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10-01-2013 дата публикации

Compositions and methods comprising magnetic resonance contrast agents

Номер: US20130011340A1

Автор: Jiyoun Lee, Preeti A. Sukerar, Teresa K. Woodruff, Thomas J. Meade

Принадлежит: Northwestern University

The present invention relates to compositions and methods for imaging with magnetic resonance contrast agents. In particular, the present invention provides targeted contrast agents for selective imaging.

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Номер записи: 1

24-01-2013 дата публикации

Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same

Номер: US20130022674A1

Автор: Panayiotis P. Constantinides, Robert E. Dudley

Принадлежит: Clarus Therapeutics Inc

A drug delivery system for oral administration of hydrophobic drugs with enhanced and extended absorption and improved pharmacokinetics is provided. In one embodiment, formulations comprising testosterone and testosterone esters, e.g., testosterone palmitate, are disclosed. Methods of treating a hormone deficiency or effecting male contraception with the inventive formulations are also provided.

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Номер записи: 2

14-02-2013 дата публикации

Chemoselective enrichment for compound isolation

Номер: US20130041106A1

Автор: Antoinette Odendaal, Darci Trader, Erin E. Carlson

Принадлежит: Indiana University Research And Technology Corp

Chemoselective isolation of hydroxyl group-containing and carboxyl group-containing compounds is accomplished via formation of polymeric silyl ethers and polymeric siloxyl esters, respectively. Preparation of chemoselective polymeric reagents for capture of hydroxyl group containing compounds and carboxyl group containing compounds is described.

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Номер записи: 3

28-02-2013 дата публикации

Method for producing silylenol ethers

Номер: US20130053567A1

Автор: Kei Kurahashi, Kiyosei Takasu, Yoshiji Takamoto

Принадлежит: KYOTO UNIVERSITY

The invention relates to a method for producing silyl enol ether compound (3) by reacting ketone or aldehyde compound (1) with allylsilane compound (2) in the presence of a base and 0.00001 to 0.5 equivalents of an acid catalyst relative to ketone or aldehyde compound (1).

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Номер записи: 4

14-03-2013 дата публикации

Methods for preparing 17-alkynyl-7-hydroxy steroids and related compounds-2

Номер: US20130066087A1

Автор: Steven K. White, Yu Ge, Yujin Huang

Принадлежит: Harbor Therapeutics Inc

The invention relates to processes for preparing 17-alkynyl-7-hydroxy-steroids, such as 17-Ethynyl-10R,13S-dimethyl 2,3,4,7,8R,9S,10,11,12,13,14S,15,16,17-hexadecahydro-1H-cyclopenta[a]phenanthrene-3R,7R,17S-triol (also referred to as 17α-ethynyl-androst-5-ene-3β,7β,17β-triol), that are essentially free of process impurities having binding activity at nuclear estrogen receptors.

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Номер записи: 5

25-04-2013 дата публикации

SHIP INHIBITORS AND USES THEREOF

Номер: US20130102577A1

Автор: Chisholm John D., KERR William G.

Принадлежит: The Research Foundation of the State University of New York

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

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Номер записи: 6

25-04-2013 дата публикации

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

Номер: US20130102578A1

Автор: Gianna Ragagnin, Torbjorn Backstrom

Принадлежит: UMECRINE AB

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

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Номер записи: 7

25-04-2013 дата публикации

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

Номер: US20130102579A1

Автор: Bäckström Torbjörn, Ragagnin Gianna

Принадлежит: UMECRINE AB

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

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Номер записи: 8

23-05-2013 дата публикации

ANTISOLVENT SOLIDIFICATION PROCESS

Номер: US20130131029A1

Автор: BAKKER Wridzer Jan Willem, Baltussen Jozef Johannes Maria, Bargeman Gerrald, GEERTMAN Robert Michael, Reedijk Marianne Frederika, Van Lare Cornelis Elizabeth Johannus

Принадлежит: MSD Oss B.V.

The present invention relates to a antisolvent solidification process wherein a liquid medium comprising at least one organic or inorganic compound which is to be solidified is forced through a membrane into one or more antisolvents, or wherein one or more antisolvents are forced through a membrane into a liquid medium comprising at least one organic or inorganic compound which is to be solidified, yielding a composition comprising solid particles comprising said organic and/or inorganic compound(s). 1. Antisolvent solidification process for preparing a solid composition comprising at least one organic or inorganic compound , wherein a liquid medium comprising at least one dissolved organic or inorganic compound is forced through a membrane into one or more antisolvents or wherein one or more antisolvents are forced through a membrane into a liquid medium comprising at least one organic or inorganic compound , yielding a composition comprising solid particles comprising said organic and/or inorganic compound(s).2. A process according to wherein the solidification is a crystallisation claim 1 , the prepared solid particles are crystalline particles claim 1 , the organic or inorganic compound is a crystallisable compound claim 1 , and claim 1 , optionally claim 1 , said crystalline particles are recovered from the process.3. A process according to wherein the process is carried out as a continuous process.4. A process according to wherein the liquid medium is separated from the one or more antisolvents by means of nanofiltration and wherein claim 1 , optionally claim 1 , the liquid medium and/or the antisolvent(s) is/are recycled.5. A process according to wherein an emulsion is formed before said composition comprising solid particles is obtained.6. A process according to wherein a nonsolvent is present in the liquid medium and/or in the one or more antisolvents.7. A process according to wherein the organic or inorganic compound is selected from the group consisting ...

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Номер записи: 9

30-05-2013 дата публикации

Process for introducing a double bond into position 15, 16 of a steroid

Номер: US20130137885A1

Автор: Florent Mouton, Gilles Pellegrino, Jean Lafay, Jean-Luc Moutou, Jean-Marc Dillenschneider

Принадлежит: Laboratoire Theramex SAM

The invention relates to a process for the preparation of a compound of formula wherein R 1 and R 2 are as defined in the description, by reaction of a compound of formula (II) with a base. Compound (I) is an intermediate useful in the preparation of gestodene.

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Номер записи: 10

20-06-2013 дата публикации

SUBSTITUTED ANDROST-4-ENE DIONES

Номер: US20130157988A1

Автор: Davies Huw, Ghosh Debashis, Morton Daniel

Принадлежит:

The disclosure relates to novel C4 and C6 substituted androst-4-ene diones as well as andros-1,4-diene diones and derivatives thereof, their process of preparation, pharmaceutical compounds containing them, and the use of said compounds for the treatment of hormone-related disorders in mammals. This includes hormone-dependent cancers, particularly those caused by elevated levels of estrogen and its intermediates. These compounds can also be used in the treatment of other hormone-related disorders, including benign prostatic hyperplasia, cardiovascular disease, and neurodegenerative disorders. 3. A compound of claim 1 , wherein R′ is an alkyl substituted with an optionally substituted aryl group.4. A compound of claim 1 , wherein R′ is alkenyl or alkynyl optionally substituted with one or more substituents.5. A compound of claim 1 , wherein the substituent is selected from OH claim 1 , phenyl claim 1 , benzyl claim 1 , naphthyl claim 1 , substituted aryl claim 1 , or Cto Calkyl group.6. The compound of claim 1 , wherein the substituent is selected from aryl claim 1 , substituted aryl claim 1 , heterocyclo claim 1 , substituted heterocyclo claim 1 , carbocyclo claim 1 , substituted carbocyclo claim 1 , or halo.7. The compound of claim 1 , wherein the substituent is selected from alkoxy (optionally substituted) claim 1 , aryloxy (optionally substituted) claim 1 , alkylester (optionally substituted) claim 1 , arylester (optionally substituted) claim 1 , alkanoyl (optionally substituted) claim 1 , or aryol (optionally substituted).8. The compound of claim 1 , selected from the list:(6R,8R,9S,10R,13S,14S)-10,13-dimethyl-6-(pentyloxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione;(6R,8R,9S,10R,13S,14S)-10,13-dimethyl-6-((E)-pent-2-en-1-yloxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione;(6R,8R,9S,10R,13S,14S)-10,13-dimethyl-6-(((Z)-pent-2-en-1-yloxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a] ...

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Номер записи: 11

20-06-2013 дата публикации

USE OF 5ALPHA-ANDROSTANE (ALKYL)-3BETA,5,6BETA-TRIOL IN PREPARATION OF NEUROPROTECTIVE DRUGS

Номер: US20130157993A1

Автор: CHEN Jiesi, HU Haiyan, LENG Tiandong, QIU Pengxin, SANG Hanfei, YAN Guangmei, YOU Xiuhua, Zhang Jingxia, ZHOU Shujia

Принадлежит:

Disclosed is the use of 5α-androstane(alkyl)-3β,5,6β-triol in preparing neuroprotective drugs. The compound has significant protective effect against neuron injuries caused by cerebral ischemia, spinal cord isehemia or hypoxia and has no obvious toxic reaction within effective dose thereof. 14-. (canceled)61. The method of claim , wherein the neuron related disease is cerebral ischemia.7. The method of claim , wherein the neuron related disease is spinal cord ischemic.81. The method of claim , wherein the neuron related disease is neuron damage caused by hypoxia. The present invention relates to a novel medical use of compound 5α-androstane (alkyl)-3β,5,6β-triol (hereinafter abbreviated as YC-6).Acute Ischemic Stroke (AIS) is conventionally treated mainly by thrombolysis or neuroprotection. Neuroprotection refers to medicament or measures, during treatment of AIS, that are able to inhibit pathological and biochemical reactions of brain tissue caused by ischemia, interfere with various pathways of ischemic cascade and prolong survival of neurons.Neuroprotection has currently become one of the research hotspots in the field of AIS treatment. Various neuroprotectants are under clinical development, the mechanism of which is to prevent or limit brain damage resulted from ischemia by blocking various harmful pathological processes due to ischemia, so as to reduce brain tissue death and promote function recovery. The neuroprotectants can reduce cerebral infarct size; do not result in hemorrhage complication that may occur during thrombolytics or anticoagulants therapy; and can be used without confirmation of etiology, making early treatment possible. The therapeutic effect of neuroprotectants is therefore promising.There is no neuroprotectant yet, however, that has been proven safe and effective. Drugs that are under clinical trials and have potential value of clinical application include calcium channel blockers (CCB), calcium channel modulators, glutamate release ...

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Номер записи: 12

08-08-2013 дата публикации

PROGESTERONE RECEPTOR ANTAGONISTS AND USES THEREOF

Номер: US20130203718A1

Автор: Alami Mouad, Brion Jean-Daniel, Hamze Abdallah, Khan Ali Junaid, Lombes Marc, Loosfelt Hugues, Rafestin-Oblin Marie-Edith, Tikad Abdellatif

Принадлежит:

The present invention relates to a compound of formula (I): for its use as progesterone receptor antagonist, in particular for its use for the prevention and/or the treatment of cancer or uterine pathologies. 4. The method of claim 1 , wherein Ris H and Ris selected from C(O)R claim 1 , OR′ claim 1 , halogen claim 1 , CH(OR)(R) claim 1 , C(OR)(C≡CR)(R) and C≡CR claim 1 , wherein:{'sub': '6', 'Ris H or an alkyl group comprising from 1 to 6 carbon atoms;'}{'sub': 7', '9, 'Ris H or an alkyl group comprising from 1 to 6 carbon atoms, or a group C(O)R,'}{'sub': 7', '9, 'R′is an alkyl group comprising from 1 to 6 carbon atoms, or a group C(O)R,'}{'sub': '8', 'Ris an alkyl group comprising from 1 to 6 carbon atoms; and'}{'sub': '9', 'Ris an alkyl group comprising from 1 to 6 carbon atoms.'}5. The method of claim 4 , wherein Ris OAc.6. The method of claim 4 , wherein Ris selected from COCH claim 4 , CH(CH)(OH) and CH(CH)(OAc).7. The method of claim 4 , wherein Ris C(C≡CH)(CH)(OH).8. The method of claim 2 , wherein Ris OH and Ris C═CR.9. The method of claim 2 , wherein n is 0 and Rand R′are H.16. A method of providing progesterone receptor antagonist activity to a subject in need thereof claim 2 , comprising{'claim-ref': {'@idref': 'CLM-00014', 'claim 14'}, 'administering to said subject a therapeutically effective amount of a compound of formula (II-2) according to .'}17. A method of preventing and/or treating cancer or uterine pathologies in a subject in need thereof claim 2 , comprising{'claim-ref': {'@idref': 'CLM-00014', 'claim 14'}, 'administering to said subject a therapeutically effective amount of a compound of formula (II-2) according to .'}18. A method of providing progesterone receptor antagonist activity to a subject in need thereof claim 2 , comprising{'claim-ref': {'@idref': 'CLM-00015', 'claim 15'}, 'administering to said subject a therapeutically effective amount of a compound of formula (II-3) according to .'}19. A method of preventing and/or treating ...

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Номер записи: 13

29-08-2013 дата публикации

Process for preparation of estradiol valerate and a novel crystalline form a of estradiol divalerate

Номер: US20130225845A1

Автор: Girij Pal Singh, Nandu Baban Bhise, Rajesh Vyas, Sachin Arun Sasane, Vijay Ashok Ahire

Принадлежит: Lupin Ltd

The present invention relates to the process for the preparation of estradiol valerate (I) which involves isolation of crystalline estradiol divalerate (III) by crystallization from an alcoholic solvent.

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Номер записи: 14

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: 15

05-12-2013 дата публикации

Process for preparation of levonorgestrel

Номер: US20130324748A1

Автор: Girij Pal Singh, Himanshu Madhav Godbole, Kishor Gulabrao Mehare, Swapnil Ajit ZADBUKE

Принадлежит: Lupin Ltd

The present invention provides an improved process for preparation of levonorgestrel (3) which comprises of hydrolysis of 13β-ethyl-3-methoxy-17α-ethynyl-gona-2,5(10)-dien-17β-ol (2) with an acid in aprotic solvent. The present invention also provides a novel process for purification of crude levonorgestrel (3) by recrystallization from N,N-dimethyl formamide-water; methanol-water mixture.

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Номер записи: 16

12-12-2013 дата публикации

CYCLOPROPYL PIDA BORONATE

Номер: US20130331585A1

Автор: Burke Michael D., Duncton Matthew

Принадлежит:

Provided are protected cyclopropylboronic acids that include a substituted cyclopropyl group and a boronic ester group having a protecting group. The protecting group is a pinene-derived iminodiacetic acid (PIDA) group or PIDA-based group. 2. The protected organoboronic acid of claim 1 , wherein Ris homochiral.3. The protected organoboronic acid of claim 1 , wherein Ris substituted cycloalkyl.4. The protected organoboronic acid of claim 1 , wherein Ris isopinocampheyl.5. The protected organoboronic acid of claim 1 , wherein one of R claim 1 , R claim 1 , R claim 1 , and Ris substituted alkyl and the others are hydrogen.6. The protected organoboronic acid of claim 1 , wherein one of R claim 1 , R claim 1 , R claim 1 , and Ris trifluoromethyl and the others are hydrogen.8. The protected organoboronic acid of claim 7 , wherein Ris substituted cycloalkyl.9. The protected organoboronic acid of claim 7 , wherein Ris isopinocampheyl.10. The protected organoboronic acid of claim 7 , wherein one of Rand Ris substituted alkyl.11. The protected organoboronic acid of claim 7 , wherein one of Rand Ris trifluoromethyl.13. The protected organoboronic acid of claim 12 , wherein Ris substituted cycloalkyl.14. The protected organoboronic acid of claim 12 , wherein Ris isopinocampheyl.15. The protected organoboronic acid of claim 12 , wherein Ris substituted alkyl.16. The protected organoboronic acid of claim 12 , wherein Ris trifluoromethyl.17. The protected organoboronic acid of claim 12 , wherein the protected organoboronic acid has a trans stereochemistry with respect to the cyclopropyl ring.19. The protected organoboronic acid of claim 18 , wherein the protected organoboronic acid has a trans stereochemistry with respect to the cyclopropyl ring.21. The method of claim 20 , wherein Ris substituted cycloalkyl.22. The method of claim 20 , wherein Ris isopinocampheyl.23. The method of claim 20 , wherein one of R claim 20 , R claim 20 , R claim 20 , and Ris substituted alkyl and the ...

