein L is independently a 2 to 8 membered heteroalkylene.14. The compound of claim 1 , wherein L is independently a 3 to 6 membered heteroalkylene.15. The compound of claim 1 , wherein L is independently —NH-(substituted or unsubstituted (C-C) alkylene).16. The compound of claim 1 , wherein L is independently —NH-(unsubstituted (C-C) alkylene).17. The compound of claim 1 , wherein L is independently —NHC(O)-(substituted or unsubstituted (C-C) alkylene).18. The compound of claim 1 , wherein L is independently —NHC(O)-(unsubstituted (C-C) alkylene).19. The compound of claim 1 , wherein Ris independently substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl.20. The compound of claim 1 , wherein Ris independently substituted or unsubstituted (C-C) alkyl or substituted or unsubstituted 2 to 10 membered heteroalkyl.21. The compound of claim 1 , wherein Ris unsubstituted methyl.22. The compound of claim 1 , wherein Ris H.23. The compound of one of claim 1 , wherein Ris independently substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl.24. The compound of claim 1 , wherein Ris independently substituted or unsubstituted (C-C) alkyl or substituted ...

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Номер записи: 96
21-03-2019 дата публикации

RAMAN TAG

Номер: US20190085019A1
Автор: Dai Mingji
Принадлежит: PURDUE RESEARCH FOUNDATION

A method of forming a probe, wherein the method includes converting cholenic acid into a compound with a terminal alkyne group, wherein the converting the cholenic acid comprises using a sequence, wherein the sequence comprises synthesizing a THP-protection group, LiAlH4 reduction, Dess-Martin oxidation, and Seyferth-Gilbert-Bestmann homologation. 7. The method of further comprising:forming alkyne cholesterol (A-Chol) by removing the THP-protection group;forming phenyl-alkyne cholesterol (PhA-Chol) from the compound with the terminal alkyne group via a palladiumcatalyzed Sonogashira reaction; andforming phenyl-diyne cholesterol (PhDY-Chol) from the compound with the terminal alkyne group via a coppercatalyzed Cadiot-Chodkiewicz reaction.8. The method of claim 1 , further comprising removing the THP-protection group via an acid. The Present U.S. patent application is a continuation of U.S. patent application Ser. No. 15/634,567, filed Jun. 27, 2017, is a continuation of U.S. patent application Ser. No. 14/850,949, filed Sep. 10, 2015, which is related to and claims the priority benefit of U.S. Provisional Patent Application Ser. No. 62/048,484, filed Sep. 10, 2014, the contents of which are hereby incorporated by reference in their entirety into this disclosure.This invention was made with government support under CA182608 awarded by the National Institutes of Health. The government has certain rights in the invention.The present disclosure generally relates to tags for imaging molecules using Raman spectroscopy, and in particular to a method and composition that uses cholesterol mimics to track the location and movement of cholesterol.This section introduces aspects that may help facilitate a better understanding of the disclosure. Accordingly, these statements are to be read in this light and are not to be understood as admissions about what is or is not prior art.An important component of cellular membrane, cholesterol controls physical properties of the membrane ...

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Номер записи: 97
19-03-2020 дата публикации

Polyethylene Glycol-Conjugated Glucocorticoid Prodrugs and Compositions and Methods Thereof

Номер: US20200085842A1
Автор: Jia Zhenshan, Wang Dong, Wang Xiaobei, Yuan Fang
Принадлежит: Board of Regents of the University of Nebraska

