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Небесная энциклопедия

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

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Мониторинг СМИ

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

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Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 2320. Отображено 100.
10-05-2012 дата публикации

Hydroxycholesterol immunoassay

Номер: US20120115169A1
Автор: James J. Donegan, Jeffrey Kroll Adams, Michael C. Mullenix, Robert Elliot Zipkin, Wayne Forrest Patton
Принадлежит: Enzo Life Sciences Inc

Provided is a derivative of 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol. Also provided is a protein conjugated to the above derivative. Further provided is an antibody composition comprising antibodies that specifically bind to 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol. Additionally, a method of making antibodies that specifically bind to 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol is provided. Also, a method of assaying for 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol is provided. Additionally provided is a kit for detecting 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol. A method of detecting an enzyme or enzymes utilized in phase II drug metabolism is also provided. Also, a method of detecting an enzyme that synthesizes 22-hydroxycholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 26-hydroxycholesterol or 27-hydroxycholesterol is provided. Further provided is a method of evaluating progression of multiple sclerosis in a patient. Also provided is a method of determining whether a treatment for multiple sclerosis in a patient is effective. Further, a method of evaluating progression of Huntington's disease in a patient is provided. Additionally provided is a method of determining whether a treatment for Huntington's disease in a patient is effective.

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Номер записи: 1
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: 2
11-04-2013 дата публикации

METHANESULFONATE SALTS OF ABIRATERONE-3-ESTERS AND RECOVERY OF SALTS OF ABIRATER ONE-3-ESTERS FROM SOLUTION IN METHYL TERT-BUTYL ETHER

Номер: US20130090468A1
Автор: Hunt Neil John
Принадлежит: BTG International Limited

A salt of a compound of formula (I) may be made with methanesulfonic acid. The salt and salts with other acids may be prepared by recovering from methyl tert-butyl ether (MTBE). 2. A salt as claimed in in which R′ represents a lower acyloxy group.3. A salt as claimed in in which R represents a hydrogen atom.4. A process for the preparation of a salt as claimed in by recovering the salt from a solution of the free base in5. A process as claimed in in which the solvent comprises an ester or an ether.6. A process as claimed in in which the solvent comprises methyl tert-butyl ether (MTBE).8. A process as claimed in in which the acid is hydrochioric claim 7 , sulfuric or toluoyltartaric or methanesulfonic acid.9. A salt as claimed in which R′ represents a lower acyloxy group.10. A salt as claimed in in which R represents a hydrogen atom. This invention relates to novel salt forms of the esters of the compound abiraterone, or a derivative thereof, and to a process for the preparation of the compound abiraterone, or a salt or derivative thereof.Abiraterone acetate of formula:is a potent selective, orally active inhibitor of the key enzyme n testosterone synthesis, 17α-hydroxylase-C17,20-lyase, also known as steroid 17α-monooxygenase inhibitor or Human Cytochrome P450. Suppression of testosterone synthesis has been demonstrated with abiraterone acetate in patients with prostate cancer.The compound was first disclosed in WO-A-93/20097, with a further synthetic method to the compound in WO-A-95/09178 (both British Technology Group Limited). In particular, WO-A-95/09178 discloses the synthesis of a compound of formula:where the 3β substituent R′ is hydrogen or a lower acyl group having 2 to 4 carbon atoms. One of the methods disclosed makes this from the corresponding ketone via the steroidal enol triflate (trifluoromethylsulfonate):The base used in the reported route, 2,6-di-tent-butyl-4-methylpyridine (DTBMP), is expensive. The present inventors have moreover observed a ...

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Номер записи: 3
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: 4
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: 5
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: 6
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: 7
15-08-2013 дата публикации

PROGESTERONE ANALOGS AND USES RELATED THERETO

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

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

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Номер записи: 8
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: 9
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: 10
26-09-2013 дата публикации

CYP11B, CYP17, AND/OR CYP21 INHIBITORS

Номер: US20130252930A1
Автор: Chu Daniel, WANG Bing, Ye Tao
Принадлежит: Biomarin Pharmaceutical Inc.

Provided herein are inhibitors of CYP11B, CYP17, and/or CYP21 enzymes of Formula (Z), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), or (XVII). Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat androgen-dependent diseases, disorders and conditions. Formula (Z) 12.-. (canceled)45.-. (canceled)79.-. (canceled)1121.-. (canceled)22. A pharmaceutical composition comprising a compound of any of , and and a pharmaceutically acceptable carrier , excipient or binder.2310. A method for treating cancer in a subject comprising administering to a subject in need thereof 1) a therapeutically effective amount of a compound of any of , and or a pharmaceutically acceptable salt or solvate thereof or 2) a pharmaceutical composition comprising a therapeutically effective amount of a compound of any of , , and or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier , excipient or binder.2435.-. (canceled)36. A method of treating a disease associated with hypercortisolism comprising administering to a subject in need thereof a therapeutically effective amount of a compound of , or , or a pharmaceutically acceptable salt or solvate thereof.3740.-. (canceled) Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat androgen-dependent diseases or conditions.The 17α-hydroxylase/Clyase enzyme complex is essential for the biosynthesis of androgens. CYP17 is a bifunctional enzyme which possess both a C-lyase activity and a C17-hydroxylase activity. These two alternative enzymatic activities of CYP17 result in the formation of critically different intermediates in steroid biosynthesis and each activity appear to be differentially and developmentally regulated.In the testes and adrenal ...

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Номер записи: 11
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: 12
14-11-2013 дата публикации

Compounds and methods for treating neoplasia

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

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

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Номер записи: 13
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: 14
19-12-2013 дата публикации

NOVEL COMPOSITIONS OF TLR7 AND/OR TLR8 AGONISTS CONJUGATED TO LIPIDS

Номер: US20130336996A1
Автор: DEBIN Arnaud, Drocourt Daniel, LIOUX Thierry, PEROUZEL Eric, TIRABY Gerard, VERNEJOUL Fabienne
Принадлежит: CAYLA

A conjugated compound of formula Q-Z—Rwherein Q is a TLR7 and/or TLR8 agonist and Z—Ris a lipid covalently linked to an amino acid or peptide coupled to a polyamine group, and a process for the manufacture of the conjugated compound, as well as a complex formed between the conjugated compound and a polyanionic molecule and a pharmaceutical composition containing the conjugated compound or complex. Also described is the use of the conjugated compound or complex in the treatment of infection, cancer or immune disorders or for use in vaccines. 5. The conjugated compound according to claim 1 , wherein Y is a single bond or —CO— claim 1 , —N(R)— claim 1 , —O— claim 1 , —S— or —S(O)— claim 1 , wherein Ris —H claim 1 , carboxyl claim 1 , —NHor a radical chosen from C-Calkyl claim 1 , C-Calkoxy claim 1 , C-Calkanoyl claim 1 , C-Caryl claim 1 , C-Cheteroaryl claim 1 , or C-Calkoxycarbonyl.6. The conjugated compound according to claim 1 , wherein X is a —(C-Carylene) claim 1 , preferably a phenylene claim 1 , a —(C-Calkylene)- claim 1 , preferably an ethylene claim 1 , a —(C-Cheteroarylene)- claim 1 , preferably a pyridinylene claim 1 , a —(C-Calkylene)-W—(C-Calkylene)- claim 1 , preferably an ethylene-W-ethylene wherein W is —O— or —NH—.7. The conjugated compound according to claim 1 , wherein s is 1.8. The conjugated compound according to claim 1 , wherein Ris —H claim 1 , —OH claim 1 , C-Calkyl claim 1 , or (C-Calkyl)-W—(C-Calkylene) claim 1 , wherein W is —O— or —NH—.9. The conjugated compound according to claim 1 , wherein A is a nitrogen atom.10. The conjugated compound according to claim 1 , wherein:{'sup': 2', '3, 'sub': 1', '6', '1', '10', '1', '10, 'A is a nitrogen atom, Ris a C-Calkylamino or C-Calkoxy-C-Calkoxy, and Ris absent or'}{'sup': 2', '3, 'sub': 6', '20, 'Rand Rform a fused C-Caryl, preferably a phenyl.'}11. The conjugated compound according to claim 1 , wherein said conjugated compound is selected from the group consisting of:bis(3,7,11,15- ...