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Номер записи: 17

26-12-2013 дата публикации

PHARMACEUTICAL SOLID STATE FORMS-2

Номер: US20130345184A1

Автор: Jansen Erin E., Lorimer Keith, White Steven K., Wolfe Brenton Skylar

Принадлежит:

The invention provides and describes solid state 17α-ethynyl-5α-androstane-3α,17β-diol including amorphous and crystalline forms and specific polymorphic forms thereof. Anhydrates and solvates of 17α-ethynyl-5α-androstane-3α,17β-diol include Form III anhydrate and Form I solvate. The invention further relates to solid and suspension formulations containing 17α-ethynyl-5α-androstane-3α,17β-diol in a described solid state form and use of the formulations to treat cancers or precancers such as prostate cancer or breast cancer in subjects or human patients. The invention also relates to methods to make liquid formulations from solid state forms of 17α-ethynyl-5α-androstane-3α,17β-diol and uses of such formulations in treating the described conditions. 1. Amorphous 17α-ethynyl-5α-androstane-3α ,17β-diol.2. The amorphous 17α-ethynyl-5α-androstane-3α claim 1 ,17β-diol of wherein the amorphous 17α-ethynyl-5α-androstane-3α claim 1 ,17β-diol is substantially free of crystalline 17α-ethynyl-5α-androstane-3α claim 1 ,17β-diol or contains less than about 10% w/w of crystalline 17α-ethynyl-5α-androstane-3α claim 1 ,17β-diol.3. The amorphous 17α-ethynyl-5α-androstane-3α claim 2 ,17β-diol of wherein the amorphous 17α-ethynyl-5α-androstane-3α claim 2 ,17β-diol is characterized by or has:{'figref': {'@idref': 'DRAWINGS', 'FIG. 20'}, '(i) an X-ray powder diffraction pattern with a broad peak at about 16 degree 2 theta or X-ray powder diffraction pattern substantially as shown at , or'}(ii) a thermogravimetric analysis thermogram weight loss of about 7% when heated from about 40° C. to about 105° C., obtained using a temperature ramp of 10° C./min, and(iii) a differential thermal analysis thermogram with a prominent endotherm at about 163° C., optionally with a broad endotherm centered at about 81° C. and a broad endotherm centered at about 120° C., obtained using a temperature ramp of 10° C./min, or(iv) a combination of the characteristics of (i), (ii) and (iii).5. The method of ...

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Номер записи: 18

26-12-2013 дата публикации

Methods of preparing pharmaceutical solid state forms

Номер: US20130345455A1

Автор: Brenton Skylar Wolfe, Erin E. Jansen, Keith Lorimer, Steven K. White

Принадлежит: Individual

The invention provides and describes solid state 17α-ethynyl-5α-androstane-3α,17β-diol including amorphous and crystalline forms and specific polymorphic forms thereof. Anhydrates and solvates of 17α-ethynyl-5α-androstane-3α,17β-diol include Form III anhydrate and Form I solvate. The invention further relates to solid and suspension formulations containing 17α-ethynyl-5α-androstane-3α,17β-diol in a described solid state form and use of the formulations to treat cancers or precancers such as prostate cancer or breast cancer in subjects or human patients. The invention also relates to methods to make liquid formulations from solid state forms of 17α-ethynyl-5α-androstane-3α,17β-diol and uses of such formulations in treating the described conditions.

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Номер записи: 19

09-01-2014 дата публикации

LOCALLY ACTIVE "SOFT" ANTIANDROGENS

Номер: US20140011785A1

Автор: Hochberg Richard

Принадлежит: YALE UNIVERSITY

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

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Номер записи: 20

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: 21

16-01-2014 дата публикации

HIGH-VALENT PALLADIUM FLUORIDE COMPLEXES AND USES THEREOF

Номер: US20140018538A1

Автор: Furuya Takeru, Kamlet Adam Seth, Lee Eunsung, Powers David C., Ritter Tobias

Принадлежит: President and Fellows of Harvard College

The present invention provides novel high-valent palladium complexes. The complexes typically include multi-dentate ligands that stabilize the octahedral coordination sphere of the palladium(IV) atom. These complexes are useful in fluorinating organic compounds and preparing high-valent palladium fluoride complexes. The invention is particularly useful for fluorinating compounds with F for PET imaging. 211.-. (canceled)12. The palladium complex of claim 1 , wherein Rand Rtaken together with the atoms to which they are attached form an aryl ring and Rand Rtaken together with the atoms to which they are attached form an aryl ring.1317.-. (canceled)18. The palladium complex of claim 1 , wherein R claim 1 , R claim 1 , Rand Rare each a 5-membered heteroaryl ring.1953.-. (canceled)56. (canceled)57. The palladium complex of claim 55 , wherein Cy taken together with the nitrogen atom to which it is attached forms a heteroaryl ring.5876.-. (canceled)79. (canceled)81. (canceled)82. The palladium complex of claim 80 , wherein each Ris hydrogen.83. (canceled)84. The palladium complex of claim 80 , wherein Z is a halide claim 80 , acetate claim 80 , tosylate claim 80 , azide claim 80 , tetrafluoroborate claim 80 , tetraphenylborate claim 80 , tetrakis(pentafluorophenyl)borate claim 80 , [B[3 claim 80 ,5-(CF)CH]] claim 80 , hexafluorophosphate claim 80 , phosphate claim 80 , sulfate claim 80 , perchlorate claim 80 , trifluoromethanesulfonate or hexafluoroantimonate.85. (canceled)86. The palladium complex of claim 80 , wherein F comprises F.87. The palladium complex of claim 80 , wherein F comprises F.90115.-. (canceled)117152.-. (canceled)154. (canceled)155. A method of fluorination claim 55 , wherein the palladium complex of is mixed with F— to produce a palladium (IV) complex and subsequently said palladium (IV) complex is reacted with an organic compound under conditions sufficient to fluorinate the compound claim 55 , thereby providing a fluorinated organic compound.156157 ...

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Номер записи: 22

27-02-2014 дата публикации

PROCESS FOR PREPARING PLATINUM-CARBENE COMPLEXES

Номер: US20140058061A1

Автор: Bellemin-Laponnaz Stephane, Chardon Edith, Guichard Gilles

Принадлежит:

Described is a process for preparing platinum-carbene complexes. 2. Process according to claim 1 , in which solvent is selected from ethanol claim 1 , methanol claim 1 , dichloromethane claim 1 , tetrahydrofuran claim 1 , toluene claim 1 , ethyl acetate.3. Process according to claim 1 , carried out in the absence of solvent claim 1 , Lbeing liquid at the reaction temperature and performing the role of solvent.4. Process according to claim 1 , comprising the addition of a base selected from a tertiary amine claim 1 , in particular selected from triethylamine claim 1 , or diisopropylethylamine claim 1 , when the ligand Lis in the form of salt.5. Process according to claim 1 , in which the salt of the ligand Lis in the form of ammonium salt claim 1 , in particular ammonium hydrochloride or ammonium trifluoroacetate.6. Process according to claim 1 , in which the temperature of the reaction is 10° C. to 65° C.7. Process according to claim 1 , in which the reaction between the compound of formula I and the ligand Lis carried out in the presence of ethanol as solvent claim 1 , at a temperature from 45° C. to 65° C. claim 1 , in particular at 55° C.8. Process according to claim 1 , in which the reaction between the compound of formula I and the ligand Lis carried out in the presence of dichloromethane as solvent claim 1 , at a temperature from 10° C. to 35° C. claim 1 , in particular at 20° C.10. Process according to claim 9 , carried out without solvent claim 9 , the ligand Lbeing liquid at the reaction temperature.11. Process according to claim 9 , in which NaXc is in excess with respect to Xa and Xb claim 9 , when Xa is different from Xb.12. Process according to claim 9 , optionally without the addition of NaXc claim 9 , when Xa and Xb are identical.13. Process according to claim 9 , in which the reaction between the compound of formula III and the ligand Lis carried out in the presence of a base claim 9 , in particular a base selected from sodium carbonate claim 9 , ...

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Номер записи: 23

27-03-2014 дата публикации

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

Номер: US20140088053A1

Автор: Donald Poirier, Jenny Roy, Rene Maltais

Принадлежит: UNIVERSITE LAVAL

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

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Номер записи: 24

06-01-2022 дата публикации

CRYSTALLINE SOLVATE FORMS OF A PHARMACEUTICAL

Номер: US20220002338A1

Автор: Andres Mark, Ivanisevic Igor, Stephens Kyle, White Steven K., Wolfe Brenton Skylar

Принадлежит:

Described herein are solid state 17α-ethynylandrost-5-ene-3β,7β,17β-triol including amorphous and crystalline forms and specific polymorphic forms thereof, and use of solid state 17α-ethynylandrost-5-ene-3β,7β,17β-triol in treating numerous diseases and disorders, including hyperglycemic conditions, such as type 2 diabetes and metabolic syndrome, autoimmune conditions, such as rheumatoid arthritis, ulcerative colitis and type 1 diabetes, among other inflammation related conditions, and neurodegenerative conditions in subjects or human patients. 1. (canceled)2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. (canceled)7. (canceled)8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. A method to treat an inflammation condition comprising administering to a human or mammal in need thereof an effective amount of a formulation comprising a solid state form of 17α-ethynylandrost-5-ene-3β ,7β ,17β-triol and at least one pharmaceutically acceptable excipient.13. The method of claim 12 , wherein the inflammation condition is an inflammatory bowel condition.14. The method of claim 12 , wherein the inflammation condition is an inflammatory lung condition.15. The method of claim 14 , wherein the inflammatory lung condition is cystic fibrosis claim 14 , asthma claim 14 , bronchitis or chronic obstructive pulmonary disease.16. The method of claim 12 , wherein the solid state form of 17α-ethynylandrost-5-ene-3β claim 12 ,7β claim 12 ,17β-triol is crystalline solvate 17α-ethynylandrost-5-ene-3β claim 12 ,7β claim 12 ,17β-triol.17. The method of claim 16 , wherein the crystalline solvate is crystalline methanolate 17α-ethynylandrost-5-ene-3β claim 16 ,7β claim 16 ,17β-triol.18. The method of claim 16 , wherein the crystalline solvate is crystalline ethanolate 17α-ethynylandrost-5-ene-3β claim 16 ,7β claim 16 ,17β-triol.19. (canceled)20. The method of claim 16 , wherein the crystalline solvate is Form III 17α-ethynylandrost-5-ene-3β claim 16 ,7β claim 16 ,17β-triol.21. ( ...

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Номер записи: 25

06-01-2022 дата публикации

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

Номер: US20220002340A1

Автор: Albert Jean Robichaud, Andrew Griffin, Boyd L. Harrison, Francesco G. Salituro, Gabriel Martinez Botella, Maria Jesus Blanco-Pillado

Принадлежит: Sage Therapeutics Inc

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

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Номер записи: 26

07-01-2021 дата публикации

INHIBITORS OF GLUCOCORTICOID RECEPTOR

Номер: US20210002324A1

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

Принадлежит:

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

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Номер записи: 27

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: 28

13-01-2022 дата публикации

Methods for Preparing Bile Acids

Номер: US20220009957A1

Автор: LEE Junho, LIU Dejun, QIAN Yingzhe, SONG Yoonseok

Принадлежит:

The present disclosure provides methods of preparing cholic acid, deoxycholic acid, or chenodeoxycholic acid, an ester thereof, or a pharmaceutically or cosmetically acceptable salt thereof, and novel and useful synthetic intermediates, for example, as described for methods 1, 1A, 1B, 2, 3, 3A, and 4. The method can start with a plant derived steroid as a starting material, such as dehydroepiandrosterone (DHEA) or Acetyl-dehydroepiandrosterone (Ac-DHEA). Also provided are pharmaceutical or cosmetic compositions and uses thereof, which comprise one or more of cholic acid, deoxycholic acid, or chenodeoxycholic acid, an ester thereof, or a pharmaceutically or cosmetically acceptable salt thereof, which is of high purity, for example, free of animal derived impurities. 176.-. (canceled)78. The compound of claim 77 , wherein Ris H claim 77 , and Rand Rare each independently a hydroxyl protecting group.79. The compound of claim 78 , wherein the hydroxyl protecting group is acetyl.82. The method of claim 80 , wherein Ris H claim 80 , and Rand Rare each independently a hydroxyl protecting group.83. The method of claim 82 , wherein the hydroxyl protecting group is acetyl. This application is a continuation of U.S. application Ser. No. 16/636,260, which is a 35 U.S.C. § 371 national phase of PCT/CN2018/098535, having an international filing date of Aug. 3, 2018, which claims priority to PCT/CN2017/095784, filed on Aug. 3, 2017, the contents of which are herein incorporated by reference in their entirety.The present disclosure is generally related to the field of steroid synthesis, e.g., methods of preparing a bile acid (e.g., cholic acid, deoxycholic acid, or chenodeoxycholic acid) from a plant derived steroid, and novel synthetic intermediates. The present disclosure is also related to pharmaceutical or cosmetic compositions comprising a bile acid (e.g., cholic acid, deoxycholic acid, or chenodeoxycholic acid) or its ester(s) or salt(s), and pharmaceutical or cosmetic uses ...

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Номер записи: 29

01-01-2015 дата публикации

PROCESS FOR ALKYNYLATING 16-SUBSTITUTED-17-KETO STEROIDS

Номер: US20150005518A1

Автор: Gutiérrez Fuentes Luis Gerardo, Sandoval Rodriguez Celso Miguel

Принадлежит:

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

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Номер записи: 30

18-01-2018 дата публикации

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

Номер: US20180016296A1

Автор: Lazari Mark Saul, Murphy Jennifer Marie

Принадлежит: The Regents of the University of California

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

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Номер записи: 31

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: 32

16-01-2020 дата публикации

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Номер: US20200017542A1

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

Принадлежит:

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

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Номер записи: 33

25-01-2018 дата публикации

PHARMACEUTICAL DELIVERY SYSTEMS FOR HYDROPHOBIC DRUGS AND COMPOSITIONS COMPRISING SAME

Номер: US20180021350A1

Автор: CONSTANTINIDES Panayiotis P., Dudley Robert E.

Принадлежит:

A drug delivery system for oral administration of hydrophobic drugs with enhanced and extended absorption and improved pharmacokinetics is provided. In one embodiment, formulations comprising testosterone and testosterone esters, e.g., testosterone palmitate, are disclosed. Methods of treating a hormone deficiency or effecting male contraception with the inventive formulations are also provided. 1. An oral pharmaceutical formulation comprising:(a) about 23 wt. % or less of a testosterone ester selected from the group consisting of testosterone enanthate, testosterone undecanoate, testosterone cypionate and testosterone palmitate,(b) lipophilic surfactant, and(c) polyoxyethylene 40 hydrogenated castor oil,wherein the weight ratio of the lipophilic surfactant to polyoxyethylene 40 hydrogenated castor oil ranges from 3.8:1 to 4.2:1.2. The oral pharmaceutical formulation of claim 1 , wherein the lipophilic surfactant is selected from the group consisting of glyceryl palmitostearate claim 1 , glyceryl monolinoleate and mixtures thereof.3. The oral pharmaceutical formulation of claim 2 , wherein the lipophilic surfactant is glyceryl monolinoleate.4. The oral pharmaceutical formulation of claim 1 , wherein the testosterone ester is present in the formation at from about 10 wt. % to about 23 wt. % thereof.5. The oral pharmaceutical formulation of claim 1 , wherein the testosterone ester is testosterone undecanoate.6. The oral pharmaceutical formulation of claim 1 , wherein the formulation is encased in a capsule. This application claims priority to U.S. provisional application Nos. 60/671,454 filed Apr. 15, 2005 and 60/721,971 filed Sep. 30, 2005, both of which disclosures have been incorporated by reference herein in their entirety.The present invention relates generally to pharmaceutical delivery systems of hydrophobic drugs and compositions comprising same. More particularly, the present invention relates to pharmaceutical compositions comprising testosterone and esters ...

