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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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Применить Всего найдено 1213. Отображено 100.
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: 1
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: 2
16-05-2013 дата публикации

4-PREGENEN-11BETA-17-21-TRIOL-3,20-DIONE DERIVATIVES

Номер: US20130123223A1
Автор: Edelman Jeffrey L., Malone Thomas C., Nehme Alissar
Принадлежит: ALLERGAN, INC.

The present invention relates to novel 4-pregenen-11β-17-21-triol-3,20-dione derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals, as modulators of glucocorticoid or mineralocorticoid receptors. The invention relates specifically to the use of these compounds and their pharmaceutical compositions to treat disorders associated with glucocorticoid or mineralocorticoid receptor modulation. 3. The compound according to wherein Ris substituted aryl.8. A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound according to and a pharmaceutically acceptable adjuvant claim 1 , diluents or carrier.12. The method according to wherein the ocular condition is selected from the group consisting of elevated intraocular pressure claim 10 , glaucoma claim 10 , uveitis claim 10 , retinal vein occlusions claim 10 , macular degeneration claim 10 , diabetic retinopathy claim 10 , various forms of macular edema claim 10 , post-surgical inflammation claim 10 , inflammatory conditions of the palpebral and bulbar conjunctiva claim 10 , cornea claim 10 , and anterior segment of the globe claim 10 , such as allergic conjunctivitis claim 10 , ocular rosacea claim 10 , dry eye claim 10 , blepharitis claim 10 , retinal detachment claim 10 , meibomian gland dysfunction claim 10 , superficial punctate keratitis claim 10 , herpes zoster keratitis claim 10 , iritis claim 10 , cyclitis claim 10 , selected infective conjunctivitis claim 10 , corneal injury from chemical claim 10 , radiation claim 10 , or thermal burns claim 10 , penetration of foreign bodies claim 10 , allergy claim 10 , or combinations thereof.13. The method according to wherein the ocular condition is selected from:dry eye, blepharitis, ocular rosacea, meibomian gland dysfunction, uveitis and macular degeneration.14. The method according to wherein the ocular condition is selected from the group consisting of ...

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Номер записи: 3
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: 4
06-06-2013 дата публикации

NUCLEAR SULFATED OXYSTEROL, POTENT REGULATOR OF LIPID HOMEOSTASIS, FOR THERAPY OF HYPERCHOLESTEROLEMIA, HYPERTRIGLYCERIDES, FATTY LIVER DISEASES, AND ATHEROSCLEROSIS

Номер: US20130143854A1
Автор: Pandak William M., REN Shunlin
Принадлежит: Virginia Commonwealth University

The sulfated oxysterol 5-cholesten-3β, 25-diol 3-sulphate, a nuclear cholesterol metabolite that decreases lipid biosynthesis and increases cholesterol secretion and degradation, is provided as an agent to lower intracellular and serum cholesterol and/or triglycerides, and to prevent or treat lipid accumulation-associated inflammation and conditions associated with such inflammation. Methods which involve the use of this sulfated oxysterol to treat conditions associated with high cholesterol and/or high triglycerides and/or inflammation (e.g. hypercholesterolemia, hypertriglyceridemia, non-alcoholic fatty liver diseases, atherosclerosis, etc.) are also provided. 14-. (canceled)5. A method to treat or prophylactically treat a pathological condition associated with high levels of one or more serum lipids in a patient in need thereof , said method comprising administering 5-cholesten-3β , 25-diol 3-sulphate to said patient in an amount sufficient to lower a level of said one or more serum lipids in said patient.6. The method of claim 5 , wherein said serum lipids include cholesterol and triglycerides.7. The method of claim 5 , wherein said pathological condition is selected from hyperlipidemia claim 5 , hypercholesterolemia claim 5 , hypertriglyceridemia claim 5 , atherosclerosis claim 5 , obesity claim 5 , type-II adult onset diabetes claim 5 , lipid accumulation-associated inflammation claim 5 , cirrhosis claim 5 , liver failure claim 5 , liver cancer claim 5 , and nonalcoholic fatty liver disease (NAFLD).8. A method of prophylactically treating or treating lipid accumulation-associated inflammation or a condition associated with lipid accumulation-associated inflammation in a patient in need thereof claim 5 , comprising administering 5-cholesten-3β claim 5 , 25-diol 3-sulphate to said patient in an amount sufficient to prophylactically treat or treat said lipid accumulation-associated inflammation or said condition associated with said lipid accumulation-associated ...

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Номер записи: 5
20-06-2013 дата публикации

BIVALENT MULTIFUNCTIONAL LIGANDS TARGETING A[BETA] OLIGOMERS AS TREATMENT FOR ALZHEIMER'S DISEASE

Номер: US20130156705A1
Автор: Guo Tai Liang, ZHANG Shujin
Принадлежит: Virginia Commonwealth University

Bivalent multifunctional Aβ oligomerization inhibitors (BMAOIs) that target multiple risk factors involved in Alzheimer's disease are provided. The BMAOIs are useful for the treatment and/or prevention of Alzheimer's disease, as well as for diagnostic imaging of Aβ plaques in brain tissue. The BMAOIs comprise i) an Aβ oligomer (ApO)-inhibitor moiety which may have antioxidant activity (e.g. curcumin, curcumin derivatives, curcumin hybrids, resveratrol, etc.); ii) a cell membrane/lipid raft (CM/LR) anchoring moiety (e.g. cholesterol, cholesterylamine, a steroid, etc.); and iii) a spacer or linker moiety that stably links i) 1. A bivalent multifunctional AP oligomerization inhibitor (BMAOI) comprisingi) a multifunctional AP oligomer (AβO)-inhibitor moiety;ii) a cell membrane/lipid raft (CM/LR) anchor; andiii) a spacer moiety which forms a chemical linkage between said AβO-inhibitor moiety and said CM/LR anchor.2. The BMAOI of claim 1 , wherein said AβO-inhibitor moiety is selected from the group consisting of curcumin claim 1 , resveratrol claim 1 , and a hybrid molecule that comprises curcumin.3. The BMOI of claim 2 , wherein said hybrid molecule comprises curcumin and melatonin.4. The BMAOI of claim 1 , wherein said CM/LR anchor is selected from the group consisting of cholesterol claim 1 , a cholesterol derivative claim 1 , and a steroid.5. The BMAOI of claim 4 , wherein said cholesterol derivative is cholesterylamine.6. The BMAOI of claim 4 , wherein said steroid is diosgenin.7. The BMAOI of claim 1 , wherein said spacer moiety is 21 atoms in length.8. The BMAOI of claim 2 , wherein said AβO-inhibitor moiety is curcumin and said spacer moiety is chemically linked to carbon at position C4 of said curcumin.9. The BMAOI of claim 4 , wherein said CM/LR anchor is cholesterol and said spacer moiety is chemically linked to O attached to position C3 of said cholesterol.10. The BMAOI of claim 5 , wherein said spacer moiety is chemically linked to N attached to position C3 ...

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Номер записи: 6
29-08-2013 дата публикации

Method for Monofluoromethylation of Organic Substrates to Prepare Biologically Active Organic Compounds

Номер: US20130225844A1
Автор: Leitao Emilia Perpetua Tavares
Принадлежит: HOVIONE INTER LTD

Described is a process for the preparation of monofluoromethylated organic biologically active compounds using monofluoromethylated reagents. Fluticasone Propionate and Fluticasone Furoate can be prepared using, for example, S-monofluoromethyl-S-phenyl-2,3,4,5-tetramethylphenylsulfonium tetrafluoroborate as monofluoromethylating reagent instead of bromofluoromethane. 5. A method according to claim 2 , wherein Ris triflate or tetrafluoroborate.6. A method according to claim 3 , wherein R claim 3 , Rand Rare ethyl groups and Ris tetrafluoroborate or triflate.7. A method according to claim 3 , wherein R claim 3 , Rare both methyl claim 3 , Ris aryl and Ris tetrafluoroborate or triflate.8. A method according to claim 3 , wherein R claim 3 , Rare both methyl claim 3 , Ris phenyl and Ris tetrafluoroborate or triflate.9. A method according to claim 4 , wherein Ris triflate or tetrafluoroborate.11. A method according to claim 10 , wherein R is propionate or furoate.12. A method according to claim 10 , wherein said monofluoromethylating reagent is reacted with 6 α claim 10 ,9 α-Difluoro-17 α-[(2-furanylcarbonyl)oxy]-11 β-hydroxy-16 α-methyl-3-oxo-androsta-1 claim 10 ,4-diene-17 β-carbothioic acid or 6 α claim 10 ,9 α-Difluoro-11 β-hydroxy claim 10 ,16 α-methyl-3-oxo-17 α-(propionyloxy) androsta-1 claim 10 ,4-diene-17 β-carbothioic acid to give the corresponding compound of formula IV.13. A method according to claim 10 , wherein the compound of formula IV is prepared using S-monofluoromethyl-S-phenyl-2 claim 10 ,3 claim 10 ,4 claim 10 ,5-tetramethylphenylsulfonium tetrafluoroborate salt as monofluoromethylating reagent.14. A method according to claim 10 , wherein the compound of formula IV is prepared using S-monofluoromethyl-S-phenyl-2 claim 10 ,3 claim 10 ,4 claim 10 ,5-tetramethylphenylsulfonium triflate salt as monofluoromethylating reagent.15. A method according to claim 10 , wherein the compound of formula IV is prepared using N-(monofluoromethyl) triethyl ammonium ...

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Номер записи: 7
19-09-2013 дата публикации

Conjugated Neuroactive Steroid Compositions And Methods Of Use

Номер: US20130245253A1
Автор: Marx Christine, Mook Robert
Принадлежит:

The present disclosure provides modified neuroactive steroids. The modified neuroactive steroids may comprise, consist of, or consist essentially of a therapeutic agent and/or a modifying moiety. The modified neuroactive steroid can have modified characteristics as compared to native neuroactive steroids that do not include a modifying moiety and/or therapeutic agent. The modified neuroactive steroid may be, for example, modified pregnenolone, pregnenolone metabolites, allopregnanolone, and/or allopregnanolone metabolites. The modified neuroactive steroids can be used to treat, prevent and/or ameliorating a phenotypic state of interest in a subject. 138-. (canceled)40. The modified neuroactive steroid of claim 39 , wherein n is an integer from 1 to 50.41. The modified neuroactive steroid of claim 39 , wherein NS is selected from the group consisting of pregnenolone claim 39 , allopregnanolone claim 39 , epiallopregnanolone claim 39 , epipregnanolone claim 39 , progesterone claim 39 , 3α-hydroxyprogesterone claim 39 , 3β-hydroxyprogesterone claim 39 , 5α-dihydroprogesterone claim 39 , 5β-dihydroprogesterone claim 39 , androsterone claim 39 , dehydroepiandrosterone claim 39 , allotetrahydrodeoxycorticosterone claim 39 , 3α claim 39 ,5α-cortisol claim 39 , 3α claim 39 ,5β-cortisol claim 39 , 3α claim 39 ,5α-11-deoxycortisol claim 39 , 3α claim 39 ,5β-11-deoxycortisol claim 39 , 5α-dihydrocortisol claim 39 , 5β-dihydrocortisol claim 39 , and pharmaceutically acceptable salts thereof claim 39 , derivatives thereof claim 39 , or combinations thereof.43. The modified neuroactive steroid of claim 39 , wherein R is a neuroactive steroid.45. The modified neuroactive steroid of claim 43 , wherein R is selected from the group consisting of pregnenolone claim 43 , allopregnanolone claim 43 , epiallopregnanolone claim 43 , epipregnanolone claim 43 , progesterone claim 43 , 3α-hydroxyprogesterone claim 43 , 3β-hydroxyprogesterone claim 43 , 5α-dihydroprogesterone claim 43 , 5β- ...

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Номер записи: 8
17-10-2013 дата публикации

METHOD FOR PREPARING FLUTICASONE FUROATE

Номер: US20130274461A1
Автор: CHU Dingjun, Hong Xiangxian, Ji Haijie
Принадлежит:

Method for preparing fluticasone furoate (6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-[(2-furoyl)oxy]-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester) by directly subjecting a compound of Formula III and a complex of a fluoromethylating reagent in presence of an organic base to a replacement reaction to obtain the target compound. Generation of impurities in a process via Compound IV is avoided; the method is simple with mild reaction conditions, suitable for industrial production, and yields products with purity of 98% by HPLC. 1. A method for preparing fluticasone furoate , comprisingreacting Compound II (6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-hydroxy-3-oxo-androsta-1,4-diene-17β-carbothioic acid) and triethylamine in a first solvent to obtain an amine salt,reacting the amine salt with furoyl chloride to obtain Compound III (6α,9α-difluoro-17-carboxylic furan-2-carboxylic thioanhydride-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17α-yl furoate),reacting a fluoromethylating reagent and an organic base in a second solvent to form a complex, andadding the Compound III to the complex to have a replacement reaction between a fluoromethyl group of the complex and a furoyl group of the Compound III to obtain Compound I (6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-[(2-furoyl)oxy]-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester).2. The method for preparing fluticasone furoate of claim 1 , wherein molar amount of the furoyl chloride is about 2 to 3 times of molar amount of the Compound II in reacting the amine salt and the furoyl chloride to obtain the Compound III.3. The method for preparing fluticasone furoate of claim 1 , wherein the first solvent is acetone claim 1 , butanone claim 1 , ethyl acetate claim 1 , or dichloromethane.4. The method for preparing fluticasone furoate of claim 1 , wherein temperature for reacting the amine salt with the furoyl chloride to obtain the Compound III is in a range of from about −10° C. to about ...

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Номер записи: 9
14-11-2013 дата публикации

PREPARATION METHOD OF ROCURONIUM

Номер: US20130303753A1
Автор: WANG Peng, Zeng Zhiwen, Zhang Wenling, Zhang Xini
Принадлежит: Zhejiang Huahai Pharmaceutical co., Ltd.

A method for preparing rocuronium is disclosed. 2β-(4-Morpholinyl)-16β-(1-pyrrolidinyl)-5α-androstan-3α-ol-17β-acetate is used as a starting material and is directly reacted with 3-bromopropene at ambient temperature to produce rocuronium. 2. The preparation method according to claim 1 , characterized in that claim 1 , the molar amount of 3-bromopropene is 2 to 10 equivalent amount of the acetate.3. The preparation method according to claim 1 , characterized in that claim 1 , the reaction temperature is 0 to 40° C.4. The preparation method according to claim 3 , characterized in that claim 3 , the reaction temperature is 10 to 25° C.5. The preparation method according to claim 1 , characterized in that claim 1 , the good solvent is acetonitrile claim 1 , dichloromethane claim 1 , acetone claim 1 , or a mixture thereof.6. The preparation method according to claim 1 , characterized in that claim 1 , the anti-solvent is ethyl ether claim 1 , methyl tert-butyl ether claim 1 , isopropyl ether claim 1 , isobutyl acetate claim 1 , or a mixture thereof. The present invention relates to the field of medicinal chemistry, and specifically relates to a method for preparing rocuronium bromide which is a steroidal muscle relaxant.Rocuronium bromide is a novel mono-quaternary ammonium muscle relaxant and is used as an anesthetic adjuvant drug for tracheal intubation during anesthetization and muscle relaxation in surgical operation. Rocuronium bromide is a non-depolarizing muscle relaxant used clinically with the most rapid onset. The characteristics thereof include rapid onset, rapid recovery, weak inhibitory effects on cardiovascular system, and no histamine releasing effects. This drug is the most widely used muscle relaxant internationally, and is the first-ranked muscle relaxant in consumption used in North America and most European countries. The chemical formula thereof is as follows:European patent EP 0287150 initially discloses the preparation method and use thereof, in ...

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Номер записи: 10
16-01-2014 дата публикации

Steroids Having 7-Oxygen and 17-Heteroaryl Substitution-2

Номер: US20140018336A1
Автор: Frincke James M.
Принадлежит: Harbor Therapeutics, Inc.

The invention relates to the use of compounds to ameliorate or treat an condition such as a cystic fibrosis, neutropenia or other exemplified conditions. Exemplary compounds that can be used include 3β-hydroxy-17β-aminoandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3α-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-16β-fluoro-17β-aminoandrost-5-ene, 1α,3β-dihydroxy-4α-fluoroandrost-5-ene-17-one, 1α,3β,17β-trihydroxy-4α-fluoroandrost-5-ene, 1β,3β-dihydroxy-6α-bromoandrost-5-ene, 1α-fluoro-3β,12α-dihydroxyandrost-5-ene-17-one, 1α-fluoro-3β,4α-dihydroxyandrost-5-ene and 4α-fluoro-3β,6α,17β-trihydroxyandrostane. 4. The compound of wherein the C-linked heterocycle is 2-pyridyl claim 3 , 3-pyridyl claim 3 , 4-pyridyl claim 3 , 5-pyridyl or 6-pyridyl.7. The compound of wherein Ris an N-linked heterocycle wherein the N-linked heterocycle is —N-pyrrolidine claim 6 , —N1-pyrazolone claim 6 , —N2-pyrazolone claim 6 , —N-imidazolidin-2-one claim 6 , —N1-imidazole claim 6 , —N1-4 claim 6 ,5-dihydroimidazole claim 6 , —N-morpholine claim 6 , —N-piperidine claim 6 , —N-indole claim 6 , —N-indoline claim 6 , —N-quinolidine or —N1-piperazine claim 6 , optionally substituted at N4 with alkyl claim 6 , aryl or heteroaryl.9. The compound of wherein{'sup': '1', 'sub': '3', 'Ris —OH, ═O or —NH—C(O)CH;'}{'sup': '2', 'sub': '3', 'Ris —OH or —OCH; and'}{'sup': '3', 'sub': 3', '2', '3, 'Ris —H, —OH, —O—C(O)CHor —O—C(O)CHCH; and'}{'sup': '4', 'Ris an N-linked heterocycle.'}10. The compound of claim 9 , wherein the N-linked heterocycle is —N-pyrrolidine claim 9 , —N1-pyrazolone claim 9 , —N2-pyrazolone claim 9 , —N-imidazolidin-2-one claim 9 , —N1-imidazole claim 9 , —N1-4 claim 9 ,5-dihydroimidazole claim 9 , —N-morpholine claim 9 , —N1-pyridine claim 9 , —N-piperidine or —N-piperazine.11. The compound of wherein{'sup': '1', 'sub': '3', 'Ris —OH, ═O or —NH—C(O)CH;'}{'sup': '2', 'sub': '3', 'Ris —OH or —OCH;'}{'sup': '3', 'sub': 3', '2', '3, 'Ris —H, —OH, —O—C(O)CHor —O—C(O ...

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Номер записи: 11
16-01-2014 дата публикации

Steroids Having 7-Oxygen and 17-Heteroaryl Substitution-3

Номер: US20140018337A1
Автор: Frincke James M.
Принадлежит: Harbor Therapeutics, Inc.

The invention relates to the use of compounds to ameliorate or treat an condition such as a cystic fibrosis, neutropenia or other exemplified conditions. Exemplary compounds that can be used include 3β-hydroxy-17β-aminoandrost-5-ene, 3β-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3α-hydroxy-16α-fluoro-17β-aminoandrost-5-ene, 3β-hydroxy-16β-fluoro-17β-aminoandrost-5-ene, 1α,3β-dihydroxy-4α-fluoroandrost-5-ene-17-one, 1α,3β,17β-trihydroxy-4α-fluoroandrost-5-ene, 1β,3β-dihydroxy-6α-bromoandrost-5-ene, 1α-fluoro-3β,12α-dihydroxyandrost-5-ene-17-one, 1α-fluoro-3β,4α-dihydroxyandrost-5-ene and 4α-fluoro-3β,6α,17β-trihydroxyandrostane. 4. The compound of wherein the C-linked heterocycle is 2-pyridyl claim 3 , 3-pyridyl claim 3 , 4-pyridyl claim 3 , 5-pyridyl or 6-pyridyl.7. The compound of wherein Ris an N-linked heterocycle wherein the N-linked heterocycle is —N-pyrrolidine claim 6 , —N1-pyrazolone claim 6 , —N2-pyrazolone claim 6 , —N-imidazolidin-2-one claim 6 , —N1-imidazole claim 6 , —N1-4 claim 6 ,5-dihydroimidazole claim 6 , —N-morpholine claim 6 , —N-piperidine claim 6 , —N-indole claim 6 , —N-indoline claim 6 , —N-quinolidine or —N1-piperazine claim 6 , optionally substituted at N4 with alkyl claim 6 , aryl or heteroaryl.9. The compound of wherein{'sup': '1', 'sub': '3', 'Ris —OH, ═O or —NH—C(O)CH;'}{'sup': '2', 'sub': '3', 'Ris —OH or —OCH; and'}{'sup': '3', 'sub': 3', '2', '3, 'Ris —H, —OH, —O—C(O)CHor —O—C(O)CHCH; and'}{'sup': '4', 'Ris an N-linked heterocycle.'}10. The compound of claim 9 , wherein the N-linked heterocycle is —N-pyrrolidine claim 9 , —N1-pyrazolone claim 9 , —N2-pyrazolone claim 9 , —N-imidazolidin-2-one claim 9 , —N1-imidazole claim 9 , —N1-4 claim 9 ,5-dihydroimidazole claim 9 , —N-morpholine claim 9 , —N1-pyridine claim 9 , —N-piperidine or —N-piperazine.11. The compound of wherein{'sup': '1', 'sub': '3', 'Ris —OH, ═O or —NH—C(O)CH;'}{'sup': '2', 'sub': '3', 'Ris —OH or —OCH;'}{'sup': '3', 'sub': 3', '2', '3, 'Ris —H, —OH, —O—C(O)CHor —O—C(O ...