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Номер записи: 15
02-01-2014 дата публикации

CONTRACEPTIVE AGENTS

Номер: US20140005132A1
Автор: Blanco Gustavo, Georg Gunda I., Syeda Shameem Sultana
Принадлежит:

The invention provides compounds of formula I, II, III, or IV: 2. The compound of claim 1 , which is a compound of formula (I).3. The compound of claim 1 , which is a compound of formula (II).4. The compound of claim 1 , which is a compound of formula (III).5. The compound of claim 1 , which is a compound of formula (IV).7. The compound of claim 1 , wherein Ris H.8. The compound of claim 1 , wherein Ris H or methoxymethyl.10. The compound of claim 1 , wherein Ris H or methoxymethyl.11. The compound of claim 1 , wherein Ris H.12. The compound of claim 1 , wherein Ris H.13. The compound of claim 1 , wherein Rand Rtaken together form —C(CH)—.16. The compound of claim 1 , wherein X is O.17. The compound of claim 1 , wherein X is ═N—N═C(NH).18. The compound of claim 1 , wherein Y is O.19. The compound of claim 1 , wherein Y is ═N—N═C(NH).20. The compound of claim 1 , wherein Ris —OH claim 1 , morpholino claim 1 , or —O—C(═O)CH(NH)R; and Ris 1-methylethyl or 4-aminobutyl.22. The compound of claim 1 , wherein the compound is not one of the compounds Compound 54 claim 1 , 12 claim 1 , 1 or 1a.23. A compound comprising:a chemical structure of one of Compounds 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 55, 56, 57a, 57b, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 77a, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, or 91.24. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a compound of formula I, II, III, or IV of , or a pharmaceutically acceptable salt thereof; and'}a pharmaceutically acceptable diluent or carrier having the compound.25. A method for decreasing sperm motility in a mammal comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'administering the compound of formula I, II, III, or IV of , or a pharmaceutically acceptable ...

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Номер записи: 16
02-01-2014 дата публикации

AMINOALKYLSTEROL COMPOUNDS WITH ANTITUMORAL AND NEUROPROTECTIVE ACTIVITY

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

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

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Номер записи: 17
09-01-2014 дата публикации

SYNTHESIS AND USE OF ANTI-TUMOR DRUG LQC-Y

Номер: US20140011786A1
Автор: Lei Haimin
Принадлежит:

Disclosed are the general structural formula of LQC-Y as well as the synthesis and use thereof. Pharmacological experiments demonstrated the marked antitumor effect of such compounds. Single day administration of LQC-Y3 to mice at a maximum dose of 6000 mg/kg showed no toxicity response during the 14-day continuous observation period, indicating the high safety of the compounds, and the compounds can be used to prepare medicaments for preventing and treating carcinomas such as liver cancer, lung cancer. In the general structural formula of LQC-Y, R represents steroid compounds such as cholic acid, deoxycholic acid, ursodeoxycholic acid, chenodeoxycholic acid, and hyodeoxycholic acid and so on; triterpenoid compounds such as oleanolic acid, ursolic acid, pachymic acid, glycyrrhetinic acid and glycosides thereof and so on; emodic acid, emodin and other mono-substituted or poly-substituted structures of anthraquinone parent nucleus; baicalein, baicalin and other flavonoid; shikimic acid, mono-substituted shikimic acid or poly-substituted shikimic acid; gardenia acid and other iridoid acid derivatives; paeonol, curcumin and structural derivatives thereof. 2. A method of treating a tumor disease comprising administering to a patient in need thereof an effective amount of a compound according to .4. The compound or the pharmaceutically acceptable salt thereof according to claim 3 , wherein the compound of formula 1 is an ester of R-acid with trimethyl pyrazine methanol claim 3 , and the R-acid is selected from the group consisting of cholic acid claim 3 , deoxycholic acid claim 3 , oleanolic acid claim 3 , glycyrrhetinic acid claim 3 , pachymic acid claim 3 , emodic acid and shikimic acid.5. The compound or the pharmaceutically acceptable salt thereof according to claim 3 , wherein the compound of formula 1 is an ether of R-phenol with trimethyl pyrazine methanol claim 3 , and R-phenol is one of chrysophanol or paeonol.9. The compound or the pharmaceutically acceptable ...

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Номер записи: 18
09-01-2014 дата публикации

SYNTHESIS OF ABIRATERONE AND RELATED COMPOUNDS

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

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

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Номер записи: 19
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: 20
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: 21
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: 22
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: 23
20-03-2014 дата публикации

SUBSTRATE REDUCTION THERAPY

Номер: US20140080769A1
Автор: Lloyd-Evans Emyr, Platt Frances Mary, Porter Forbes Dennison
Принадлежит:

The present invention provides a compound which is an inhibitor of sphingolipid biosynthesis for use in the treatment of a disease which has a secondary Niemann-Pick type C disease like cellular phenotype. 1. A method of treating a subject having a disease which has a secondary Niemann-Pick type C disease like cellular phenotype , provided that the disease is other than mucopolysaccharidosis and other than mucolipidosis IV , wherein the method comprises selecting the subject having the disease , and administering to the subject an effective amount of an inhibitor of sphingolipid biosynthesis.26-. (canceled)10. The method of wherein the inhibitor of sphingolipid biosynthesis is selected from N-butyldeoxynojirimycin; N-nonyldeoxynojirimycin; N-butyldeoxygalactonojirimycin; N-5-adamantane-1-yl-methoxypentyl-deoxynojirimycin; alpha-homogalactonojirimycin; nojirimycin; deoxynojirimycin; N7-oxadecyl-deoxynojirimycin; deoxygalactonojirimycin; N-butyl-deoxygalactonojirimycin; N-nonyl-deoxygalactonojirimycin; N-nonyl-6deoxygalactonojirimycin; N7-oxanonyl-6deoxy-DGJ; alpha-homoallonojirimycin; beta-1-C-butyl-deoxygalactonojirimycin; 1 claim 1 ,5-dideoxy-1 claim 1 ,5-imino-D-glucitol claim 1 , 1 claim 1 ,5-(Butylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Methylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Hexylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Nonylylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(2-Ethylbutylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(2-Methylpentylimino)-1 claim 1 ,5-dideoxy-D-glucitol; 1 claim 1 ,5-(Benzyloxycarbonylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Phenylacetylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Benzoylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Butylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , tetraacetate; 1 claim 1 ,5-(Ethyl malonylimino)-1 claim 1 ,5-dideoxy-D-glucitol claim 1 , ...

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Номер записи: 24
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: 25
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: 26
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: 27
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: 28
02-01-2020 дата публикации

AMINOSTEROID DERIVATIVES AND PROCESS FOR PRODUCING SAME

Номер: US20200002372A1
Автор: MALTAIS René, PERREAULT Martin, POIRIER Donald
Принадлежит:

Estrane-based and androstane-based aminosteroid derivatives are described herein. More specifically, the following piperazinyl-steroid compounds of Formula I, Formula II, Formula III, and Formula IV are described. The compounds display cytotoxicity on a variety of cancer cell lines. A process for producing the compounds and their use in the manufacture of pharmaceutical formulations and/or combinations is also disclosed. 521.-. (canceled)2627.-. (canceled)36. A pharmaceutical composition comprising a pharmaceutically acceptable amount of the aminosteroid derivative according to and a pharmaceutically acceptable carrier.37. A pharmaceutical combination comprising an aminosteroid derivative according to and one or more agents selected from a taxane claim 1 , an epothitone claim 1 , an anti-androgen and a platinum derivative.38. The pharmaceutical combination of claim 37 , wherein the one or more agents are at least one of docetaxel claim 37 , paclitaxel claim 37 , taxol claim 37 , ixabepitone claim 37 , patupitone claim 37 , sagopitone; mitoxantrone; predinisotone; dexamethasone; estramustin; vinblastin; vincristin; doxorubicin; adriamycin; idarubicin; daunorubicin; bleomycin; etoposide; cyctophosphamide; ifosfamide; procarbazine; metphalan; 5-fluorouracil; capecitabine; fludarabine; cytarabine; ara-C; 2-chloro-2″-deoxyadenosine claim 37 , thioguanine claim 37 , flutamide claim 37 , cyproterone acetate claim 37 , bicatutamide claim 37 , bortezomib claim 37 , cisplatin claim 37 , carboplatin; chlorambucil; methotrexate or rituximab.3947.-. (canceled)48. A method of treating a disease in a subject comprising administering to the subject an aminosteroid derivative according to .49. The method of claim 48 , wherein the aminosteroid derivative is administered intravenously claim 48 , intra-arterially claim 48 , subcutaneously claim 48 , topically claim 48 , or intramuscularly.50. The method of claim 48 , wherein the aminosteroid derivative is administered systemically ...