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Номер записи: 34

25-01-2018 дата публикации

PHARMACEUTICAL DELIVERY SYSTEMS FOR HYDROPHOBIC DRUGS AND COMPOSITIONS COMPRISING SAME

Номер: US20180021351A1

Автор: CONSTANTINIDES Panayiotis P., Dudley Robert E.

Принадлежит:

A drug delivery system for oral administration of hydrophobic drugs with enhanced and extended absorption and improved pharmacokinetics is provided. In one embodiment, formulations comprising testosterone and testosterone esters, e.g., testosterone palmitate, are disclosed. Methods of treating a hormone deficiency or effecting male contraception with the inventive formulations are also provided. 1. An oral pharmaceutical formulation comprising(a) a testosterone ester chosen from testosterone enanthate, testosterone undecanoate, testosterone cypionate and testosterone palmitate;(b) 67 wt. % of a surfactant having a HLB value of 1 to less than 10 selected from the group consisting of mono- and/or di-glycerides of fatty acids, transesterification products of natural or hydrogenated vegetable oil triglyceride and a polyalkylene polyol, and mixtures thereof, and(c) 17 wt. % polyoxyethylene 40 hydrogenated castor oil.2. The oral pharmaceutical formulation of claim 1 , wherein the testosterone ester is testosterone undecanoate.3. The oral pharmaceutical formulation of claim 1 , wherein the surfactant having a HLB value of from 1 to less than 10 includes a mono- and/or di-glyceride of a fatty acid.4. The oral pharmaceutical formulation of claim 3 , wherein the surfactant is glyceryl monolinoleate.5. The oral pharmaceutical formulation of claim 4 , wherein the testosterone ester is testosterone undecanoate.6. The oral pharmaceutical formulation according to claim 4 , wherein the testosterone ester is present in the formation at from about 10 wt. % to about 20 wt. % thereof.7. The oral pharmaceutical formulation of claim 1 , wherein the formulation is encased within a capsule. This application claims priority to United States provisional application Nos. 60/671,454 filed Apr. 15, 2005 and 60/721,971 filed Sep. 30, 2005, both of which disclosures have been incorporated by reference herein in their entirety.The present invention relates generally to pharmaceutical delivery ...

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Номер записи: 35

17-04-2014 дата публикации

PROCESS FOR THE PRODUCTION OF ESTETROL INTERMEDIATES

Номер: US20140107091A1

Автор: Pascal Jean-Claude

Принадлежит: ESTETRA S.A.

The present invention relates to a process for the preparation of a compound of formula (I) comprising the steps of a) reacting a compound of formula (II) with a silylating or an acylating agent to produce compound of formula (III), wherein Pis a protecting group selected from RSi—RRor RCO—, Ris a group selected from Calkyl or Ccycloalkyl, each group being optionally substituted by one or more substituents independently selected from fluoro or Calkyl; R, Rand Rare each independently a group selected from Calkyl or phenyl, each group being optionally substituted by one or more substituents independently selected from fluoro or Calkyl; b) halogenation or sulfinylation of the compound of formula (III) to produce a compound of formula (IV); wherein X is halo, or —O—SO—R, and Ris a group selected from Caryl or heteroaryl, each group being optionally substituted by one or more substituents independently selected from chloro or Calkyl; c) dehalogenation or desulfinylation of the compound of formula (IV) to produce compound of formula (V); and d) reacting the compound of formula (V) with a reducing agent to produce compound of formula (I). 2. The process according to claim 1 , wherein step (b) is a sulfinylation and the sulfinylation is performed by reacting the compound of formula (III) with a base and with a sulfinylation reagent.3. The process according to wherein step (b) is a sulfinylation and a sulfinylation reagent is methyl 2-pyridinesulfinate claim 1 , methyl benzenesulfinate claim 1 , methyl 4-methyl-benzenesulfinate claim 1 , methyl 4-chloro-benzene sulfinate.4. The process according to claim 2 , wherein the base used in the sulfinylation step is selected from the group comprising potassium hydride claim 2 , potassium terbutylate claim 2 , sodium hydride claim 2 , sodium terbutylate and a mixture thereof.5. The process according to claim 1 , wherein step (b) is a halogenation and the halogenation is performed by reacting the compound of formula (III) with a ...

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Номер записи: 36

17-04-2014 дата публикации

CHEMOSELECTIVE ENRICHMENT FOR COMPOUND ISOLATION

Номер: US20140107328A1

Автор: CARLSON Erin E., TRADER Darci

Принадлежит:

Chemoselective isolation of aliphatic hydroxyl group-containing and aromatic hydroxyl group-containing compounds is accomplished via formation of polymeric siloxyl ethers. Chemoselective release of aliphatic hydroxyl group-containing and aromatic hydroxyl group-containing compounds from polymeric siloxyl reagents is described. 1. A process for preparing a second mixture selectively enriched in aromatic-hydroxyl group containing compounds from a first mixture comprising hydroxyl group containing compounds , where the hydroxyl group containing compounds include one or more functional groups selected from aromatic-hydroxyl groups and aliphatic-hydroxyl groups , the method comprising the steps(a) contacting the first mixture with a polymeric reagent{'sub': 2', 'n, 'sup': 1', '2, 'comprising a polymer having one or more functional groups of formula (CH)—O—Si(R)(R)X covalently attached to the polymer, wherein'}the functional group is capable of reacting with hydroxyl group containing compounds when the mixture containing the compounds contacts the reagent;n is 1 to 4;{'sup': 1', '2, 'sub': 1', '8', '3', '8, 'Rand Rare independently selected in each instance from the group consisting of C-Calkyl and C-Ccycloalkyl; and'}{'sub': 2', '3, 'X is selected from the group consisting of Cl, Br, and OS(O)CF.;'}wherein one or more of the functional groups forms a covalent bond with the hydroxyl group of one or more of the hydroxyl group containing compounds;{'sub': 5', '10', '1', '5', '1', '5', '2', '5', '1', '4', '1', '4, '(b) washing the polymer resulting from step (a) with a solvent selected from the group consisting of optionally branched C-Calkanes, optionally-branched C-Calcohols, benzene, toluene, xylenes, C-Calkyl C-Calkanoates, where each of the alkyl or the alkanoate is optionally branched, C-Calkylnitriles, DMF, THF, dioxane, DMSO, C-Chaloalkanes, and combinations thereof; and'}{'sup': 3', '3, 'sub': 2', '1', '8, '(c) contacting the polymer resulting from step (b) with a ...

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Номер записи: 37

17-04-2014 дата публикации

PROCESS FOR THE PRODUCTION OF ESTETROL INTERMEDIATES

Номер: US20140107358A1

Автор: Pascal Jean-Claude

Принадлежит: ESTETRA S.A.

The present invention relates to a process for the preparation of a compound of formula (I) said process comprising the steps of: a) reacting a compound of formula (II), with an acylating or a silylating agent to produce a compound of formula (III), wherein Pand Pare each independently a protecting group selected from RSi—RR, or RCO—, wherein Ris a group selected from Calkyl or Ccycloalkyl, each group being optionally substituted by one or more substituents independently selected from fluoro or Calkyl; R, Rand Rare each independently a group selected from Calkyl or phenyl, each group being optionally substituted by one or more substituents independently selected from fluoro or Calkyl; b) reacting the compound of formula (III) in the presence of palladium acetate or a derivative thereof to produce compound of formula (IV); and c) reacting the compound of formula (IV) with a reducing agent to produce compound of formula (I). 2. The process according to claim 1 , wherein Pis RCO—.3. The process according to claim 1 , wherein Pis RSi—RR.4. The process according to claim 3 , wherein Pis RSi—RR.5. The process according to claim 1 , wherein Pis RCO—.7. The process according to claim 1 , wherein the acylating agent is CalkenylCalkanoate or CalkenylCcycloalkanoate.8. The process according to claim 1 , wherein the silylating agent is selected from the group comprising Calkylsilylchloride claim 1 , Calkylsilyltriflate claim 1 , phenylsilyl chloride claim 1 , phenylsilyltriflate claim 1 , Calkylphenylsilylchloride claim 1 , Calkylphenylsilyltriflate claim 1 , each group being optionally substituted by one or more substituents independently selected from fluoro or Calkyl.9. The process according to claim 1 , wherein step (b) is performed in the presence of a Calkylene carbonate and an organotin compound.10. The process according to claim 1 , wherein said palladium acetate is present in stoichiometric amounts.11. The process according to claim 1 , wherein said reaction is ...

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Номер записи: 38

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: 39

23-01-2020 дата публикации

Methods for the epigenetic analysis of dna, particularly cell-free dna

Номер: US20200024643A1

Автор: Chunxiao Song, Damek SPACEK, Patrick A. Arensdorf

Принадлежит: Bluestar Genomics Inc

Methods are provided for the epigenetic analysis of cell-free DNA using organic boranes to convert oxidized 5-methylcytosine residues in the cell-free DNA to dihydrouracil (DHU) residues. Cell-free DNA is contacted with an organic borane selected to successively bring about reduction, deamination, and decarboxylation of oxidized 5-methylcytosine residues such as 5-carboxymethylcytosine and 5-formylcytosine, resulting in DHU residues in place thereof. Following amplification, the treated cell-free DNA is sequenced, with the DHU residues read as thymine residues. Reaction mixtures, kits and additional methods are also provided, as are related methods for the epigenetic analysis of DNA, including cell-free DNA.

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Номер записи: 40

28-01-2021 дата публикации

METHODS FOR MODULATION OF LIPOPROTEIN LIPASE AND APOLIPOPROTEIN C2 EXPRESSION AND/OR ACTIVITY IN THE TREATMENT OF PERIPHERAL AND CENTRAL NERVOUS SYSTEM TISSUE DISEASE STATES

Номер: US20210024568A1

Автор: Yarger James G.

Принадлежит:

Methods for modulating lipoprotein lipase (LPL) and Apoliprotein C2 (ApoC2) expression and/or activity in the treatment of peripheral and central nervous system tissue disease states with C-6 substituted estradiol derivatives are presented herein. 2. A method for modulating lipoprotein lipase (LPL) or apolipoprotein C(ApoC2) expression and/or activity claim 1 , the method comprising contacting a cell capable of expressing LPL and/or ApoC2 with an effective amount of the compound according to .3. The method of claim 2 , wherein the cell is a microglial cell or a macrophage cell.4. The method of claim 2 , wherein LPL and/or ApoC2 is upregulated.5. A method for switching claim 1 , polarizing claim 1 , or altering an inflammatory phenotype claim 1 , the method comprising contacting a cell having a pro-inflammatory phenotype with an effective amount of the compound according to claim 1 , thereby switching claim 1 , polarizing claim 1 , or altering the inflammatory phenotype to an anti-inflammatory phenotype.6. The method of claim 5 , wherein the cell is a microglial cell or a macrophage cell.7. The method of claim 5 , wherein an inflammatory gene is down-regulated.8. The method of claim 5 , wherein a reparative gene is upregulated.9. A method for treating a condition claim 1 , disease claim 1 , or disorder in a subject claim 1 , the method comprising administering a therapeutically-effective amount of the compound according to to the subject claim 1 , wherein the subject is in need of a treatment for inflammation.10. The method of claim 9 , wherein the subject is in need of a treatment for inflammation associated with a cell having a pro-inflammatory phenotype and wherein administration of the therapeutically-effective amount of the compound switches claim 9 , polarizes claim 9 , or alters the pro-inflammatory phenotype to an anti-inflammatory phenotype.11. The method of claim 10 , wherein the inflammation is induced by an infection.12. The method of claim 11 , wherein ...

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Номер записи: 41

28-01-2021 дата публикации

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

Номер: US20210024572A1

Автор: DUGAR Sundeep, Mahajan Dinesh, SCHREINER George Frederic

Принадлежит:

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

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Номер записи: 42

01-02-2018 дата публикации

PHARMACEUTICAL DELIVERY SYSTEMS FOR HYDROPHOBIC DRUGS AND COMPOSITIONS COMPRISING SAME

Номер: US20180028542A1

Автор: CONSTANTINIDES Panayiotis P., Dudley Robert E.

Принадлежит:

A drug delivery system for oral administration of hydrophobic drugs with enhanced and extended absorption and improved pharmacokinetics is provided. In one embodiment, formulations comprising testosterone and testosterone esters, e.g., testosterone palmitate, are disclosed. Methods of treating a hormone deficiency or effecting male contraception with the inventive formulations are also provided. 1. An oral pharmaceutical formulation comprising(a) 10-20 wt. % of a testosterone ester selected from the group consisting of testosterone enanthate, testosterone undecanoate, testosterone cypionate and testosterone palmitate,(b) surfactant having a HLB value of from 1 to less than 10 selected from the group consisting of mono- and/or di-glycerides of fatty acids, transesterification products of natural or hydrogenated vegetable oil triglyceride and a polyalkylene polyol, and mixtures thereof, and(c) polyoxyethylene 40 hydrogenated castor oil,wherein the weight ratio of the surfactant having a HLB value of 1 to less than 10 to polyoxyethylene 40 hydrogenated castor oil is 3.9:1.2. The oral formulation of claim 1 , wherein the testosterone ester is present in the formulation at 15 wt. % thereof.3. The oral pharmaceutical formulation of claim 1 , wherein the testosterone ester is testosterone undecanoate.4. The oral pharmaceutical formulation of claim 1 , wherein the surfactant having a HLB value of from 1 to less than 10 includes a mono- and/or di-glyceride of a fatty acid.5. The oral pharmaceutical formulation of claim 4 , wherein the surfactant having a HLB value of from 1 to less than 10 is glyceryl monolinoleate.6. The oral pharmaceutical formulation of claim 5 , wherein the testosterone ester is present in the formulation at 15 wt. % thereof.7. The oral pharmaceutical formulation of claim 1 , wherein the formulation is encased in a capsule. This application claims priority to U.S. provisional application nos. 60/671,454 filed Apr. 15, 2005 and 60/721,971 filed Sep. 30, ...

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Номер записи: 43

01-02-2018 дата публикации

SYNTHESIS OF A RADIOACTIVE AGENT COMPOSITION

Номер: US20180028695A1

Автор: VIOT Gilles

Принадлежит:

The present invention relates to a method for the synthesis of a radioactive agent composition comprising at least a purification step carried out in the presence of an antioxidant, to the composition obtained by this method comprising radioactive agent and excipient, and to the method for preventing radiolysis of radioactive agent composition comprising the synthesis of said radioactive agent according to the method of the invention. 1. A method for the synthesis of a radioactive agent composition comprising at least a purification step carried out in the presence of an antioxidant.2. The method according to for which the radioactive agent is a halogen-labeled agent claim 1 , preferably a fluoro-labeled agent.3. The method according to for which the radioactive agent is [18F]-fluoroestradiol (FES).4. The method according to comprising the following steps:{'sup': 18', '−, 'i) Radioelement synthesis from 18-oxygen enriched water in order to get F;'}{'sup': 18', '−, 'ii) Radiolabeling of FES precursor with F obtained at step i);'}iii) Purification of crude FES obtained at step ii) in the presence of an antioxidant.5. The method according to further comprising the step of formulating purified radioactive agent obtained after the purification step with excipient.6. The method according to for which the formulation step is carried out in the presence of an antioxidant.7. The method according to for which the radiolabeling step is carried out in the presence of an antioxidant.8. The method according to for which the antioxidant is chosen amongst ascorbic acid claim 1 , polyphenols claim 1 , glutathione claim 1 , tocopherol claim 1 , caffeic acid claim 1 , alkali metal salts or alkaline earth metal salts of ascorbic acid.9. The method according to for which the antioxidant is chosen amongst ascorbic acid claim 1 , alkali metal salts or alkaline earth metal salts of ascorbic acid.10. The method according to for which the antioxidant is sodium ascorbate.11. The method ...