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Номер записи: 12
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: 13
27-02-2014 дата публикации

Bile Acid Derivatives as FXR Ligands for the Prevention or Treatment of FXR-Mediated Diseases or Conditions

Номер: US20140057886A1
Автор: Fiorucci Stefano, Pellicciari Roberto, Pruzanski Mark
Принадлежит: Intercept Pharmaceuticals, Inc.

The present invention relates to compounds of formula (I): 2. The compound of claim 1 , wherein the hydroxy group at position 7 is in the alpha position and R is hydrogen.3. The compound of claim 1 , wherein the hydroxy group at position 7 is in the beta position and R is hydrogen.4. The compound of claim 1 , wherein the hydroxy group at position 7 is in the alpha position and R is alpha-hydroxy.5. The compound of claim 1 , wherein the hydroxy group at position 7 is in the beta position and R is alpha-hydroxy.8. A method for the prevention or treatment of an FXR-mediated disease or condition in a mammal claim 1 , comprising administering to the mammal suffering from an FXR-mediated disease or condition a therapeutically effective amount of the compound of .9. The method of claim 8 , wherein the FXR-mediated disease or condition is selected from the group consisting of chronic liver disease claim 8 , gastrointestinal disease claim 8 , renal disease claim 8 , cardiovascular disease claim 8 , and metabolic disease.10. The method of claim 9 , wherein the chronic liver disease is selected from the group consisting of primary biliary cirrhosis (PBC) claim 9 , cerebrotendinous xanthomatosis (CTX) claim 9 , primary sclerosing cholangitis (PSC) claim 9 , drug induced cholestasis claim 9 , intrahepatic cholestasis of pregnancy claim 9 , parenteral nutrition associated cholestasis (PNAC) claim 9 , bacterial overgrowth or sepsis associated cholestasis claim 9 , autoimmune hepatitis claim 9 , chronic viral hepatitis claim 9 , alcoholic liver disease claim 9 , nonalcoholic fatty liver disease (NAFLD) claim 9 , nonalcoholic steatohepatitis (NASH) claim 9 , liver transplant associated graft versus host disease claim 9 , living donor transplant liver regeneration claim 9 , congenital hepatic fibrosis claim 9 , choledocholithiasis claim 9 , granulomatous liver disease claim 9 , intra- or extra-hepatic malignancy claim 9 , Sjogren's syndrome claim 9 , Sarcoidosis claim 9 , Wilson's ...

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Номер записи: 14
03-04-2014 дата публикации

TGR5 Modulators and Methods of Use Thereof

Номер: US20140094443A1
Автор: Pellicciari Roberto
Принадлежит: Intercept Pharmaceuticals, Inc.

The invention relates to compounds of Formula A: 5. The compound of claim 1 , wherein Ris hydrogen.6. The compound of claim 5 , wherein Ris α-hydroxy.7. The compound of claim 6 , wherein Ris hydroxy and Ris hydrogen.8. The compound of claim 7 , wherein Rand Rtaken together form a carbonyl and Ris R.9. The compound of claim 8 , wherein Ris hydroxy.10. The compound of claim 9 , wherein Ris unsubstituted alkyl.11. The compound of claim 10 , wherein Ris in the S-configuration.12. The compound of claim 1 , wherein Ris unsubstituted alkyl.13. A composition comprising the compound of or a salt claim 1 , solvate claim 1 , hydrate claim 1 , or prodrug thereof claim 1 , and at least one pharmaceutically acceptable excipient.14. A method of treating or preventing disease in a subject in need thereof by administering a compound of claim 1 , wherein the disease is selected from obesity claim 1 , insulin sensitivity claim 1 , inflammation claim 1 , cholestasis claim 1 , and bile desaturation. This application is continuation of U.S. application Ser. No. 12/523,670, filed Apr. 30, 2010, now U.S. Pat. No. 8,410,083, and is a 35 U.S.C. §371 National Phase Application of PCT/US2008/000658, filed Jan. 18, 2008, which claims priority from EP07001143.2, filed Jan. 19, 2007 and EP07012079.5, filed Jun. 20, 2007, each of which is incorporated by reference in its entirety.The invention concerns relates to compounds that modulate TGR5 and compositions useful in methods for the treatment and/or prevention of various diseases.TGR5 receptor is a G-protein-coupled receptor that has been identified as a cell-surface receptor that is responsive to bile acids. The primary structure of TGR5 and its responsiveness to bile acids has been found to be highly conserved in TGR5 among human, bovine, rabbit, rat, and mouse, and thus suggests that TGR5 has important physiological functions. TGR5 has been found to be widely distributed in not only lymphoid tissues but also in other tissues. High levels of ...

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Номер записи: 15
07-01-2016 дата публикации

Process for Making Crystals

Номер: US20160001252A1
Автор: ROBINSON JAMES, Ruecroft Graham
Принадлежит: PROSONIX LIMITED

A process for preparing crystalline particles of an active principal in the presence of ultrasonic irradiation that comprises contacting a solution of a solute in a solvent in a first flowing stream with an anti-solvent in a second flowing stream causing the mixing thereof, wherein the flow rate ratio of the anti-solvent: solvent is higher than 20:1, and collecting crystals that are generated. 1. A process for preparing crystalline particles of at least one active principal in the presence of ultrasonic irradiation , the process comprising a closed flow loop comprising a feed chamber , an ultrasonic flow cell chamber and a pump , the process comprising contacting , in the ultrasonic flow cell chamber , a solution of at least one solute in a solvent in a first flowing stream with an anti-solvent in a second flowing stream pumped from the feed chamber , causing the mixing thereof , wherein the flow rate ratio of the anti-solvent: solvent is higher than 20:1 , the mixture in the ultrasonic flow cell chamber being subjected to ultrasonic irradiation , the ultrasonic irradiation inducing nucleation and subsequent crystallisation of the at least one solute , the mixture flowing out of the ultrasonic flow cell chamber and into the feed chamber completing the closed flow loop , recirculating the second flowing stream around the closed flow loop and collecting the crystalline particles that are generated.2. A process according to claim 1 , wherein the crystalline particles comprise a mixture of two active principals.3. A process according to claim 1 , wherein the crystalline particles comprise a combination of a corticosteroid and a b2-agonist.4. A process according to claim 1 , wherein the active principal is fluticasone propionate.5. A process according to claim 1 , wherein the active principal comprises at least one of an anti-allergic claim 1 , bronchodilator claim 1 , or anti-inflammatory steroid.6. A process according to claim 1 , wherein the anti-solvent is miscible ...

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Номер записи: 16
07-01-2016 дата публикации

NOVEL COMPOSITIONS AND METHODS FOR TREATING PROSTATE CANCER

Номер: US20160002283A1
Автор: Casebier David Scott, Moreton Richard Christian, Sentissi Abdellah, Turnbull Mark
Принадлежит:

Described herein are compounds, methods of making such compounds, pharmaceutical compositions, and medicaments comprising such compounds, and methods of using such compounds to treat androgen receptor mediated diseases or conditions. In some embodiments, the solid matrix comprises a polymer. In some embodiments, the polymer is soluble in an aqueous solution. In particular embodiments, the aqueous solution is water. In other embodiments, the aqueous solution has a pH of 5.0 or greater. 1204-. (canceled)206. The pharmaceutical composition of claim 205 , wherein said compound is substantially in a non-crystalline form after storage of the composition for at least about one week.207. The pharmaceutical composition of claim 205 , wherein said compound is substantially in a non-crystalline form after storage of the composition for at least about one month.208. The pharmaceutical composition of claim 206 , wherein said composition is stored at about 25-40° C. and/or about 60-75% relative humidity.209. The pharmaceutical composition of claim 207 , wherein said composition is stored at about 25-40° C. and/or about 60-75% relative humidity.210. The pharmaceutical composition of claim 205 , wherein said composition is spray dried. This application claims the benefit of U.S. Provisional Application No. 61/508,823, filed Jul. 18, 2011, which application is incorporated herein by reference.Cancer represents a significant burden on human health, accounting for an estimated 13% of all deaths each year. In particular, several common cancers and diseases are associated with androgen hormone signaling, such as, for example, prostate cancer, breast cancer, ovarian cancer, polycystic ovary disease. For example, prostate cancer is the most common cancer in men. The majority of prostate cancer deaths are due to the development of metastatic disease that is unresponsive to conventional androgen deprivation therapy. Androgen deprivation therapy has been the standard of care in subjects with ...

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Номер записи: 17
03-01-2019 дата публикации

3-DESOXY DERIVATIVE AND PHARMACEUTICAL COMPOSITIONS THEREOF

Номер: US20190002493A1
Автор: Gioiello Antimo, Pellicciari Roberto
Принадлежит:

The present application provides Compound 1: 2. The free acid of the compound of .3. The pharmaceutically acceptable salt of the compound of .4. The amino acid conjugate of the compound of claim 1 , wherein the amino acid is glycine or sarcosine.5. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier or excipient.6. A method for treating or preventing a disease or condition activated by FXR claim 1 , comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , wherein the disease or condition activated by FXR is selected from cardiovascular disease claim 1 , chronic liver disease claim 1 , lipid disorder claim 1 , gastrointestinal disease claim 1 , renal disease claim 1 , metabolic disease claim 1 , cancer claim 1 , and neurological disease. Liver disorders occur widely in the population and are a risk factor for early mortality. For example, non-alcoholic fatty liver disease (NAFLD) is a disorder affecting millions of adults in the United States, and refers to conditions where there is an accumulation of excess fat in the liver of people who drink little or no alcohol. The most common form of NAFLD is a non-serious condition called hepatic steatosis (fatty liver), in which fat accumulates in the liver cells. NAFLD most often presents itself in individuals with a constellation of risk factors called metabolic syndrome, which is characterized by elevated fasting plasma glucose with or without intolerance to post-prandial glucose, being overweight or obese, high blood lipids such as cholesterol and triglycerides and low high-density lipoprotein cholesterol levels, and high blood pressure; but not all patients have all the manifestations of metabolic syndrome. Obesity is thought to be the most common cause of NAFLD and some experts estimate that about two-thirds of obese adults and one-half of obese children may have fatty liver.People with NAFLD may develop a more serious condition ...

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Номер записи: 18
01-01-2015 дата публикации

PROCESS FOR THE PREPARATION OF ABIRATERONE AND INTERMEDIATES THEREOF

Номер: US20150005489A1
Автор: Chang Yu-Sheng, Fang Hsiao-Ping, Kuo Lung-Huang, WU MING-FENG
Принадлежит:

The present invention provides intermediates for preparing abiraterone, and processes for preparing abiraterone and intermediates thereof. The intermediates include a compound of formula (IV): 3. The process according to or , wherein the hydroxy-protecting group is selected from the group consisting of trimethylsilyl (TMS) , tert-butyldimethylsilyl (TBS) , tetrahydropyranyl (THP) , triethylsilyl (TES) , triisopropylsilyl (TIPS) , dimethylphenylsilyl , diphenylmethylsilyl , tert-butyldiphenylsilyl (TBDPS) and triphenylmethyl (trityl , Tr).4. The process of claim 3 , wherein the hydroxy-protecting group is trimethylsilyl (TMS).5. The process according to claim 2 , wherein the triflating agent is selected from the group consisting of N-phenyl-bis(trifluoromethanesulfonimide) claim 2 , N-(5-chloro-2-pyridyl)triflimide or N-(2-pyridyl)triflimide.6. The process of claim 5 , wherein the triflating agent is N-phenyl-bis(trifluoromethanesulfonimide).7. (canceled)8. The process of claim 2 , wherein the strong base is an amide based organometallic reagent selected from the group consisting of sodium hexamethyldisilazide (NaHMDS) claim 2 , potassium hexamethyldisilazide (KHMDS) claim 2 , lithium hexamethyldisilazide (LiHMDS) and lithium diisopropylamide (LDA).9. The process of claim 8 , wherein the amide based organometallic reagent is sodium hexamethyldisilazide (NaHMDS).10. The process of claim 2 , wherein X has the formula —BY claim 2 , wherein Y is selected from alkyl claim 2 , alkoxy or hydroxy group.11. The process of claim 10 , wherein Y is selected from the group consisting of ethyl and hydroxy.12. The process of claim 2 , wherein step (d) is performed in the presence of a palladium catalyst selected from the group consisting of bis(triphenylphosphine)palladium(II) dichloride (PdCl(PPh)) claim 2 , tetrakis(triphenylphosphine)palladium (Pd(PPh)) claim 2 , tris(dibenzylideneacetone)dipalladium (Pd(dba)) claim 2 , palladium acetate (Pd(OAc)) claim 2 , dichloro(1 claim 2 ,2 ...

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Номер записи: 19
01-01-2015 дата публикации

PROCESS FOR ALKYNYLATING 16-SUBSTITUTED-17-KETO STEROIDS

Номер: US20150005518A1
Автор: Gutiérrez Fuentes Luis Gerardo, Sandoval Rodriguez Celso Miguel
Принадлежит:

A process ethynylates 16-methylene-17-keto steroids to the corresponding 16-methylene-17α-ethynyl-17β-hydroxy steroids by treatment with silyl-protected lithium acetylides followed by further desilylation. The resulting products are useful intermediates in the preparation of several pharmaceutically active agents, such as e.g. Nestorone® or melengestrol acetate. 4. Process according to claim 2 , wherein{'sup': 3', '1', '1, 'sub': 1', '3, 'Ris selected from O or —OR, wherein Ris a C-Calkyl;'}{'sup': '6', 'Ris selected from H, F, methyl and methylene;'}{'sup': '9', 'Ris selected from H and F;'}{'sup': 11', '9', '11, 'sub': 9', '11, 'Ris selected from H and OH, or there is a double bond between Cand Cand Rand Rare absent;'}{'sup': '18', 'Ris selected from methyl and ethyl;'}{'sup': '19', 'Ris selected from H and methyl.'}6. Process according to claim 1 , wherein each R is independently selected from C-Calkyl and phenyl.7. Process according to claim 1 , wherein the compound of formula (I) is lithium trimethylsilylacetylene.8. Process according to claim 1 , wherein desilylation step (b) is performed by treatment with potassium carbonate.9. Process according to claim 1 , wherein the ethynylated product is further converted to a compound selected from the group formed by Nestorone® claim 1 , nestorone alcohol and melengestrol acetate.15. Process for the preparation of a compound selected from the group formed by Nestorone® claim 12 , nestorone alcohol and melengestrol acetate claim 12 , said process comprising the use of a compound as defined in .16. Process according to claim 2 , comprising one of the following conditions (a) to (d):{'sub': 1', '3, '(a) wherein each R is independently selected from C-Calkyl and phenyl;'}(b) wherein the compound of formula (I) is lithium trimethylsilylacetylene;(c) wherein desilylation step (b) is performed by treatment with potassium carbonate;(d) wherein the ethynylated product is further converted to a compound selected from the group ...

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Номер записи: 20
14-01-2016 дата публикации

BERBERINE-URSODEOXYCHOLIC ACID CONJUGATE FOR TREATING THE LIVER

Номер: US20160009754A1
Автор: Andrali Shiva Sreenath, Tekumalla Venkatesh
Принадлежит:

The present invention is a method and compound for treating liver cancer. The invention treats liver cancer by directing a cancer-fighting drug into the liver hepatoportal circuit. The cancer-fighting drug is attached to a natural produced molecule which functions primarily in the hepatoportal circuit and has organotropism for the hepatoportal circuit. 2. The compound of claim 1 , wherein said R is a hydrogen atom.3. The compound of claim 1 , wherein said R is a functional group.4. The compound of claim 1 , wherein said R is an ethyl group.6. The method of synthesizing a molecule of claim 5 , further comprising the steps:cooling said first synthesized compound; andrecrystallizing said first synthesized compound to create a crystalized solid.7. The method of synthesizing a molecule of claim 6 , further comprising the steps:mixing said crystallized solid with a first solvent and adding 1,6-dibromohexane to create a first mixture;heating said first mixture;diluting with a first precipitation solvent to create a first precipitate; andfiltering said first precipitate and washing said first precipitate with a first washing solvent to create a first crude compound.8. The method of synthesizing a molecule of claim 7 , further comprising the steps:purifying said first crude compound to create a first purified compound.9. The method of synthesizing a molecule of claim 8 , further comprising the steps:dissolving said first purified compound in a second solvent;adding aqueous ammonia and ammonium chloride; andstirring to create a second mixture.10. The method of synthesizing a molecule of claim 9 , further comprising the steps:evaporating said second mixture to create a second crude compound.11. The method of synthesizing a molecule of claim 10 , further comprising the steps:purifying said second crude compound to create a second purified compound.12. The method of synthesizing a molecule of claim 11 , further comprising the steps:mixing said second purified compound and ...

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Номер записи: 21
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: 22
18-01-2018 дата публикации

METHOD FOR FULLY AUTOMATED SYNTHESIS OF 16Beta-18F-FLUORO-5Alpha-DIHYDROTESTOSTERONE (18F-FDHT)

Номер: US20180016296A1
Автор: Lazari Mark Saul, Murphy Jennifer Marie
Принадлежит: The Regents of the University of California

The automated synthesis of clinically relevant amounts of 16β-F-fluoro-5α-dihydrotestosterone (F-FDHT) using a commercially available radiosynthesizer. Synthesis was performed in 90 minutes with a decay-corrected radiochemical yield of 29±5%. The specific activity was 4.6 Ci/μmol (170 GBq/μmol) at end of formulation with a starting activity of 1.0 Ci (37 GBq). The formulated F-FDHT yielded sufficient activity for multiple patient doses and passed all quality control tests required for routine clinical use. 1. A method for the automated synthesis of 16β-F-fluoro-5α-dihydrotestosterone (F-FDHT) comprising:loading a plurality of reagents in an automated radiosynthesizer, the automated radiosynthesizer comprising a cassette and a reactor disposed beneath the cassette, wherein at least some of the reagents are stored on the cassette; [{'sup': '18', 'eluting F-fluoride into a reactor vial contained in the reactor via the cassette;'}, 'adding acetonitrile reagent via the cassette into the reactor vial and evaporating the contents thereof with the reactor;', 'cooling the reactor vial and adding a precursor solution comprising 16α-[[(trifluoromethyl)sulfonyl]oxy]-3,3-(ethylenedioxy)androstan-17-one via the cassette;', 'reacting the precursor solution within the reactor vial at elevated temperature under stirring conditions;', {'sub': '4', 'cooling the reactor vial to approximately room temperature and adding a solution of LiAlHvia the cassette followed by stirring;'}, 'adding acetone-THF solution into the reactor vial via the cassette followed by stirring;', 'adding HCl solution into the reactor vial via the cassette and reacting the same at elevated temperature under stirring conditions;', 'cooling the reactor vial and transferring the contents through a hydrophilic-lipophilic balanced (HLB) cartridge so as to trap product therein;', 'rinsing the reaction container and the HLB cartridge with water;', 'drying the HLB cartridge under an inert gas; and', {'sup': '18', 'passing ...

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Номер записи: 23
18-01-2018 дата публикации

CRYSTALLINE FORMS OF S-[4-(3-FLUORO-3-METHYLBUTYRYLOXY)BUT-2-YNYL] 6-ALPHA,9-ALPHA-DIFLUORO-17-ALPHA-(FURAN-2-YL)CARBONYLOXY-11-BETA-HYDROXY-16-ALPHA-METHYL-3-OXOANDROSTA-1,4-DIENE-17-BETA-CARBOTHIOATE

Номер: US20180016297A1
Автор: Chitturi Ttrinadha Rao, Patel Gopalkumar Chimanlal, Patel Jiten Ranchhodbhai, Sheth Gaurav Sanjivkumar
Принадлежит:

The present invention relates to crystalline forms of S-[4-(3-fluoro-3-methylbutyryloxy)but-2-ynyl] 6α,9α-difluoro-17α-(furan-2-yl)carbonyloxy-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate, an anti-inflammatory and anti-allergic glucocorticoid compound. 2. The compound of wherein the crystalline form is Form 1 and is characterized by X-ray powder diffraction peaks at 15.7 claim 1 , 19.3 claim 1 , 24.1 and 29.9 (±0.1) degree 2θ.3. The crystalline Form 1 of claim 2 , which is further characterized by X-ray diffraction peaks at 12.3 claim 2 , 14.9 claim 2 , 17.0 claim 2 , 24.7 claim 2 , 25.8 claim 2 , 28.3 claim 2 , 28.7 claim 2 , 31.7 claim 2 , 35.1 and 36.5 (±0.1) degree 2θ.4. A crystalline Form 1 of further characterized by a differential scanning calorimetry thermogram with an endoderm at 141.0° C. (±2.0° C.) and a melting endotherm at 180.0° C. (±2° C.).5. The compound of wherein the crystalline form is Form 2 and is characterized by X-ray powder diffraction peaks at 15.2 claim 1 , 18.5 claim 1 , 19.7 claim 1 , 23.7 and 27.3 (±0.1) degree 2θ.6. The crystalline Form 2 of claim 5 , which is further characterized by X-ray diffraction peaks at 13.4 claim 5 , 14.3 claim 5 , 16.3 claim 5 , 17.3 claim 5 , 20.0 claim 5 , 22.3 claim 5 , 26.5 and 28.0 (±0.1) degree 2θ.7. The crystalline Form 2 of further characterized by a differential scanning calorimetry thermogram with an endoderm at 145.5° C. (±0.5° C.) and a melting endotherm at 179.0° C. (±2.0° C.).8. The compound of wherein the crystalline form is Form 3 and is characterized by X-ray powder diffraction peaks at 6.0 claim 1 , 8.3 claim 1 , 14.0 and 16.8 (±0.1) degree 2θ.9. The crystalline Form 3 of claim 8 , which is further characterized by X-ray diffraction peaks at 12.0 claim 8 , 13.3 claim 8 , 16.4 claim 8 , 17.2 claim 8 , 17.9 claim 8 , 21.75 claim 8 , 22.8 claim 8 , 23.1 claim 8 , 25.5 and 30.3 (±0.1) degree 2θ.10. The crystalline Form 3 of further characterized by a differential scanning ...