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Номер записи: 29
07-01-2021 дата публикации

CHEMILUMINESCENT ANDROSTENEDIONE CONJUGATES

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

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

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Номер записи: 30
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: 31
20-01-2022 дата публикации

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

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

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

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Номер записи: 32
10-01-2019 дата публикации

COMPOUNDS AND METHODS FOR TRANS-MEMBRANE DELIVERY OF MOLECULES

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

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

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Номер записи: 33
14-01-2016 дата публикации

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

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

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

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Номер записи: 34
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: 35
27-01-2022 дата публикации

OXYSTEROLS AND METHODS OF USE THEREOF

Номер: US20220024968A1
Автор: Griffin Andrew, Harrison Boyd L., 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, R, 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. 140-. (canceled)4243-. (canceled)44. The pharmaceutical composition of claim 41 , wherein Ris substituted or unsubstituted C-Calkyl.45. The pharmaceutical composition of claim 41 , wherein Ris —CH claim 41 , —CF claim 41 , —CHCH claim 41 , or —CHOR claim 41 , wherein Ris substituted or unsubstituted C-Calkyl.4647-. (canceled)48. The pharmaceutical composition of claim 41 , wherein each of Rand Ris independently hydrogen or substituted or unsubstituted alkyl.49. (canceled)50. The pharmaceutical composition of claim 41 , wherein each of Rand Ris independently hydrogen claim 41 , —CF claim 41 , or —CH.51. (canceled)52. The pharmaceutical composition of claim 41 , wherein Rand R claim 41 , together with the carbon atom to which they are attached form an oxo group.5354-. (canceled)55. The pharmaceutical composition of claim 41 , wherein Rand Rare hydrogen.56. The pharmaceutical composition of claim 41 , wherein Ris substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl and Ris hydrogen.57. The pharmaceutical composition of claim 41 , wherein Ris substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl and Ris hydrogen.5859-. (canceled)6193-. (canceled)95. The pharmaceutical composition of claim 94 , wherein Ris substituted or unsubstituted C-Calkyl.96. The pharmaceutical composition of claim 94 , wherein Ris —CH claim 94 , —CF claim 94 , —CHCH claim 94 , or —CHOR claim 94 , wherein Ris substituted or unsubstituted C-Calkyl.97. The pharmaceutical composition of claim 94 , wherein each of Rand Ris independently hydrogen or substituted or unsubstituted alkyl.98. The pharmaceutical composition of claim 94 , wherein each ...

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Номер записи: 36
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: 37
08-01-2015 дата публикации

Protected Linker Compounds

Номер: US20150011746A1
Автор: Stefan Berger, Stefan Pitsch
Принадлежит: RESEACHEM GmbH

The invention features protected linker compounds which comprise at one terminus a protected amino group and at another other terminus a phosphorous activating group, such as a phosphoramidite group. These protected linker compounds are introduced chemically at the 5′-end of oligonucleotides for the purpose of preparing 5′-amino modified oligonucleotides. After deprotection, the thereby introduced amino group then allows further modification (e.g. attachment of dyes) or immobilization (on surfaces or beads) of the oligonucleotide. Specifically, the presented amino protecting group is designed to provide such protected linker compounds in a solid form, which facilitates efficient purification by precipitation or crystallization and aliquoting for distribution and storage.

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Номер записи: 38
21-01-2016 дата публикации

FATTY ACID CONJUGATES OF STATIN AND FXR AGONISTS: COMPOSITIONS AND METHODS OF USE

Номер: US20160015819A1
Автор: Jirousek Michael R., Milne Jill C., Ting Amal, Vu Chi B., Wensley Allison
Принадлежит: CATABASIS PHARMACEUTICALS, INC.

The invention relates to fatty acid statin conjugates and fatty acid FXR agonist conjugates; compositions comprising an effective amount of a fatty acid statin conjugate or a fatty acid FXR agonist conjugate; and methods for treating or preventing a metabolic disease comprising the administration of an effective amount of a fatty acid statin conjugate or a fatty acid FXR agonist conjugate.

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Номер записи: 39
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: 40
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: 41
16-01-2020 дата публикации

19-NOR C3, 3-DISUBSTITUTED C21-C-BOUND HETEROARYL STEROIDS AND METHODS OF USE THEREOF

Номер: US20200016178A1
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 steroids of Formula (I): 127-. (canceled)30. The method of claim 28 , wherein Ris —CH claim 28 , —CHCH claim 28 , —CHF claim 28 , —CHF claim 28 , —CF claim 28 , —CHOCH claim 28 , or substituted or unsubstituted cyclopropyl.31. The method of claim 30 , wherein Ris —CH.32. The method of claim 28 , wherein Ris hydrogen.33. The method of claim 28 , wherein Rand Rare both hydrogen.34. The method of claim 28 , wherein represents a single bond claim 28 , and both of Rand Rare hydrogen.35. The method of claim 28 , wherein represents a single bond claim 28 , and both of Rand Rare fluoro.36. The method of claim 28 , wherein at least one of R claim 28 , R claim 28 , R claim 28 , R claim 28 , and Ris substituted or unsubstituted Calkyl claim 28 , —COR claim 28 , —C(═O)R claim 28 , —CN claim 28 , —NO claim 28 , or halogen claim 28 , wherein Ris substituted or unsubstituted Calkyl.37. The method of claim 36 , wherein at least one of R claim 36 , R claim 36 , R claim 36 , R claim 36 , and Ris substituted or unsubstituted —CH.38. The method of claim 28 , wherein R claim 28 , R claim 28 , R claim 28 , R claim 28 , and Rare hydrogen.42. The method of claim 28 , wherein the human subject has a CNS-related disorder.43. The method of claim 42 , wherein the CNS-related disorder is a sleep disorder claim 42 , a mood disorder claim 42 , a schizophrenia spectrum disorder claim 42 , a convulsive disorder claim 42 , a disorder of memory and/or cognition claim 42 , a movement disorder claim 42 , a personality disorder claim 42 , autism spectrum disorder claim 42 , pain claim 42 , traumatic brain injury claim 42 , a vascular disease claim 42 , a substance abuse disorder and/or withdrawal syndrome claim 42 , or tinnitus.44. The method of claim 43 , wherein the mood disorder is depression.45. The method of claim 44 , wherein the depression is postnatal depression.46. The method of claim 43 , wherein the sleep disorder is insomnia.47. The method of ...

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Номер записи: 42
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: 43
21-01-2021 дата публикации

INHIBITORS OF GLUCOCORTICOID RECEPTOR

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

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

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Номер записи: 44
21-01-2021 дата публикации

INHIBITORS OF GLUCOCORTICOID RECEPTOR

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

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

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Номер записи: 45
16-01-2020 дата публикации

METHOD FOR MEASURING AN ABILITY OF HIGH-DENSITY LIPOPROTEIN TO UPTAKE CHOLESTEROL

Номер: US20200018755A1
Автор: IINO Takuya, MIWA Keiko, MURAKAMI Katsuhiro, PENG Xiaoling, Saiki Naoya
Принадлежит: SYSMEX CORPORATION

Provided is a monoclonal antibody or antigen-binding fragment thereof which binds to a peptide consisting of 51st to 110th amino acid sequence or a peptide consisting of 201st to 267th amino acid sequence of an amino acid sequence of SEQ ID NO: 1, and is capable of binding to high-density lipoproteins of (1) to (3) below; 2. The method according to claim 1 , wherein the monoclonal antibody or antigen-binding fragment thereof binds to a peptide consisting of 91st to 110th amino acid sequence of the amino acid sequence of SEQ ID NO: 1 and does not bind to a range of 101st to 160th of the amino acid sequence of SEQ ID NO: 1.3. The method according to claim 1 , wherein the monoclonal antibody or antigen-binding fragment thereof binds to non-denatured high-density lipoprotein present in a sample under non-denatured conditions.4. The method according to claim 1 , wherein the monoclonal antibody or antigen-binding fragment thereof comprises HCDR1 claim 1 , HCDR2 claim 1 , HCDR3 claim 1 , LCDR1 claim 1 , LCDR2 and LCDR3 comprising amino acid sequences that are respectively same as amino acid sequences of HCDR1 claim 1 , HCDR2 claim 1 , HCDR3 claim 1 , LCDR1 claim 1 , LCDR2 and LCDR3 of monoclonal antibody produced from a hybridoma of accession No. NITE BP-02442 or accession No. NITE BP-02443 or its progeny claim 1 , and wherein HCDR represents a heavy chain complementarity determining region and LCDR represents a light chain complementarity determining region.5. The method according to claim 1 , wherein the monoclonal antibody contains a heavy chain variable region and a light chain variable region consisting of amino acid sequences that are respectively same as amino acid sequences of a heavy chain variable region and a light chain variable region of monoclonal antibodies produced from a hybridoma of accession No. NITE BP-02442 or accession No. NITE BP-02443 or its progeny.6. The method according to claim 1 , wherein the monoclonal antibody contains an amino acid sequence ...