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Номер записи: 44

29-01-2015 дата публикации

COMBINED SYNTHESIS ROUTE FOR DESOGESTREL AND ETONOGESTREL

Номер: US20150031875A1

Автор: Ostendorf Martin

Принадлежит:

The present invention relates to a synthesis route and to steroid derivatives of general formula VI and VII useful in the synthesis of desogestrel and etonogestrel. 3. The process according to comprising steps 1 claim 2 , 2 and 3.4. The process according to comprising steps 1 claim 2 , 2 claim 2 , 3 and 4.5. The process according to comprising steps 4 claim 2 , 5 and 6.6. The process according to comprising steps 5 and 6.7. The process according claim 2 , wherein in step 4 claim 2 , the 11-keto group is converted into a methylene group using Peterson reaction conditions and the 11-methylene 17-acetal claim 2 ,3-dithioacetal steroid derivative of general formula VII is reacted without isolation.8. The process according to claim 2 , wherein in step 4 claim 2 , the 11-keto group is converted into a 11-methylene group using Wittig reaction conditions.10. The process according to claim 9 , wherein in step 7 the 3-dithioacetal is converted into a carbonyl using stabilized 2-iodobenzoic acid (SIBX) and β-cyclodextrin (β-CD).12. The process according to claim 9 , wherein{'sub': 1', '2, 'Rand R, together with the sulphur atoms to which they are attached, form a 1,3-dithiolane;'}{'sub': 3', '4, 'Rand R, together with the oxygen atoms to which they are attached, form a 1,3-dioxolane;'}in step 3, the 11-hydroxy group in the 17-acetal,-3-dithioacetal steroid derivative of general formula V is oxidised using pyridinium dichromate;in step 4, the 11-keto-17-acetal-3-dithioacetal steroid derivative of general formula VI is methylenylated using Peterson reaction conditions followed by deprotection of the 17-diacetal (step 5) using hydrochloric acid without isolation of the 11-methylene-17-acetal-3-dithioacetal steroid derivative of general formula VII and in step 7, the 3-dithioacetal is deprotected using periodic acid.13. The process according to claim 11 , wherein{'sub': 1', '2, 'Rand R, together with the sulphur atoms to which they are attached, form a 1,3-dithiolane;'}{'sub': 3', ...

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Номер записи: 45

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: 46

11-02-2016 дата публикации

2ß,3a,5a-TRIHYDROXY-ANDROST-6-ONE AND PREPARATION METHODS AND USE THEREOF

Номер: US20160039862A1

Автор: Lin Suizhen, Xie Minyu, Zhang Jingxia

Принадлежит:

The present invention discloses compound 2β,3α,5α-trihydroxy-androst-6-one, having the structure of formula (I). The present invention also discloses a plurality of methods for preparing the compound and a use of the compound. 2. A pharmaceutical composition claim 1 , comprising a therapeutically effective amount of the compound of claim 1 , or a prodrug or solvate thereof claim 1 , and a pharmaceutically acceptable carrier.3. The pharmaceutical composition of claim 1 , further comprising a second neuron protective agent.4. The pharmaceutical composition of claim 3 , wherein the second neuron protective agent is a retinal ganglion cell protective agent.5. The pharmaceutical composition of claim 1 , further comprising a second anti-tumor drug.6. (canceled)7. (canceled)8. A method for preparing the compound of claim 1 , wherein the method comprises:(a) using androst-5-en-3-ol as starting material to obtain a compound VI, that is 3β-p-toluensulfonyloxy-5α-hydroxy-androst-6-one;(b) subjecting the compound VI to an elimination reaction to obtain compound IX, that is 5α-hydroxy-androst-2-en-6-one; and{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(c) subjecting the compound IX to oxidation at the 2-position double bond and hydrolysis to obtain the compound of .'} The present application claims priority from Chinese patent application No. 201310104162.5 filed on Mar. 28, 2013, the entire content of which is hereby incorporated herein by reference.The present invention relates to a polyhydric sterone, in particular 2β,3α,5α-trihydroxy-androst-6-one, and its preparation methods and medical uses.Polyhydric sterones are a group of important compounds that are widely naturally occurred. Many polyhydric sterones isolated from marine organisms and terrestrial plants have important physiological functions such as antineoplastic and immunity enhancement effects. For example, ecdysterones and brassinosteroids are growth-promoting compounds for plants.However, naturally occurring ...

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Номер записи: 47

11-02-2016 дата публикации

METHOD FOR PREPARING SUBSTITUTED 3,7-DIHYDROXY STEROIDS

Номер: US20160039863A1

Автор: Ge Yu, Huang Yugin, White Steven K.

Принадлежит:

The invention relates to processes for preparing 17-alkynyl-7-hydroxy-steroids, such as 17-Ethynyl-10R,13S-dimethyl 2,3,4,7,8R,9S, 10,11,12,13,14S,15,16,17-hexadecahydro-1H-cyclopenta[a]phenanthrene-3R,7R,17S-triol (also referred to as 17α-ethynyl-androst-5-ene-3β, 7β, 17β-triol), that are essentially free of process impurities having binding activity at nuclear estrogen receptors. 2. The method of wherein Ris Calkyl or phenyl.3. The method of wherein Ris —CH.4. The method of wherein Rand Rare —CH.5. The method of wherein M is Li claim 1 , Mg or Zn.6. The method of wherein Ris —CH.7. The method of wherein M is Li and Ris —CH.8. The method of wherein comprising the additional step of purifying the 17α-alkynyl-androst-5-ene-3β claim 1 ,7β claim 1 ,17β-triol compound of step (f) by recrystallization.9. The method of wherein Ris —CH.10. The method of wherein Rand Rare —CH.11. The method of wherein M is Li claim 8 , Mg or Zn.12. The method of wherein Ris —CH.13. The method of wherein M is Li and Ris —CH.14. The method of wherein the 17α-alkynyl-androst-5-ene-3β claim 8 ,7β claim 8 ,17β-triol compound of step (f) is purified by recrystallization from methanol-water.15. The method of wherein Ris —CH.16. The method of wherein M is Li claim 14 , Mg or Zn.17. The method of wherein Ris —CH.18. The method of wherein the 17α-alkynyl-androst-5-ene-3β claim 1 ,7β claim 1 ,17β-triol compound is 17α-ethynyl-androst-5-ene-3β claim 1 ,7β claim 1 ,17β-triol.19. The method of wherein the 17α-alkynyl-androst-5-ene-3β claim 8 ,7β claim 8 ,17β-triol compound is 17α-ethynyl-androst-5-ene-3β claim 8 ,7β claim 8 ,17β-triol.20. The method of wherein the 17α-alkynyl-androst-5-ene-3β claim 14 ,7β claim 14 ,17β-triol compound is 17α-ethynyl-androst-5-ene-3β claim 14 ,7β claim 14 ,17β-triol. This non-provisional U.S. patent application is a divisional application of and claims priority to pending U.S. non-provisional application Ser. No. 12/479,626, filed Jun. 5, 2009 and issued on Nov. 13, 2012 ...

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Номер записи: 48

09-02-2017 дата публикации

COPPER CATALYZEDFLUORINATION OF IODONIUM SALTS

Номер: US20170036980A1

Автор: Brooks Allen F., Ichiishi Naoko, Rodick Melissa, Sanford Melanie S., Scott Peter J. H., Topczewski Joseph J.

Принадлежит:

Copper-catalyzed radiofluorination of iodonium salts, iodonium salts, and compounds obtained by copper-catalyzed radiofluorination of iodonium salts are disclosed. Diagnostic and therapeutic methods involving such compounds also are disclosed. 3. The method of claim 2 , wherein Rand R claim 2 , taken together with the carbon atoms to which they are attached claim 2 , form a substituted 4- to 8-membered ring.9. The method of claim 1 , wherein Xis selected from the group consisting of fluoride claim 1 , chloride claim 1 , bromide claim 1 , iodide claim 1 , trifluoromethanesulfonate claim 1 , toluene sulfonate claim 1 , tetrafluoroborate claim 1 , hexafluorophosphate claim 1 , methanesulfonate claim 1 , hexafluoropropanesulfonate claim 1 , nonafluorobutanesulfonate claim 1 , nitrophenyl sulfonate claim 1 , bromophenyl sulfonate claim 1 , perfluoroalkyl sulfonate claim 1 , tetraphenylborate claim 1 , trifluoroacetate claim 1 , perfluoroalkylcarboxylate claim 1 , perchlorate claim 1 , hexafluorostibate claim 1 , hexachlorostibate claim 1 , acetate claim 1 , and benzoate.10. The method of claim 1 , wherein Xis selected from the group consisting of BF claim 1 , PF claim 1 , OTs claim 1 , OTf claim 1 , and Br.11. The method of claim 1 , wherein the copper source is selected from the group consisting of Cu(OTf) claim 1 , CuCO.Cu(OH) claim 1 , CuOTftoluene claim 1 , and (CHCN)CuOTf.12. The method of claim 1 , wherein the F source is selected from the group consisting of F-labeled alkali metal fluorides claim 1 , F-labeled alkaline earth metal fluorides claim 1 , F-labeled ammonium fluorides claim 1 , and complexes thereof.13. The method of claim 1 , wherein the F source is selected from the group consisting of F lithium fluoride claim 1 , F sodium fluoride claim 1 , F potassium fluoride claim 1 , F rubidium fluoride claim 1 , F cesium fluoride claim 1 , F beryllium fluoride claim 1 , F magnesium fluoride claim 1 , F calcium fluoride claim 1 , F-labeled tetraalkylammonium ...

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Номер записи: 49

12-02-2015 дата публикации

CRYSTALLINE FORMS OF 5alpha-ANDROSTANE-3beta,5,6beta-TRIOL AND PREPARATION METHODS THEREFOR

Номер: US20150045566A1

Автор: Li Xinhua, Lin Suizhen, Zhang Jingxia

Принадлежит:

The present invention relates to four crystalline forms (crystalline forms A, B, C and D) of 5α-androstane-3β,5,6β-triol (YC-6) and preparation methods therefor. The four crystalline forms have significant difference in their lattice parameters, 2θ values and intensity in X-ray power diffraction, and melting points, etc. The study on its polymorphism is very important for further studying its effect, bioavailability and stability. 1. A crystalline form of 5α-androstane-3β ,5 ,6β-triol , wherein the crystalline form is a transparent block-shaped crystal , and belongs to monoclinic crystal system and space group P2 , andwherein the crystalline form is characterized by lattice parameters of a=17.8±0.2 Å, b=7.3±0.2 Å, c=22.1±0.2 Å, α=90.0°, β=103.3±0.5°, γ=90.0°; and characterized by diffraction peaks at diffraction angle 2θ values of 4.4±0.2, 8.7±0.2, 9.3±0.2, 12.6±0.2, 13.0±0.2, 15.0±0.2, 15.6±0.2, 16.6±0.2, 17.3±0.2, 18.5±0.2, 19.6±0.2, 21.0±0.2, 21.8±0.2, 24.3±0.2, 27.9±0.2 degrees; andcharacterized by an endothermic transition temperature of 225±2° C.2. A method for preparing the crystalline form of claim 1 , comprising:dissolving 5α-androstane-3β,5,6β-triol in a solvent at room temperature or at 50˜80° C., with a ratio of the 5α-androstane-3β,5,6β-triol to the solvent being 1 g:10˜40 mL;adding another solvent to dilute; andallowing to form a crystalline precipitate.3. The method of claim 2 , wherein the solvent for dissolving is acetone claim 2 , methanol claim 2 , ethanol claim 2 , isopropanol claim 2 , dioxane or tetrahydrofuran claim 2 , and the solvent for diluting is an original solvent or a poor solvent claim 2 , wherein the original solvent is acetone claim 2 , methanol claim 2 , ethanol claim 2 , isopropanol or dioxane with a dilution rate of 0˜5:1 claim 2 , and the poor solvent is water with a dilution rate of 0˜2:1.4. A crystalline form of 5α-androstane-3β claim 2 ,5 claim 2 ,6β-triol claim 2 , wherein the crystalline form is a transparent needle-shaped ...

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Номер записи: 50

06-02-2020 дата публикации

CLOSED EVAPORATION SYSTEM

Номер: US20200043620A1

Автор: Franci Xavier, LANGE Audrey, LIGNON Steve

Принадлежит:

The present invention provides a system for evaporating a radioactive fluid, a method for the synthesis of a radiolabelled compound including this system, and a cassette for the synthesis of a radiolabelled compound comprising this system. The present invention provides advantages over known methods for evaporation of a radioactive fluid as it reduces drastically the amount of radioactive gaseous chemicals that are released in the hot cell. It is gentler and more secure compared to the known process and provides access to radiosyntheic processes that may not been acceptable for safety reasons related to release of volatile radioactive gases during evaporation. In addition, the process yields are higher because the radioactive volatiles are labelled intermediate species. 121-. (canceled)22. A method for the synthesis of a radiolabelled compound wherein said method comprises:(i) radiolabelling a protected precursor compound in a fixed volume container to obtain a protected radiolabelled compound;(ii) deprotecting the protected radiolabelled compound obtained from radiolabelling step (i) to obtain said radiolabelled compound wherein said deprotection is effected using a hydrolysis medium;(iii) connecting the fixed volume container via a 3-way valve to an expandable volume; and,(iv) heating the radioactive fluid in the fixed volume container above its boiling point to reach the equilibrium gas/liquid phase causing said liquid to vaporise and move into the expandable volume where it condenses due to the drop in temperature to form a volume of radioactive fluid in the expandable volume.23. The method as defined in wherein said fixed volume container is a reaction vessel.24. The system as defined in wherein said expandable volume is a syringe.25. The method as defined in wherein said radiolabelled compound is a radiopharmaceutical.26. The method as defined in wherein said radiopharmaceutical is a diagnostic radiopharmaceutical.27. The method as defined in wherein said ...

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Номер записи: 51

08-05-2014 дата публикации

Temperature-responsive monolithic porous body, method for producing same, and temperature-responsive chromatography method using same

Номер: US20140124445A1

Автор: Akihiko Kikuchi, Hideko Kanazawa, Jun Kobayashi, Kenichi Nagase, Teruo Okano, Yoshikatsu Akiyama

Принадлежит: Cellseed Inc, Hideko Kanazawa, TOKYO WOMENS MEDICAL UNIVERSITY

A temperature responsive monolithic porous material is obtained that comprises a polymer having a hydration ability that changes in a temperature range of 0 to 80° C. and being immobilized to a surface of the porous material at a high density by binding an atom transfer radical polymerization initiator to a surface of the porous material, and inducing a growth reaction of a polymer, having a hydration ability that changes in a temperature range of 0 to 80° C., from the initiator using an atom transfer radical process under a presence of a catalyst.