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Номер записи: 24
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: 25
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: 26
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: 27
25-01-2018 дата публикации

PREPARATIONS OF HYDROPHOBIC THERAPEUTIC AGENTS, METHODS OF MANUFACTURE AND USE THEREOF

Номер: US20180022775A1
Автор: Barman Shikha P., CAVANAGH Thomas, Hao Tian, Leland Thomas B., Thekkedath Ritesh V.
Принадлежит:

The present invention further provides method of preparing nanocrystals of a hydrophobic therapeutic agent such as fluticasone or triamcinolone, pharmaceutical compositions (e.g., topical or intranasal compositions) thereof and methods for treating and/or preventing the signs and/or symptoms of disorders such as blepharitis, meibomian gland dysfunction or skin inflammation or a respiratory disease (e.g., asthma). 158-. (canceled)59. Nanocrystals of fluticasone propionate polymorph 1 having a crystalline habit (Form A) characterized in that the [001] crystallographic axis is substantially normal to the surfaces that define the thickness of the nanocrystal , wherein the nanocrystals have a size distribution of about 100-1000 nm and a X-ray powder diffraction pattern with characteristic peaks at about 7.8 , 15.7 , 20.8 , 23.7 , 24.5 , 32.5 degrees 2θ and additional peaks at about 9.9 , 13.0 , 14.6 , 16.0 , 16.9 , 18.1 , and 34.3 degrees 2θ.60. Nanocrystals according to claim 59 , characterized in that they are monoclinic crystals claim 59 , space group P 21 with the following cell parameters:a=7.7116 Å,b=14.170 Å,c=11.306 Å,beta=98.285 degrees, and{'sup': '3', 'volume=1222.6 Å'}61. Nanocrystals of fluticasone propionate of having a thickness ranging from about 5 nm to 500 nm.62. Nanocrystals of fluticasone propionate of characterized by a melting point of 299.5° C. with a melting range of 10° C.63. Nanocrystals of fluticasone propionate of having a purity of greater than 99% by weight.64. Nanocrystals of fluticasone propionate according to having dissolution rate in water of about 1 μg/g/day in water at room temperature.65. Nanocrystals of fluticasone propionate of having a size distribution of about 400-800 nm.66. Nanocrystals of fluticasone propionate of having a size distribution of about 400-600 nm.67. Nanocrystals of fluticasone propionate according to having a tap density of 0.5786 g/cm.68. Nanocrystals of fluticasone propionate according to characterized by a ...

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Номер записи: 28
23-01-2020 дата публикации

CRYSTALLINE FORMS OF A BILE ACID DERIVATIVE

Номер: US20200024299A1
Автор: Eberlin Alex, Espinosa Rosa Maria, Schaab Kevin, Strazik Rachel Pineda
Принадлежит:

A crystalline form of a bile acid compound and methods of preparation and use thereof are described. 1. A crystalline form of Compound 1-Na , characterized by having X-ray powder diffraction (XRPD) peaks at approximately 8.5 , 15.8 , and 16.7° 2θ (theta) using Cu Kα radiation.2. The crystalline form of claim 1 , characterized by having XRPD peaks at approximately 4.0 claim 1 , 8.5 claim 1 , 15.8 claim 1 , 16.7 claim 1 , 17.8 claim 1 , and 18.2° 2θ (theta) using Cu Kα radiation.3. The crystalline form of claim 1 , characterized by having XRPD peaks at approximately 4.0 claim 1 , 6.6 claim 1 , 7.1 claim 1 , 8.5 claim 1 , 11.5 claim 1 , 13.5 claim 1 , 15.8 claim 1 , 16.7 claim 1 , 17.8 claim 1 , and 18.2° 2θ (theta) using Cu Kα radiation.4. The crystalline form of claim 1 , characterized by having an XRPD pattern substantially similar to that shown in claim 1 , claim 1 , or .5. The crystalline form of claim 1 , further characterized by a Differential Scanning calorimetry (DSC) having an onset temperature between about 165° C. and about 169° C.6. The crystalline form of claim 1 , further characterized by a DSC having an onset temperature at approximately 165° C. or 167° C.7. The crystalline form of claim 1 , further characterized by a DSC having an onset temperature at about 30° C.8. The crystalline form of claim 1 , further characterized by a DSC having an onset temperature at approximately 29° C.9. The crystalline form of claim 1 , further characterized by a DSC having a first onset temperature at about 30° C. and a second onset temperature between about 165° C. and about 169° C.10. The crystalline form of claim 1 , further characterized by a DSC having a first onset temperature at approximately 29° C. and a second onset temperature at approximately 165° C. or 169° C.11. A crystalline form of Compound 1-Na claim 1 , characterized by having an orthorhombic crystal system with the following unit cell parameters: a=approximately 8.7 Å claim 1 , b=approximately 27.0 Å ...

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Номер записи: 29
23-01-2020 дата публикации

C7 SUBSTITUTED OXYSTEROLS AND METHODS OF USE THEREOF

Номер: US20200024300A1
Автор: Griffin Andrew, Harrison Boyd L., LA Daniel, Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Compounds are provided according to Formula (A): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R, R, n, R, 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. The compound of claim 1 , where n is 1.3. The compound of claim 1 , where n is 2.4. The compound of claim 1 , that when R claim 1 , R claim 1 , and Rare hydrogen and Ris unsubstituted isopropyl claim 1 , then Rand R claim 1 , together with the carbon atom to which they are attached do not form an oxo group; and{'sup': 4', '3', '1A', '1B', '2A', '2B, 'sub': 3', '3, 'when Ris absent, Ris hydrogen, and Rand Rare —CH, then Ris not —CHand Ris not —OH.'}5. The compound of claim 1 , that when Ris absent claim 1 , Ris —OH claim 1 , Ris hydrogen or —CF claim 1 , and Rand Rare —CH claim 1 , then Ris not hydrogen; and{'sup': 1A', '1B', '3', '2A', '2B, 'sub': '3', 'when Rand Rare —CHand Ris hydrogen, then Rand R, together with the carbon atom to which they are attached do not form an oxo group.'}612-. (canceled)13. The compound of claim 1 , wherein Ris absent claim 1 , one of Rand Ris —OH claim 1 , and Ris not hydrogen.14. The compound of claim 1 , wherein each of Rand Ris independently unsubstituted or substituted alkyl.15. The compound of claim 14 , wherein each of Rand Ris independently selected from the group consisting of haloalkyl claim 14 , alkoxyalkyl claim 14 , —CH claim 14 , —CHCH claim 14 , —CH(CH) claim 14 , —CFand —CHOCH.1620-. (canceled)21. The compound of claim 1 , wherein Rand R claim 1 , together with the carbon atom to which they are attached form a 3-8 membered ring.22. The compound of claim 1 , wherein Ris hydrogen and Ris alkyl claim 1 , carbocyclyl claim 1 , heterocyclyl claim 1 , aryl claim 1 , or heteroaryl.23. (canceled)24. The compound of claim 1 , wherein each of Rand Ris independently substituted or unsubstituted alkyl.2527-. (canceled)28. ...

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Номер записи: 30
01-02-2018 дата публикации

CRYSTAL FORM OF ABIRATERONE PROPIONATE AND PREPARATION METHOD THEREFOR

Номер: US20180030085A1
Автор: CHEN Fanglu, SHANGGUAN Yan, XING Naiguo, ZHENG Deping
Принадлежит: CHONGQING PHARMACEUTICAL RESEARCH INSTITUTE CO., LTD

The present invention relates to the field of pharmaceutical chemistry, and particularly to a crystal form of Abiraterone propionate and a preparation method therefor. Characteristic diffraction peaks occur at positions, where the 2θ value is 5.7°, 11.9°, 12.4°, 14.9°, 15.8°, 16.7°, 18.5°, 19.1°, 21.7°, 22.4°, and 39.9°±0.2°, in an X-ray powder diffraction spectrum of the crystal form of Abiraterone propionate. 1. A crystal form A of Abiraterone propionate , wherein X-ray powder diffraction pattern thereof has characteristic diffraction peaks at 2θ±0.2° , and the 2θ is 5.7° , 11.9° , 12.4° , 14.9° , 15.8° , 16.7° , 18.5° , 19.1° , 21.7° , 22.4° , and 39.9°.2. The crystal form A of claim 1 , wherein the X-ray powder diffraction pattern has a diffraction peaks at 2θ±0.2° claim 1 , and the 2θ is 5.3° claim 1 , 5.7° claim 1 , 11.9° claim 1 , 12.4° claim 1 , 14.2° claim 1 , 14.9° claim 1 , 15.8° claim 1 , 16.7° claim 1 , 17.0° claim 1 , 18.5° claim 1 , 19.1° claim 1 , 20.3° claim 1 , 21.7° claim 1 , 22.4° claim 1 , 22.9° claim 1 , 23.4° claim 1 , 24.9° claim 1 , 25.7° claim 1 , 26.9° claim 1 , 27.6° claim 1 , 27.9° claim 1 , 28.2° claim 1 , 30.0° claim 1 , 32.4° claim 1 , 34.6° claim 1 , 37.1° claim 1 , 37.8° claim 1 , 39.1° claim 1 , and 39.9°.3. A method for preparing the crystal form A of Abiraterone propionate claim 1 , comprising the following steps:a) dissolving Abiraterone propionate in an organic solvent;b) performing cooling crystallization under stirring and/or crystallization by adding a poor solvent; andc) separating solid.4. The method according to claim 3 , wherein the organic solvent is selected from methanol claim 3 , ethanol claim 3 , isopropanol claim 3 , acetone claim 3 , ethyl acetate claim 3 , methyl acetate claim 3 , dichloromethane claim 3 , chloroform claim 3 , acetonitrile claim 3 , tetrahydrofuran and n-heptane claim 3 , or a mixture thereof.5. The method according to claim 3 , wherein the temperature at which Abiraterone propionate is dissolved ...

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Номер записи: 31
16-02-2017 дата публикации

PROCEDURE FOR THE PREPARATION OF ABIRATERONE ACETATE AND INTERMEDIATES THEREOF

Номер: US20170044207A1
Автор: Alpegiani Marco, Cristiano Tania
Принадлежит:

Disclosed is a process for the preparation of abiraterone and abiraterone acetate with high yields and purity. A key element of the method is the isolation of a crystalline intermediate that makes the process particularly suitable for implementation on an industrial scale. 1. The compound of formula (14). This non-provisional application is a continuation of U.S. Ser. No. 15/114,089, filed on Jul. 26, 2016, which is a U.S. National Stage of PCT/IB2015/050613, filed on 27 Jan. 2015, which claims priority to and the benefit of Italian Application No. MI2014A000111 filed on 28 Jan. 2014, the contents of which are all incorporated by reference in their entireties.The present invention relates to a process for the preparation of abiraterone and abiraterone acetate with high yields and purity. A key element of the process is the isolation of a crystalline intermediate that makes the process particularly suitable for implementation on an industrial scale.Abiraterone acetate, the chemical name of which is (3β)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate of formula (1), is the prodrug of the active metabolite abiraterone (2), a selective inhibitor of enzyme CYP17.Abiraterone acetate forms the basis of the novel medicament Zytiga®, a tablet formulation containing 250 mg of active ingredient, which is administered orally at a single daily dose. When combined with prednisone or prednisolone it is indicated for the treatment of metastatic, castration-resistant prostate cancer in adult males in whom the disorder appears during or after a chemotherapy regimen based on docetaxel.Numerous processes are reported in the literature for the preparation of abiraterone or derivatives thereof. In most cases the starting product is prasterone (dehydroepiandrosterone).The preparation of abiraterone acetate was originally disclosed in EP0633893. Its synthesis involves conversion of the carbonyl at the 17 position of dehydroepiandrosterone-3-acetate (prasterone acetate, 3) to the ...

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Номер записи: 32
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: 33
25-02-2016 дата публикации

TGR5 MODULATORS AND METHODS OF USE THEREOF

Номер: US20160052956A1
Автор: Pellicciari Roberto
Принадлежит:

The invention relates to compounds of Formula A: 2. A pharmaceutical composition comprising a compound according to and at least one pharmaceutically acceptable excipient. This application is a continuation of U.S. Ser. No. 13/056,797, filed on Mar. 22, 2011, now U.S. Pat. No. 8,796,249, which is a national stage application of International Application No. PCT/US2009/052290, filed on Jul. 30, 2009, which claims priority to EP Application No. 08013676.5, filed on Jul. 30, 2008, the contents of each of which are incorporated by reference in their entirety.The invention concerns relates to compounds containing a sulfate or sulfonic acid moiety that modulate TGR5 and pharmaceutical compositions containing such compounds useful in methods for the treatment and prevention of disease.TGR5 receptor is a G-protein-coupled receptor that has been identified as a cell-surface receptor that is responsive to bile acids (BAs). The primary structure of TGR5 and its responsiveness to bile acids has been found to be highly conserved in TGR5 among human, bovine, rabbit, rat, and mouse, and thus suggests that TGR5 has important physiological functions. TGR5 has been found to be widely distributed in not only lymphoid tissues but also in other tissues. High levels of TGR5 mRNA have been detected in placenta, spleen, and monocytes/macrophages. 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. Bio. Chem., 278, 9435. TGR5 has been found to be identical to hGPCR19 reported by Takeda et al. 2002, FEBS Lett. 520, 97-101.TGR5 is associated with the intracellular accumulation of cAMP, that is widely expressed in diverse cell types. While the activation of this membrane receptor in macrophages decreases pro-inflammatory cytokine production, (Kawamata, Y.; Fujii, R.; Hosoya, M.; Harada, M.; Yoshida, H.; Miwa, M.; Fukusumi, S.; Habata, Y.; Itoh, T.; Shintani, Y.; Hinuma, S.; Fujisawa, Y.; Fujino, M., A ...

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Номер записи: 34
25-02-2021 дата публикации

CYCLIN-DEPENDENT KINASE DEGRADERS AND METHODS OF USE

Номер: US20210054020A1
Автор: Gray Nathanael S., Hatcher John
Принадлежит: Dana-Farber Cancer Institute, Inc.

The present application provides bifunctional compounds of Formula (Ia): (Ia), or an enantiomer, diastereomer, stereoisomer, or pharmaceutically acceptable salt thereof, which act as protein degradation inducing moieties for one or mor of cyclin-dependent kinase 8 (CDK8) and cyclin-dependent kinase 19 (CDK19). The present application also relates to methods for the targeted degradation of CDK8 and/or CDK19 through the use of the bifumtional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 and/or CDK19 which can be utilized in the treatment of disorders modulated by CDK8 and/or CDK19. 45.-. (canceled)7. (canceled)8. The bifunctional compound of claim 2 , wherein X is —O— claim 2 , —NR— claim 2 , or -Het- claim 2 , wherein{'sub': '5', 'Ris methyl and'}{'sub': '2', 'Hetis selected from aziridine, azetidine, pyrrolidine, dihydropyrrole, piperidine, piperazine, dihydropyridine, tetrahydropyridine, azepane, oxaziridine, oxazetidine, isoxazoline, isoxazolidine, oxazoline, oxazolidine, thiazoline, thiazolidine, isothiazoline, isothiazolidine, pyrazoline, pyrazolidine, imidazoline, imidazolidine, morpholine, oxazinane, thiomorpholine, thiazinane, and triazole.'}913.-. (canceled)14. The bifunctional compound of claim 8 , wherein Hetis morpholine claim 8 , or iperazine.1516.-. (canceled)17. The bifunctional compound of claim 2 , wherein Hetis 6-isoquinolinyl claim 2 , 7-isoquinolinyl claim 2 , 6-quinazolinyl claim 2 , 6-phthalazinyl claim 2 , 6-indazolyl claim 2 , 6-indazolyl-3-amine claim 2 , or 5-indazolyl.18. (canceled)2023.-. (canceled)25. The bifunctional compound of claim 24 , whereinp2 is 0,p3 is 2,each W is O,{'sub': '3', 'Zis C(O), and'}Q is absent.27. (canceled)29. The bifunctional compound of claim 28 , wherein{'sub': 1', '2', '1', '2', '1', '2', '2, 'at least one of Zand Z is C(O), or wherein Zis C(O), or wherein Zand Zare each is C(O), or wherein Zis C(O) and Zis CH.'}3032.-. (canceled)33. The bifunctional ...

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Номер записи: 35
13-02-2020 дата публикации

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Номер: US20200048300A1
Автор: Beresis Richard Thomas, Harrison Boyd L., Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (1): and pharmaceutical compositions thereof. 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, 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, tinnitus, and status epilepticus. 141-. (canceled)60. The method of claim 42 , wherein the method is a method of treating a sleep disorder.61. The method of claim 60 , wherein the sleep disorder is insomnia.62. The method of claim 42 , wherein the method is a method of treating a mood disorder.63. The method of claim 42 , wherein the mood disorder is depression.64. The method of claim 63 , wherein the depression is postnatal depression.65. The method of claim 64 , wherein the compound or pharmaceutical composition is administered orally. 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 the cell exterior. The potential (voltage) is the result of ion (K, Na, organic anions) balance across the neuronal semipermeable membrane. Neurotransmitters are stored in presynaptic vesicles and are released under the influence of neuronal action potentials. When released into the synaptic cleft, an excitatory chemical transmitter such as acetylcholine will cause membrane depolarization (change of potential from −70 mV to −50 mV). This effect is mediated by postsynaptic ...

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Номер записи: 36
22-02-2018 дата публикации

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Номер: US20180051052A1
Автор: Beresis Richard Thomas, Harrison Boyd L., Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (1): and pharmaceutical compositions thereof. 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, 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, tinnitus, and status epilepticus. 237-. (canceled)39. The method of claim 38 , wherein the CNS-related disorder is a sleep disorder claim 38 , a mood disorder claim 38 , a schizophrenia spectrum disorder claim 38 , a convulsive disorder claim 38 , a disorder of memory and/or cognition claim 38 , a movement disorder claim 38 , a personality disorder claim 38 , autism spectrum disorder claim 38 , pain claim 38 , traumatic brain injury claim 38 , a vascular disease claim 38 , a substance abuse disorder and/or withdrawal syndrome claim 38 , tinnitus claim 38 , or status epilepticus.40. The method of or wherein the compound is administered orally claim 38 , subcutaneously claim 38 , intravenously claim 38 , or intramuscularly.41. The method of or wherein the compound is administered chronically. 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 the cell exterior. The potential (voltage) is the result of ion (K, Na, Cl, organic anions) balance across the neuronal semipermeable membrane.Neurotransmitters are stored in presynaptic vesicles and are released under the ...

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Номер записи: 37
23-02-2017 дата публикации

PROCESS FOR ABIRATERONE ACETATE

Номер: US20170051009A1
Автор: Krishna Bandi Vamshi, Reddy Bandi Parthasaradhi, Reddy Dasari Muralidhara, Reddy Katham Srinivasa, Reddy Kura Rathnakar
Принадлежит:

The present invention provides a novel process for the preparation of abiraterone. The present invention also provides a novel process for the preparation of abiraterone acetate. 1. A process for the preparation of abiraterone , which comprises:a) reacting dehydroepiandrosterone-3-acetate in a chlorinated solvent with trifluoromethanesulfonic anhydride in the presence of a base selected from the group consisting of n-methylpyrrolidone, N-methylpiperidine or tetramethylethylenediamine in a chlorinated solvent;b) concentrating the reaction mass to obtain a residual mass;c) reacting the residual mass obtained in step (b) in an ether solvent with diethyl(3-pyridyl)borane in the presence of bis(triphenylphosphine)pailadium(II) chloride;d) adding a base and water to the reaction mass;e) concentrating the reaction mass to obtain a residual mass;f) adding a base and an alcoholic solvent to the residual mass obtained in step);g) adding water to the reaction mass;h) pH of the reaction mass was adjusted with hydrochloric acid;i) adding chlorinated solvent to the reaction mass;j) removing the solvent from the reaction mass to obtain a residual solid;k) slurring the residual solid obtained in step (j) with a hydrocarbon solvent; andl) isolating the abiraterone.2. The process as claimed in claim 1 , wherein the chlorinated solvent used in step (a) and (i) is a solvent or a mixture of solvents selected from methylene chloride claim 1 , chloroform claim 1 , carbontetrachloride and ethylene dichloride.3. The process as claimed in claim 1 , wherein the ether solvent used in step (c) is a solvent or a mixture of solvents selected from tetrahydrofuran claim 1 , methyl tetrahydrofuran claim 1 , methyl tert-butyl ether claim 1 , ethyl tert-butyl ether claim 1 , 1 claim 1 ,4-dioxane claim 1 , diisopropyl ether claim 1 , diethyl ether and tetrahydropyran.4. The process as claimed in claim 1 , wherein the base used in step (d) and (f) is organic base or inorganic base.5. The process as ...