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Номер записи: 46
28-01-2016 дата публикации

ESTRA-1,3,5(10),16-TETRAENE-3-CARBOXAMIDES FOR INHIBITION OF 17.BETA.-HYDROXYSTEROID DEHYDROGENASE (AKR1 C3)

Номер: US20160024142A1
Автор: Barak Naomi, Bothe Ulrich, Busemann Matthias, Fischer Oliver Martin, Marquardt Tobias, Rotgeri Andrea
Принадлежит: BAYER PHARMA AKTIENGESELLSCHAFT

The invention relates to AKR1C3 inhibitors of formula (I) and to processes for preparation thereof, to the use thereof for treatment and/or prophylaxis of diseases and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of bleeding disorders and endometriosis. 2. The compound of claim 1 ,whereinX is carbon substituted by hydrogen,{'sup': '2', 'Y is carbon or nitrogen, where the carbon may be substituted by R,'}{'sup': '2', 'sub': '3', 'Ris hydrogen, fluorine, chlorine, nitrile, methoxy, ethoxy, trifluoromethoxy, methyl, ethyl, trifluoromethyl, —(C═O)CH,'}{'sup': '3', 'Ris hydrogen or fluorine,'}{'sup': '4', 'Ris hydrogen, methyl, ethyl, isopropyl, propyl, butyl, cyclopropyl or 2,2,2-trifluoroethyl,'}{'sup': '5', 'claim-text': 'or', 'Ris hydrogen, methyl, ethyl, propyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2-fluoroethyl, 2-sulphamoylethyl, 3-sulphamoylpropyl, (1S,2R)-2-hydroxycyclopentyl, 3-hydroxy-2,2-dimethylpropyl, (1S,2S)-2-hydroxycyclopentyl, (3R)-4-hydroxy-3-methylbutyl, 1-(hydroxymethyl)cyclopentyl, (2S)-1-hydroxybutan-2-yl, (2R)-1-hydroxy-3-methylbutan-2-yl, 3-hydroxybutan-2-yl, 2-hydroxyethyl, 3,3,3-trifluoro-2-hydroxypropyl, 2-(1H-tetrazol-5-yl)ethyl, 1H-tetrazol-5-ylmethyl, 2-(methylsulphamoyl)ethyl, 3-amino-3-oxopropyl, 3-(methylamino)-3-oxopropyl, 2-methyl-2-[(methylsulphonyl)amino]propyl, (2S)-2,3-dihydroxypropyl, 3-hydroxypropyl, 4-hydroxybutyl, (2RS)-2,3-dihydroxypropyl, (2R)-2,3-dihydroxypropyl, 2,3-dihydroxybutyl, 2-(methylsulphinyl)ethyl, 3-(methylsulphinyl)propyl, 2-(methylsulphonyl)ethyl, 3-(methylsulphonyl)propyl, 2-(S-methylsulphonimidoyl)ethyl, (2R)-2-hydroxypropyl, (2S)-1-hydroxypropan-2-yl, 2-methoxyethyl, 3-methoxypropyl, 2-(isopropylsulphonyl)ethyl, (3-methyloxetan-3-yl)methyl, (2S)-2-hydroxypropyl, 2-(2-hydroxyethoxy)ethyl,'}{'sup': 4', '5, 'Rand Rtogether with the directly joining nitrogen atom are piperidinyl, pyrrolidinyl, morpholinyl, N-methylpiperazinyl, 1- ...

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Номер записи: 47
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: 48
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: 49
10-02-2022 дата публикации

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

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

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

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Номер записи: 50
28-01-2021 дата публикации

INHIBITORS OF GLUCOCORTICOID RECEPTOR

Номер: US20210023095A1
Автор: BALBAS Minna Delarae, Du Xiaohui, EKSTEROWICZ John, FANTIN Valeria R., McGee Lawrence R., MEDINA Julio C., REW Yosup, SUN Daqing, YAN Xuelei, ZHOU Haiying, ZHU Liusheng
Принадлежит:

The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism. 2. The compound of or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or prodrug thereof claim 1 , wherein{'sup': 1', '3', '6', '3', '3', '4', '3', '6', '3', '3', '4', '3', '3', '4', '3', '4', '6, 'sub': 2', '2', '2', '2', '2', '2, 'Ris —NRS(O)R, —NRS(O)NRR, -alkyNRS(O)R, -alkyNRS(O)NRR, —NRaralkyl, —C(O)NRR, —S(O)NRR, or —S(O)R;'}{'sup': 3', '4', '10', '6, 'sub': 2', '2, 'Rand Rare each independently —H, optionally substituted alkyl, fluoroalkyl, optionally substituted carbocyclyl, optionally substituted carbocyclylalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, —C(O)N(R), or —S(O)R;'}{'sup': 3', '4, 'or Rand Rattached to the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted 3-, 4-, 5-, or 6-membered heterocycle;'}{'sup': '5', 'Ris optionally substituted alkyl, fluoroalkyl, optionally substituted carbocyclyl, or optionally substituted heterocyclyl;'}{'sup': '6', 'Ris optionally substituted alkyl, fluoroalkyl, optionally substituted carbocyclyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, or optionally substituted heteroaryl;'}{'sup': 7', '8', '5', '3', '4', '3', '4, 'Rand Rare each independently —H, optionally substituted alkyl, fluoroalkyl, halo, —OR, —NRR, —C(O)NRR, —CN, optionally substituted carbocyclyl, or optionally substituted carbocyclylalkyl;'}{'sup': 7', '8', '6, 'sub': '2', 'or Rand Rare taken ...

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Номер записи: 51
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: 52
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: 53
23-01-2020 дата публикации

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Номер: US20200024303A1
Автор: Qian Xiangping
Принадлежит:

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

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Номер записи: 54
04-02-2016 дата публикации

INHIBITORS OF CYP17A1

Номер: US20160031929A1
Автор: Aube Jeffrey, Fehl Charlie, Scott Emily E.
Принадлежит:

Compounds according to formula I or II are provided. Such compounds are useful in treating cancers, such as leukemia, colon cancer, breast cancer, or prostate cancer by beneficially inhibiting CYP17A1. Pharmaceutical compositions and methods including the compounds are also provided. 2. The compound of claim 1 , wherein Zand Zare each N.4. The compound of claim 3 , wherein Z claim 3 , Z claim 3 , and Zare each independently N.5. The compound of claim 3 , wherein{'sup': '1', 'Yis O or a bond;'}{'sup': '2', 'Yis a bond; and'}{'sup': 1', '2', '16', '17', '18, 'Xand Xare each independently C(O)NRR, C(O)OR, nitro, or cyano.'}6. The compound of claim 3 , wherein Rand Rare each independently H claim 3 , OH claim 3 , NRR claim 3 , or trifluoromethoxy; or Rand Rtogether are ═O or ═N—OH.8. The compound of claim 7 , wherein the compound of formula II is a compound according to formula VI.10. A pharmaceutical composition claim 2 , comprising an effective amount of the compound of and a pharmaceutically acceptable carrier.11. A method comprising inhibiting CYP17A1 by administration of the compound of .12. The method of claim 11 , comprising inhibiting CYP17A1 by administration of a pharmaceutical composition wherein the pharmaceutical composition comprises an effective amount of the compound and a pharmaceutically acceptable carrier.13. The method of claim 11 , wherein administration of the compound selectively inhibits CYP17A1.14. The method of claim 13 , wherein administration of the compound selectively inhibits CYP17A1 over CYP21A2.16. A method of treating a biological condition comprising administering to a subject suffering from a biological condition selected from leukemia claim 2 , colon cancer claim 2 , breast cancer claim 2 , or prostate cancer claim 2 , an effective amount of the compound of .17. The method of claim 16 , wherein the method comprises administering a pharmaceutical composition claim 16 , wherein the pharmaceutical composition comprises the effective ...