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Номер записи: 52

13-02-2020 дата публикации

Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same

Номер: US20200046733A1

Автор: Panayiotis P. Constantinides, Robert E. Dudley

Принадлежит: Clarus Therapeutics Inc

A drug delivery system for oral administration of hydrophobic drugs with enhanced and extended absorption and improved pharmacokinetics is provided. In one embodiment, formulations comprising testosterone and testosterone esters, e.g., testosterone palmitate, are disclosed. Methods of treating a hormone deficiency or effecting male contraception with the inventive formulations are also provided.

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Номер записи: 53

14-02-2019 дата публикации

Process and intermediates for the production of 17(20)-ene b-seco steroids

Номер: US20190047939A1

Автор: Denis Viktorovich Arefyev, George Petros Yiannikouros, Panos Kalaritis

Принадлежит: Patheon Austria GmbH and Co KG

The invention pertains to a process for producing a compound of formula (11) wherein R7 and R8 are each independently selected from H, halogen, alkyl, aryl, or alkylaryl, R42 is H or a protective group, R43 is H or R3, wherein R3 is a protective group, by contacting a compound of formula (10) with an olefmation reagent, wherein compound of formula (10) comprises a counter acid X1 when R42═H and R43═H.

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Номер записи: 54

14-02-2019 дата публикации

PREPARATION OF BILE ACIDS AND INTERMEDIATES THEREOF

Номер: US20190048037A1

Автор: JR. Roy A., Moriarty Robert M., Prasad Achampeta Rathan, Reid John Gregory, Sahoo Akhila Kumar, Swaringen

Принадлежит: Kythera Biopharmaceuticals, Inc.

Synthetic methods for preparing deoxycholic acid and intermediates thereof are provided. 2. The composition of claim 1 , further comprising a solvent.3. The composition of claim 1 , wherein the hydrogenation catalyst comprises Pd/C.4. The composition of claim 2 , wherein the solvent is DMF.7. The composition of claim 6 , further comprising a solvent.8. The composition of claim 6 , wherein the olefination reagent is PhPCHCHBr.11. The composition of claim 10 , wherein the composition further comprises a solvent.12. The composition of claim 10 , wherein —OP is —OAc and —COR is —COMe.1316.-. (canceled)18. The composition of claim 17 , wherein the composition further comprises a solvent.19. The composition of claim 17 , wherein the reducing agent is lithium tri-tert-butoxyaluminum hydride.20. The composition of claim 17 , wherein —OP is —OAc and —COR is —COMe. This application is a divisional of U.S. patent application Ser. No. 14/696,204, filed Apr. 24, 2015, which is a divisional of U.S. patent application Ser. No. 13/752,175, filed Jan. 28, 2013; which is a continuation of U.S. patent application Ser. No. 13/010,727, filed Jan. 20, 2011, issued as U.S. Pat. No. 8,362,285; which is a divisional of U.S. patent application Ser. No. 12/613,969, filed Nov. 6, 2009, issued as U.S. Pat. No. 7,994,351 on Aug. 9, 2011; which is a continuation of U.S. patent application Ser. No. 12/153,446, filed May 16, 2008, issued as U.S. Pat. No. 7,902,387 on Feb. 16, 2011; which claims the benefit under 35 U.S.C. 119(a) of United Kingdom Application Serial No. 0807615.0, filed Apr. 25, 2008; each of which are hereby incorporated by reference into this application in their entirety.The present invention relates to the synthesis of deoxycholoic acid and pharmaceutically acceptable salts and intermediates thereof.Rapid removal of body fat is an age-old ideal, and many substances have been claimed to accomplish such results, although few have shown results. “Mesotherapy”, or the use of ...

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Номер записи: 55

23-02-2017 дата публикации

SHIP INHIBITORS AND USES THEREOF

Номер: US20170051006A1

Автор: Chisholm John D., KERR William G.

Принадлежит: The Research Foundation for The State University of New York

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

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Номер записи: 56

03-03-2016 дата публикации

Ester derivatives of 7-alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl)-estra-1,3,5(10)-triene-3,17beta-diol having anticancer activity and preparation method thereof

Номер: US20160060288A1

Автор: Hu Renle, Jiao Yaqi, Wang Jiucheng

Принадлежит:

The present invention provides a class of fulvestrant ester derivatives and preparation method thereof. Such a compound is an aliphatic ester formed by esterifying the —OH at positions C-3 and C-17 of fulvestrant, having a structure of the following formula: 2. The compound of claim 1 , characterized in that claim 1 ,substituent R′ is H, and substituent R is selected from alkanoyl or alkenoyl having 11 to 22 carbon atoms.3. The compound of claim 1 , characterized in that claim 1 ,said substituent R is selected from alkanoyl having 11 to 22 carbon atoms, preferably undecanoyl, hexadecanoyl, docosanoyl or 2-[(3′,3′)-dimethyl-1′-methyl]butyl-5-methyl-(7,7)-dimethyl-octanoyl.4. The compound of claim 1 , characterized in that claim 1 ,said substituent R is selected from alkenoyl containing 1 to 6 carbon-carbon double bonds and having 11 to 22 carbon atoms, wherein said carbon-carbon double bonds can either be distributed in the main chain, or in the branched chain.5. The compound of claim 13 , characterized in that claim 13 ,said substituent R is selected from undec-2-enoyl, eicosa-5,8,11,14,17-pentaenoyl and docosa-(4,7,10,13,16,19)-hexaenoyl.6. The compound of claim 1 , characterized in that claim 1 ,when substituent R′ is selected from alkanoyl having 2 to 4 carbon atoms, said alkanoyl is acetyl or butyryl.7. The compound of claim 1 , characterized in that claim 1 ,said substituent R is selected from alkanoyl or alkenoyl having 11 to 22 carbon atoms, preferably 2-[(3′,3′)-dimethyl-1′-methyl]butyl-5-methyl-(7,7)-dimethyl-octanoyl or undec-2-enoyl.9. The process of claim 8 , characterized in that claim 8 , in step a) claim 8 , said alkaline reagent is selected from pyridine claim 8 , 2-methylpyridine claim 8 , 3-methylpyridine claim 8 , 4-methylpyridine claim 8 , 2-ethylpyridine claim 8 , 3-ethylpyridine claim 8 , 4-ethylpyridine claim 8 , 5-ethylpyridine claim 8 , 2-methyl-5-ethylpyridine claim 8 , 2-dimethylaminopyridine claim 8 , 4-dimethylaminopyridine claim 8 , ...

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Номер записи: 57

04-03-2021 дата публикации

AQUEOUS SUSPENSION COMPOSITIONS, FORMULATIONS, AND WATER DISPERSIBLE DRY COMPOSITIONS COMPRISING 16ALPHA-BROMO-3BETA-HYDROXY-5ALPHA-ANDROSTAN-17-KETONE AND HYDRATES, DERIVATIVES, AND ANALOGS THEREOF

Номер: US20210061846A1

Автор: Ge Yu

Принадлежит:

Method of treating a subject in need of a treatment for modulating immune system or anti-microbial infection, comprising administering a stable aqueous suspension formulation, which may be reconstituted from a water dispersible dry composition, comprising compound of Formula I in the form of particles stabilized in an aqueous suspension. It causes little or no injection site irritation and has superior properties over non-aqueous formulations. It stimulates autophagy, enhance innate immunity, down-regulates unproductive inflammation and exerts a Th1 immune bias. It demonstrates better efficacy in both in vitro and in vivo models. 2. The method for treating a subject as described in claim 1 , wherein the treatment is by a parenteral claim 1 , oral claim 1 , or aerosol route.3. The method for treating a subject as described in claim 1 , wherein the composition is in an injectable suspension comprising 0.3% to 25% (w/v) of the compound of Formula I.4. The method for treating a subject as described in claim 1 , wherein the composition is a reconstituted composition from mixing a diluent with a water dispersible dry composition that is prepared by freeze-drying the composition comprising at least 30% w/w water based on total weight of the composition and the compound of Formula I as described in .5. The method for treating a subject as described in claim 1 , wherein R is the protecting group that is a trialkyl silyl group —Si-(alkyl)with each of the three alkyls independently selected from the group consisting of a methyl claim 1 , an ethyl claim 1 , a propyl claim 1 , a butyl claim 1 , a pentyl claim 1 , and a hexyl claim 1 , a phosphate —P(O)(O)—O—R claim 1 , a phosphonate —P(O)(OR)—R claim 1 , an N-acyl sulfonamide —NH—S(═O)—R claim 1 , an acyl group —C(O)—R claim 1 , a thioacyl group —C(S)—R claim 1 , a thioacetyl group —C(O)—S—R claim 1 , a carbonate group —C(O)—O—R claim 1 , a carbamate —C(O)—NR—R claim 1 , an alkyl having 1 to 8 carbon atoms claim 1 , a phenyl ...

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Номер записи: 58

04-03-2021 дата публикации

AQUEOUS SUSPENSION COMPOSITIONS, FORMULATIONS, AND WATER DISPERSIBLE DRY COMPOSITIONS COMPRISING 16ALPHA-BROMO-3BETA-HYDROXY-5ALPHA-ANDROSTAN-17-KETONE AND HYDRATES, DERIVATIVES, AND ANALOGS THEREOF

Номер: US20210061847A1

Автор: Ge Yu

Принадлежит:

Composition comprising a stable aqueous suspension formulation, which may be reconstituted from a water dispersible dry composition, comprising compound of Formula I in the form of particles stabilized in an aqueous suspension. It causes little or no injection site irritation and has superior properties over non-aqueous formulations. It stimulates autophagy, enhance innate immunity, down-regulates unproductive inflammation and exerts a Th1 immune bias. It demonstrates better efficacy in both in vitro and in vivo models. 2. The composition of claim 1 , wherein the protecting group R is an acyl group —C(O)—R claim 1 , a thioacyl group —C(S)—R claim 1 , a thioacetyl group —C(O)—S—R claim 1 , a carbonate group —C(O)—O—R claim 1 , a carbamate —C(O)—NR—R claim 1 , an alkyl having 1 to 8 carbon atoms claim 1 , a phenyl claim 1 , a naphthyl claim 1 , a phosphate —P(O)(O)—O—R claim 1 , a phosphonate —P(O)(OR)—R claim 1 , an N-acyl sulfonamide —NH—S(═O)—R claim 1 , a nucleoside claim 1 , or a monosaccharide; and each Ris independently a hydrogen or an organic moiety having 1 to 8 carbon atoms.3. The composition of claim 2 , wherein Ris an alkyl having 1 to 6 carbon atoms claim 2 , an alkenyl having 1 to 6 carbon atoms claim 2 , an alkynyl having 1 to 6 carbon atoms claim 2 , or a heterocycle having 3 to 9 carbon atoms.4. The composition of claim 1 , wherein the protecting group is acetate ester.5. The composition of claim 1 , wherein the compound of Formula I is metabolized to 16alpha-bromo-3beta-hydroxy-5alpha-androstan-17-ketone (BEA) in vivo after being administered to a subject.6. The composition of claim 1 , wherein size of the particles is in a range of 0.01 μm to 15 μm.7. The composition of claim 1 , wherein 90% of the particles are less than 15 μm in size.8. The composition of claim 1 , further comprising a surfactant claim 1 , a suspending agent claim 1 , and a pharmaceutical excipient.9. The composition of claim 8 , wherein the surfactant is a poloxamer claim 8 , ...

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Номер записи: 59

04-03-2021 дата публикации

NEUROACTIVE STERIODS, COMPOSITIONS, AND USES THEREOF

Номер: US20210061850A1

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): 134-. (canceled) 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 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 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 nicotinic receptors which are stimulated by acetylcholine to increase membrane permeability to Na ions. The reduced membrane potential stimulates neuronal excitability in the form of a postsynaptic action potential.In the case of the GABA receptor complex (GRC), the effect on brain excitability is mediated by GABA, a neurotransmitter. GABA has a profound influence on overall brain excitability because up to 40% of the neurons in the brain utilize GABA as a neurotransmitter. GABA regulates the excitability of individual ...

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Номер записи: 60

09-03-2017 дата публикации

TEMPERATURE-RESPONSIVE MONOLITHIC POROUS BODY, METHOD FOR PRODUCING SAME, AND TEMPERATURE-RESPONSIVE CHROMATOGRAPHY METHOD USING SAME

Номер: US20170067861A1

Автор: Akiyama Yoshikatsu, KANAZAWA Hideko, KIKUCHI Akihiko, Kobayashi Jun, Nagase Kenichi, OKANO Teruo

Принадлежит:

A temperature responsive monolithic porous material is obtained that comprises a polymer having a hydration ability that changes in a temperature range of 0 to 80° C. and being immobilized to a surface of the porous material at a high density by binding an atom transfer radical polymerization initiator to a surface of the porous material, and inducing a growth reaction of a polymer, having a hydration ability that changes in a temperature range of 0 to 80° C., from the initiator using an atom transfer radical process under a presence of a catalyst. 1. A temperature responsive monolithic porous material comprising a polymer having a hydration ability that changes in a temperature range of 0 to 80° C. and being bound to a surface of the porous material at a density of 0.01 molecular chain/nmor higher.2. The temperature responsive monolithic porous material of claim 1 , wherein the porous material consists of silica.3. The temperature responsive monolithic porous material according to claim 1 , wherein an amount of bound-polymer on the surface of the porous material is 0.2 to 10.0 mg/m.4. The temperature responsive monolithic porous material according to claim 1 , wherein a polymer molecular chain is non-crosslinked.5. The temperature responsive monolithic porous material according to claim 1 , wherein the polymer is one or a plurality of poly-N-substituted acrylamide derivative claim 1 , poly-N-substituted methacrylamide derivative claim 1 , their copolymer claim 1 , polyvinylmethyl ether claim 1 , a partially acetylated polyvinyl alcohol.6. The temperature responsive monolithic porous material according to claim 1 , wherein the polymer is poly-N-isopropylacrylamide.7. The temperature responsive monolithic porous material according to claim 5 , wherein the polymer is a copolymer containing a hydrophilic molecule claim 5 , a hydrophobic molecule and an ionic molecule in a polymer molecular chain claim 5 , at a range that retains a feature of the hydration ability to ...

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Номер записи: 61

07-03-2019 дата публикации

PHARMACEUTICAL DELIVERY SYSTEMS FOR HYDROPHOBIC DRUGS AND COMPOSITIONS COMPRISING SAME

Номер: US20190070196A1

Автор: CONSTANTINIDES Panayiotis P., Dudley Robert E.

Принадлежит:

A drug delivery system for oral administration of hydrophobic drugs with enhanced and extended absorption and improved pharmacokinetics is provided. In one embodiment, formulations comprising testosterone and testosterone esters, e.g., testosterone palmitate, are disclosed. Methods of treating a hormone deficiency or effecting male contraception with the inventive formulations are also provided. 17.-. (canceled)8. An oral pharmaceutical composition comprising a(a) means for providing a serum testosterone ranging from about 300 to about 1100 ng/dL; and(b) a pharmaceutically acceptable carrier.9. The pharmaceutical composition of claim 8 , wherein the means for providing a serum testosterone ranging from about 300 to about 1100 ng/dL is a testosterone ester.10. The pharmaceutical composition of claim 9 , wherein the testosterone ester is chosen from testosterone palmitate claim 9 , testosterone enanthate; testosterone undecanoate; testosterone cypionate. This application claims priority to U.S. provisional application Nos. 60/671,454 filed Apr. 15, 2005 and 60/721,971 filed Sep. 30, 2005, both of which disclosures have been incorporated by reference herein in their entirety.The present invention relates generally to pharmaceutical delivery systems of hydrophobic drugs and compositions comprising same. More particularly, the present invention relates to pharmaceutical compositions comprising testosterone and esters thereof with enhanced and extended absorption and pharmacokinetics.Many pharmaceutically active compounds intended for oral administration are poorly soluble in water providing a challenge to formulate these drugs in a drug delivery system that exhibits the desirable pharmacokinetic profiles in vivo. Poor oral bioavailability may lead to ineffective therapy, the need for higher dosing and/or undesirable side effects. As well, pharmaceutical preparations with relatively short half-lives require frequent dosing at the expense of patient inconvenience and ...