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Номер записи: 38
10-03-2022 дата публикации

ORGANIC COMPOUNDS

Номер: US20220073558A1
Автор: Davis Robert, Li Peng, Qiao Yupu, VANOVER Kimberly
Принадлежит:

The invention relates to particular prodrugs and analogs of (3α,5α)-3-hydroxy-21-(1H-imidazol-1-yl)-3-methoxymethyl)-pregnan-20-one, in free or pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use as sedatives, hypnotics, anxiolytics, and/or anesthetics, and methods for treatment of depression, anxiety, insomnia, epilepsy, and other central nervous system disorders, as well as to combinations with other agents. 2. A compound according to claim 1 , wherein X is H.3. A compound according to claim 1 , wherein X is selected from —(C═O)—R claim 1 , —CH—(C═O)—O—R claim 1 , and —CH—(C═O)—N(R)(R).4. A compound according to claim 1 , wherein X is —(C═O)—R.5. A compound according to claim 1 , wherein X is —CH—(C═O)—O—R.6. A compound according to claim 1 , wherein X is CH—(C═O)—N(R)(R).7. A compound according to claim 1 , wherein X is CH—(C═O)—N(R)(R) and Ris H.8. A compound according to claim 1 , wherein Ris CH.9. A compound according to claim 1 , wherein Ris CD.10. A compound according to claim 1 , wherein any one or two or three or four of Rto Ris D.11. A compound according to claim 1 , wherein Rand Rare D.12. A compound according to claim 1 , wherein Rto Rare D.13. A compound according to claim 1 , wherein any one claim 1 , two or three of Rto Rare D.15. A compound according to claim 1 , in the salt form claim 1 , e.g. claim 1 , in the form of a pharmaceutically acceptable salt.16. A compound according to claim 1 , having greater than 50% incorporation of deuterium at one or more of the indicated positions of the structure (i.e. claim 1 , greater than 50 atom % D) claim 1 , e.g. claim 1 , greater than 60% claim 1 , or greater than 70% claim 1 , or greater than 80% claim 1 , or greater than 90% or greater than 95% claim 1 , or greater than 96% claim 1 , or greater than 97% claim 1 , or greater than 98% claim 1 , or greater than 99%.17. A pharmaceutical composition comprising a compound ...

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Номер записи: 39
05-03-2015 дата публикации

SULFATED OLIGOSACCHARIDE DERIVATIVES

Номер: US20150065440A1
Автор: Ferro Vito, Hammond Edward Timothy, Handley Paul Newton, Johnstone Kenneth David, Karoli Tomislav, Liu Ligong, Wimmer Norbert
Принадлежит:

The invention relates to novel compounds that have utility as inhibitors of heparan sulfate-binding proteins; compositions comprising the compounds, and use of the compounds and compositions thereof for the antiangiogenic, antimetastatic, anti-inflammatory, antimicrobial, anticoagulant and/or antithrombotic treatment of a mammalian subject. 2. The pharmaceutical or veterinary composition according to claim 1 , wherein in said at least one compound Ris cholestanyl.3. The pharmaceutical or veterinary composition according to claim 1 , wherein in said at least one compound Ris propylstearamide.4. The pharmaceutical or veterinary composition according to claim 1 , wherein said at least one compound is selected from the group consisting of:{'smallcaps': D', 'D', 'D', 'D, '3β-cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β--glucopyranoside (compound 65);'}{'smallcaps': D', 'D', 'D, '4-(cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α--glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β--glucopyranoside (compound 70);'}{'smallcaps': D', 'D', 'D, '4-(cholestan-3β-yl-oxymethyl)[1,2,3]triazol-1-yl-2,3,4,6-tetra-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α--glucopyranosyl-(1→4)-1-deoxy-2,3,6-tri-O-sodium sulfonato-β--glucopyranoside (compound 76);'}{'smallcaps': D', 'D', 'D, '3β-cholestanyl-2,3,4,6-tetra-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sodium sulfonato-β--glucopyranoside (compound 87);'}{'smallcaps': D', 'D', 'D, '3-stearamidopropyl-2,3,4,6-tetra-O-sulfo-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α--glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β--glucopyranoside, decasodium salt (compound 123); and'}{'smallcaps': D', 'D', 'D', 'D, '3- ...

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Номер записи: 40
28-02-2019 дата публикации

METHODS FOR THE PREPARATION OF OBETICHOLIC ACID AND DERIVATIVES THEREOF

Номер: US20190062367A1
Автор: Galvin Gabriel M
Принадлежит:

The present application relates to a method of preparing a bile acid derivative, or a pharmaceutical acceptable salt, solvate, or amino acid conjugate thereof, comprising direct alkylation at the C-6 position of KLCA. 3. The method of or , wherein the alkylating agent is selected from alkyl halide , alkyl tosylate , alkyl mesylate , sulfonate ester , alkyl oxonium salt , dialkyl sulfate , dialkyl carbonate , and tetraalkylammonium salt.4. The method of claim 3 , wherein the alkylating agent is alkyl halide.5. The method of claim 4 , wherein the alkyl halide is ethyl bromide or ethyl iodide.6. The method of or claim 4 , wherein the alkylation is conducted in an aprotic solvent.7. The method of claim 6 , wherein the aprotic solvent is selected from tetrahydrofuran (THF) claim 6 , ethyl acetate (EtOAc) claim 6 , acetone claim 6 , dimethylformamide (DMF) claim 6 , acetonitrile (MeCN) claim 6 , dimethyl sulfoxide (DMSO) claim 6 , toluene claim 6 , hexane claim 6 , benzene claim 6 , 1 claim 6 ,4-dioxane claim 6 , chloroform claim 6 , dichloromethane (DCM) claim 6 , diethyl ether claim 6 , and methyl test-butyl ether (MTBE).8. The method of or claim 6 , wherein the alkylation is conducted in the presence of a deprotonating agent.9. The method of claim 8 , wherein the deprotonating agent is selected from C-Calkoxide claim 8 , metal hydroxide claim 8 , and metal hydride.10. The method of or claim 8 , further comprising claim 8 , deprotonating Compound 1 before Compound 1 is alkylated.11. The method of claim 10 , wherein the deprotonating agent is selected from C-Calkoxide claim 10 , metal hydroxide claim 10 , and metal hydride.12. The method of or claim 10 , further comprising deprotecting Compound 1 after alkylation of the carbon atom at the C-6 position.13. The method of claim 12 , comprising deprotecting the hydroxyl group at the C-3 position.14. The method of claim 13 , further comprising deprotecting the carboxylic group at the C-24 position claim 13 , wherein the ...

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Номер записи: 41
17-03-2022 дата публикации

C7 SUBSTITUTED OXYSTEROLS AND METHODS OF USE THEREOF

Номер: US20220081465A1
Автор: Griffin Andrew, Harrison Boyd L., LA Daniel, Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Compounds are provided according to Formula (A): 167.-. (canceled)69. (canceled)7176.-. (canceled)78174.-. (canceled)175. The method according to any one of , or , wherein n is 1.176. The method according to any one of , or , where n is 2.177. The method according to any one of , or , wherein each of Rand Ris independently unsubstituted or substituted alkyl.178. The method according to any one of , or , wherein each of Rand Ris independently selected from the group consisting of haloalkyl , alkoxyalkyl , —CH , CHCH , —CH(CH) , —CFand —CHOCH.179. The method according to any one of , or , wherein Rand R , together with the carbon atom to which they are attached form a 3-8 membered ring.180. The method according to any one of , or , wherein Ris hydrogen and Ris alkyl , carbocyclyl , heterocyclyl , aryl , or heteroaryl.181. The method according to any one of , or , wherein each of Rand Ris independently substituted or unsubstituted alkyl.182. The method according to any one of , or , wherein Ris substituted or unsubstituted alkyl. This application is a divisional of U.S. patent application Ser. No. 16/338,315, filed Mar. 29, 2019, which is a U.S. National Phase Application under 35 U.S.C. § 371 of International Application PCT/US2017/054657, filed Sep. 30, 2017, which claims priority to and the benefit of U.S. Provisional Application No. 62/402,789, filed Sep. 30, 2016, and U.S. Provisional Application No. 62/402,797, filed Sep. 30, 2016. The disclosures of each of the foregoing applications are incorporated herein by reference in their entirety.NMDA receptors are heteromeric complexes comprised of NR1, NR2, and/or NR3 subunits and possess distinct recognition sites for exogenous and endogenous ligands. These recognition sites include binding sites for glycine, and glutamate agonists and modulators. NMDA receptors are expressed in the peripheral tissues and the CNS, where they are involved in excitatory synaptic transmission. Activating these receptors contributes to ...

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Номер записи: 42
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: 43
10-03-2016 дата публикации

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Номер: US20160068563A1
Автор: Beresis Richard Thomas, Harrison Boyd L., Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (I): and pharmaceutical compositions thereof. 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, 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, tinnitus, status epilepticus. 6. The compound of claim 5 , wherein Ris substituted or unsubstituted hydrogen claim 5 , substituted or unsubstituted Calkyl claim 5 , —C(═O)R claim 5 , —C(═O)OR claim 5 , —C(═O)N(R) claim 5 , or —S(═O)R.9. The compound of claim 1 , wherein e is 1.10. The compound of claim 1 , wherein Ris substituted or unsubstituted Calkyl.11. The compound of claim 1 , wherein Ris —CH.12. The compound of claim 1 , wherein Ris ORwherein Ris hydrogen or substituted or unsubstituted Calkyl.13. The compound of claim 1 , wherein Ris OH.14. The compound of claim 1 , wherein Ris —S(═O)Rwherein Ris substituted or unsubstituted Calkyl.15. The compound of claim 1 , wherein Ris —S(═O)CH.16. The compound of claim 1 , wherein Ris —C(═O)Rwherein Ris substituted or unsubstituted Calkyl.17. The compound of claim 1 , wherein Ris —C(═O)CH.18. The compound of claim 1 , wherein Ris —C(═O)N(R)wherein Ris hydrogen or substituted or unsubstituted Calkyl.19. The compound of claim 1 , wherein Ris —C(═O)NHCH.20. The compound of claim 1 , wherein between C5 and C6 is a double bond and Ris absent.21. The compound of claim 1 , wherein between C5 and C6 is a single bond.23. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.24. A method for treating a CNS-related disorder in a subject in need thereof claim 1 , comprising administering to the ...

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Номер записи: 44
29-05-2014 дата публикации

NOVEL 17B-HETEROARYL-SUBSTITUTED STEROIDS AS MODULATORS OF GABAA RECEPTORS

Номер: US20140148412A1
Автор: Hogenkamp Derk J.
Принадлежит: THE REGENTS OF THE UNIVERSITY OF CLAIFORNIA

The invention is directed to novel 17β-heteroaryl substituted steroids of Formula I, pharmaceutical compositions thereof, and their use as modulators of GABAreceptors. 1518-. (canceled)19. A 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 , R claim 1 , R claim 1 , and Rare hydrogen claim 1 , Ris selected from the group Calkyl claim 1 , and Chaloalkyl; each Ris independently hydrogen claim 1 , halogen claim 1 , optionally substituted Calkyl claim 1 , and Chaloalkyl; C1 to C2 claim 1 , C4 to C5 claim 1 , and C11 to C12 are single bonds claim 1 , or a pharmaceutically acceptable salts claim 1 , solvates claim 1 , or prodrugs thereof.2021-. (canceled)22. A compound of wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare hydrogen; Ris selected from the group consisting of Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , and Chaloalkyl; Ris hydrogen or methyl; each Ris independently hydrogen claim 1 , halogen claim 1 , Calkyl claim 1 , optionally substituted with hydroxy claim 1 , and halogen; HET is selected from the group consisting of 5-isoxazolyl claim 1 , 3-isoxazolyl claim 1 , 2-oxazolyl claim 1 , 4-oxazolyl and 5-oxazolyl claim 1 , all optionally substituted with 1 to 2 Rgroups; C1 to C2 claim 1 , C4 to C5 claim 1 , and C11 to C12 are single bonds claim 1 , a*d or a pharmaceutically acceptable salts claim 1 , solvates claim 1 , or prodrugs thereof.23. A compound of wherein Ris methyl; Ris a 5α-hydrogen atom; Ris methyl; each Ris independently hydrogen claim 22 , Calkyl and hydroxymethyl; or a pharmaceutically acceptable salts claim 22 , solvates claim 22 , or prodrugs thereof.24. A compound of wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare hydrogen; Ris selected from the group consisting of Calkyl claim 1 , Calkenyl claim 1 , Calkynyl claim 1 , and ...

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Номер записи: 45
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: 46
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: 47
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: 48
05-03-2020 дата публикации

SALTS AND CRYSTAL FORMS OF GABA-A POSITIVE ALLOSTERIC MODULATOR

Номер: US20200071350A1
Автор: BOTELLA Gabriel Martinez, LASKAR Paul A., OLIVIER Nelson B., REDDY Kiran, RONN Magnus
Принадлежит:

The invention relates to salts of Compound 1, crystalline forms thereof, methods of their preparation, pharmaceutical compositions thereof and methods of their use 191.-. (canceled)93. The citrate salt of claim 92 , wherein the Form A exhibits an XRPD pattern comprising peaks at about 5.7±0.2; 20.1±0.2 and 20.3±0.2 degrees two-theta.94. The citrate salt of claim 92 , wherein the Form A exhibits an XRPD pattern substantially similar to .95. The citrate salt of claim 92 , wherein the Form A is defined by unit cell parameters substantially similar to the following:a=8.9 Åb=12.2 Åc=16.5 Åα=73.7°β=76.6°γ=83.2°Space group P1,Molecules/asymmetric unit 2,wherein the crystalline form is at about 120 K.96. The citrate salt of claim 92 , wherein the Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 89.0±2.0° C. or about 139.5±2.0° C.97. A pharmaceutical composition comprising the citrate salt of and a pharmaceutically acceptable carrier.98. The pharmaceutical composition of claim 97 , wherein the composition is a tablet.100. The hydrobromide salt of claim 99 , wherein the Form A exhibits an XRPD pattern comprising peaks at about 15.2±0.2 claim 99 , 15.5±0.2 claim 99 , and 16.3±0.2 degrees two-theta.101. The hydrobromide salt of claim 99 , wherein the Form A exhibits an XRPD pattern substantially similar to .102. The hydrobromide salt of claim 99 , wherein the Form A exhibits a differential scanning calorimetry thermogram having a peak value at about 243.1±2.0° C.103. A pharmaceutical composition comprising the hydrobromide salt of and a pharmaceutically acceptable carrier.104. The pharmaceutical composition of claim 103 , wherein the composition is a tablet.106. The hydrobromide salt of claim 105 , wherein the Form E exhibits an XRPD pattern comprising peaks at about 15.2±0.2 and 16.3±0.2 degrees two-theta.107. The hydrobromide salt of claim 105 , wherein the Form E exhibits an XRPD pattern substantially similar to .108. The ...

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Номер записи: 49
05-06-2014 дата публикации

PROCESS AND INTERMEDIATES FOR THE PREPARATION OF ABIRATERONE ACETATE

Номер: US20140155363A1
Автор: Marom Ehud, Mizhiritskii Michael, Rubnov Shai
Принадлежит: MAPI PHARMA LTD.

The present invention relates to a process for the synthesis of (3beta)17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate (Abiraterone acetate) represented by the structure of formula (1), and salts thereof, especially salts with pharmaceutically acceptable acids. The present invention further relates to certain intermediates in such processes. 120-. (canceled)22. The process according to claim 21 , wherein the hydroxyl protecting group PG is selected from the group consisting of acetate (Ac) claim 21 , benzyl (Bzl) claim 21 , Si(R) claim 21 , tetrahydropyranyl (THP) and trityl (Trt) claim 21 , wherein Ris a substituted or unsubstituted alkyl claim 21 , cycloalkyl claim 21 , alkylaryl or aryl.23. The process according to claim 21 , wherein M is Li or MgX claim 21 , wherein X is Cl claim 21 , Br or I.24. The process according to claim 21 , wherein step (a) is carried out by reacting compound (10) with 3-Py-Li in an organic solvent at a temperature of about −70° C. to about 0° C. claim 21 , in the absence or presence of one or more additives.25. The process according to claim 24 , wherein step (a) is carried out in the presence of an additive selected from the group consisting of: (i) an amine; (ii) an amide; (iii) an inorganic salt; (iv) a rare earth element salt; and (v) salt mixtures or complex salts.26. The process according to claim 25 , wherein(i) the amine is N,N′-tetramethylethylenediamine;(ii) the amide is 1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU);(iii) the inorganic salt is selected from lithium chloride, lithium perchlorate, cadmium chloride, magnesium chloride, zinc chloride and ferric chloride;(iv) the rare earth element salt is a lanthanide salt selected from lathanium chloride and cerium chloride;{'sub': 3', '3', '3', '3', '3', '3, '(v) the salt mixtures of complex salts are selected from YCl.2LiCl, CeCl.2LiCl, NdCl.2LiCl, PrCl.2LiCl, DyCl.2LiCl and ErCl.2LiCl.'}27. The process according to claim 26 , wherein the additive is lithium ...

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Номер записи: 50
22-03-2018 дата публикации

PROCESS FOR PREPARING BILE ACID DERIVATIVES

Номер: US20180079776A1
Автор: Gioiello Antimo, Pellicciari Roberto
Принадлежит:

The present invention relates to processes for preparing compounds of formula I: 19-. (canceled)11. The process of claim 10 , wherein Ris ethyl.13. (canceled)15. (canceled)17. (canceled)1920-. (canceled) The present invention relates to processes for preparing a compound of formula I:or a pharmaceutically acceptable salt or solvate thereof, whereinthe dashed bond (----) at position 7 indicates that the substituent is in an α or β stereochemistry;R is hydrogen or hydroxy; andRis hydrogen or C-Calkyl.Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In the case of conflict, the present specification, including definitions, will control. In the specification, the singular forms also include the plural unless the context clearly dictates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference. The references cited herein are not admitted to be prior art to the claimed invention. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting.Other features and advantages of the invention will be apparent from the following detailed description and claims.The present invention relates to processes for preparing a compound of formula I:or a pharmaceutically acceptable salt or solvate thereof, whereinthe dashed bond (----) at position 7 indicates that the substituent is in an α or β stereochemistry;R is hydrogen or hydroxy; andRis hydrogen or C-Calkyl.In one aspect, a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof, can be prepared starting from a compound of formula II in a 4-step process. See Scheme ...

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Номер записи: 51
24-03-2016 дата публикации

Process for producing a solid form of abiraterone acetate

Номер: US20160083416A1
Автор: Livius Cotarca, Massimiliano Forcato, Patricia Poirier, Pierrick Morice, Yvon Derrien
Принадлежит: Zach System SA

The present invention relates to a process for the preparation of 17-substituted steroids and, more particularly, to an improved method of preparing micro size abiraterone or derivatives thereof in high yield and purity by means of a spherical agglomeration process.

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Номер записи: 52
24-03-2016 дата публикации

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Номер: US20160083418A1
Автор: Beresis Richard Thomas, Harrison Boyd L., Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (I): and pharmaceutical compositions thereof. 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, 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, tinnitus, and status epilepticus. 2. (canceled)2434-. (canceled)37. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.38. A method for treating a CNS-related disorder in a subject in need thereof claim 1 , comprising administering to the subject an effective amount of a compound claim 1 , or a pharmaceutically acceptable salt thereof.39. The method of claim 38 , wherein the CNS-related disorder is a sleep disorder claim 38 , a mood disorder claim 38 , a schizophrenia spectrum disorder claim 38 , a convulsive disorder claim 38 , a disorder of memory and/or cognition claim 38 , a movement disorder claim 38 , a personality disorder claim 38 , autism spectrum disorder claim 38 , pain claim 38 , traumatic brain injury claim 38 , a vascular disease claim 38 , a substance abuse disorder and/or withdrawal syndrome claim 38 , tinnitus claim 38 , or status epilepticus.4041-. (canceled) 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 the cell exterior. The potential ( ...

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Номер записи: 53
23-03-2017 дата публикации

THERAPEUTICALLY ACTIVE ESTRATRIENTHIAZOLE DERIVATIVES AS INHIBITORS OF 17.BETA-HYDROXY-STEROID DEHYDROGENASE, TYPE 1

Номер: US20170081356A1
Автор: HIRVELÄ Leena, KANGAS Lauri, KOSKIMIES Pasi, Lammintausta Risto, Unkila Mikko
Принадлежит: FORENDO PHARMA LTD

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof wherein R2, R3, R4, R7 and R8 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17β-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof. 4. A compound as claimed in claim 2 , wherein R8 is selected from the group consisting of C-alkyl claim 2 , C-haloalkyl claim 2 , C-perhaloalkyl claim 2 , (CH)CN claim 2 , (CH)OH claim 2 , (CH)N(R′) claim 2 , (CH)C(O)OR′ claim 2 , C(O)N(R′) claim 2 , and (CH)C(O)NH.5. A compound as claimed in claim 3 , wherein R8 is selected from the group consisting of C-alkyl claim 3 , C-haloalkyl claim 3 , C-perhaloalkyl claim 3 , (CH)CN claim 3 , (CH)OH claim 3 , (CH)N(R′) claim 3 , (CH)C(O)OR′ claim 3 , C(O)N(R′) claim 3 , and (CH)C(O)NH.7. A compound as claimed in claim 1 , wherein R2 and R4 are each independently selected from the group consisting of H claim 1 , halogen claim 1 , C-alkyl claim 1 , C-haloalkyl claim 1 , C-perhaloalkyl claim 1 , CN claim 1 , NO claim 1 , N claim 1 , N(R′) claim 1 , (CH)N(R′) claim 1 , OR′ claim 1 , (CH)OR′ claim 1 , COR′ claim 1 , CONHR′ claim 1 , COR″ claim 1 , NHCOR″ claim 1 , SCOR′ claim 1 , or COR′″; and{'sub': 1-6', '1-3', '1-3', '2', '2', 'n', '2', '2', 'n', '3', '3', '3', '2', 'n', '2', '2', '2', '2', '2', '2', '2', 'n', '2, 'R3 is selected from the group consisting of H, halogen, C-alkyl, C-haloalkyl, C-perhaloalkyl, N(R′), (CH)NH, (CH)OR % N, and OR′, wherein R′ is selected from the group consisting of R′, benzyl, ...