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Номер записи: 55
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: 56
08-02-2018 дата публикации

Novel c-17-heteroaryl steroidal cyp17 inhibitors/antiandrogens, in vitro biological activities, pharmacokinetics and antitumor activity

Номер: US20180036320A1
Автор: Angela Brodie, Vincent C.O. Njar
Принадлежит: University of Maryland at 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.

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Номер записи: 57
11-02-2016 дата публикации

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS

Номер: US20160039865A1
Автор: Qian Xiangping
Принадлежит: NeuPharma, Inc.

Chemical entities that are novel compounds, pharmaceutical compositions and methods of treatment of cancer are described. 2. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , Rand Rare independently chosen from hydrogen claim 1 , hydroxy claim 1 , optionally substituted alkyl claim 1 , optionally substituted alkoxy claim 1 , optionally substituted aminocarbonyloxy claim 1 , optionally substituted acyloxy claim 1 , optionally substituted alkoxycarbonyloxy claim 1 , and optionally substituted amino.3. The compound of claim 2 , wherein R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , R claim 2 , Rand Rare independently chosen from hydrogen claim 2 , hydroxy claim 2 , and optionally substituted alkyl.4. (canceled)5. The compound of claim 1 , wherein Ris hydroxy.6. The compound of claim 1 , wherein Rand Rare joined together with any intervening atoms to form an optionally substituted 3- to 8-membered heterocycloalkyl ring.7. (canceled)8. The compound of claim 1 , wherein Ris chosen from hydrogen claim 1 , hydroxy claim 1 , optionally substituted alkoxy claim 1 , optionally substituted aminocarbonyloxy claim 1 , optionally substituted acyloxy claim 1 , optionally substituted alkoxycarbonyloxy claim 1 , and optionally substituted amino.9. (canceled)10. The compound of claim 1 , wherein Ris chosen from hydrogen and —OCOCH.11. The compound of claim 1 , wherein Rand Ware independently chosen from hydrogen and optionally substituted alkyl.12. (canceled)13. The compound of claim 1 , wherein Ris chosen from hydrogen claim 1 , methyl claim 1 , and hydroxymethyl.14. The compound of claim 1 , wherein Y is chosen from O claim 1 , NH and NCH.15. (canceled)16. The compound of claim 1 , wherein Ris chosen from cyano claim 1 , halo claim 1 , hydroxy claim 1 , carboxy claim 1 , sufonyl claim 1 , optionally substituted alkoxy claim 1 , optionally substituted alkoxycarbonyl ...

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Номер записи: 58
07-02-2019 дата публикации

STEROIDAL COMPOUND, COMPOSITION CONTAINING THE SAME AND USE THEREOF

Номер: US20190040098A1
Автор: Ren Xingye, Wang Yihan
Принадлежит: Shenzhen TargetRx, Inc.

Disclosed are a steroidal compound as shown in formula (I) and a drug composition containing the same, or a crystal form, a pharmaceutically acceptable salt, a hydrate or solvate, a stereoisomer, a prodrug, a metabolite or an isotopic variant thereof. The compound can be used as a CYP17 enzyme inhibitor, and has better pharmacokinetic parameters, which can improve drug concentration of the compound in an animal, thereby improving the efficacy and safety of the drug, and in turn the compound may be applied in the preparation of the drug for treating CYP17 enzyme-related diseases (such as prostate cancer). 114-. (canceled)16. The compound according to claim 15 , wherein R claim 15 , R claim 15 , R claim 15 , and Rare each independently deuterium or hydrogen.17. The compound according to claim 15 , wherein at least one of R claim 15 , R claim 15 , R claim 15 , and Ris deuterium.18. The compound according to claim 15 , wherein R claim 15 , R claim 15 , R claim 15 , R claim 15 , R claim 15 , R claim 15 , R claim 15 , R claim 15 , R claim 15 , Rand Rare each independently deuterium or hydrogen.19. The compound according to claim 15 , wherein Ris deuterium.20. The compound according to claim 19 , wherein Y is an acetyl group substituted with three deuteriums.21. The compound according to claim 15 , wherein Xand Xare independently selected from a methyl or an ethyl group claim 15 , which are substituted with one or more deuteriums.22. The compound according to claim 15 , wherein Y is selected from hydrogen claim 15 , deuterium claim 15 , and an acetyl group substituted with one or more deuteriums.23. The compound according to claim 15 , wherein Xand Xare a methyl group substituted with three deuteriums.24. The compound according to claim 15 , wherein Y is an acetyl group substituted with three deuteriums.28. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00015', 'claim 15'}, 'the compound according to or a pharmaceutically acceptable salt thereof; and ...

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Номер записи: 59
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: 60
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: 61
19-02-2015 дата публикации

NOVEL STEROIDAL CYP17 INHIBITORS/ANTIANDROGENS

Номер: US20150051179A1
Автор: Casebier David
Принадлежит:

Steroidal C-17 nitrogen-containing heterocycles of Formula I: 2. The compound of claim 1 , wherein each position of the ABC ring structure is independently optionally substituted with one or more of alkyl claim 1 , halogenated alkyl claim 1 , alkenyl claim 1 , halogenated alkenyl claim 1 , halogen claim 1 , amino claim 1 , aminoalkylene claim 1 , hydroxyimino claim 1 , and hydroxy.3. The compound of claim 2 , wherein X is optionally substituted with one or more of halogen claim 2 , amino claim 2 , aminoalkylene claim 2 , hydroxy claim 2 , —SH claim 2 , —S-alkyl claim 2 , alkyl and halogenated C-C-alkyl.4. The compound of claim 3 , wherein Y is OH.6. The compound of claim 3 , wherein Y is a physiological precursor of a 3-hydroxyl group.7. The compound of claim 6 , wherein Y is O-acetyl claim 6 , O-propionyl claim 6 , O-betaine claim 6 , O-carnitine claim 6 , an amino acid group claim 6 , or a peptidyl group.10. The compound of claim 9 , wherein the EF group is 1-azaazulene claim 9 , 2-alkylindazole claim 9 , pyrazolo-[1 claim 9 ,5-a]-pyridine claim 9 , imidazo-[1 claim 9 ,2-a]-pyridine claim 9 , pyrrolo-[2 claim 9 ,3-a]-pyrimidine claim 9 , pyrrolo-[2 claim 9 ,3-c]-pyrimidine claim 9 , imidazo-[1 claim 9 ,2-c]-pyrimidine claim 9 , imidazo-[1 claim 9 ,2-a]-pyrimidines4-alkylpyrazolo-[1 claim 9 ,5-a]imidazole claim 9 , 2 claim 9 ,1-benzoxazoles claim 9 , 2 claim 9 ,1-benzthiazole claim 9 , imidazo[2 claim 9 ,1-b][1 claim 9 ,3]oxazole claim 9 , imidazo[2 claim 9 ,1-b][1 claim 9 ,3]thiazole claim 9 , imidazo-[2 claim 9 ,1-b][1 claim 9 ,2]isoxazole claim 9 , or cyclopenta[b]pyrrole claim 9 , any of which is optionally substituted with halogen claim 9 , amino claim 9 , aminoalkylene claim 9 , hydroxy claim 9 , —SH claim 9 , —S-alkyl claim 9 , alkyl and halogenated C-C-alkyl.11. A pharmaceutical composition comprising a therapeutically-effective amount of one or more compounds of and one or more pharmaceutically-acceptable excipients claim 1 , bulking agents claim 1 , ...