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Номер записи: 62

22-03-2018 дата публикации

PHARMACEUTICAL DELIVERY SYSTEMS FOR HYDROPHOBIC DRUGS AND COMPOSITIONS COMPRISING SAME

Номер: US20180078566A1

Автор: CONSTANTINIDES Panayiotis P., Dudley Robert E.

Принадлежит:

A drug delivery system for oral administration of hydrophobic drugs with enhanced and extended absorption and improved pharmacokinetics is provided. In one embodiment, formulations comprising testosterone and testosterone esters, e.g., testosterone palmitate, are disclosed. Methods of treating a hormone deficiency or effecting male contraception with the inventive formulations are also provided. 1. An oral pharmaceutical formulation comprisingabout 23 wt. % or less of a testosterone ester chose from testosterone enanthate; testosterone undecanoate; testosterone cypionate, and testosterone palmitate,about 63 wt. % of a lipophilic surfactant chosen from mono- and/or di-glycerides of fatty acids, andabout 15% of polyoxyl 40 hydrogenated castor oil.2. The oral pharmaceutical formulation of claim 1 , wherein the testosterone ester is testosterone undecanoate.3. The pharmaceutical composition of claim 2 , wherein the lipophilic surfactant is glyceryl palmitosterate claim 2 , glyceryl monolinoleate claim 2 , or a combination thereof.4. The oral pharmaceutical formulation of claim 1 , wherein the lipophilic surfactant is glyceryl palmitosterate claim 1 , glyceryl monolinoleate claim 1 , or a combination thereof.5. An oral pharmaceutical formulation comprisingabout 23 wt. % or less of a testosterone ester selected from the group consisting of testosterone enanthate, testosterone undecanoate, testosterone cypionate, and testosterone palmitate,about 55-65 wt. % of one or more lipophilic surfactants, andabout 15-45 wt. % of a hydrophilic surfactant having an HLB value greater than 10.6. The oral pharmaceutical formulation of claim 5 , wherein the lipophilic surfactant is a mono- and/or di-glyceride of fatty acids.7. The oral pharmaceutical formulation of claim 5 , wherein the lipophilic surfactant is selected from the group consisting of glyceryl caprylate/caprate claim 5 , glyceryl palmitosterate claim 5 , glyceryl monolinoleate and glyceryl monooleate.8. The oral ...

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Номер записи: 63

14-03-2019 дата публикации

Methods for preparing deoxycholic acid

Номер: US20190077826A1

Автор: Cheng-Gang LIN, LI Gui, PAN Chen, Tong-Wei GUAN, Yu-Ling Lu, Yuan-Yuan YIN, Zhi-Xuan WANG

Принадлежит: Noratech Pharmaceuticals Inc

The present invention discloses method for preparing deoxycholic acid (DCA) or an ester thereof or a pharmaceutically acceptable salt thereof. Said compounds may be applied to remove a fat deposition.

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Номер записи: 64

22-03-2018 дата публикации

METHOD FOR PREPARING SUBSTITUTED 3,7-DIHYDROXY STEROIDS

Номер: US20180079775A9

Автор: Ge Yu, Huang Yujin, White Steven K.

Принадлежит:

The invention relates to processes for preparing 17-alkynyl-7-hydroxy-steroids, such as 17-Ethynyl-10R,13S-dimethyl 2,3,4,7,8R,9S, 10,11,12,13,14S,15,16,17-hexadecahydro-1H-cyclopenta[a]phenanthrene-3R,7R,17S-triol (also referred to as 17α-ethynyl-androst-5-ene-3β, 7β, 17β-triol), that are essentially free of process impurities having binding activity at nuclear estrogen receptors. 2. The method of wherein Ris Calkyl or phenyl.3. The method of wherein Ris —CH.4. The method of wherein Rand Rare —CH.5. The method of wherein M is Li claim 1 , Mg or Zn.6. The method of wherein Ris —CH.7. The method of wherein M is Li and Ris —CH.8. The method of wherein comprising the additional step of purifying the 17α-alkynyl-androst-5-ene-3β claim 1 ,7β claim 1 ,17β-triol compound of step (f) by recrystallization.9. The method of wherein Ris —CH.10. The method of wherein Rand Rare —CH.11. The method of wherein M is Li claim 8 , Mg or Zn.12. The method of wherein Ris —CH.13. The method of wherein M is Li and Ris —CH.14. The method of wherein the 17α-alkynyl-androst-5-ene-3β claim 8 ,7β claim 8 ,17β-triol compound of step (f) is purified by recrystallization from methanol-water.15. The method of wherein Ris —CH.16. The method of wherein M is Li claim 14 , Mg or Zn.17. The method of wherein Ris —CH.18. The method of wherein the 17α-alkynyl-androst-5-ene-3β claim 1 ,7β claim 1 ,17β-triol compound is 17α-ethynyl-androst-5-ene-3β claim 1 ,7β claim 1 ,17β-triol.19. The method of wherein the 17α-alkynyl-androst-5-ene-3β claim 8 ,7β claim 8 ,17β-triol compound is 17α-ethynyl-androst-5-ene-3β claim 8 ,7β claim 8 ,17β-triol.20. The method of wherein the 17α-alkynyl-androst-5-ene-3β claim 14 ,7β claim 14 ,17β-triol compound is 17α-ethynyl-androst-5-ene-3β claim 14 ,7β claim 14 ,17β-triol. This non-provisional U.S. patent application is a divisional application of and claims priority to pending U.S. non-provisional application Ser. No. 12/479,626, filed Jun. 5, 2009 and issued on Nov. 13, 2012 ...

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Номер записи: 65

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: 66

29-03-2018 дата публикации

Synthesis of a substituted indene derivative

Номер: US20180086691A9

Автор: Curtis Harwig, Jeyaprakashnarayanan Seenisamy, Lakshindra Chetia, Mahesh Narayan Keregadde

Принадлежит: Aquinox Pharmaceuticals Canada Inc

This invention is directed to methods of preparing AQX-1125 having the formula: This invention is also directed to intermediates utilized in the methods of preparing AQX-1125.

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Номер записи: 67

02-04-2015 дата публикации

Compositions and methods for increasing telomerase activity

Номер: US20150093455A1

Автор: Allison C. Chin, Calvin Bruce Harley, David M. Miller-Martini, Nancy Yuk-yu Ip, Tsutomu Akama, Yung-Hou Wong

Принадлежит: Telomerase Activation Sciences Inc

The present invention relates to methods and compositions for increasing telomerase activity in cells. Such compositions include pharmaceutical, including topical, and nutraceutical formulations. The methods and compositions are useful for treating diseases subject to treatment by an increase in telomerase activity in cells or tissue of a patient, such as, for example, HIV infection, various degenerative diseases, and acute or chronic skin ailments. They are also useful for enhancing replicative capacity of cells in culture, as in ex vivo cell therapy and proliferation of stem cells.

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Номер записи: 68

19-03-2020 дата публикации

LIF/LIFR ANTAGONIST IN ONCOLOGY AND NONMALIGNANT DISEASES

Номер: US20200087340A1

Автор: Ahmed Gulzar, Nair Hareesh, Nickisch Klaus, Santhamma Bindu

Принадлежит:

Described herein are methods of using compounds that inhibit leukemia inhibitory factor (LIF) and/or block of the leukemia inhibitory factor receptor for treatment of liver fibrosis, proliferation of spinal tumors, and in combination therapy with an immunotherapeutic agent. 119-. (canceled)20. A method of treating cancer in a subject comprising administering to a subject a medicament comprising an effective amount of an immunotherapeutic agent and a small molecule compound that inhibits leukemia inhibitory factor or leukemia inhibitory factor receptor.21. The method of claim 20 , wherein the small molecule compound increases tumor specific infiltration of leucocytes.22. The method of claim 20 , wherein the small molecule compound upregulates formation of CD3+T cells claim 20 , CD4+T cells claim 20 , CD8+T cells claim 20 , or combinations thereof.25. The method of claim 24 , where:{'sup': 2', '3, 'Rand Rare F;'}{'sup': 4', '6', '6, 'sub': 2', '2', '2, 'Ris H, alkyl, —CH—OH, —COR, —CON(R); and'}{'sup': '5', 'Ris alkyl, alkenyl, aryl, or, cycloalkyl.'}27. The method of claim 26 , where{'sup': '5', 'Ris alkyl, alkenyl, aryl, or cycloalkyl.'}29. A method of treating cancer in a subject comprising administering to a subject a medicament comprising an effective amount of a PD-1 or PD-L1 inhibitor and a small molecule compound that inhibits leukemia inhibitory factor or leukemia inhibitory factor receptor.32. The method of claim 31 , where:{'sup': 2', '3, 'Rand Rare F;'}{'sup': 4', '6', '6, 'sub': 2', '2', '2, 'Ris H, alkyl, —CH—OH, —COR, —CON(R); and'}{'sup': '5', 'Ris alkyl, alkenyl, aryl, or, cycloalkyl.'}34. The method of claim 33 , where{'sup': '5', 'Ris alkyl, alkenyl, aryl, or cycloalkyl.'}3642-. (canceled) The invention generally relates to new anti-cancer compounds, acting through a new mechanism of action by simultaneous inhibition of leukemia inhibitory factor (LIF) and MDM2.Cancer is a group of diseases characterized by the uncontrolled growth and spread of ...

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Номер записи: 69

01-04-2021 дата публикации

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Номер: US20210094981A1

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

Принадлежит:

Described herein are steroids of Formula (I): 2. The method of claim 1 , wherein Ris methyl.3. The method of claim 1 , wherein both Rand Rare hydrogen.4. The method of claim 1 , wherein Ris C-Calkyl claim 1 , C-Calkenyl claim 1 , C-Calkynyl claim 1 , carbocyclyl claim 1 , heterocyclyl claim 1 , C(O)R claim 1 , —C(O)OR claim 1 , or —C(O)NRR.5. The method of claim 4 , wherein Ris —C(O)NRR.6. The method of claim 1 , wherein Ris hydrogen claim 1 , C-Calkyl claim 1 , or —OH.7. The method of claim 6 , wherein Ris hydrogen.8. The method of claim 1 , wherein both Rand Rare hydrogen claim 1 , the between —CRand —CRRis a single bond claim 1 , and both Rand Rare hydrogen.9. The method of claim 1 , wherein Z is —CH—.10. The method of claim 1 , wherein Ris hydrogen and Ris C-Calkyl.12. The method of claim 11 , wherein Ris methyl.13. The method of claim 11 , wherein Ris C-Calkyl claim 11 , C-Calkenyl claim 11 , C-Calkynyl claim 11 , carbocyclyl claim 11 , heterocyclyl claim 11 , —C(I)R claim 11 , —C(O)OR claim 11 , or —C(O)NRR.14. The method of claim 11 , wherein Ris C-Calkyl.15. The method of claim 11 , wherein Ris hydrogen.16. The method of claim 11 , wherein both Rand Rare hydrogen and both Rand Rare hydrogen.19. The method of claim 18 , wherein Ris methyl.20. The method of claim 18 , wherein Ris C-Calkyl claim 18 , C-Calkenyl claim 18 , C-Calkynyl claim 18 , carbocyclyl claim 18 , heterocyclyl claim 18 , —C(O)R claim 18 , —C(O)OR claim 18 , or —C(O)NRR.21. The method of claim 18 , wherein Ris C-Calkyl.22. The method of claim 20 , wherein Ris —C(O)NRR.23. The method of claim 18 , wherein Ris —OH.24. The method of claim 18 , wherein Ris hydrogen.25. The method of claim 18 , wherein both Rand Rare hydrogen and both Rand Rare hydrogen.27. (canceled)28. (canceled)29. (canceled)30. The method of claim 1 , wherein the CNS-related disorder is a major depressive disorder.31. The method of claim 1 , wherein the CNS-related disorder is tremor.32. The method of claim 31 , wherein the ...

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Номер записи: 70

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: 71

16-04-2015 дата публикации

Synthesis of estetrol via estrone derived steroids

Номер: US20150105362A1

Автор: Erwin Gerardus Jacobus Warmerdam, Mark Theodoor Verhaar, Thomas Koch

Принадлежит: Pantarhei Bioscience BV

A process is provided for the making of estetrol starting from a 3-A-oxy-estra-1,3,5(10),15-tetraen-17-one, wherein A is an C 1 -C 5 alkyl group, preferably a methyl group, or a C 7 -C 12 benzylic group, preferably a benzyl group. This process is particularly suitable to industry.

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Номер записи: 72

26-03-2020 дата публикации

METHODS FOR THE PURIFICATION OF DEOXYCHOLIC ACID

Номер: US20200095274A1

Автор: JR. Roy A., Moriarty Robert M., Prasad Achampeta Rathan, Reid John Gregory, Swaringen

Принадлежит: ALLERGAN SALES, LLC

Synthetic methods for preparing deoxycholic acid and intermediates thereof, high purity synthetic deoxycholic acid, compositions and methods of use are provided. Also, provided are processes for the synthesis of 12-keto or 12-α-hydroxysteroids from Δ-9,11-ene, 11-keto or 11-hydroxy-β-steroids. This invention is also directed to novel compounds prepared during the synthesis. This invention is also directed to the synthesis of deoxycholic acid starting from hydrocortisone. 18-. (canceled)10. The process of claim 9 , wherein compound 4 is contacted with more than one equivalent of tert-butyl hydroperoxide and in the presence of CuI.11. The process of claim 9 , wherein the co-oxidant is selected from the group consisting of aqueous sodium hypochlorite claim 9 , palladium on carbon claim 9 , Pd(OCOCF) claim 9 , Pd(OAc)and CuI.14. The process of claim 9 , wherein Rand Rtogether with the carbon atom attached thereto form a keto group.16. The process of claim 9 , wherein R is hydrogen.17. The process of claim 9 , wherein the reducing conditions comprise contact with aqueous sodium sulfite.18. The process of claim 9 , wherein the oxidizing agent is pyridinium chlorochromate. This application is a continuation of U.S. patent application Ser. No. 15/990,135, filed May 25, 2018, which is a continuation of U.S. patent application Ser. No. 15/603,290, filed May 23, 2017, now U.S. Pat. No. 10,005,813, which is a continuation of U.S. patent application Ser. No. 14/532,940, filed Nov. 4, 2014, now U.S. Pat. No. 9,683,007, which is a continuation of U.S. patent application Ser. No. 13/140,421, filed Sep. 24, 2012, which is a U.S. national stage of PCT/US2010/061150, filed Dec. 17, 2010, which claims the benefit of U.S. provisional application Ser. No. 61/288,132, filed on 18 Dec. 2009, U.S. provisional application Ser. No. 61/302,007, filed on 5 Feb. 2010, U.S. provisional application Ser. No. 61/303,816, filed on 12 Feb. 2010, U.K. Application No. 1008726.0 filed on 25 May 2010, and ...

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Номер записи: 73

02-06-2022 дата публикации

Methods of carbon-carbon bond fragmentation

Номер: US20220169580A1

Автор: Andrew Smaligo, Ohyun Kwon

Принадлежит: UNIVERSITY OF CALIFORNIA

The present disclosure relates to methods of carbon-carbon bond fragmentation.

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Номер записи: 74

19-04-2018 дата публикации

(17-ß)-3-Oxoandrost-4-En-17-Yl Undecanoate Compositions and Methods of Their Preparation and Use

Номер: US20180104257A1

Автор: Chidambaram Nachiappan, Frank Joel, Nachaegari Satish Kumar, Patel Mahesh V., Portlock Amy Jo, Venkateshwaran Srinivansan

Принадлежит: LIPOCINE INC.