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Номер записи: 54
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: 55
29-03-2018 дата публикации

ADHESIVE COMPOSITION, BIO-ELECTRODE, METHOD FOR MANUFACTURING A BIO-ELECTRODE, AND SALT

Номер: US20180086948A1
Автор: Hatakeyama Jun, IWABUCHI Motoaki, KURODA Yasuyoshi, OHASHI Masaki
Принадлежит: SHIN-ETSU CHEMICAL CO., LTD.

An adhesive composition including a resin and electro-conductive material, wherein the electro-conductive material is an ammonium salt of fluorosulfonic acid having 5 or more carbon atoms shown by the general formula (1): (R—X—Z—SO)M (1), wherein, Rrepresents a monovalent hydrocarbon group having 1 to 40 carbon atoms and optionally substituted by a heteroatom or optionally interposed by heteroatom; X represents any of a single bond, ether group, ester group, and amide group; Z represents an alkylene group having 2 to 4 carbon atoms, containing 1 to 6 fluorine atoms, and optionally containing a carbonyl group; M represents a cation having one or two ammonium cation structures. This can form a living body contact layer for a bio-electrode with excellent electric conductivity, biocompatibility, and light weight, which manufactures at low cost and does not cause large lowering of the electric conductivity even when it is wetted with water or dried. 3. The adhesive composition according to claim 1 , wherein the electro-conductive material has a polymerizable double bond or a hydroxy group in either or both of the anion and the cation.4. The adhesive composition according to claim 2 , wherein the electro-conductive material has a polymerizable double bond or a hydroxy group in either or both of the anion and the cation.5. The adhesive composition according to claim 1 , wherein the resin is one or more resins selected from silicone resin claim 1 , acrylic resin claim 1 , and urethane resin.6. The adhesive composition according to claim 2 , wherein the resin is one or more resins selected from silicone resin claim 2 , acrylic resin claim 2 , and urethane resin.7. The adhesive composition according to claim 1 , further comprising a carbon material.8. The adhesive composition according to claim 2 , further comprising a carbon material.9. The adhesive composition according to claim 7 , wherein the carbon material is either or both of carbon black and carbon nanotube.10. The ...

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Номер записи: 56
02-04-2015 дата публикации

SUBSTITUTED ARYL ONIUM MATERIALS

Номер: US20150093708A1
Автор: LaBeaume Paul J.
Принадлежит:

Acid generators comprising a carbocyclic or heteroaromatic group substituted with at least one diester moiety are provided. These acid generators are particularly useful as a photoresist composition component. 2. An acid generator of claim 1 , wherein W is —(C═O)O— or —C(═O)O(CX′X″)nC(═O)O—.7. The acid generator of claim 1 , wherein Z is selected from the group consisting of carboxylate claim 1 , sulfamate claim 1 , or non-fluorinated sulfonate.8. The acid generator of claim 1 , wherein Z contains a polymerizable moiety.9. A photoresist composition comprising one or more acid generators of .10. A method for providing a photoresist relief image claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00009', 'claim 9'}, 'a) applying a coating layer of a photoresist composition of on a substrate; and'}b) exposing the photoresist composition layer to activating radiation and developing the exposed photoresist composition coating layer. In one aspect, the present invention relates to new onium acid generators that comprise a substituted carbocyclic, aryl, or heteroaromatic group.Photoresists are photosensitive films for transfer of images to a substrate. They form negative or positive images. After coating a photoresist on a substrate, the coating is exposed through a patterned photomask to a source of activating energy such as ultraviolet light to form a latent image in the photoresist coating. The photomask has areas opaque and transparent to activating radiation that define an image desired to be transferred to the underlying substrate. A relief image is provided by development of the latent image pattern in the resist coating.Known photoresists can provide features having resolution and dimension sufficient for many existing commercial applications. However for many other applications, the need exists for new photoresists that can provide highly resolved images of submicron dimension.Various attempts have been made to alter the make-up of photoresist compositions to ...

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Номер записи: 57
30-03-2017 дата публикации

Method for Monofluoromethylation of Organic Substrates to Prepare Biologically Active Organic Compounds

Номер: US20170088578A1
Автор: Leitao Emilia Perpetua Tavares
Принадлежит: HOVIONE INTER LIMITED

Described is a process for the preparation of monofluoromethylated organic biologically active compounds using monofluoromethylated reagents. Fluticasone Propionate and Fluticasone Furoate can be prepared using, for example, S-monofluoromethyl-S-phenyl--tetramethylphenylsulfonium tetrafluoroborate as monofluoromethylating reagent instead of bromofluoromethane. 4. A method according to claim 2 , wherein R claim 2 , Rand Rare ethyl groups and Ris tetrafluoroborate or triflate.5. A method according to claim 2 , wherein R claim 2 , Rare both methyl claim 2 , Ris aryl and Ris tetrafluoroborate or triflate.6. A method according to claim 2 , wherein R claim 2 , Rare both methyl claim 2 , Ris phenyl and Ris tetrafluoroborate or triflate.7. A method according to claim 3 , wherein Ris triflate or tetrafluoroborate.9. A method according to claim 8 , wherein R is propionate or furoate.10. A method according to claim 8 , wherein said monofluoromethylating reagent is reacted with 6α claim 8 ,9α-Difluoro-17α-[(2-furanylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androsta-1 claim 8 ,4-diene-17β-carbothioic acid or 6α claim 8 ,9α-Difluoro-11β-hydroxy claim 8 , 16α-methyl-3-oxo-17α-(propionyloxy) androsta-1 claim 8 ,4-diene-17β-carbothioic acid to give the corresponding compound of formula IV.11. A method according to claim 8 , wherein the compound of formula IV is prepared using S-monofluoromethyl-S-phenyl-2 claim 8 ,3 claim 8 ,4 claim 8 ,5-tetramethylphenylsulfonium tetrafluoroborate salt as monofluoromethylating reagent.12. A method according to claim 8 , wherein the compound of formula IV is prepared using S-monofluoromethyl-S-phenyl-2 claim 8 ,3 claim 8 ,4 claim 8 ,5-tetramethylphenylsulfonium triflate salt as monofluoromethylating reagent.13. A method according to claim 8 , wherein the compound of formula IV is prepared using N-(monofluoromethyl) triethyl ammonium triflate salt as monofluoromethylating reagent.14. A method according to claim 8 , wherein the compound of formula ...

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Номер записи: 58
30-03-2017 дата публикации

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Номер: US20170088580A1
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 3 , wherein R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , R claim 3 , Rand Rare independently chosen from hydrogen claim 3 , hydroxy claim 3 , 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)1312. The compound of claim 1 , wherein Ris chosen from hydrogen claim 1 , methyl claim 1 , and hydroxymethyl.14. (canceled)15. The compound of claim 1 , wherein Y is O.16. (canceled)17. The compound of claim 1 , wherein m is 0.18. The compound of claim 1 , wherein represents a single bond.19. The compound of claim 1 , wherein represents a double bond.29. The compound of claim 1 , wherein Z is OR.30. The compound of claim 29 , wherein Ris chosen from optionally substituted alkyl claim 29 , optionally substituted cycloalkyl claim 29 , and optionally substituted heterocycloalkyl.31. (canceled)32. The compound of claim 30 , wherein Ris chosen from 2-morpholinoethyl claim 30 , 2-(pyrrolidin-1-yl)ethyl claim 30 , and 2-(3-oxopiperazin-1-yl)ethyl.33. The compound of claim 1 , wherein Z is NRR.34. (canceled)35. The compound of claim 33 , wherein Ris hydrogen and Ris chosen from optionally substituted alkyl.3640-. (canceled)41. A compound 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,1 la-dimethyl-1-(2-oxo-2H-pyran-5-yl)hexadecahydronaphtho[1′,2′:6,7] ...

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Номер записи: 59
07-04-2016 дата публикации

METHODS OF PREPARING INTERMEDIATE OF FLUTICASONE PROPIONATE

Номер: US20160096863A1
Автор: CHEN Song, Liu Yong, Qiu Yinhua, Wu Zhengyuan, Zhang Haoning
Принадлежит:

A method of preparing a thioic acid intermediate of fluticasone propionate includes: treating a 17β-[(N,N-dimethyl carbamoyl)thio]carbonyl compound in a solution including an alcohol and an alkali metal hydroxide, an alkaline-earth metal hydroxide, or a mixture thereof to cleave an amide from the 17β-[(N,N-dimethyl carbamoyl)thio]carbonyl compound; treating the solution to separate an aqueous portion; and adding an acid to the aqueous portion to obtain the thioic acid intermediate of fluticasone propionate. A method of preparing fluticasone propionate includes preparing the thioic acid intermediate of fluticasone propionate, and alkylating the thioic acid intermediate of fluticasone propionate to prepare the fluticasone propionate. 3. (canceled)4. The method of claim 1 , wherein the treating of the solution removes impurities and comprises evaporating at least a portion of the alcohol claim 1 , adding water and an organic solvent claim 1 , and stirring to separate the aqueous portion from the solution.5. The method of claim 1 , wherein the adding of the acid comprises adding the acid dropwise to the aqueous portion.6. The method of claim 1 , wherein the alkali metal hydroxide comprises lithium hydroxide claim 1 , sodium hydroxide claim 1 , potassium hydroxide claim 1 , or a mixture thereof claim 1 , andwherein the alkaline-earth metal hydroxide comprises magnesium hydroxide, calcium hydroxide, or a mixture thereof.7. The method of claim 1 , wherein the alkali metal hydroxide comprises sodium hydroxide claim 1 , andwherein the alkaline-earth metal hydroxide comprises calcium hydroxide.8. The method of claim 1 , wherein the mole ratio of the total amount of the alkali metal hydroxide and the alkaline-earth metal hydroxide to the amount of Compound 4 is about 1:1 to about 5:1.9. The method of claim 8 , wherein the mole ratio of the total amount of the alkali metal hydroxide and the alkaline-earth metal hydroxide to the amount of Compound 4 is about 1.5:1.10. The method ...

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Номер записи: 60
08-04-2021 дата публикации

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Номер: US20210101928A1
Автор: Blanco-Pillado Maria Jesus, Harrison Boyd L., LA Daniel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Provided herein are compounds of Formula (I-I): and pharmaceutically acceptable alts thereof; wherein p, R, R, R, R, R, R, and Rare defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I-X) and methods of using the compounds, e.g., in the treatment of CNS-related disorders. 2. The compound of claim 1 , wherein Ris hydrogen.3. The compound of claim 1 , wherein Ris methyl.4. The compound of any one of - claim 1 , wherein le is substituted or unsubstitued alkyl.5. The compound of any one of - claim 1 , wherein le is substituted or unsubstitued heteroaryl.6. The compound of any one of - claim 1 , wherein le is substituted or unsubstitued heteroaryl claim 1 , wherein the heteroaryl contains at least one nitrogen atom.7. The compound of any one of - claim 1 , wherein le is substituted or unsubstitued heteroaryl claim 1 , wherein the heteroaryl is a bicyclic.9. The compound of any one of - claim 1 , wherein Ris Calkyl optionally substituted with alkoxy or one to two halo groups (e.g. claim 1 , fluoro) claim 1 , and at least one of R claim 1 , R claim 1 , and Ris halogen (e.g. claim 1 , —F claim 1 , —Cl claim 1 , —Br) claim 1 , —NO claim 1 , —CN claim 1 , —OR claim 1 , —N(R) claim 1 , —C(═O)R claim 1 , —C(═O)OR claim 1 , —SR claim 1 , —S(O)R claim 1 , e.g. claim 1 , —S(═O)R claim 1 , —S(═O)R claim 1 , —SOS(═O)R. —S(═O)N(R) claim 1 , substituted or unsubstituted Calkyl (e.g. claim 1 , —CH claim 1 , —CHCH claim 1 , haloalkyl claim 1 , e.g. claim 1 , —CF) claim 1 , wherein Ris substituted or unsubstituted Calkyl.12. The compound of any one of - claim 1 , wherein Ris unsubstituted Calkyl.13. The compound of any one of - claim 1 , wherein Ris a Calkyl optionally substituted with alkoxy.14. The compound of any one of - claim 1 , wherein Ris a Calkyl optionally substituted with one or two halo (e.g. claim 1 , fluoro).15. The compound of any one of - claim 1 , wherein Ris —CH claim 1 , —CHCH claim 1 , —CHF claim 1 , —CHF claim 1 , — ...

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Номер записи: 61
13-04-2017 дата публикации

FARNESOID X RECEPTOR MODULATORS

Номер: US20170101434A1
Автор: Gioiello Antimo, Pellicciari Roberto
Принадлежит:

The present application provides a compound of formula I: 4. The compound of claim 1 , wherein Ris OH claim 1 , alkoxy claim 1 , or oxo.58-. (canceled)9. The compound of claim 1 , wherein Ris H.1011-. (canceled)12. The compound of claim 1 , wherein Ris OH or H.13. (canceled)16. The compound of claim 1 , wherein Ris OH claim 1 , OSOH claim 1 , SOH claim 1 , OSONH claim 1 , SONH claim 1 , OPOH claim 1 , POH claim 1 , COH claim 1 , or C(O)NHOH.1723-. (canceled)24. The compound of claim 1 , wherein Ris tetrazolyl claim 1 , oxadiazolyl claim 1 , thiadiazolyl claim 1 , 5-oxo-1 claim 1 ,2 claim 1 ,4-oxadiazolyl claim 1 , 5-oxo-1 claim 1 ,2 claim 1 ,4-thiadiazolyl claim 1 , oxazolidine-dionyl claim 1 , thiazolidine-dionyl claim 1 , 3-hydroxyisoxazolyl claim 1 , 3-hydroxyisothiazolyl claim 1 , or 2 claim 1 ,4-difluoro-3-hydroxyphenyl.25. (canceled)26. The compound of claim 1 , wherein Ris OH.2728-. (canceled)29. The compound of claim 1 , wherein Ris OH or H.3034-. (canceled)35. The compound of claim 1 , wherein Ris methyl claim 1 , ethyl claim 1 , or propyl.3640-. (canceled)41. The compound of claim 1 , wherein Ris in the α-position.42. The compound of claim 1 , wherein Ris in the β-position.44. A salt of the compound of .45. The compound of claim 44 , wherein Ris OSO.46. The compound of claim 45 , wherein Ris OSONa.4751-. (canceled)52. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable carrier or excipient.53. A method of treating or preventing a disease or condition in a subject in need thereof comprising administering an effective amount of the compound of or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or amino acid conjugate thereof claim 1 , and wherein the disease or condition is mediated by FXR.54. The method of claim 53 , wherein the disease is selected from cardiovascular disease claim 53 , chronic liver disease claim 53 , lipid disorder claim 53 , gastrointestinal disease claim 53 , renal disease claim 53 , ...

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Номер записи: 62
05-05-2016 дата публикации

Compounds and methods for trans-membrane delivery of molecules

Номер: US20160120996A1
Автор: IIan Ziv
Принадлежит: APOSENSE LTD

A novel delivery system for drugs, and especially macromolecules such as proteins or oligonucleotides through biological membranes is provided, and specifically delivery of siRNA. The delivery system comprises conjugation of the macromolecule drug to a moiety that enables effective passage through the membranes. Respectively, novel compounds and pharmaceutical compositions are provided, utilizing said delivery system. In one aspect of the invention, the compounds may be utilized in medical practice, for example, in delivery of siRNA or antisense oligonucleotides across biological membranes for the treatment of medical disorders.

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Номер записи: 63
17-07-2014 дата публикации

Antagonists of CB1 Receptor

Номер: US20140200200A1
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 4-Pregnen-17 claim 33 ,20α-diol-3-one claim 33 , 4-Pregnen-20α-ol-3-one claim 33 , 17α-Methylprogesterone. or 17α-Benzylprogesterone.36. The method according to claim 35 , wherein said compound is 5β-Pregnan-3β-ol-20-one or 5β-Pregnan-3 claim 35 ,20-dione.38. The method according to claim 37 , wherein said compound is 5-pregnen-3β-O-benzyl-20-one or 5-pregnen-3β-azido-20-one.40. The method according to claim 39 , wherein said compound is 17α-Allyl-3β-methoxypregnenolone claim 39 , 17α-Benzyl-3β-fluoropregnenolone claim 39 , 3β-Fluoro-17α-methylpregnenolone claim 39 , 3β-Methoxy-17α-methylpregnenolone claim 39 , 17α-Benzyl-3β-methoxypregnenolone claim 39 , 3β-Benzyloxy-17α-methylpregnenolone or 17α-Benzyl-3β-benzyloxypregnenolone.42. The method according to claim 41 , wherein said compound is 17α-Benzylpregnenolone claim 41 , 17α-Ethylpregnenolone claim 41 , 17α-Methylpregnenolone or 17-Methoxypregnenolone.44. The method according to claim 43 , wherein said compound is 20-Deoxypregnenolone or 20-Methylamino-5-pregnen-3β-ol.46. The method according to claim 45 , wherein said compound is 5 claim 45 ,16-Pregnadien-20-one.47. The ...

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Номер записи: 64
17-07-2014 дата публикации

Method for purifying rocuronium bromide

Номер: US20140200340A1
Автор: PENG Wang, Wenling Zhang, Xini Zhang, Zhiwen Zeng
Принадлежит: Zhejiang Huahai Pharmaceutical Co Ltd

Provided is a method for purifying rocuronium bromide, which comprises: formulating crude rocuronium bromide to be purified into an aqueous solution, distilling off excess residue solvents at reduced pressure, absorbing by adding active carbon or silica gel, then filtrating, quick freezing the filtrate into ice, and then lyophilizing to obtain rocuronium bromide.

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Номер записи: 65
17-07-2014 дата публикации

Method for the Production of Fluoromethyl Esters of Androstan-17 beta Carboxylic Acids

Номер: US20140200341A1
Автор: Leitao Emilia Perpetua Tavares, Maycock Christopher, Ventura Maria Rita
Принадлежит: HOVIONE INTER LIMITED

Described herein are processes for the preparation of monofluoromethylated organic biologically active compounds, starting from protected intermediates and/or reagents to obtain compounds such as fluticasone propionate and fluticasone furoate, in presence of decarboxylating reagents XeFand BrF, or using FCHSH as a reagent. 2. A method according to claim 1 , wherein:{'sub': '1', 'Ris selected from a group consisting of hydroxyl, propionate and furoate; and/or'}{'sub': '2', 'Ris selected from a group consisting of H and methyl; and/or'}{'sub': '3', 'Ris (tert-butylcarboxy)methyl; and/or'}{'sub': '4', 'Ris trifluoroacetate or trichloroacetate; and/or'}{'sub': 1', '2, 'X═X═F; and/or'}{'sub': '3', 'Xis S.'}3. A method according to claim 1 , wherein the fluorodecarboxylating agent is selected from XeFand BrF.4. A method according to claim 1 , wherein the organic biologically active of formula (I) is chosen from a group consisting of Fluticasone claim 1 , Fluticasone Propionate and Fluticasone Furoate.9. A method of making an organic biologically active compound containing a “—CHF” moiety of claim 1 , wherein a compound of formula (III) is used.10. The method according to claim 1 , wherein the organic biologically active compound is a compound of formula (I) as defined in .11. The method according to claim 10 , wherein the compound of formula (I) is Fluticasone claim 10 , Fluticasone Propionate or Fluticasone Furoate.12. A method according to claim 2 , wherein the fluorodecarboxylating agent is selected from XeFand BrF.13. A method according to claim 2 , wherein the organic biologically active of formula (I) is chosen from a group consisting of Fluticasone claim 2 , Fluticasone Propionate and Fluticasone Furoate.14. A method according to claim 3 , wherein the organic biologically active of formula (I) is chosen from a group consisting of Fluticasone claim 3 , Fluticasone Propionate and Fluticasone Furoate.15. A method of making an organic biologically active compound ...

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Номер записи: 66
12-05-2016 дата публикации

Electrophilic Reagents for Monohalomethylation, Their Preparation and Their Uses

Номер: US20160130223A1
Автор: Leitao Emilia Perpetua Tavares
Принадлежит: HOVIONE INTER LIMITED

The invention provides a compound of formula A, B, C or D, methods for making them, intermediates therefor, and their use in making organic biologically active compounds: 2. A compound of formula A according to claim 1 , wherein:X=F, Cl or Br;{'sub': 1', '10, 'R1, R2, R3, R4, R5, R6, R7, R8, R9, R10=H, alkyl, or C-Calkyl; and'}R11=tetrafluoroborate or triflate.3. A compound of formula A according to claim 2 , wherein:R1, R2, R3, R4, R5, R6, R7, R8, R9, R10=H or methyl.4. A compound of formula A according to claim 1 , wherein:X=F;R1=R2=R3=R4=R5=R7=R8=R10=H;R6=R9=methyl; andR11=tetrafluoroborate.5. A compound of formula A according to claim 1 , wherein:X=F;R1=R2=R4=R5=R6=R7=R10=H;R3=R8=R9=methyl; andR11=tetrafluoroborate.6. A compound of formula A according to claim 1 , wherein:X=F;R1=R2=R4=R5=R7=R8=R10=H;R3=R6=R9=methyl; andR11=tetrafluoroborate.7. A compound of formula A according to claim 1 , wherein:X=F;R1=R2=R4=R5=H;R3=methyl;one of R6, R7, R8, R9, or R10 is isopropyl; andR11=tetrafluoroborate.8. A compound of formula A according to claim 1 , wherein:X=F;R1=R2=R4=R5=H;R3=methyl;one of R6, R7, R8, R9, or R10 is tert-butyl; andR11=triflate.9. A compound of formula A according to claim 1 , wherein:X=F;R1=R2=R4=R5=H;R3=methyl;one of R6, R7, R8, R9, or R10 is tert-butyl; andR11=tetrafluoroborate. This is continuation application filed under 35 U.S.C. §111(a), which claims priority to U.S. application Ser. No. 13/882,127, filed under 37 CFR §1.371 on Jul. 5, 2013, now allowed; which is a national stage application of international application PCT/GB2011/001541, filed under the authority of the Patent Cooperation Treaty on Oct. 27, 2011, published; which claims priority to Ser. PT/105356 filed on Oct. 27, 2010, and to Ser. PT/105942, filed on Oct. 18, 2011. The entire disclosures of all the aforementioned applications are expressly incorporated herein by reference.The present invention provides electrophilic monohalomethylating reagents, methods for their preparation ...