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Номер записи: 62
25-02-2016 дата публикации

BIMODAL LIGANDS WITH MACROCYCLIC AND ACYCLIC BINDING MOIETIES, COMPLEXES AND COMPOSITIONS THEREOF, AND METHODS OF USING

Номер: US20160052894A1
Автор: Chong Hyun-Soon
Принадлежит:

Substituted 1,4,7-triazacyclononane-N,N′,N″-triacetic acid and 1,4,7,10-tetraazacycicododecane-N,N′,N″,N′″-tetraacetic acid compounds with a pendant amino or hydroxyl group, metal complexes thereof, compositions thereof, and methods of making and use in diagnostic imaging and treatment of cellular disorders. 2. A complex comprising the compound of and a metal ion claim 1 , a radioactive isotope of the metal ion claim 1 , or a radioactive isotope of carbon claim 1 , nitrogen claim 1 , iodine claim 1 , fluorine claim 1 , oxygen claim 1 , or helium.3. A conjugate comprising the complex of and a targeting moiety claim 2 , a fluorescence moiety claim 2 , or a nanoparticle.4. The complex of claim 2 , wherein the metal ion is selected from the group consisting of Ac claim 2 , Al claim 2 , Bi claim 2 , Pb claim 2 , Y claim 2 , Mn claim 2 , Cr claim 2 , Fe claim 2 , Co claim 2 , Zn claim 2 , Ni claim 2 , Tc claim 2 , Gd claim 2 , In claim 2 , Ga claim 2 , Cu claim 2 , Re claim 2 , Sm claim 2 , Pm claim 2 , Ho claim 2 , Zr claim 2 , Ra claim 2 , Sr claim 2 , Cs claim 2 , Th claim 2 , Am claim 2 , U claim 2 , an alkali metal claim 2 , an alkaline earth metal claim 2 , a transition metal claim 2 , a lanthanide claim 2 , and an actinide.5. A conjugate comprising the complex of and a targeting moiety claim 4 , a fluorescence moiety claim 4 , or a nanoparticle.6. A conjugate comprising the compound of and a targeting moiety claim 1 , a fluorescence moiety claim 1 , a ligand claim 1 , or a nanoparticle.7. The conjugate according to claim 6 , comprising the targeting moiety claim 6 , wherein the targeting moiety comprises a biomolecule selected from a hormone claim 6 , a bile acid claim 6 , an amino acid claim 6 , a peptide claim 6 , a peptidomimetic claim 6 , a protein claim 6 , a deoxyribonucleic acid (DNA) claim 6 , a ribonucleic acid (RNA) claim 6 , a lipid claim 6 , an albumin claim 6 , a receptor molecule claim 6 , a receptor binding molecule claim 6 , a hapten claim 6 , a ...

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Номер записи: 63
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: 64
25-02-2016 дата публикации

Progesterone analogs and uses related thereto

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

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

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Номер записи: 65
25-02-2016 дата публикации

PROCESS FOR THE PURIFICATION OF ABIRATERONE ACETATE

Номер: US20160052958A1
Автор: Alpegiani Marco, Cristiano Tania, Cucchetti Eugenio
Принадлежит:

The invention relates to a process for the purification of crude abiraterone acetate by treatment with polymer resins in aqueous solvent. The purified product is recovered by simple concentration and filtration. 1. A process for the purification of abiraterone acetate starting from crude products , which comprisespreparing a solution of the crude product, adsorbing it on a polymer resin andeluting abiraterone acetate from the resin using a mixture of water/aqueous buffer and a polar solvent as eluent.2. A process according to wherein the polymer resin is a resin suitable for hydrophobic interaction chromatography.3. A process according to wherein the resins are selected from resins with an acrylic or styrene-divinyl benzene matrix free from functional groups.4. A process according to wherein the resin has a particle size distribution ranging from 50 to 600 μm claim 2 , preferably from 60 to 200 μm.5. A process according to wherein the crude abiraterone acetate is dissolved in methanol claim 1 , ethanol claim 1 , isopropanol claim 1 , n-propanol claim 1 , acetonitrile claim 1 , dimethylsulphoxide claim 1 , tetrahydrofuran or acetone or in a mixture of said solvents with water.6. A process according to wherein the eluent used for eluting the resin is a mixture of water or aqueous buffering agents with one or more solvents selected from methanol claim 1 , isopropanol claim 1 , ethanol claim 1 , acetonitrile claim 1 , acetone or a mixture thereof.7. A process according to wherein the isocratic or gradient elution is carried out with mixtures with increasing solvent concentrations.8. (canceled) The invention relates to a process for the purification of crude abiraterone acetate by treatment with polymer resins in aqueous solvent. The purified product is recovered by simple concentration and filtration.Abiraterone acetate, the chemical name of which is (3β)-17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate, is the prodrug of the active metabolite abiraterone, a selective ...

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Номер записи: 66
25-02-2016 дата публикации

Radiolabeled cationic steroid antimicrobials and diagnostic methods

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

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

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Номер записи: 67
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: 68
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: 69
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: 70
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: 71
22-02-2018 дата публикации

Conjugate of Estradiol and Applications Thereof

Номер: US20180052180A1
Автор: Iven Jose, Rahul VERMA, Shubhada Ve Chiplunkar, Vinay Jha Pillat
Принадлежит: CHRIST UNIVERSITY

The present invention relates to conjugate of 17-β estradiol with an analogue of indocyanine green dye for the detection of cancers. The invention also provides a method of preparation of the conjugate and method of detection of cancer cells.

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Номер записи: 72
10-03-2022 дата публикации

FLUORINATED BILE ACIDS

Номер: US20220073557A1
Автор: Bandmann Oliver, Hastings Christopher, Linclau Bruno Jan Pol, Mortiboys Heather, Packer Gemma, Watts Joseph, Weymouth-Wilson Alexander Charles
Принадлежит:

Compounds of general formula (1): 2. (canceled)4. A compound according to which is a compound of general formula (IA).5. A compound according to which is a compound of general formula (IB).6. A compound according to claim 1 , wherein both Rand Rare F.7. (canceled)8. A compound according to claim 1 , wherein Y is —CHCH—.9. (canceled)10. A compound according to claim 1 , wherein{'sup': ['12', '16', '10', '11'], '#text': 'Ris selected from H methyl, and ethyl, and is optionally substituted with Ror N(R)(R); or'}{'sup': ['3', '12', '13', '12', '13', '12', '15', '16', '12', '12', '15', '16', '12'], 'sub': ['2', '2', 'n', '2', 'n'], '#text': 'Ris selected from C(O)NRS(O)R, NHC(O)NRS(O)R, C(O)NR[CH(R)]R, and C(O)NRC(O)CHNR[CH(R)]R; and Ris H or methyl; and/or'}{'sup': ['13', '16', '13', '16'], '#text': 'Ris a 5- or 6-membered carbocyclic ring or heterocyclic ring optionally substituted with Ror ═O; or Ris phenyl optionally substituted with R; or'}{'sup': ['3', '12', '13', '12', '13', '12', '13', '16'], 'sub': '2', '#text': 'Ris selected from C(O)NRRand S(O)NRRand Rand Rtogether with the nitrogen atom to which they are attached form a 5- or 6-membered heterocyclic ring optionally substituted with one or more substituents selected from Rand ═O and optionally comprising one or more further heteroatoms selected from O, N and S; and/or'}{'sup': '16', 'sub': ['2', '2', '1-6', '2'], '#text': 'Ris selected from C(O)OH, S(O)OH, S(O)(Calkyl), and OS(O)OH; or'}{'sup': '16', 'sub': ['2', '2', '2'], '#text': 'Ris selected from C(O)OH, S(O)OH, OS(O)OH and P(O)(OH), and the compound is in the form of a pharmaceutically acceptable salt.'}1112-. (canceled)13. A compound according to wherein Ris C(O)NR[CH(R)]Ror a pharmaceutically acceptable salt thereof claim 1 ,{'sup': ['12', '16'], '#text': 'wherein Ris H, methyl or methyl substituted with R;'}{'sup': '16', 'sub': ['2', '2', '1-6', '2'], '#text': 'where Ris C(O)OH, S(O)OH, S(O)(Calkyl) or OS(O)OH.'}1415-. (canceled)16. A compound ...