Polyethylene glycol (PEG)-conjugated glucocorticoid prodrugs, methods of preparation, and use for the treatment of diseases and disorders are disclosed. In particular, PEG-conjugated dexamethasone compounds and methods of using them for treating inflammatory and autoimmune diseases, including but not limited to lupus, are disclosed. 2. The pharmaceutical composition of claim 1 , wherein E is a linker comprising a branched structure capable of covalently bonding to two or more Rgroups claim 1 , said linker optionally comprising one or more heteroatoms independently selected from the group consisting of O claim 1 , S claim 1 , and N.3. The pharmaceutical composition of claim 1 , wherein Z is a linker comprising a branched structure capable of covalently bonding to two or more dexamethasone moieties claim 1 , said linker optionally comprising one or more heteroatoms independently selected from the group consisting of O claim 1 , S claim 1 , and N.17. The pharmaceutical composition of claim 1 , wherein n is 40 to 50.18. The pharmaceutical composition of claim 1 , wherein the composition is in oral claim 1 , nasal claim 1 , topical claim 1 , buccal claim 1 , sublingual claim 1 , rectal claim 1 , vaginal claim 1 , intravenous claim 1 , intramuscular claim 1 , intraperitoneal claim 1 , or other parenteral form.19. The pharmaceutical composition of in vaporization-ready claim 1 , nebulization-ready claim 1 , nanoparticle formulation claim 1 , or liposomal formulation.20. The pharmaceutical composition of claim 1 , further comprising a second therapeutic agent selected from the group consisting of a NSAID (e.g. Aspirin claim 1 , Naproxen claim 1 , Celebrex) claim 1 , a Glucocorticoid (e.g. Dexamethasone claim 1 , Prednisone claim 1 , Betamethasone) claim 1 , and a DMARD (e.g. Methotrexate claim 1 , Leflunomide claim 1 , Sulfasalazine claim 1 , Hydroxychoroquine) claim 1 , and a biologic drug.21. A method of treating an autoimmune disease and/or inflammatory disorder claim 1 ...

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Номер записи: 98
19-03-2020 дата публикации

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Номер: US20200085846A1
Автор: Qian Xiangping
Принадлежит:

Chemical entities that are bufalin derivatives, pharmaceutical compositions and methods of treatment of cancer are described. 131.-. (canceled)32. A compound selected from the group consisting of:(R)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-aminopropanoate;(S)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-aminopropanoate;(R)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-amino-3-methylbutanoate;(S)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-amino-3-methylbutanoate;(R)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-amino-4-methylpentanoate;(S)-(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 2-amino-4-methylpentanoate;(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrrolidin-1-yl)ethyl) carbonate;(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl) carbonate;(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-(pyrrolidin-1-yl)ethyl)carbamate;(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl (2-morpholinoethyl)carbamate;(3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl piperazine-1-carboxylate;4-(((((3S,5R,8R,9S,10S,13R,14S,17R)-14-hydroxy-10,13-dimethyl-17-(2-oxo-2H-pyran-5- ...

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Номер записи: 99
19-03-2020 дата публикации

THERAPEUTIC DNP DERIVATIVES AND METHODS USING SAME

Номер: US20200087242A1
Автор: SHULMAN Gerald I., SPIEGEL DAVID A.
Принадлежит:

The present invention includes DNP derivatives that are useful for preventing or treating a metabolic disease or disorder in a subject in need thereof. In certain embodiments, the subject is further administered at least one additional therapeutic agent. 119-. (canceled)20. A method of ameliorating a disease or disorder in a subject in need thereof , wherein the disease or disorder is at least one selected from the group consisting of hypertriglyceridemia , fatty liver , and insulin resistance , the method comprising:{'sub': '6', 'administering to the subject a therapeutically effective amount of a nitrophenyl derivative selected from the group consisting of 2,4-dinitrophenyl vinyl ether, 2,4-dinitrophenyl methyl ether-d, and solvates thereof.'}21. The method of claim 20 , wherein the method further comprises administering to the subject at least one additional therapeutic agent.22. The method of claim 21 , wherein the nitrophenyl derivative and the at least one additional therapeutic agent are co-administered to the subject.23. The method of claim 22 , wherein the nitrophenyl derivative and the at least one additional therapeutic agent are co-formulated.24. The method of claim 20 , wherein the subject is a mammal.25. The method of claim 24 , wherein the mammal is human.26. The method of claim 20 , wherein the administering is by an administration route selected from the group consisting of oral claim 20 , transdermal claim 20 , transmucosal claim 20 , intravesical claim 20 , intrapulmonary claim 20 , intraduodenal claim 20 , intragastrical claim 20 , intrathecal claim 20 , subcutaneous claim 20 , intramuscular claim 20 , intradermal claim 20 , intra-arterial claim 20 , intravenous claim 20 , intrabronchial claim 20 , inhalation claim 20 , and topical.27. The method of claim 26 , wherein the administering is oral and wherein the nitrophenyl derivative is formulated as a tablets claim 26 , dragee claim 26 , liquid claim 26 , drop claim 26 , capsule claim 26 , caplet ...

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Номер записи: 100