Disclosed herein are compositions having a lipophilic active agent and methods of their use. 1. Substantially pure (17-β)-3-Oxoandrost-4-en-17-yl undecanoate suitable for administration to human subject in need of 17 beta-hydroxy androst-4-en-3-one.2. The substantially pure (17-β)-3-Oxoandrost-4-en-17-yl undecanoate of that has greater than 90% potency with respect to (17-β)-3-Oxoandrost-4-en-17-yl undecanoate.3. The substantially pure (17-β)-3-Oxoandrost-4-en-17-yl undecanoate of that is substantially free of impurities.4. The substantially pure (17-β)-3-Oxoandrost-4-en-17-yl undecanoate of having 10% or less of total impurities.5. The substantially pure (17-β)-3-Oxoandrost-4-en-17-yl undecanoate of having 10% or less of total known impurities.6. The substantially pure (17-β)-3-Oxoandrost-4-en-17-yl undecanoate of having 10% or less of total unknown impurities.7. The substantially pure (17-β)-3-Oxoandrost-4-en-17-yl undecanoate of having 10% or less of any single known impurity.8. The substantially pure (17-β)-3-Oxoandrost-4-en-17-yl undecanoate of having 10% or less of beta-hydroxy androst-4-en-3-one.9. The substantially pure (17-β)-3-Oxoandrost-4-en-17-yl undecanoate of having 2% or less of any single unknown impurity.10. The substantially (17-β)-3-Oxoandrost-4-en-17-yl undecanoate of comprising less than 50 claim 1 ,000 PPM organic solvent.11. The human subject of wherein the human is a male.12. The male of is a hypogonadal male.13. A pharmaceutical composition comprising or made from a substantially pure (17-β)-3-Oxoandrost-4-en-17-yl undecanoate and a pharmaceutically acceptable carrier for administration to human subject in need of (17-β)-hydroxy-4-androsten-3-one.14. The pharmaceutical composition of suitable for dosing up to 2000 mg per day (17-β)-3-Oxoandrost-4-en-17-yl undecanoate to an individual in need of (17-β)-hydroxy-4-androsten-3-one in single or divided doses.15. The pharmaceutical composition of which is a liquid claim 13 , solution claim 13 , ...

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Номер записи: 75

11-04-2019 дата публикации

LYMPH DIRECTING PRODRUGS

Номер: US20190105299A1

Автор: HAN Sifei, HU Luojuan, Porter Christopher John Hamilton, QUACH Tim, SIMPSON Jamie, TREVASKIS Natalie

Принадлежит:

The present invention relates to compounds and their uses, in particular, compounds in the form of prodrugs that promote transport of a pharmaceutical agent to the lymphatic system and subsequently enhance release of the parent drug. 123-. (canceled)26. The compound of claim 24 , wherein —Y— is substituted.27. The compound of claim 24 , wherein —Z— is —C(O)R—.28. The compound of claim 24 , wherein —Y— is substituted and —Z— is —C(O)R—.29. The compound of claim 24 , wherein —Y— represents a —C-Calkyl- claim 24 , —C-Calkenyl- claim 24 , or —C-Calkynyl- group optionally substituted with one or more groups selected from hydroxyl claim 24 , alkyl claim 24 , alkoxy claim 24 , alkoxycarbonyl claim 24 , alkenyl claim 24 , alkenyloxy claim 24 , alkynyl claim 24 , alkynyloxy claim 24 , amino claim 24 , aminoacyl claim 24 , thio claim 24 , arylalkyl claim 24 , arylalkoxy claim 24 , aryl claim 24 , aryloxy claim 24 , acylamino claim 24 , carboxy claim 24 , cyano claim 24 , halogen claim 24 , nitro claim 24 , sulfo claim 24 , phosphono claim 24 , phosphorylamino claim 24 , phosphinyl claim 24 , heteroaryl claim 24 , heteroaryloxy claim 24 , heterocyclyl claim 24 , heterocycloxy claim 24 , trihalomethyl claim 24 , pentafluoroethyl claim 24 , trifluoromethoxy claim 24 , difluoromethoxy claim 24 , trifluoromethanethio claim 24 , trifluoroethenyl claim 24 , mono- and di-alkylamino claim 24 , mono- and di-(substituted alkyl)amino claim 24 , mono- and di-arylamino claim 24 , mono- and di-heteroarylamino claim 24 , mono- and di-heterocyclyl claim 24 , amino claim 24 , and unsymmetric di-substituted amines having different substituents selected from alkyl claim 24 , aryl claim 24 , heteroaryl claim 24 , and heterocyclyl claim 24 , wherein one or more of the carbon atoms in the —C-Calkyl- claim 24 , —C-Calkenyl- claim 24 , or —C-Calkynyl- group of —Y— may be replaced with NH claim 24 , S claim 24 , or O.30. The compound of claim 25 , wherein —Y— represents a —C-Calkyl- claim 25 , —C- ...

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Номер записи: 76

26-04-2018 дата публикации

METHODS FOR PREPARING DEOXYCHOLIC ACID

Номер: US20180111960A1

Автор: CHEN Pan, GUAN Tong-Wei, GUI Li, LIN Cheng-Gang, LU Yu-Ling, WANG Zhi-Xuan, YIN Yuan-Yuan

Принадлежит: NORATECH PHARMACEUTICALS, INC.

The present invention discloses method for preparing deoxycholic acid (DCA) or an ester thereof or a pharmaceutically acceptable salt thereof. Said compounds may be applied to remove a fat deposition. 2. The method of claim 1 , wherein the hydrogenation condition in c) is pd/C as a catalyst and N-Methylpyrrolidone as a solvent.3. The method of claim 1 , wherein the condition of the carbonyl reduction and deprotection in d) is dissolving the compound 1.5 in tetrahydrofuran claim 1 , dropwise adding LiAl (OtBu) H at −5 to 5° C. claim 1 , stirring at room temperature claim 1 , and followed by dropwise adding p-toluenesulfonic acid.4. The method of claim 1 , wherein the dicarbene transfer reagent in f) is PhPCHCHBr claim 1 , KOtBu; the Lewis acid in g) is EtAlCl; the hydrogenation condition in h) comprises pd/C or PtOas a catalyst; the hydrogenation condition in i) comprises tert-butylhydroperoxide and pyridinium chlorochromate; the hydrogenation condition in j) comprises pd/C or PtOas a catalyst; the reducing agent in k) is LiAl(OtBu)H.5. The method of claim 1 , wherein the deprotection and the hydrolysis condition in 1) comprise reacting the compound 6 with an alkali metal hydroxide claim 1 , an alkali metal alcoholate claim 1 , an alkaline earth metal hydroxide claim 1 , an alkaline earth metal alcoholate claim 1 , or a mixture thereof6. The method of claim 5 , wherein the alkali metal hydroxide is NaOH.8. An intermediate compound selected from the group consisting of:(Z)-3α-benzoxy-5β-pregna-9 (11), 17 (20)-diene (1);(E)-3α-benzoxy-5β-cholo-9 (11), 16-diene-24-acid methyl ester(2);3α-benzoxy-5β-cholo-9(11)-alkene-24-acid methyl ester(3);3α-benzoxy-5β-cholo-9(11) -en-12-ketone-24-carboxylate(4);3α-benzoxy-5β-cholane-12-ketone-24-acid methyl ester(5);3α-benzoxy-5β-cholo-9(11) -en-12-hydroxy-24-acid methyl ester(5a);3α-benzoxy-5β-cholane-12β-hydroxy-24-acid methyl ester(5b);3α-benzoxy-5β-cholane-12α-hydroxy-24-acid methyl ester(6); and5β-androstane-9(11)-alkene-17-(1,3 ...

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Номер записи: 77

09-04-2020 дата публикации

TARGETED, METAL-CATALYZED FLUORINATION OF COMPLEX COMPOUNDS WITH FLUORIDE ION VIA DECARBOXYLATION

Номер: US20200108380A1

Автор: Groves John T., Huang Xiongyi

Принадлежит: THE TRUSTEES OF PRINCETON UNIVERSITY

Methods of preparing fluorinated compounds by carboxylative fluorination using fluoride are contained herein. Fluorinated compounds are provided. Methods of using fluorinated compounds are contained herein. 1. A method of targeted fluorination comprising combining a mono-fluoro-aryl iodine-(III) carboxylate and a manganese catalyst.2. The method of claim 1 , wherein the manganese catalyst is a manganese porphyrin or a manganese salen.3. The method of further comprising mixing a compound containing a carboxyl group claim 1 , a nucleophilic fluoride source claim 1 , a solvent and an iodine (III) oxidant to form the mono-fluoro-aryl iodine-(III) carboxylate prior to the step of combining.4. The method of further comprising maintaining the mono-fluoro-aryl iodine-(III) carboxylate at a temperature from 25° C. to 80° C.5. The method of claim 3 , wherein the nucleophilic fluoride source is trialkyl amine trihydrofluoride.6. The method of claim 5 , wherein the trialkyl amine trihydrofluoride is triethylamine trihydrofluoride.7. The method of claim 1 , wherein the step of combining is performed under an inert atmosphere.8. The method of claim 3 , wherein the nucleophilic fluoride source is [F]-fluoride.9. The method of claim 3 , wherein prior to the step of mixing claim 3 , the method comprises obtaining an aqueous [F] fluoride solution from a cyclotron claim 3 , loading the aqueous [F] fluoride solution onto an ion exchange cartridge and releasing the [F] fluoride from the ion exchange cartridge with an alkaline solution. This application is a divisional of U.S. patent application Ser. No. 15/019,673, which was filed Feb. 9, 2016 as a continuation-in-part of U.S. patent application Ser. No. 14/239,719, which was filed Apr. 8, 2014 and was a 35 U.S.C § 371 national stage of International Patent Application No. PCT/US2012/051628, which was filed Aug. 20, 2012. U.S. patent application Ser. No. 14/239,719 claimed the benefit of U.S. Provisional Application No. 62/113,847, ...

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Номер записи: 78

13-05-2021 дата публикации

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

Номер: US20210139530A1

Автор: Bao Rudi, CHEN Xiaopo, DENG Haining, SU Yidong, ZHANG Fujun

Принадлежит:

Steroid derivative regulators, a method for preparing the same, and uses thereof are described. Specifically, a compound of formula (I), a preparation method therefor, a pharmaceutical composition containing the compound, and uses thereof as a regulator the of GABAreceptor 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. 21. The compound of any formula claim 5 , the stereoisomer thereof claim 5 , or the pharmaceutically acceptable salt thereof according to claim 5 , wherein Z is selected from the group consisting of —CH— claim 5 , —CHNH— claim 5 , —CHO— claim 5 , —CH— claim 5 , —NH— and —NHSO—;{'sub': 2', '2', '2', '2', '2', '2', '2', '23', '2, 'Y is selected from the group consisting of —C(O)—, —C(O)CH—, —C(O)O—, —C(O)CHNH—, —C(O)CHO—, —SCH—, —S(O)CH—, —S(O)CH—, —P(O)R—, —C(O)NH— and —C(O)NHSO—;'}{'sup': 'a', 'sub': 1-6', '2-6', '3-6', '1-6', '3-8', '1-6', '1-6', '2', 'n1', '23', '2', 'n1', '23', '2', 'n1', '23', '2', 'n1', '23', '2', 'n1', '23', '24', '2', 'n1', 'm1', '23', '1-6', '2-6', '3-6', '1-6', '3-6', '1-6', '1-6', '1-6', '3-6, 'Ris selected from the group consisting of hydrogen atom, halogen, amino, cyano, nitro, Calkyl, Calkynyl, Ccycloalkyl, Chaloalkyl, Chalocycloalkyl, Calkoxy, Chydroxyalkyl, —(CH)OR, —(CH)SR, —(CH)C(O)R, —(CH)C(O)OR, —(CH)C(O)NRRand —(CH)S(O)R, wherein the Calkyl, Calkynyl, Ccycloalkyl, Chaloalkyl, Chalocycloalkyl, Calkoxy and Chydroxyalkyl are each optionally substituted by one or more substituents selected from the group consisting of hydrogen atom, halogen, cyano, hydroxy, Calkyl, Ccycloalkyl and 3 to 6 membered heterocyclyl;'}{'sup': 'd', 'sub': 1-6', '2-6', '3-6', '1-6', '3-8', '1-6', '1-6, 'Ris selected from the group consisting of hydrogen atom, halogen, amino, cyano, nitro, Calkyl, Calkynyl, Ccycloalkyl, Chaloalkyl, Chalocycloalkyl, Calkoxy and Chydroxyalkyl;'}{'sub': 23', '24', '1-6', '3-8', '1-6', ...

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Номер записи: 79

13-05-2021 дата публикации

19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF

Номер: US20210139531A1

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

Принадлежит:

Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (I): 12-. (canceled)48-. (canceled)9. The compound or pharmaceutically acceptable salt of claim 3 , wherein e is 1.10. The compound or pharmaceutically acceptable salt of claim 9 , wherein Ris substituted or unsubstituted Calkyl.11. The compound or pharmaceutically acceptable salt of claim 10 , wherein Ris —CH.12. The compound or pharmaceutically acceptable salt of claim 9 , wherein Ris —ORwherein Ris hydrogen or substituted or unsubstituted Calkyl.13. The compound or pharmaceutically acceptable salt of claim 12 , wherein Ris —OH.14. The compound or pharmaceutically acceptable salt of claim 9 , wherein Ris —S(═O)Rwherein Ris substituted or unsubstituted Calkyl.15. The compound or pharmaceutically acceptable salt of claim 14 , wherein Ris —S(═O)CH.16. The compound or pharmaceutically acceptable salt of claim 9 , wherein Ris —C(═O)Rwherein Ris substituted or unsubstituted Calkyl.17. The compound or pharmaceutically acceptable salt of claim 16 , wherein Ris —C(═O)CH.18. The compound or pharmaceutically acceptable salt of claim 9 , wherein Ris —C(═O)N(R)wherein Ris hydrogen or substituted or unsubstituted Calkyl.19. The compound or pharmaceutically acceptable salt of claim 18 , wherein Ris —C(═O)NHCH.20. (canceled)21. The compound or pharmaceutically acceptable salt of claim 3 , wherein between C5 and C6 is a single bond.23. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 3 , or a pharmaceutically acceptable salt thereof.2427-. (canceled)28. A method for positively modulating a GABA receptor in a subject in need thereof claim 3 , comprising administering to the subject an effective amount of a compound of or a pharmaceutically acceptable salt thereof.29. The method of claim 28 , wherein the subject has a CNS-related disorder.30. The method of claim 29 , wherein the CNS-related disorder is a sleep disorder claim 29 , a mood disorder ...