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Номер записи: 73
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: 74
04-03-2021 дата публикации

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Номер: US20210061848A1
Автор: Harrison Boyd L., Herr Robert Jason, Kargbo Robert Borbo, Martinez Botella Gabriel, Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

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. 190-. (canceled)92. The compound of claim 91 , wherein each is a single bond and Ris hydrogen.93. The compound of claim 92 , wherein Ris methyl claim 92 , ethyl claim 92 , or isopropyl claim 92 , each of which is unsubstituted.94. The compound of claim 93 , wherein Ris unsubstituted methyl or unsubstituted ethyl.95. The compound of claim 91 , wherein Ris unsubstituted Calkyl.96. The compound of claim 91 , wherein Ris methyl or —CF.99. The compound of claim 91 , wherein ring A is an optionally substituted 5-membered or 6-membered monocyclic heteroaryl claim 91 , wherein the heteroaryl of ring A comprises 2 claim 91 , 3 claim 91 , or 4 nitrogen atoms and wherein the heteroaryl of ring A is linked through a nitrogen atom.103. The compound of claim 100 , wherein n is 1 or 2 claim 100 , and each Ris independently cyano claim 100 , halo claim 100 , Calkyl claim 100 , Calkoxy claim 100 , —C(O)R claim 100 , or —S(O)R.104. The compound of claim 103 , wherein n is 1 claim 103 , and Ris —C(O)CH claim 103 , —S(O)CH claim 103 , cyano claim 103 , halo claim 103 , or Calkyl.108. The compound of claim 105 , wherein n is 1 or 2 claim 105 , and each Ris independently cyano claim 105 , halo claim 105 , Calkyl claim 105 , Calkoxy claim 105 , —C(O)R claim 105 , or —S(O)R.109. The compound of claim 108 , wherein n is 1 claim 108 , and Ris —C(O)CH claim 108 , —S(O)CH claim 108 , cyano claim 108 , halo claim 108 , or Calkyl.113. The compound of claim 110 , wherein n is 1 or 2 claim 110 , and each Ris independently cyano claim 110 , halo claim 110 , ...

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Номер записи: 75
04-03-2021 дата публикации

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Номер: US20210061849A1
Автор: Beresis Richard Thomas, BOTELLA Gabriel Martinez, Harrison Boyd L., Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I): 134-. (canceled)36. The method of claim 35 , wherein step (a) is performed at a temperature of about 60° C.38. The method of any one of - claim 35 , wherein the solvent of step (a) is THF.41. The method of claim 39 , wherein the solvent system comprises CHClsaturated with water.42. The method of or claim 39 , wherein the reaction of step (d) is performed under stirring conditions.44. The method of claim 43 , wherein the solvent of step (e) is DMSO.45. The method of or claim 43 , wherein step (e) is performed under stirring conditions at room temperature.47. The method of claim 46 , wherein the HCl of step (f) is reacted at a concentration of 2M.48. The method of or claim 46 , wherein step (f) is performed under stirring conditions for about 12 hours.49. The method of any one of - claim 46 , wherein step (f) is performed at room temperature.51. The method of claim 50 , wherein step (g) is performed in the presence of NaOH.52. The method of claim 51 , wherein the NaOH is provided as about 10% aqueous NaOH.53. The method of or claim 51 , wherein step (g) is performed in the presence of HO.54. The method of claim 53 , wherein the HOis provided as an about 30% aqueous solution of HO.56. The method of claim 55 , wherein step (a) is performed at a temperature of about 60° C.; and the solvent of step (a) is THF. This application is a continuation of U.S. Ser. No. 15/314,565 filed Nov. 29, 2016, which is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/CN2015/080216, filed May 29, 2015, published as International Publication No. WO2015/180679 on Dec. 3, 2015, which claims priority to international application No. PCT/CN2014/078820, filed May 29, 2014, the entire contents of each of which are incorporated herein by reference in their entirety.Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is ...

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Номер записи: 76
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: 77
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: 78
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: 79
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: 80
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: 81
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: 82
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: 83
24-03-2022 дата публикации

TETRAZOLONE SUBSTITUTED STEROIDS AND USE THEREOF

Номер: US20220089636A1
Автор: Li Hui, SONG Yuntao
Принадлежит:

The present disclosure relates to compounds of formula (AI), (I), (AII), and (II), or a pharmaceutically acceptable salt, solvate, stereoisomer, or tautomer thereof, a pharmaceutical composition comprising a compound of formula (AI), (I), (AII), and (II), and use thereof, wherein R2, R3, R4, R5, R6, R7, R10, R11a, R11b, R12, R16, R19a, R19b, and R20 are described herein. Such compounds are envisioned useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, movement disorders, convulsive disorders, schizophrenin spectrum disorders, disorders of memory and/or cognition, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, or tinnitus etc. 3. The compound of or , wherein the substituents are selected from fluoro , chloro , bromo , cyano , nitro , hydroxy , methoxy , ethoxy , propoxy , isopropoxy , methyl , ethyl , propyl , isopropyl , butyl , i-butyl , s-butyl , t-butyl , —CHCN , —CHCHCN , —CHF , —CHF , —CF , —CHOCH , —CHSCH , -methylhydroxy , morpholine , pyrrolidine , piperidine , piperazine , phenyl , benzyl , pyridine , pyrimidine , oxazole , pyrazole , cyclopropyl , cyclobutyl , cyclopentyl , cyclohexyl , —OCHF , —OCHF , —OCF , -ethylmethoxy , -methylcyclopropyl , —OR , —C(═O)R , —C(═O)OR , —OC(═O)R , —OC(═O)OR , —C(═O)NRR , —NRR , —NRC(═O)R , —OC(═O)NRR , —NRC(═O)OR , —NRC(═O)NRR , —SR , —S(═O)R , —S(═O)R , —S(═O)OR , —OS(═O)R , —S(═O)NRR , or —NRS(═O)R , wherein Ris independently hydrogen , methyl , ethyl , propyl , isopropyl , cyclopropyl , cyclobutyl , cyclopentyl , cyclohexyl , —CHF , —CHF , —CF , phenyl , benzyl , pyridine , pyrimidine , -ethylmethoxy , or -methylcyclopropyl , or two Rgroups can be taken together with the atoms to which they are attached to , to form a heterocylyl or heteroaryl ring.4. The compound of any one of - , wherein Ris hydrogen , —OH , —OCH , —OCHCH , — ...

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Номер записи: 84
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: 85
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: 86
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: 87
24-03-2016 дата публикации

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

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

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

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Номер записи: 88
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: 89
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: 90
23-03-2017 дата публикации

THERAPEUTICALLY ACTIVE 17-NITROGEN SUBSTITUTED ESTRATREINTHIAZOLE DERIVATIVES AS INHIBITORS OF 17.BETA-HYDROXYSTEROID DEHYDROGENASE

Номер: US20170081357A1
Автор: ELORANTA Maire, 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 to R7 are as defined in the claims. The invention further relates to their use as inhibitors of 17β-HSD and in treatment or prevention of steroid hormone de-pendent 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 afore-mentioned compounds or pharmaceutically acceptable salts thereof. 3. A compound as claimed in claim 2 , wherein R7′ is selected from the group consisting of H claim 2 , methyl claim 2 , ethyl claim 2 , allyl claim 2 , and carboxymethylenyl.4. A compound as claimed in claim 1 , wherein R5 and R6 are both H.8. A compound as claimed in claim 1 , wherein{'sub': 1-6', '1-3', '1-3', '2', '3', '2', '2', 'n', '2, '(i-a) R2 and R4 are each independently selected from the group consisting of H, halogen, C-alkyl, C-haloalkyl, C-perhaloalkyl, CN, NO, N, N(R′), (CH)(R′), C(═N—OH)R″, and C(═N—OMe)R″.'}9. A compound as claimed in claim 1 , wherein{'sub': 1-6', '1-3', '2', '3, 'R3 is selected from a group consisting of H, C-alkyl, C-perhaloalkyl, N(R′), N, and OR′.'}10. A compound as claimed in claim 9 , wherein R3 is H or OR′.11. A compound as claimed in claim 1 , wherein R2 and R3 or R3 and R4 claim 1 , together with the ring carbon atoms to which they are attached claim 1 , form an oxazolone or 1 claim 1 ,3-oxazole ring claim 1 , optionally substituted with methyl.12. A compound as claimed in claim 11 , wherein R4 or R2 claim 11 , respectively claim 11 , is selected from the group consisting of H claim 11 , F claim 11 , Cl claim 11 , Br claim 11 , and I.13. A compound as claimed in claim 1 , wherein{'sub': 1-6', '1-3', '1-3', '2', '3', ...