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Номер записи: 67
12-05-2016 дата публикации

BILE ACID ANALOGS AS FXR/TGR5 AGONISTS AND METHODS OF USE THEREOF

Номер: US20160130297A1
Автор: Or Yat Sun, Shen Ruichao, Wang Guoqiang, Xing Xuechao
Принадлежит:

The present invention relates to compounds of Formula (I), 12. A method for the prevention or treatment of an FXR-mediated disease or condition in a mammal comprising administering to the mammal suffering from an FXR-mediated disease or condition a therapeutically effective amount of a compound according to .13. The method according to claim 12 , wherein the FXR-mediated disease or condition is selected from the group consisting of chronic liver disease claim 12 , gastrointestinal disease claim 12 , renal disease claim 12 , cardiovascular disease claim 12 , and metabolic disease.14. The method according to claim 13 , wherein the chronic liver disease is selected from the group consisting of primary biliary cirrhosis (PBC) claim 13 , cerebrotendinous xanthomatosis (CTX) claim 13 , primary sclerosing cholangitis (PSC) claim 13 , drug induced cholestasis claim 13 , intrahepatic cholestasis of pregnancy claim 13 , parenteral nutrition associated cholestasis (PNAC) claim 13 , bacterial overgrowth or sepsis associated cholestasis claim 13 , autoimmune hepatitis claim 13 , chronic viral hepatitis claim 13 , alcoholic liver disease claim 13 , nonalcoholic fatty liver disease (NAFLD) claim 13 , nonalcoholic steatohepatitis (NASH) claim 13 , liver transplant associated graft versus host disease claim 13 , living donor transplant liver regeneration claim 13 , congenital hepatic fibrosis claim 13 , choledocholithiasis claim 13 , granulomatous liver disease claim 13 , intra- or extrahepatic malignancy claim 13 , Sjogren's syndrome claim 13 , Sarcoidosis claim 13 , Wilson's disease claim 13 , Gaucher's disease claim 13 , hemochromatosis claim 13 , and alpha 1-antitrypsin deficiency.15. The method according to claim 13 , wherein the renal disease is selected from the group consisting of diabetic nephropathy claim 13 , focal segmental glomerulosclerosis (FSGS) claim 13 , hypertensive nephrosclerosis claim 13 , chronic glomerulonephritis claim 13 , chronic transplant glomerulopathy ...

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Номер записи: 68
10-05-2018 дата публикации

NOVEL CHOLESTEROL METABOLITE, 5-CHOLESTEN, 3BETA-25-DIOL, DISULFATE (25HCDS) FOR THERAPY OF METABOLIC DISORDERS, HYPERLIPIDEMIA, DIABETES, FATTY LIVERS DISEASES AND ATHEROSCLEROSIS

Номер: US20180127457A1
Автор: REN Shunlin
Принадлежит:

5-cholesten, 3β,25-diol, disulfate (25HCDS) has been found to be an authentic PPARγ agonist and LXR antagonist, and is used for the therapy of lipid disorders and inflammatory diseases, including without limitation fatty liver, inflammatory bowel, and atherosclerotic diseases. 34-. (canceled)5. A method of treating a subject claim 1 , which method comprises administration to the subject of an effective amount of a compound as defined in claim 1 , wherein said method is selected from: a method for reducing lipids in a subject in need thereof; a method of reducing cholesterol and lipid biosynthesis in a subject in need thereof; a method of reducing inflammation in a subject in need thereof; a method of treating diabetes in a subject in need thereof; a method of treating hyperlipidemia in a subject in need thereof; a method of treating atherosclerosis in a subject in need thereof; a method of treating fatty liver disease in a subject in need thereof; and a method of treating inflammatory disease in a subject in need thereof.6. The method of wherein:said compound is administered in an amount ranging from 0.1 mg/kg to 100 mg/kg based on body mass of said subject, or said compound is administered in an amount ranging from 1 mg/kg to 10 mg/kg, based on body mass of said subject; and/orthe administration comprises at least one of oral administration, enteric administration, sublingual administration, transdermal administration, intravenous administration, peritoneal administration, parenteral administration, administration by injection, subcutaneous injection and intramuscular injection.7. (canceled)8. The compound according to claim 1 , which is an isolated compound.9. The compound according to claim 1 , which is substantially pure.10. (canceled)11. The compound according to claim 1 , which is:in powder form; and/orin freeze-dried form.12. A pharmaceutical composition comprising: (i) 5-cholesten-3 claim 1 ,25-diol claim 1 , disulfate (25HCDS) or a pharmaceutically ...

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Номер записи: 69
09-05-2019 дата публикации

NOVEL CHOLESTEROL METABOLITE, 5-CHOLESTEN, 3BETA-25-DIOL, DISULFATE (25HCDS) FOR THERAPY OF METABOLIC DISORDERS, HYPERLIPIDEMIA, DIABETES, FATTY LIVERS DISEASES AND ATHEROSCLEROSIS

Номер: US20190135856A1
Автор: REN Shunlin
Принадлежит:

5-cholesten, 3β, 25-diol, disulfate (25HCDS) has been found to be an authentic PPARagonist and LXR antagonist, and is used for the therapy of lipid disorders and inflammatory diseases, including without limitation fatty liver, inflammatory bowel, and atherosclerotic diseases. 34.-. (canceled)5. A method of treating a subject claim 1 , which method comprises administration to the subject of an effective amount of a compound as defined in claim 1 , wherein said method is selected from: a method for reducing lipids in a subject in need thereof; a method of reducing cholesterol and lipid biosynthesis in a subject in need thereof; a method of reducing inflammation in a subject in need thereof; a method of treating diabetes in a subject in need thereof; a method of treating hyperlipidemia in a subject in need thereof; a method of treating atherosclerosis in a subject in need thereof; a method of treating fatty liver disease in a subject in need thereof; and a method of treating inflammatory disease in a subject in need thereof.6. The method of wherein:said compound is administered in an amount ranging from 0.1 mg/kg to 100 mg/kg based on body mass of said subject, or said compound is administered in an amount ranging from 1 mg/kg to 10 mg/kg, based on body mass of said subject; and/orthe administration comprises at least one of oral administration, enteric administration, sublingual administration, transdermal administration, intravenous administration, peritoneal administration, parenteral administration, administration by injection, subcutaneous injection and intramuscular injection.7. (canceled)8. The compound according to claim 1 , which is an isolated compound.9. The compound according to claim 1 , which is substantially pure.10. (canceled)11. The compound according to claim 1 , which is:in powder form; and/orin freeze-dried form.12. A pharmaceutical composition comprising: (i) 5-cholesten-3 claim 1 , 25-diol claim 1 , disulfate (25HCDS) or a pharmaceutically ...

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Номер записи: 70
26-05-2016 дата публикации

BILE ACID ANALOGS AS FXR/TGR5 AGONISTS AND METHODS OF USE THEREOF

Номер: US20160145296A1
Автор: Dai Peng, Long Jiang, Or Yat Sun, Shen Ruichao, Wang Guoqiang, Xing Xuechao
Принадлежит:

The present invention relates to compounds of Formula (IA) and Formula (IB), 8. A method for the prevention or treatment of an FXR-mediated disease or condition in a mammal comprising administering to the mammal suffering from an FXR-mediated disease or condition a therapeutically effective amount of a compound according to .9. A method according to claim 8 , wherein the FXR-mediated disease or condition is selected from the group consisting of chronic liver disease claim 8 , gastrointestinal disease claim 8 , renal disease claim 8 , cardiovascular disease claim 8 , and metabolic disease.10. A method according to claim 9 , wherein the chronic liver disease is selected from the group consisting of primary biliary cirrhosis (PBC) claim 9 , cerebrotendinous xanthomatosis (CTX) claim 9 , primary sclerosing cholangitis (PSC) claim 9 , drug induced cholestasis claim 9 , intrahepatic cholestasis of pregnancy claim 9 , parenteral nutrition associated cholestasis (PNAC) claim 9 , bacterial overgrowth or sepsis associated cholestasis claim 9 , autoimmune hepatitis claim 9 , chronic viral hepatitis claim 9 , alcoholic liver disease claim 9 , nonalcoholic fatty liver disease (NAFLD) claim 9 , nonalcoholic steatohepatitis (NASH) claim 9 , liver transplant associated graft versus host disease claim 9 , living donor transplant liver regeneration claim 9 , congenital hepatic fibrosis claim 9 , choledocholithiasis claim 9 , granulomatous liver disease claim 9 , intra- or extrahepatic malignancy claim 9 , Sjogren's syndrome claim 9 , Sarcoidosis claim 9 , Wilson's disease claim 9 , Gaucher's disease claim 9 , hemochromatosis claim 9 , and alpha 1-antitrypsin deficiency.11. A method according to claim 9 , wherein the renal disease is selected from the group consisting of diabetic nephropathy claim 9 , focal segmental glomerulosclerosis (FSGS) claim 9 , hypertensive nephrosclerosis claim 9 , chronic glomerulonephritis claim 9 , chronic transplant glomerulopathy claim 9 , chronic ...

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Номер записи: 71
10-06-2021 дата публикации

CRYSTALLINE FORMS OF SELECTIVE PROGESTERONE RECEPTOR MODULATOR, PROCESSES FOR PREPARATION THEREOF

Номер: US20210171568A1
Автор: Chen Minhua, Liu Kai, Zhang Jing, Zhang Xiaoyu, ZHANG Yanfeng
Принадлежит:

The present disclosure relates to novel crystalline forms of compound I and processes for preparation thereof. The present disclosure also relates to pharmaceutical composition containing crystalline forms, and use of crystalline forms for preparing drugs containing selective progesterone receptor modulator, and use of crystalline forms for preparing drugs treating uterine fibroids and/or endometriosis. The crystalline forms of the present disclosure have one or more improved properties compared with prior art and have significant values for future drug optimization and development. 1. A crystalline form CS2 of BAY-1002670 , wherein the X-ray powder diffraction pattern shows characteristic peaks at 2theta values of 4.0°±0.2° , 15.9°±0.2° and 17.9°±0.2° using CuKα radiation.2. The crystalline form CS2 according to claim 1 , wherein the X-ray powder diffraction pattern shows one or two or three characteristic peaks at 2theta values of 19.0°±0.2° claim 1 , 20.4°±0.2° and 21.4°±0.2° using CuKα radiation.3. The crystalline form CS2 according to claim 1 , wherein the X-ray powder diffraction pattern shows one or two or three characteristic peaks at 2theta values of 11.8°±0.2° claim 1 , 15.0°±0.2° and 25.1°±0.2° using CuKα radiation.4. The crystalline form CS2 according to claim 1 , wherein the crystalline form CS2 belongs to monoclinic system claim 1 , the space group of crystalline form CS2 is C2 claim 1 , and the crystal axes are: a=21.432(2) Å claim 1 , b=10.7076(10) Å claim 1 , c=22.438(2) Å claim 1 , the interaxial angles are: α=90° claim 1 , β=98.346(3°) claim 1 , γ=90°.5. A process for preparing crystalline form CS2 according to claim 1 , wherein the process comprises:(1) adding BAY-1002670 into a mixture of ketones and water, and stirring to obtain crystalline form CS2; or(2) dissolving BAY-1002670 in alcohols, esters, or ketones, putting the solution in a closed system with water vapor to obtain crystalline form CS2 by liquid vapor diffusion; or(3) dissolving BAY ...

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Номер записи: 72
01-06-2017 дата публикации

INHIBITORS OF THE FARNESOID X RECEPTOR AND USES IN MEDICINE

Номер: US20170152283A1
Автор: Amin Shantu, Desai Dhimant, Gonzalez Frank J., Jiang Changtao, Li Fei, Mitchell James B., Patterson Andrew D., Xie Cen
Принадлежит:

Disclosed are inhibitors of the farnesoid X receptor, for example of formula (I), wherein R, R, R, X, Y, Z, m, and n are as defined herein, which are useful in treating or preventing obesity, type 2 diabetes/insulin resistance and non-alcoholic fatty liver disease in a mammal in need thereof. Also disclosed is a composition comprising a pharmaceutically suitable carrier and at least one compound of the invention, a method of method of inhibiting a farnesoid X receptor in a mammal, and a method of treating or preventing obesity in a mammal. 142.-. (canceled)4549.-. (canceled)50. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound or salt of .51. The compound of claim 43 , wherein Ris glycine. This patent application is a continuation of copending U.S. patent application Ser. No. 14/909,263, filed Feb. 1, 2016, which is a 371 of International Patent Application No. PCT/US2014/049460, filed Aug. 1, 2014, which claims the benefit of U.S. Provisional Patent Applications Nos. 61/861,109, filed Aug. 1, 2013, and 62/004,436, filed May 29, 2014, which are incorporated by reference for all purposes.Obesity has reached epidemic proportions worldwide and is associated with chronic diseases such as type 2 diabetes mellitus, cardiovascular diseases, hepatosteatosis, and cancer. Obesity develops as a result of energy intake that exceeds energy expenditure, leading to a net storage of excess calories in the form of fat in adipose tissue. Obesity is metabolically linked with type 2 diabetes (insulin resistance) and hepatosteatosis, the latter of which can lead to steatohepatitis, hepatocarcinogenesis and liver failure. Thus, a pharmaceutical approach that suppresses appetite, blocks dietary fat absorption, induces fat mobilization, or increases metabolism would be ideal in the treatment of obesity and related metabolic disorders.Farnesoid X Receptor (FXR) is an orphan nuclear receptor initially identified from a rat liver cDNA library (Forman ...

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Номер записи: 73
07-06-2018 дата публикации

SELECTIVE PROGESTERONE RECEPTOR MODULATOR (SPRM) REGIMEN

Номер: US20180155388A1
Автор: Knauthe Rudolf, SEITZ Christian, ZEUN Susan
Принадлежит:

The invention is directed to a pharmaceutical composition comprising a progesterone receptor antagonist namely (11β,17β)-17-Hydroxy-11-[4-(methylsulphonyl)phenyl]-17-(pentafluoroethy)estra-4,9-dien-3-one for the treatment and/or prophylaxis of Uterine Fibroids (myomas, uterine leiomyoma) that is administered to a patient diagnosed with Uterine Fibroids following a specific regimen. Additionally, the invention is directed to a method for treating Uterine Fibroids (myomas, uterine leiomyoma) and/or for reducing Uterine Fibroids (myomas, uterine leiomyoma) size and symptoms related to Uterine Fibroids following a specific regimen as well as treatment of Heavy Menstrual Bleeding (HMB). 2. The pharmaceutical composition according to wherein the administration period of (11β claim 1 ,17β)-17-Hydroxy-11-[4-(methylsulphonyl)phenyl]-17-(pentafluoroethyl)estra-4 claim 1 ,9-dien-3-one (Compound 1) is followed by a break period wherein administration of Compound 1 is discontinued until one (1) or two (2) bleeding episodes occur and administration and break periods are repeated at least one (1) time.3. The pharmaceutical composition according to wherein Compound 1 is administered during a period of twelve (12) weeks claim 1 , sixteen (16) weeks claim 1 , twenty (20) weeks or twenty-four (24) weeks.7. The method according to wherein Compound 1 is administered during a period of twelve (12) weeks claim 3 , sixteen (16) weeks claim 3 , twenty (20) weeks or twenty-four (24) weeks.9. The compound according to where step a) is followed byb) a break period wherein administration of Compound 1 is discontinued and encompass one (1) or two (2) bleeding episodes andc) step a) and/or b) are/is repeated at least one (1) time.10. The compound according to where amenorrhea is reached during step a).11. The compound according to where ovulation inhibition is reached during step a). The invention is directed to a pharmaceutical composition comprising a progesterone receptor modulator namely (11 ...

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Номер записи: 74
22-09-2022 дата публикации

METHODS OF MAKING CHOLIC ACID DERIVATIVES AND STARTING MATERIALS THEREFOR

Номер: US20220298202A1
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. 124-) (canceled)26) The method of claim 25 , further comprising reacting the 24-carboxylic acid or ester group with a reagent and converting the carboxylic acid or ester group to a derivative that can act as an acylating agent claim 25 , and reacting the derivative with taurine to form TUDCA or a pharmaceutically acceptable salt thereof.29) (canceled)30) The method of claim 26 , wherein the reagent is selected from the group consisting of SOCl claim 26 , ClCOCOCl claim 26 , COCl claim 26 , SOBr claim 26 , TPP/NBS claim 26 , ImCO claim 26 , EtOCOCl claim 26 , (CH)CCOCl claim 26 , (MeO)P(O)Cl claim 26 , Diisopropylcarbodiimide claim 26 , Diisopropylcarbodiimide+HOBt claim 26 , Diisopropylcarbodiimide+HOSu claim 26 , 2-Chloro-1-methylpyridinium iodide claim 26 , and (Py)PBr (PF).31) The method of claim 25 , further comprising contacting the 24-carboxylic acid or ester group with means for converting the 24-carboxylic acid or ester group to a derivative that can act as an acylating agent claim 25 , and reacting the derivative with taurine to form TUDCA or a pharmaceutically acceptable salt thereof. The present invention relates generally to 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.Cholic acid and its derivatives find utility in numerous medical applications and research initiatives. Cholic acid itself, sold under the brand name CHOLBAM® (cholic acid), is approved for use as a treatment for children and adults with bile acid synthesis disorders due to single enzyme defects, and for peroxisomal disorders (such as Zellweger ...

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Номер записи: 75
23-05-2019 дата публикации

NOVEL CYTOTOXIC AGENTS THAT PREFERENTIALLY TARGET LEUKEMIA INHIBITORY FACTOR (LIF) FOR THE TREATMENT OF MALIGNANCIES AND AS NEW CONTRACEPTIVE AGENTS

Номер: US20190153018A1
Автор: Nair Hareesh, Nickisch Klaus, Santhamma Bindu
Принадлежит:

Described herein are new anti-cancer compounds and methods of using such compounds, acting through a new mechanism of action by simultaneous inhibition of leukemia inhibitory factor (LIF) and MDM2. 131-. (canceled)35. The cytotoxic compound of claim 32 , wherein Ris quinolinyl.36. The cytotoxic compound of claim 32 , wherein Ris 1 claim 32 ,3-imidazolyl.37. The cytotoxic compound of claim 32 , wherein Ris isoquinolinyl.38. The cytotoxic compound of claim 32 , wherein Ris indolyl.39. The cytotoxic compound of claim 32 , wherein Ris dibenzofuranyl.40. The cytotoxic compound of claim 32 , wherein Ris furanyl.42. The method of claim 41 , wherein the cancer is a cancer that overexpresses leukemia inhibitory factor.43. The method of claim 41 , wherein the cancer exhibits a desmoplastic stromal response.44. The method of claim 41 , wherein the cancer exhibits cancer initiating stem cells (CISC) or cancer associated stem cells (CASC). The present application is a continuation of U.S. patent application Ser. No. 15/077,099, filed Mar. 22, 2016, which claims priority to U.S. Provisional Application Ser. No. 62/136,813 entitled “NOVEL CYTOTOXIC AGENTS THAT PREFERENTIALLY TARGET LEUKEMIA INHIBITORY FACTOR (LIF) AND MDM2 FOR THE TREATMENT OF MALIGNANCIES AND AS NEW CONTRACEPTIVE AGENTS” filed Mar. 23, 2015, both of which are incorporated herein by reference in their entirety.The invention generally relates to new anti-cancer compounds, acting through a new mechanism of action by simultaneous inhibition of leukemia inhibitory factor (LIF) and MDM2.Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. If the spread is not controlled, it can result in death. Cancer may affect people at all ages, but risk for the more common varieties tends to increase with age. Cancer is caused by external factors, such as tobacco, infectious organisms, and an unhealthy diet, and internal factors, such as inherited genetic mutations, hormones, and ...

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Номер записи: 76
18-06-2015 дата публикации

TREATMENT OF PROSTATE CANCER

Номер: US20150166599A1
Автор: Casebier David Scott, Morrison Jodie Pope, Stein Cy Aaron
Принадлежит:

Described herein are compounds, methods of making such compounds, pharmaceutical compositions, and medicaments comprising such compounds, and methods of using such compounds to treat androgen receptor mediated diseases or conditions. The present invention provides therapies and therapeutic regimens for the treatment of prostate cancer. 152-. (canceled)54. (canceled)55. The method of claim 53 , wherein the initial form is a crystalline form.56. The method of claim 53 , wherein the initial form is an amorphous form.57. The method of claim 56 , wherein the amorphous form is dissolved in an aqueous solvent to form a mixture.58. The method of claim 57 , wherein the mixture is subjected to a series of heat-cool cycles.59. The method of claim 58 , wherein a heat-cool cycle lasts 8 hours.60. The method of claim 58 , wherein a heat-cool cycle ranges from room temperature to 50° C.61. The method of claim 53 , wherein the collected crystalline form is dehydrated to about below 40% relative humidity.62. The method of claim 61 , wherein the dehydration is performed using gravimetric vapor sorption.6468-. (canceled)69. The method of claim 63 , wherein the initial form is a crystalline form.70. The method of claim 63 , wherein the initial form is an amorphous form.71. The method of claim 70 , wherein the amorphous form is dissolved in an aqueous solvent to form a mixture.72. The method of claim 71 , wherein the mixture is subjected to a series of heat-cool cycles.73. The method of claim 72 , wherein a heat-cool cycle lasts for 8 hours.74. The method of claim 72 , wherein a heat-cool cycle ranges from room temperature to 50° C.7678-. (canceled)79. The method of claim 75 , wherein the initial form is a crystalline form.80. The method of claim 75 , wherein the initial form is an amorphous form.81. The method of claim 80 , wherein the amorphous form of compound (I) is dissolved in an aqueous solvent to form a mixture.82. The method of claim 81 , wherein the mixture is subjected to a ...