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Номер записи: 91
31-03-2022 дата публикации

COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS

Номер: US20220098231A1
Автор: Robichaud Albert Jean, Salituro Francesco G.
Принадлежит:

Provided herein is a compound of Formula (I) 2. The compound of claim 1 , wherein Ris C-Calkyl substituted with 0-7 independent occurrences of deuterium or X—OX claim 1 , wherein Xis C-Calkylene substituted with 0-7 independent occurrences of deuterium and Xis C-Calkylene substituted with 0-7 independent occurrences of deuterium.3. The compound of or claim 1 , wherein if Ris —CH claim 1 , then at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris deuterium claim 1 , or if all of 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 , then Ris a methyl group substituted with 1-3 independent occurrences of deuterium.4. The compound of claim 1 , wherein Ris selected from the group consisting of —CHand CD.5. The compound of or claim 1 , wherein Ris —CH.6. The compound of or claim 1 , wherein Ris —CD.7. The compound any one of - claim 1 , wherein at least one of 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 , 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 , R claim 1 , R claim 1 , and Ris deuterium.8. The compound of claim any one of - claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris deuterium.9. The compound of any one of - claim 1 , wherein Ris —CHand at least one of 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 , 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 , R claim 1 , R claim 1 , and Ris deuterium.10. The compound of any one of - claim 1 , wherein Ris —CHand at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris deuterium.11. The compound of any one of - claim 1 , wherein Rand Rare hydrogen.12. ...

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Номер записи: 92
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: 93
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: 94
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: 95
19-03-2020 дата публикации

NUCLEOTIDE AND OLIGONUCLEOTIDE PRODRUGS

Номер: US20200087338A1
Автор: Iyer Radhakrishnan P., Padmanabhan Seetharamaiyer
Принадлежит:

The present invention discloses compounds of formula (I): 2. The method of claim 1 , wherein said compound is administered together with other agents.3. The method of claim 1 , wherein the subject is infected with a resistant strain of HCV. This application is a continuation of U.S. patent application Ser. No. 15/922,581, filed Mar. 15, 2018, which is a continuation of U.S. patent application Ser. No. 14/939,397, filed Nov. 12, 2015, which is a continuation of U.S. patent application Ser. No. 14/186,768, filed on Feb. 21, 2014, which is a continuation of U.S. Pat. No. 8,691,787, filed on Nov. 14, 2011, which is a continuation of U.S. Pat. No. 8,076,303, filed on Dec. 12, 2006, which claims priority to U.S. Provisional Application No. 60/800,294, filed on May 15, 2006, and U.S. Provisional Application No. 60/750,036, filed on Dec. 13, 2005. The contents of each of the foregoing applications are hereby incorporated by reference in their entirety.The invention was supported, in whole or in part by NIH Grant number 5 UO1 AI058270-02/03.The present invention relates to the design, synthesis, and evaluation of prodrug analogs of nucleosides, nucleotides, and oligonucleotides. The compounds, compositions and methods of the present invention are useful for the treatment of hepatitis B virus (HBV) infections and liver diseases associated with HBV. Specifically compounds and compositions related to S-alkyl esters of novel anti-HBV agents phosphorothioate di-, and tri-nucleotides. The compounds and combinations can be administered either alone or in combination with other anti-HBV agents.Acute and chronic liver infections caused by Hepatitis B virus (HBV) constitute a major worldwide public health crisis affecting nearly 2 billion people including 1.7 million in the US (WHO report). There are an estimated 350 million chronic carriers of HBV worldwide. According to the Centers for Disease Control, nearly 3 to 7 million people die each year from complications associated with the ...

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Номер записи: 96
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: 97
09-04-2015 дата публикации

Aminosteroids for the Treatment of a PTP1B Associated Disease

Номер: US20150099727A1
Автор: Maloy W. Lee, MCLANE Michael, Ruiz-White Inez, Wolfe Henry R.
Принадлежит: Ohr Pharmaceutical Inc.

This application is directed to the use of aminosteroid compounds for the selective inhibition of the enzyme PTP1B in a mammal for the treatment of diabetes. 2. A pharmaceutical composition comprising the compound of and a pharmaceutically acceptable diluent or carrier.3. A method of treating a disorder in a mammal mediated by inhibition of protein tyrosine phosphatase PTP1B comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.7. A method of treating a disorder in a mammal mediated by inhibition of protein tyrosine phosphatase PTP1B comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 4 , or a pharmaceutically acceptable salt thereof.8. The method of claim 7 , wherein the disorder is selected from the group consisting of diabetes claim 7 , obesity claim 7 , high serum cholesterol claim 7 , sleep apnea and nonalcoholic steatohepatitis.9. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable diluent or carrier.10. A method of treating a disorder in a mammal mediated by inhibition of protein tyrosine phosphatase PTP1B comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt thereof.11. A method of treating a disorder in a mammal mediated by inhibition of protein tyrosine phosphatase PTP1B comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of claim 6 , or a pharmaceutically acceptable salt thereof.12. The method of claim 10 , wherein the disorder is selected from the group consisting of diabetes claim 10 , obesity claim 10 , high serum cholesterol claim 10 , sleep apnea and nonalcoholic steatohepatitis.13. The method of claim 11 , wherein the disorder is selected from the group consisting of diabetes claim 11 , obesity claim 11 , high serum ...

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Номер записи: 98
05-04-2018 дата публикации

Progesterone Phosphate Analogs and Uses Related Thereto

Номер: US20180094018A1
Автор: Guthrie David Brian, Liotta Dennis C., Lockwood Mark Andrew, Natchus Michael G., Sayeed Iqbal, Stein Donald G.
Принадлежит:

This disclosure relates to progesterone phophate derivatives and uses related thereto. In certain embodiments, the disclosure relates to compounds disclosed herein and uses for managing inflammation such as those resulting from traumatic brain injury or stroke. 2. The method of claim 1 , wherein X is N—OCRROPZ(OR)and Y is O.3. The method of claim 1 , wherein Y is N—OCRROPZ(OR)and X is O.4. The method of claim 1 , wherein Rand Rare hydrogen or alkyl.5. The method of claim 1 , wherein Rand Rform a cyclopropyl ring.6. The method of claim 1 , wherein Ris phosphate ion claim 1 , hydrogen claim 1 , alkanoyl claim 1 , or alkyl.9. A method of treating or preventing inflammation or CNS injury comprising administering an effective amount of a pharmaceutical composition comprising (E)-(((1-(10 claim 1 ,13-dimethyl-3-oxo-2 claim 1 ,3 claim 1 ,6 claim 1 ,7 claim 1 ,8 claim 1 ,9 claim 1 ,10 claim 1 ,11 claim 1 ,12 claim 1 ,13 claim 1 ,14 claim 1 ,15 claim 1 ,16 claim 1 ,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethylidene)amino)oxy)methyl dihydrogen phosphate or salts thereof claim 1 , to a subject in need thereof.10. The method of claim 1 , wherein the pharmaceutical composition is administered to a subject that incurred trauma to the head or other organ or tissue.11. The method of claim 1 , wherein the pharmaceutical composition is administered after a medical procedure.12. The method of claim 1 , wherein the pharmaceutical composition is administered in combination with a second anti-inflammatory agent.13. A method of treating stroke or traumatic brain injury comprising administering an effective amount of a pharmaceutical composition of to a subject in need thereof.14. A method of treating a neurodegenerative disease or condition comprising administering an effective amount of a pharmaceutical composition of to a subject in need thereof.15. The method of claim 14 , wherein the neurodegenerative disease or condition is selected from Alzheimer's disease claim 14 , ...

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Номер записи: 99
28-03-2019 дата публикации

Process and new intermediates for the preparation of 11-methylene steroids

Номер: US20190092807A1
Автор: Celso Miguel Sandoval Rodriguez, Ignacio HERRÁIZ SIERRA, Jesús Miguel Iglesias Retuerto, lvano MESSINA
Принадлежит: Bionice SL

The invention relates to a process for the preparation of 11-methylene steroids through selective olefination of the ketone at position 11. The resulting products are useful intermediates in the preparation of several pharmaceutically active agents, such as Etonogestrel and Desogestrel.

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Номер записи: 100