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Номер записи: 77
16-06-2016 дата публикации

Process for the preparation of abiraterone or abiraterone acetate

Номер: US20160168191A1
Автор: Riccardo DI BRISCO, Roberto Lenna
Принадлежит: Industriale Chimica SRL

The present invention relates to a novel process for the synthesis of abiraterone and in particular abiraterone acetate, a compound of formula (I) reported below: having pharmacological activity suitable for slowing down the progression of advanced stage prostate cancer. The process is characterised by the fact that the intermediate triflation step is carried out on prasterone (DHEA) or its 3-acetate using Ar—N(OTf) 2 as the triflation reagent, but where Ar is not phenyl, and by the fact that the base used in this step is an alkali metal alcoholate.

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Номер записи: 78
16-06-2016 дата публикации

PROCESS FOR THE PREPARATION OF ABIRATERONE AND ABIRATERONE ACETATE

Номер: US20160168192A1
Автор: DI BRISCO Riccardo, LENNA Roberto
Принадлежит:

18-. (canceled)12. Process according to wherein said bis(trifluoromethanesuifonimide) is N-phenyl-bis(trifluoromethanesulfonimide).13. Process according to wherein said bis(trifluoromethanesulfonimide) is N-(2-pyridyl)-bis(trifluoromethanesulfonimide).14. Process according to claim 9 , wherein said bis(trifluoromethanesulfonimide) is used in an amount between 0.6 and 2 times by weight with respect to the starting prasterone or prasterone acetate.15. Process according to claim 9 , wherein said base is selected from potassium hexamethyldisilazane claim 9 , lithium hexamethyldisilazane claim 9 , sodium hexamethyldisilazane claim 9 , lithium diisopropylamide claim 9 , lithium tri-sec-butylborohydride claim 9 , potassium tri-sec-butylborohydride claim 9 , sodium tert-butoxide and potassium tert-butoxide.16. Process according to claim 9 , wherein the reaction temperature is between −80° C. and 30° C. and the reaction time is between 2 and 24 hours.18. Process according to wherein said palladium (II) catalyst is bis(triphenylphosphine)palladium(II)dichloride claim 17 , Pd(PPh)Cl. The present invention relates to the field of processes for the synthesis of active ingredients for pharmaceutical use and in particular to a process for the preparation of abiraterone and abiraterone acetate on an industrial scale.The compound of formula (I) reported below, the chemical name of which is (β)-17-(pyridin-3-yl)androsta-5,16-dien-3-ol acetate, is commonly referred to by the name abiraterone acetate:Abiraterone acetate is a steroid with pharmacological activity that is useful for slowing down the progression of prostate cancer at an advanced stage.Carcinoma of the prostate is the principal tumor in the male population in Western countries, where it is also the second cause of cancer death.Abiraterone acetate has proved capable of prolonging the life of these patients and of improving their quality of life, and is the first element of a new class of non-chemotherapeutic medicinal ...

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Номер записи: 79
21-05-2020 дата публикации

19-NOR C3, 3-DISUBSTITUTED C21-N-PYRAZOLYL STEROIDS AND METHODS OF USE THEREOF

Номер: US20200155576A1
Автор: Beresis Richard Thomas, Harrison Boyd L., Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Provided herein are 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula (I): 147-. (canceled)49. The method of claim 48 , wherein the compound is administered orally claim 48 , subcutaneously claim 48 , intravenously claim 48 , or intramuscularly.50. The method of claim 48 , wherein the compound is administered chronically.51. The method of claim 49 , wherein the compound is administered orally.52. The method of claim 49 , wherein the compound is administered intravenously.54. The method of claim 53 , wherein the compound is administered orally claim 53 , subcutaneously claim 53 , intravenously claim 53 , or intramuscularly.55. The method of claim 53 , wherein the compound is administered chronically.56. The method of claim 54 , wherein the compound is administered orally.57. The method of claim 54 , wherein the compound is administered intravenously.59. The method of claim 58 , wherein the pharmaceutical composition is administered orally claim 58 , subcutaneously claim 58 , intravenously claim 58 , or intramuscularly.60. The method of claim 58 , wherein the pharmaceutical composition is administered chronically.61. The method of claim 59 , wherein the pharmaceutical composition is administered orally.62. The method of claim 59 , wherein the pharmaceutical composition is administered intravenously. This application is a divisional of U.S. Ser. No. 16/020,641 filed Jun. 27, 2018, which is a divisional of U.S. Ser. No. 15/297,845 filed Oct. 19, 2016, which is a divisional of U.S. Ser. No. 14/785,171, which issued as U.S. Pat. No. 9,512,165, filed Oct. 16, 2015, which is a national stage application under U.S.C. § 371 of International Application No. PCT/CN2014/075594, filed Apr. 17, 2014, published as International Publication No. WO2014/169833 on Oct. 23, 2014, which claims priority to International Application No. PCT/CN2013/074323, filed Apr. 17, 2013, the contents of each of which is incorporated herein by reference in its entirety.Brain excitability is ...

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Номер записи: 80
21-05-2020 дата публикации

NOVEL CHOLESTEROL METABOLITE, 5-CHOLESTEN, 3BETA-25-DIOL, DISULFATE (25HCDS) FOR THERAPY OF METABOLIC DISORDERS, HYPERLIPIDEMIA, DIABETES, FATTY LIVERS DISEASES AND ATHEROSCLEROSIS

Номер: US20200157140A1
Автор: REN Shunlin
Принадлежит:

5-cholesten, 3β, 25-diol, disulfate (25HCDS) has been found to be an authentic PPARagonist and LXR antagonist, and is used for the therapy of lipid disorders and inflammatory diseases, including without limitation fatty liver, inflammatory bowel, and atherosclerotic diseases. 34.-. (canceled)5. A method of treating a subject claim 1 , which method comprises administration to the subject of an effective amount of a compound as defined in claim 1 , wherein said method is selected from: a method for reducing lipids in a subject in need thereof; a method of reducing cholesterol and lipid biosynthesis in a subject in need thereof; a method of reducing inflammation in a subject in need thereof; a method of treating diabetes in a subject in need thereof; a method of treating hyperlipidemia in a subject in need thereof; a method of treating atherosclerosis in a subject in need thereof; a method of treating fatty liver disease in a subject in need thereof; and a method of treating inflammatory disease in a subject in need thereof.6. The method of wherein:said compound is administered in an amount ranging from 0.1 mg/kg to 100 mg/kg based on body mass of said subject, or said compound is administered in an amount ranging from 1 mg/kg to 10 mg/kg, based on body mass of said subject; and/orthe administration comprises at least one of oral administration, enteric administration, sublingual administration, transdermal administration, intravenous administration, peritoneal administration, parenteral administration, administration by injection, subcutaneous injection and intramuscular injection.7. (canceled)8. The compound according to claim 1 , which is an isolated compound.9. The compound according to claim 1 , which is substantially pure.10. (canceled)11. The compound according to claim 1 , which is:in powder form; and/orin freeze-dried form.12. A pharmaceutical composition comprising: (i) 5-cholesten-3 claim 1 , 25-diol claim 1 , disulfate (25HCDS) or a pharmaceutically ...

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Номер записи: 81
11-09-2014 дата публикации

PROCESS FOR PREPARING 17-SUBSTITUTED STEROIDS

Номер: US20140256932A1
Автор: Cotarca Livius, DERRIEN Yvon, FORCATO Massimiliano, Graindorge Laurence, Meunier Sebastien, Pintus Tony, POIRIER Patricia
Принадлежит: ZACH SYSTEM

The present invention relates to a process for the preparation of 17-substituted steroids and, more particularly, to an improved method of synthesizing abiraterone or derivatives thereof in high yield and purity by means of a key 3-formate intermediate.

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Номер записи: 82
23-06-2016 дата публикации

PROCESS FOR PREPARATION OF ABIRATERONE ACETATE

Номер: US20160176915A1
Автор: Kansara Riteshkumar Rajnikant, Patel Nischalkumar Vinodbhai, REHANI Rajeev Budhdev, Thennati Rajamannar
Принадлежит:

The present invention relates to improvement in the process of preparation of abiraterone acetate or a pharmaceutically acceptable salt thereof wherein the improvement comprises purifying the crude 3-&-acetoxyandrosta-5,16-diene-17-yl trifluoromethane sulphonate by crystallization from a solvent to obtain acetoxyandrosta-5,16-diene-17-yl trifluoromethane sulphonate as a crystalline solid and converting it to abiraterone acetate or pharmaceutically acceptable salt thereof. 1. An improvement in the process of preparation of abiraterone acetate or a pharmaceutically acceptable salt thereof which process comprises a first step in which dehydroepiandrosterone-3-acetate (DHEAA) is triflated in the presence of a base and a solvent to form crude 3-β-acetoxyandrosta-5 ,16-diene-17-yl trifluoromethane sulphonate and a second step wherein the crude 3-β-acetoxyandrosta-5 ,16-diene-17-yl trifluoromethane sulphonate is converted to abiraterone acetate or a salt thereof , wherein the improvement comprises an intermediate step of purifying the crude 3-β-acetoxyandrosta-5 ,16-diene-17-yl trifluoromethane sulphonate by crystallization from a solvent to obtain acetoxyandrosta-5 ,16-diene-17-yl trifluoromethane sulphonate as a crystalline solid.2. The improvement as in wherein the improvement further comprises monitoring the unreacted DHEAA during the first step and obtaining and purifying crude 3-β-acetoxyandrosta-5 claim 1 ,16-diene-17-yl trifluoromethane sulphonate after less than 5% DHEAA remains unreacted.3. The improvement as in wherein in the first step DHEAA is triflated in the presence of a base in an aromatic hydrocarbon solvent4. The improvement as in wherein the ratio of DHEAA:triflating agent is at least 1:25. The improvement as in wherein the base is N claim 3 ,N-Dimethylaniline6. The improvement as in wherein the solvent used in the intermediate step is a mixture of a water miscible organic solvent and water.7. The improvement as in wherein the water miscible solvent is ...

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Номер записи: 83
23-06-2016 дата публикации

Bile Acid Derivatives as FXR/TGR5 Agonists and Methods of Use Thereof

Номер: US20160176917A1
Автор: Guoqiang Wang, Jiang Long, Jing He, Peng Dai, Ruichao Shen, Xuechao Xing, Yat Sun Or
Принадлежит: Enanta Pharmaceuticals Inc

The present invention provides compounds of Formula I, pharmaceutical compositions comprising these compounds and methods of using these compounds to prevent or treat FXR-mediated or TGR5-mediated diseases or conditions.

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Номер записи: 84
22-06-2017 дата публикации

Process for the purification of fluticasone propionate using a ketone solvent and water as anti-solvent

Номер: US20170174719A1
Автор: Chandersingh Bohara, Ghanshyam Wagh, Maheshkumar Gadakar, Sakharam Jadhav, Vinayak Govind Gore
Принадлежит: MYLAN LABORATORIES LTD

The present disclosure relates to an improved process for the purification of fluticasone propionate by: a) dissolving fluticasone propionate in a ketone solvent to produce a mixture, b) heating the mixture slowly for 1-2 hours to get a clear solution, c) adding water to the step (b) solution at 50-60° C., d) cooling to −5° C. to 10° C., and e) isolating fluticasone propionate.

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Номер записи: 85
06-06-2019 дата публикации

PREPARATIONS OF HYDROPHOBIC THERAPEUTIC AGENTS, METHODS OF MANUFACTURE AND USE THEREOF

Номер: US20190169224A1
Автор: Barman Shikha P., CAVANAGH Thomas, Hao Tian, Leland Thomas B., Thekkedath Ritesh V.
Принадлежит:

The present invention further provides method of preparing nanocrystals of a hydrophobic therapeutic agent such as fluticasone or triamcinolone, pharmaceutical compositions (e.g., topical or intranasal compositions) thereof and methods for treating and/or preventing the signs and/or symptoms of disorders such as blepharitis, meibomian gland dysfunction or skin inflammation or a respiratory disease (e.g., asthma). 158-. (canceled)59. Nanocrystals of fluticasone propionate polymorph 1 having a crystalline habit (Form A) characterized in that the [001] crystallographic axis is substantially normal to the surfaces that define the thickness of the nanoplates , wherein the nanocrystals have an average size of between 100 nm to 1000 nm and a X-ray powder diffraction pattern with characteristic peaks at about 7.8 , 15.7 , 20.8 , 23.7 , 24.5 , 32.5 degrees 2θ and additional peaks at about 9.9 , 13.0 , 14.6 , 16.0 , 16.9 , 18.1 , and 34.3 degrees 2θ.60. Nanocrystals of fluticasone propionate of having an average size of between 400 nm to 800 nm.61. Pharmaceutical composition in the form of topical formulation comprising a suspension of nanocrystals of fluticasone propionate of between 0.0001% to 10%.62. The topical pharmaceutical formulation according to wherein the concentration of nanocrystals of fluticasone propionate is between 0.001% to 5% and a pharmaceutical acceptable aqueous excipient.63. The topical pharmaceutical formulation according to further containing about 0.002% to 0.01% of benzalkonium chloride.64. The topical pharmaceutical formulation according to further containing one or more coating dispersants claim 62 , one or more tissue wetting agents claim 62 , one or more polymeric stabilizers claim 62 , one or more buffering agents claim 62 , and one or more tonicity adjusting agents.65. A method for the treatment of blepharitis comprising administering to a subject in need a therapeutically effective amount of the topical formulation of .66. The method of ...

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Номер записи: 86
06-06-2019 дата публикации

Nuclear Sulfated Oxysterol, Potent Regulator of Lipid Homeostasis, for Therapy of Hypercholesterolemia, Hypertriglycerides, Fatty Liver Diseases, and Atherosclerosis

Номер: US20190169225A1
Автор: Pandak William M., REN Shunlin
Принадлежит:

The sulfated oxysterol 5-cholesten-3β, 25-diol 3-sulphate, a nuclear cholesterol metabolite that decreases lipid biosynthesis and increases cholesterol secretion and degradation, is provided as an agent to lower intracellular and serum cholesterol and/or triglycerides, and to prevent or treat lipid accumulation-associated inflammation and conditions associated with such inflammation. Methods which involve the use of this sulfated oxysterol to treat conditions associated with high cholesterol and/or high triglycerides and/or inflammation (e.g. hypercholesterolemia, hypertriglyceridemia, non-alcoholic fatty liver diseases, atherosclerosis, etc.) are also provided. 111.-. (canceled)12. A method of decreasing fat accumulation in liver cells of a patient in need thereof , the method comprising administering a salt of 5-cholesten-3β , 25-diol 3-sulphate to the patient in an amount sufficient to decrease fat accumulation in the liver cells of the patient.13. The method of claim 12 , wherein the salt is selected from a sodium salt claim 12 , a potassium salt claim 12 , a calcium salt claim 12 , a lithium salt claim 12 , and an ammonium salt.14. The method of claim 12 , wherein the salt is a sodium salt.15. The method of claim 12 , wherein the fat comprises triglycerides.16. The method of claim 13 , wherein the fat comprises triglycerides.17. The method of claim 14 , wherein the fat comprises triglycerides.18. A method of making a sodium salt of 5-cholesten-3β claim 14 , 25-diol 3-sulphate claim 14 , comprising:sulfating a 3β position of 25-hydroxycholesterol to form 5-cholesten-3β, 25-diol 3-sulphate; andcombining the 5-cholesten-3β, 25-diol 3-sulphate with an alkaline solvent to form a solution comprising the sodium salt of 5-cholesten-3β, 25-diol 3-sulphate.19. The method of claim 18 , wherein the alkaline solvent is an alcohol.20. The method of claim 19 , wherein the alcohol is methanol.21. The method of claim 18 , further comprising forming a solid comprising the sodium ...

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Номер записи: 87
28-05-2020 дата публикации

Process and intermediates for the synthesis of obeticholic acid and derivatives thereof

Номер: US20200165289A1
Автор: Alfonso PÉREZ ENCABO, Carlos CORDOVILLA LOSADA, Ignacio HERRÁIZ SIERRA, José Angel TURIEL HERNANDEZ, Yolanda Fernandez Sainz
Принадлежит: Bionice SL

A process for the preparation of obeticholic acid and derivatives thereof by: (a) hydrogenation of the double bond and reductive opening of the epoxide of a compound of formula (II) or a salt or solvate thereof to obtain a compound of formula (IIIa) and/or (IIIb), or salts or solvates thereof and (b) conversion of a compound of formula (IIIa) and/or a compound of formula (IIIb), or a salt or solvate thereof, into a compound of formula (I), or a salt or solvate thereof

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Номер записи: 88
18-09-2014 дата публикации

NOVEL PRODRUGS OF C-17-HETEROARYL STEROIDAL CYP17 INHIBITORS/ANTIANDROGENS: SYNTHESIS, IN VITRO BIOLOGICAL ACTIVITIES, PHARMACOKINETICS AND ANTITUMOR ACTIVITY

Номер: US20140274983A1
Автор: Brodie Angela, Gediya Lalji K., Njar Vincent
Принадлежит: University of Maryland, Baltimore

Prodrugs of steroidal C-17 benzoazoles, pyrimidinoazoles (az-abenzoazoles) and diazines. Methods of synthesis are also described, whereby a prodrug group is substituted for a functional group at A ring portion of the ABC ring structure of the steroid. Suitable pro-drug groups include amino acid groups, succinate groups, phosphate groups, or sulfamate groups. The prodrugs of the disclosed compounds allow for improved oral bioavailability of the compounds that are inhibitors of human CYP 17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds and the corresponding prodrugs are useful for the treatment of conditions such as human prostate cancer, breast cancer, and prostate hyperplasia. 2. The method of claim 1 , wherein the cell cycle arrest is evidenced by downregulation of Cyclin D1 protein expression claim 1 , downregulation of cyclin E2 mRNA claim 1 , induction of G1/G0 growth arrest claim 1 , downregulation of genes involved in cell cycle progression claim 1 , or any combination thereof.3. The method of claim 2 , wherein the G1/G0 growth arrest is evidenced by FACS analysis of DNA content.4. The method of claim 1 , wherein the cell is a prostate cell.5. The method of claim 4 , wherein the prostate cell is a cultured cell.6. The method of claim 5 , wherein the cultured cell is a PC3 cell.7. The method of claim 1 , wherein the cell originates from a prostate hyperplasia claim 1 , prostate cancer claim 1 , breast cancer claim 1 , or other urogenital cancer.8. The method of claim 1 , wherein the amount of compound 5 sufficient to induce cell cycle arrest is 20 μM of compound 5.9. The method of claim 1 , wherein the induction of cell cycle arrest is associated with an increase in intracellular calcium levels in the cell.10. The method of claim 1 , wherein the compound is formulated as a pharmaceutical composition.11. The method of claim 10 , wherein the pharmaceutical composition is formulated for oral administration ...

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Номер записи: 89
06-07-2017 дата публикации

CHOLANE DERIVATIVES FOR USE IN THE TREATMENT AND/OR PREVENTION OF FXR AND TGR5/GPBAR1 MEDIATED DISEASES

Номер: US20170190731A1
Автор: Fiorucci Stefano, Zampella Angela
Принадлежит: BAR PHARMACEUTICALS S.R.L.

The present invention relates to compounds having cholane scaffolds of formula (I), said compounds for use in the treatment and/or prevention of FXR and TGR5/GPBAR1 mediated diseases. 2. The compound according to wherein Ris Et or ═CH—CH claim 1 , Ris OH and{'sub': 2', '1', '2', '2', '3', '1, 'if n is 0 or 1, then R is CHOH or CN when Ris alpha-OH or R is CHOH, CHOSOH or COOH when Ris beta-OH or H;'}{'sub': 1', '3, 'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'if n is 3 then R, Rand R are as defined in .'}3. The compound according to wherein{'sub': 2', '1', '2', '2', '3', '1, 'n is 0 or 1, R is CHOH or CN and Ris alpha-OH or n is 0 or 1, R is COOH, CHOH or CHOSOH and Ris beta-OH or H.'}4. The compound according to wherein Ris Et claim 2 , n is 3 claim 2 , Ris alpha-OH and Ris alpha-OH.5. The compound according to wherein Ris H and{'sub': 1', '3', '2', '2', '3', '2, 'if Ris alpha-OH and Ris beta-OH then R is CHOH or CHOSOH when n is 0 or R is CHOH or COOH when n is 3;'}{'sub': 1', '3', '2', '3, 'if Ris H, n is 1 and Ris alpha-OH then R is CHOSOH;'}{'sub': 1', '3', '2', '3', '2', '3, 'if Rand Rare H then R is CHOSOH or COOH when n is 0 or R is CHOSOH when n is 1.'}7. The method according to claim 6 , wherein Ris Et or ═CH—CH claim 6 , Ris OH and{'sub': 2', '1', '2', '2', '3', '1, 'if n is 0 or 1, then R is CHOH or CN when Ris alpha-OH or R is CHOH CHOSOH or COOH when Ris beta-OH or H;'}{'sub': 1', '3, 'claim-ref': {'@idref': 'CLM-00006', 'claim 6'}, 'if n is 3 then R, Rand R are as defined in .'}9. The method according to claim 6 , wherein the diseases are gastrointestinal disorders claim 6 , liver diseases claim 6 , cardiovascular diseases claim 6 , atherosclerosis claim 6 , metabolic diseases claim 6 , infectious diseases claim 6 , cancer claim 6 , renal disorders claim 6 , inflammatory disorders claim 6 , or neurological disorders.10. A pharmaceutical composition comprising a compound of formula (I) and at least another pharmaceutical ingredient; said compound ...

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Номер записи: 90
23-07-2015 дата публикации

TREATMENT OF PROSTATE CANCER

Номер: US20150203528A1
Автор: Casebier David Scott, Morrison Jodie Pope, Stein Cy Aaron
Принадлежит:

Described herein are compounds, methods of making such compounds, pharmaceutical compositions, and medicaments comprising such compounds, and methods of using such compounds to treat androgen receptor mediated diseases or conditions. The present invention provides therapies and therapeutic regimens for the treatment of prostate cancer. 152-. (canceled)54. (canceled)55. The compound of claim 53 , wherein the compound claim 53 , or the pharmaceutically-acceptable salt thereof claim 53 , is in a micronized crystalline form.56. The compound of claim 53 , wherein the pharmaceutically-acceptable salt is a hydrochloride salt.5862-. (canceled)63. The compound of claim 57 , wherein the compound claim 57 , or the pharmaceutically-acceptable salt thereof claim 57 , is in a micronized crystalline form.64. The compound of claim 57 , wherein the pharmaceutically-acceptable salt is a hydrochloride salt.6668-. (canceled)69. The compound of claim 65 , wherein the compound claim 65 , or the pharmaceutically-acceptable salt thereof claim 65 , is in a micronized crystalline form.70. The compound of claim 65 , wherein the pharmaceutically-acceptable salt thereof is a hydrochloride salt.7275-. (canceled)76. The compound of claim 71 , wherein the compound claim 71 , or the pharmaceutically-acceptable salt thereof claim 71 , is in a micronized crystalline form.77. The compound of claim 71 , wherein the pharmaceutically-acceptable salt is a hydrochloride salt.7987-. (canceled)88. The composition of claim 78 , wherein the second crystalline form is characterized by a powder X-ray diffraction pattern having characteristic peaks in angle 2-theta at about 13.1° and about 14.1°.89. The composition of claim 78 , wherein the second crystalline form is characterized by a powder X-ray diffraction pattern having characteristic peaks in angle 2-theta at about 17.2° claim 78 , about 18.5° claim 78 , about 19.1° claim 78 , about 16.2° claim 78 , and about 29.6°.90. The composition of claim 78 , wherein ...

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Номер записи: 91
25-09-2014 дата публикации

NOVEL C-17-HETEROARYL STEROIDAL CYP17 INHIBITORS/ANTIANDROGENS, IN VITRO BIOLOGICAL ACTIVITIES, PHARMACOKINETICS AND ANTITUMOR ACTIVITY

Номер: US20140288036A1
Автор: Brodie Angela, Njar Vincent
Принадлежит: the University of Maryland, Baltimore

Described are steroidal C-17 benzoazoles, pyrimidinoazoles (azabenzoazoles) and diazines. Methods for their synthesis are also described, which include methods having a step of nucleophilic vinylic “addition-elimination” substitution reaction of 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene or analogs thereof and benzoazole or pyrimidinoazole nucleophiles and methods having a palladium catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3β-ol or analogs thereof with tributylstannyl diazines. The compounds are potent inhibitors of human CYP17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds are useful for the treatment of human prostate cancer. 2. The pharmaceutical composition of claim 1 , wherein the pharmaceutical compound is present in an amount sufficient to treat one or more symptoms associated with a prostate disease.3. The pharmaceutical composition of claim 1 , wherein the composition is in a solid dosage form.4. The pharmaceutical composition of claim 1 , wherein the solid dosage form is a tablet.5. The pharmaceutical composition of claim 3 , wherein the solid dosage form is a capsule.6. The pharmaceutical composition of or claim 3 , wherein the composition isformulated to deliver from about 1 mg to about 500 mg of the compound after administration to a subject.7. The pharmaceutical composition of or claim 3 , wherein the composition isformulated to deliver from about 50 mg to about 150 mg of the compound after administration to a subject.8. The pharmaceutical composition of or claim 3 , wherein the pharmaceutical compound is in a single crystalline form having a melting point of 189-190 degrees Celsius claim 3 , and wherein the crystalline form is obtained from a crystallization using ethyl acetate and methanol.9. The pharmaceutical composition of claim 1 , wherein the tissue is tumor claim 1 , liver claim 1 , testes claim 1 , or blood. This invention was made with government support ...

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Номер записи: 92
25-09-2014 дата публикации

NOVEL COMPOSITIONS AND METHODS FOR TREATING PROSTATE CANCER

Номер: US20140288037A1
Автор: Casebier David Scott, Moreton Richard Christian, Sentissi Abdellah, Turnbull Mark
Принадлежит: Tokai Pharmaceuticals, Inc.

Described herein are compounds, methods of making such compounds, pharmaceutical compositions, and medicaments comprising such compounds, and methods of using such compounds to treat androgen receptor mediated diseases or conditions. In some embodiments, the solid matrix comprises a polymer. In some embodiments, the polymer is soluble in an aqueous solution. In particular embodiments, the aqueous solution is water. In other embodiments, the aqueous solution has a pH of 5.0 or greater. 2. The solid dispersion pharmaceutical composition of claim 1 , wherein said solid matrix comprises a polymer.3. The solid dispersion pharmaceutical composition of claim 2 , wherein said polymer is soluble in an aqueous solution.4. The solid dispersion pharmaceutical composition of claim 3 , wherein said aqueous solution is water.5. The solid dispersion pharmaceutical composition of claim 3 , wherein said aqueous solution has a pH of 5.0 or greater.683-. (canceled)84. The solid dispersion pharmaceutical composition of claim 1 , wherein said compound is substantially in a non-crystalline form claim 1 , and wherein the bioavailability of the compound when administered to a subject in a fasted state is substantially the same as the bioavailability of the drug when administered to said subject in a fed state.8596-. (canceled)98103-. (canceled)105125-. (canceled)127139-. (canceled)140. A method for treating prostate cancer in a subject in need thereof claim 97 , comprising administering to said subject a solid dispersion pharmaceutical composition of .141. (canceled)142. The method of claim 140 , wherein said prostate cancer is castration resistant prostate cancer.143149-. (canceled)150. The method of claim 140 , wherein said composition is administered in multiple unit doses.151166-. (canceled)167. The method of claim 150 , wherein the unit dose is a solid dosage form.168169-. (canceled)170. The method of claim 167 , wherein the solid dosage form is a tablet.171189-. (canceled)190. The ...

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Номер записи: 93
27-07-2017 дата публикации

GUGGULPHOSPHOLIPID METHODS AND COMPOSITIONS

Номер: US20170210775A1
Автор: AHMAD Ateeq, AHMAD Imran, AHMAD Moghis U., ALI Shoukath M., SHEIKH Saifuddin
Принадлежит:

The present invention relates to the methods for preparing synthetic guggulphospholipids, their fatty acid analogues and other bioactive molecules. The present invention relates to E-guggulsterone and Z-guggulsterone or mixture of E- and Z-guggulsterones, and E-guggulsterol and Z-guggulsterol or mixture of E- and Z-guggulsterols synthetically modified to guggulphospholipids and analogues and salts thereof, fatty acid analogues of guggulsterols, guggulsulfate and salts thereof, guggulphosphate and salts thereof; and guggulsterols conjugated with drugs for use as prodrugs. Also the present invention provides a novel method for the preparation of E-guggulsterol and Z-guggulsterol or mixture of E- and Z-guggulsterols from a mixture of E- and Z-guggulsterones. The present invention further relates to guggulphospholipids and other bioactive molecules incorporated into complexes such as liposomes, complexes, emulsions, vesicles, micelles, and mixed micelles, which can include other active agents, such as hydrophobic or hydrophilic drugs for use, e.g., in treatment of human and animal diseases. 4. The method of claim 3 , wherein said guggulsterone I is an E-isomer or Z-isomer or a mixture of E and Z isomers.5. The method of claim 2 , wherein said guggulsterol IIA is an E-isomer or Z-isomer claim 2 , or a mixture of E- and Z-isomer.6. The method of claim 2 , wherein said guggulsterol is optically pure claim 2 , and wherein said guggulsterol is a mixture of optical isomers.7. A method of preparing guggulsterol IIA claim 2 , comprising treating guggulsterone I in one of more steps to produce preparing guggulsterol IIA.8. A method of preparing a compound of formula IV claim 2 , V claim 2 , VI claim 2 , VIII claim 2 , IX or X of claim 2 , claim 2 , or claim 2 , wherein at least one step comprises the use of a phosphoramidite reagent or a phosphorylating agent.9. The method of claim 8 , wherein said phosphoramidite reagent is selected from the group consisting of NN- ...

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Номер записи: 94
05-08-2021 дата публикации

NOVEL CHOLESTEROL METABOLITE, 5-CHOLESTEN, 3BETA-25-DIOL, DISULFATE (25HCDS) FOR THERAPY OF METABOLIC DISORDERS, HYPERLIPIDEMIA, DIABETES, FATTY LIVERS DISEASES AND ATHEROSCLEROSIS

Номер: US20210238219A1
Автор: REN Shunlin
Принадлежит:

5-cholesten, 3(3, 25-diol, disulfate (25HCDS) has been found to be an authentic PPAR agonist and LXR antagonist, and is used for the therapy of lipid disorders and inflammatory diseases, including without limitation fatty liver, inflammatory bowel, and atherosclerotic disease. 34.-. (canceled)5. A method of treating a subject claim 1 , which method comprises administration to the subject of an effective amount of a compound as defined in claim 1 , wherein said method is selected from: a method for reducing lipids in a subject in need thereof; a method of reducing cholesterol and lipid biosynthesis in a subject in need thereof; a method of reducing inflammation in a subject in need thereof; a method of treating diabetes in a subject in need thereof; a method of treating hyperlipidemia in a subject in need thereof; a method of treating atherosclerosis in a subject in need thereof; a method of treating fatty liver disease in a subject in need thereof; and a method of treating inflammatory disease in a subject in need thereof.6. The method of wherein:said compound is administered in an amount ranging from 0.1 mg/kg to 100 mg/kg based on body mass of said subject, or said compound is administered in an amount ranging from 1 mg/kg to 10 mg/kg, based on body mass of said subject; and/orthe administration comprises at least one of oral administration, enteric administration, sublingual administration, transdermal administration, intravenous administration, peritoneal administration, parenteral administration, administration by injection, subcutaneous injection and intramuscular injection.7. (canceled)8. The compound according to claim 1 , which is an isolated compound.9. The compound according to claim 7 , which is substantially pure.10. (canceled)11. The compound according to claim 1 , which is:in powder form; and/orin freeze-dried form.12. A pharmaceutical composition comprising: (i) 5 cholesten-3 claim 1 , 25-diol claim 1 , disulfate (25HCDS) or a pharmaceutically ...

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Номер записи: 95
11-07-2019 дата публикации

METHODS FOR THE PREPARATION OF OBETICHOLIC ACID AND DERIVATIVES THEREOF

Номер: US20190211052A1
Автор: Chandra DE, List Benjamin, Qinggang WANG
Принадлежит:

The present application relates to a method of preparing a bile acid derivative, or a pharmaceutical acceptable salt, solvate, or amino acid conjugate thereof, comprising reacting Compound 2 with paraldehyde to form Compound 3: 3. (canceled)4. The method of claim 2 , wherein the triflimide catalyst is selected from (Tf)NH claim 2 , (Tf)N—(C-Calkyl) claim 2 , and (Tf)N-tri-C-Calkylsilyl.5. The method of claim 4 , wherein the triflimide catalyst is (Tf)N-trimethylsilyl.7. The method of claim 6 , wherein the molar ratio of paraldehyde to Compound 2 is between about 3:1 and about 6:1.8. The method of claim 2 , wherein the reaction is conducted at a temperature between about 10° C. and about 30° C.9. The method of claim 2 , wherein the reaction is conducted for about 10 min to 4 hr.11. (canceled)12. The method of claim 10 , wherein the metal hydroxide is sodium hydroxide or potassium hydroxide.13. The method of claim 12 , wherein the metal hydroxide is potassium hydroxide.14. The method of claim 10 , wherein the reaction is conducted in a solvent selected from methanol claim 10 , ethanol claim 10 , propanol claim 10 , isopropanol claim 10 , water claim 10 , and a mixture thereof.15. The method of claim 14 , wherein the solvent is a mixture of ethanol and water claim 14 , at an ethanol/water ratio of between 1:3 to 3:1 claim 14 , between 1:2 to 2:1 claim 14 , between 1:1.5 to 1.5:1 claim 14 , between 1:1.2 to 1.2:1 claim 14 , or about 1:1 (vol/vol).17. (canceled)19. (canceled) Farnesoid X receptor (FXR) is a nuclear receptor that functions as a bile acid sensor controlling bile acid homeostasis. FXR is expressed in various organs and shown to be involved in the regulation of many diseases and conditions, such as liver diseases, lung diseases, renal diseases, intestinal diseases, and heart diseases, and biological processes, including glucose metabolism, insulin metabolism, and lipid metabolism.Numerous bile acid derivatives are FXR agonists, and are able to regulate FXR- ...

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Номер записи: 96
11-07-2019 дата публикации

SELECTIVE PROGESTERONE RECEPTOR MODULATOR (SPRM) REGIMEN

Номер: US20190211053A1
Автор: Knauthe Rudolf, SEITZ Christian, ZEUN Susan
Принадлежит:

The invention is directed to a pharmaceutical composition comprising a progesterone receptor antagonist namely (11β,17β)-17-Hydroxy-11-[4-(methylsulphonyl)phenyl]-17-(pentafluoroethyl)estra-4,9-dien-3-one for the treatment and/or prophylaxis of Uterine Fibroids (myomas, uterine leiomyoma) that is administered to a patient diagnosed with Uterine Fibroids following a specific regimen. Additionally, the invention is directed to a method for treating Uterine Fibroids (myomas, uterine leiomyoma) and/or for reducing Uterine Fibroids (myomas, uterine leiomyoma) size and symptoms related to Uterine Fibroids following a specific regimen as well as treatment of Heavy Menstrual Bleeding (HMB). 111-. (canceled)13. The method of wherein the administrating step and the discontinuing step are repeated at least one (1) time.14. The method of wherein the period is from twelve (12) weeks up to twenty-four (24) weeks.15. The method of wherein the period is selected from the group consisting oftwelve (12) weeks;sixteen (16) weeks;twenty (20) weeks; andtwenty-four (24) weeks.17. The method of wherein the administrating step and the discontinuing step are repeated at least one (1) time.18. The method of wherein the period is from twelve (12) weeks up to twenty-four (24) weeks.19. The method of wherein the period is selected from the group consisting of twelve (12) weeks; sixteen (16) weeks; twenty (20) weeks; and twenty-four (24) weeks.21. The method of wherein the administrating step and the discontinuing step are repeated at least one (1) time.22. The method of wherein the period is from twelve (12) weeks up to twenty-four (24) weeks.23. The method of wherein the period is selected from the group consisting of twelve (12) weeks; sixteen (16) weeks; twenty (20) weeks; and twenty-four (24) weeks. The invention is directed to a pharmaceutical composition comprising a progesterone receptor modulator namely (11β,17β)-17-Hydroxy-11-[4-(methylsulphonyl)phenyl]-17-(pentafluoroethyl)estra-4,9- ...

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Номер записи: 97
11-07-2019 дата публикации

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Номер: US20190211054A9
Автор: Beresis Richard Thomas, Harrison Boyd L., Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (1): and pharmaceutical compositions thereof. 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, 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, tinnitus, and status epilepticus. 237-. (canceled)39. The method of claim 38 , wherein the CNS-related disorder is a sleep disorder claim 38 , a mood disorder claim 38 , a schizophrenia spectrum disorder claim 38 , a convulsive disorder claim 38 , a disorder of memory and/or cognition claim 38 , a movement disorder claim 38 , a personality disorder claim 38 , autism spectrum disorder claim 38 , pain claim 38 , traumatic brain injury claim 38 , a vascular disease claim 38 , a substance abuse disorder and/or withdrawal syndrome claim 38 , tinnitus claim 38 , or status epilepticus.40. The method of or wherein the compound is administered orally claim 38 , subcutaneously claim 38 , intravenously claim 38 , or intramuscularly.41. The method of or wherein the compound is administered chronically. 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 the cell exterior. The potential (voltage) is the result of ion (K, Na, Cl, organic anions) balance across the neuronal semipermeable membrane.Neurotransmitters are stored in presynaptic vesicles and are released under the ...

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Номер записи: 98
11-08-2016 дата публикации

BILE ACID ANALOGS AS FXR/TGR5 AGONISTS AND METHODS OF USE THEREOF

Номер: US20160229886A1
Автор: Or Yat Sun, Shen Ruichao, Wang Guoqiang
Принадлежит:

The present invention provides compounds of Formula I: 14. A method for the prevention or treatment of an FXR-mediated disease or condition in a mammal comprising administering to the mammal suffering from an FXR-mediated disease or condition a therapeutically effective amount of a compound according to .15. The method according to claim 14 , wherein the FXR-mediated disease or condition is selected from the group consisting of chronic liver disease claim 14 , gastrointestinal disease claim 14 , renal disease claim 14 , cardiovascular disease claim 14 , and metabolic disease.16. The method according to claim 15 , wherein the chronic liver disease is selected from the group consisting of primary biliary cirrhosis (PBC) claim 15 , cerebrotendinous xanthomatosis (CTX) claim 15 , primary sclerosing cholangitis (PSC) claim 15 , drug induced cholestasis claim 15 , intrahepatic cholestasis of pregnancy claim 15 , parenteral nutrition associated cholestasis (PNAC) claim 15 , bacterial overgrowth or sepsis associated cholestasis claim 15 , autoimmune hepatitis claim 15 , chronic viral hepatitis claim 15 , alcoholic liver disease claim 15 , nonalcoholic fatty liver disease (NAFLD) claim 15 , nonalcoholic steatohepatitis (NASH) claim 15 , liver transplant associated graft versus host disease claim 15 , living donor transplant liver regeneration claim 15 , congenital hepatic fibrosis claim 15 , choledocholithiasis claim 15 , granulomatous liver disease claim 15 , intra- or extrahepatic malignancy claim 15 , Sjogren's syndrome claim 15 , Sarcoidosis claim 15 , Wilson's disease claim 15 , Gaucher's disease claim 15 , hemochromatosis claim 15 , and alpha 1-antitrypsin deficiency.17. The method according to claim 15 , wherein the renal disease is selected from the group consisting of diabetic nephropathy claim 15 , focal segmental glomerulosclerosis (FSGS) claim 15 , hypertensive nephrosclerosis claim 15 , chronic glomerulonephritis claim 15 , chronic transplant glomerulopathy ...

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Номер записи: 99
11-08-2016 дата публикации

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Номер: US20160229887A1
Автор: Harrison Boyd L., Herr Robert Jason, Kargbo Robert Borbo, Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco Gerald
Принадлежит: SAGE THERAPEUTICS, INC.

Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein -------, R, R, R, A and L 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. 213-. (canceled)15. (canceled)16. The compound of claim 14 , wherein n is 0.1722-. (canceled)23. The compound of claim 14 , wherein Ris C-Calkyl.2425-. (canceled)2829-. (canceled)32. The compound of claim 27 , wherein A is monocyclic.33. The compound of claim 27 , wherein A is bicyclic.3436-. (canceled)37. The compound of claim 27 , wherein A is a 5-membered or 6-membered heteroaryl or heterocyclyl comprising 1 claim 27 , 2 claim 27 , 3 claim 27 , or 4 nitrogen atoms.38. (canceled)39. The compound of claim 37 , wherein A is morpholine or piperazine.4041-. (canceled)42. The compound of claim 27 , wherein the heteroaryl is benzotriazole claim 27 , azabenzotriazole claim 27 , diazabenzotriazole claim 27 , benzopyrazole claim 27 , azabenzopyrazole claim 27 , or diazabenzopyrazole.4345-. (canceled)46. The compound of claim 37 , wherein A is pyrazole claim 37 , triazole claim 37 , or tetrazole.47. The compound of claim 27 , wherein Ris C-Calkyl claim 27 , C-Calkenyl claim 27 , C-Calkynyl claim 27 , carbocyclyl claim 27 , or heterocyclyl.48. (canceled)49. The compound of claim 47 , wherein Ris methyl claim 47 , ethyl claim 47 , or isopropyl.50. (canceled)51. The compound of claim 27 , wherein Ris methyl.52. The compound of claim 27 , wherein n is 0.53. The compound of claim 27 , wherein n is 1 or 2 claim 27 , and Ris cyano claim 27 , halo claim 27 , C-Calkyl claim 27 , C-Calkoxy claim 27 , —C(O)R claim 27 , or —S(O)R.5459-. (canceled)60. The compound of claim 53 , wherein Ris C-Calkyl.61. The compound of claim 60 , wherein Ris methyl ...

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Номер записи: 100