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Номер записи: 80

05-05-2016 дата публикации

Compounds and methods for trans-membrane delivery of molecules

Номер: US20160120996A1

Автор: IIan Ziv

Принадлежит: APOSENSE LTD

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

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Номер записи: 81

05-05-2016 дата публикации

PROCESSES FOR THE PREPARATION OF DEHYDROEPIANDROSTERONE AND ITS INTERMEDIATES

Номер: US20160122382A1

Автор: ALIETI Sanjay Reddy, DAHANUKAR Vilas, DINNE Naresh Kumar Reddy, Fryszkowska Anna, GORANTLA Srikanth Sarat Chandra, POREDDY Srinivas Reddy, QUIRMBACH Michael Siegfried, TIMMANNA Upadhya

Принадлежит:

The present application relates to a regioselective and stereoselective processes for the preparation of dehydroepiandrosterone (DHEA) and processes for its intermediates. 2. The process of claim 1 , wherein compound of formula (I) is converted to Abiraterone acetate.3. The process of claim 1 , wherein the compound of formula (I) is converted to DHEA Enanthate.9. The process of claim 8 , wherein the ketoreductase enzyme is having Sequence ID No: 1.10. The process of claim 8 , wherein compound of formula (I) is converted to Abiraterone acetate.11. The process of claim 8 , wherein the compound of formula (I) is converted to DHEA Enanthate. The present application relates to a regioselective and stereoselective processes for the preparation of dehydroepiandrosterone (DHEA) and processes for its intermediates.Dehydroepiandrosterone (DHEA) also known as androstenolone or prasterone or 3β-hydroxyandrost-5-en-17-one or 5-androsten-3β-ol-17-one, is an important endogenous steroid hormone and has the structure of formula (I).Dehydroepiandrosterone (DHEA) is a key intermediate in the synthesis of steroidal molecules, including but not limited to abiraterone acetate, a drug used in the treatment of castration-resistant prostate cancer.An article by J. Bryan Jones et al., “Steroids and steroidases.VI. On the C-17 specificity of the Δ5-3-ketoisomerase of Psudomonas testosterone and evidence for substrate micelle formation,” Candian Journal of Chemistry, 46,1459-1465 (1968) describes a process for the preparation of androst-5-ene-3,17-dione, an intermediate used for the preparation of DHEA. The process disclosed in the said reference involves reacting androst-4-ene-3,17-dione with potassium t-butoxide in t-butyl alcohol under nitrogen atmosphere for 90 minutes at 20° C., followed by quenching the reaction mass by rapid addition of 10% aqueous acetic acid, adding excess sodium bicarbonate, extracting with ether, evaporating at room temperature and recrystallization from acetone to ...

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Номер записи: 82

16-04-2020 дата публикации

NEUROACTIVE 19-ALKOXY-17-SUBSTITUTED STEROIDS, PRODRUGS THEREOF, AND METHODS OF TREATMENT USING SAME

Номер: US20200113916A1

Автор: Covey Douglas, Robichaud Albert Jean

Принадлежит:

The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds. 153-. (canceled)55. The compound of claim 54 , wherein the Rgroup is selected from the group consisting of H claim 54 , methyl claim 54 , and trifluoromethyl.56. The compound of claim 54 , wherein Ris selected from the group consisting of H claim 54 , methoxy claim 54 , ethoxy claim 54 , and an optionally substituted morpholinyl ring.57. The compound of claim 54 , wherein Ris H.58. The compound of claim 54 , wherein each instance of - - - between C-Cand C-Cis absent and C—H is in the alpha position.59. The compound of claim 54 , wherein each instance of - - - between C-Cand C-Cis absent and C—H is in the beta position.60. The compound of claim 54 , wherein each instance of - - - between C-Cis absent and Ris in the beta position.61. The compound of claim 54 , wherein Ris ═O claim 54 , methoxy or H.62. The compound of claim 54 , wherein Ris methyl.63. The compound of claim 54 , wherein Ris beta-methoxy.64. The compound of claim 54 , wherein Ris beta-spirooxirane.65. The compound of claim 54 , wherein Ris beta-cyano.66. The compound of claim 54 , wherein Ris ═O.67. The compound of claim 54 , wherein Ris beta-nitro.68. The compound of claim 54 , wherein Ris beta-CHC(O)—.69. The compound of claim 54 , wherein Ris beta-HOCHC(O)—.73. The method of claim 72 , wherein the disorder is selected from the group consisting of insomnia claim 72 , mood disorders claim 72 , convulsive disorders claim 72 , anxiety claim 72 , or symptoms of ethanol withdrawal. This application is a continuation application and claims priority to U.S. patent application Ser. No. 15/459,492, filed on Mar. 15, 2017, which claims ...

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Номер записи: 83

02-05-2019 дата публикации

C-HALOGEN BOND FORMATION

Номер: US20190127311A1

Автор: Groves John T., Liu Wei

Принадлежит: THE TRUSTEES OF PRINCETON UNIVERSITY

Methods of halogenating a carbon containing compound having an sp3 C—H bond are provided. Methods of fluorinating a carbon containing compound comprising halogenation with Cl or Br followed by nucleophilic substitution with F are provided. Methods of direct oxidative C—H fluorination of a carbon containing compound having an sp3 C—H bond are provided. The halogenated products of the methods are provided. 1. A composition comprising at least two or more of a carbon containing compound having an sp3 C—H bond hydrogen , a halogenating agent , a halogenating catalyst , or a phase transfer catalyst.2. The composition of claim 1 , wherein the carbon containing compound includes a compound selected from the group consisting of neopentane; toluene; cyclohexane; norcarane; trans-decalin; 5α-cholestane; sclareolide; 1 claim 1 , 3 claim 1 , 5(10)-estratrien-17-one; (1R claim 1 ,4aS claim 1 , 8aS)-octahydro-5 claim 1 ,5 claim 1 ,8a-trimethyl-1-(3-oxobutyl)-naphtalenone; (1R claim 1 , 4S claim 1 , 6S claim 1 , 10S)-4 claim 1 , 12 claim 1 , 12-trimethyl-tricyclo[8.2.0.04 claim 1 ,6]dodecan-9-one; levomethorphan; lupine; 20-methyl-5alpha(H)-pregnane; isolongifolanone; caryophyllene acetate; N-acetyl-gabapentin methyl ester; acetyl-amantidine; phthalimido-amantadine; methyloctanoate; saturated fatty acid esters; N-acetyl-Lyrica methyl ester; artemisinin claim 1 , adapalene; finasteride; N-acetyl-methylphenidate; mecamylamine; N-acetyl-mecamylamine; N-acetyl-memantine; phthalimidi-memantine; N-acetyl-enanapril precursor methyl ester; progesterone; artemisinin; adapalene; dopamine derivative; pregabalin; cholestane; finasteride; methylphenidate derivative; mecamylamine; gabapentin; memantine derivative; gabapentin; rimantadine derivative; isoleucine derivative; leucine derivative; valine derivative; pregesterone; tramadol; enalapril precursor; (1R claim 1 , 4aS claim 1 , 8aS)-5 claim 1 , 5 claim 1 , 8a-trimethyl-1-(3-oxobutyl)octahydronaphthalen-2(1H)-one; phenylalanine; donepezil ...

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Номер записи: 84

09-05-2019 дата публикации

Small molecules active against gram-negative bacteria

Номер: US20190135821A1

Автор: Alfredo Garcia, Andrew Riley, Bryon Drown, Martin Chavez, Michelle RICHTER, Paul J. Hergenrother, Sarah Tasker

Принадлежит: University of Illinois

Disclosed are compounds that accumulate in Gram-negative bacteria. Also disclosed are method of antimicrobial treatment using the compounds.

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Номер записи: 85

09-05-2019 дата публикации

6-Substituted Estradiol Derivatives and Methods of Use

Номер: US20190135853A1

Автор: Yarger James G.

Принадлежит:

Disclosed are compounds of the formula: 3. A compound according to whereinY is selected from ═O and —OH;{'sub': 4', '1', '6, 'Ris selected from hydrogen, halo and C-Calkyl;'}{'sub': '2', 'Ris selected from hydrogen, —OH and halo; and'}{'sub': '3', 'Ris selected from hydrogen, halo and —OH.'}4. A compound according to wherein:Y is (S)-configured —OH;{'sub': '4', 'Ris selected from hydrogen and alkyl;'}{'sub': 2', '3, 'Rand Rare hydrogen;'}{'sub': 2', 'm', '2', 'n', '3', '2', 'm', '2', 'n', '3, 'X is selected from —(CH)—O—(CH)CHand —(CH)—S—(CH)CH;'}n is an integer selected from 0-3; andthe C-13 methyl group is (S)-configured.6. A compound according to wherein:{'sub': '1', 'Ris selected from hydrogen, —OH and halo;'}{'sub': 4', '1', '6, 'Ris selected from hydrogen, halo and C-Calkyl;'}{'sub': '2', 'Ris selected from hydrogen and halo; and'}{'sub': '3', 'Ris selected from hydrogen, halo and —OH.'}7. A compound according to wherein:{'sub': '1', 'Ris hydrogen;'}{'sub': '4', 'Ris selected from hydrogen and alkyl;'}{'sub': 2', '3, 'Rand Rare hydrogen;'}{'sub': 2', 'n', '2', 'n', '3', '2', 'm', '2', 'n', '3, 'X is selected from —(CH)—O—(CH)CHand —(CH)—S—(CH)CH; and'}n is an integer selected from 0-3,wherein both the C-13 methyl and C-17 hydroxyl are (S)-configured.9. A compound according to wherein:{'sub': 11', '1', '6, 'Ris selected from hydrogen and C-Calkyl;'}{'sub': 4', '1', '6, 'Ris selected from hydrogen, halo and C-Calkyl;'}{'sub': '2', 'Ris selected from hydrogen and halo; and'}{'sub': '3', 'Ris selected from hydrogen, halo and —OH.'}10. A compound according to wherein:{'sub': '11', 'Ris hydrogen;'}{'sub': '4', 'Ris selected from hydrogen and alkyl;'}{'sub': 2', '3, 'Rand Rare hydrogen;'}{'sub': 2', 'n', '2', 'n', '3', '2', 'm', '2', 'n', '3, 'X is selected from —(CH)—O—(CH)CHand —(CH)—S—(CH)CH; and'}n is an integer selected from 0-3,wherein both the C-13 methyl and C-17 hydroxyl are (S)-configured.12. A compound according to wherein:{'sub': '1', 'Ris selected from ...

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Номер записи: 86

24-05-2018 дата публикации

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

Номер: US20180141971A1

Автор: Beresis Richard T., Harrison Boyd L., Martinez Botella Gabriel, Robichaud Albert J., Salituro Francesco G.

Принадлежит:

Provided herein are 19-nor C3,3-disubstituted steroids of Formula (I): 3. The method of claim 1 , wherein Ris —CH claim 1 , —CHCH claim 1 , —CHF claim 1 , —CHF claim 1 , —CF claim 1 , —CHOCH claim 1 , or substituted or unsubstituted cyclopropyl.4. The method of claim 3 , wherein Ris —CH.5. The method of claim 1 , wherein Ris —OH claim 1 , —OCH claim 1 , —OCHCH claim 1 , —OCHCHCH claim 1 , —CH claim 1 , —CHCH claim 1 , —CHCHCH claim 1 , substituted or unsubstituted cyclopropyl claim 1 , fluoro claim 1 , or chloro.6. The method of claim 1 , wherein Ris H.7. The method of claim 1 , wherein Rand Rare both hydrogen.8. The method of claim 1 , wherein Rand Rare joined to form ═O (oxo).9. The method of claim 1 , wherein represents a double bond claim 1 , and Ris hydrogen claim 1 , fluoro claim 1 , —CH claim 1 , or —CF.10. The method of claim 1 , wherein represents a single bond claim 1 , and both of Rand Rare hydrogen.11. The method of claim 1 , wherein represents a single bond claim 1 , and both of Rand Rare —CHor —CF.12. The method of claim 1 , wherein represents a single bond claim 1 , and both of Rand Rare fluoro.13. The method of claim 1 , wherein represents a single bond claim 1 , and Ris substituted or unsubstituted Calkyl claim 1 , or halogen claim 1 , and Ris hydrogen.14. The method of claim 13 , wherein Ris fluoro.15. The method of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris hydrogen.16. The method of claim 1 , wherein at least one of R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Ris substituted or unsubstituted Calkyl claim 1 , —COR claim 1 , —C(═O)R claim 1 , —CN claim 1 , —NO claim 1 , or halogen claim 1 , wherein Ris substituted or unsubstituted Calkyl.17. The method of claim 16 , wherein at least one of R claim 16 , R claim 16 , R claim 16 , R claim 16 , and Ris substituted or unsubstituted —CH.18. The method of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , R claim 1 , and Rare hydrogen.22. A method ...

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Номер записи: 87

14-08-2014 дата публикации

C-HALOGEN BOND FORMATION

Номер: US20140227184A1

Автор: Groves John T., Huang Xiongyi, Liu Wei

Принадлежит: THE TRUSTEES OF PRINCETON UNIVERSITY

Methods of halogenating a carbon containing compound having an sp3 C—H bond are provided. Methods of fluorinating a carbon containing compound comprising halogenation with Cl or Br followed by nucleophilic substitution with F are provided. Methods of direct oxidative C—H fluorination of a carbon containing compound having an sp3 C—H bond are provided. The halogenated products of the methods are provided. 1. A method of direct oxidative C—H fluorination of a carbon containing compound having an sp3 C—H bond to form an sp3 C—F bond , the method comprising:combining a carbon containing compound having an sp3 C—H bond, a fluorinating agent, a fluorinating catalyst, and an oxidant, wherein the fluorinating agent is a fluoride ion source.2. The method of claim 1 , wherein the carbon containing compound is added in a concentration from 1 mM to 5 M claim 1 , the fluorinating agent is added in a concentration from 1 mM to 5 M claim 1 , the fluorinating catalyst is added in a concentration from 1 mol % to 20 mol % claim 1 , and the oxidant is added in a concentration from 1 mM to 1 M in each addition.3. The method of claim 1 , further comprising allowing the combined carbon containing compound claim 1 , fluorinating agent claim 1 , fluorinating catalyst claim 1 , and oxidant to react for 30 minutes to 12 hours.4. The method of claim 1 , further comprising maintaining the carbon containing compound claim 1 , the fluorinating agent claim 1 , the fluorinating catalyst claim 1 , and the oxidant at a temperature from −20° C. to +100° C.5. The method of claim 1 , wherein combining further comprises:mixing the fluorinating catalyst, the fluorinating agent, and the carbon containing compound in a solvent to form a first mixture;providing an inert gas over the first mixture; andadding the oxidant to the first mixture to form a second mixture.6. The method of claim 1 , wherein the carbon containing compound includes a compound selected from the group consisting of neopentane; toluene; ...

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Номер записи: 88

11-06-2015 дата публикации

NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF

Номер: US20150158903A1

Автор: Askew, Dodart Jean-Cosme, Harrison Boyd L., Jr. Benny C., Robichaud Albert J., Salituro Francesco G., Upasani Ravindra B.

Принадлежит: SAGE THERAPEUTICS, INC.

Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, wherein Z is a group of the formula (i), (ii), (iii), (iv), or (v), and wherein L, L, L, X, X, Y, R, R, R, n, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, R, and Rare as defined herein, and pharmaceutical compositions thereof. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of CNS-related conditions in mammals. 11. The compound of claim 10 , wherein Y is —O— and Lis an alkylene or heteroalkylene group.14. The compound of claim 13 , wherein Y is —O— and Lis an alkylene or heteroalkylene.16. The compound of claim 1 , wherein the group —XRis in the beta position claim 1 , and Ris in the alpha position.17. The compound of claim 1 , wherein —XRis —OH.18. The compound of claim 1 , wherein Ris hydrogen.19. The compound of claim 1 , wherein Ris substituted or unsubstituted alkyl.20. The compound of claim 1 , wherein represents a double bond and Ris halo or substituted or unsubstituted alkyl21. The compound of claim 1 , wherein Ris halo or substituted or unsubstituted alkyl.22. The compound of claim 1 , wherein Ris hydrogen.23. The compound of claim 1 , wherein Ris —OR.24. The compound of claim 1 , wherein Ris hydrogen or —OR claim 1 , and Ris hydrogen.25. The compound of claim 1 , wherein Rand Rtogether form an oxo group.26. The compound of claim 1 , wherein represents a single bond claim 1 , and the hydrogen at C5 is in the alpha position.27. The compound of claim 1 , wherein represents a double bond.28. The compound of claim 1 , wherein Ris —CH.30. (canceled)36. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound of any one of the preceding claims.37. A method for preventing claim 1 , treating claim 1 , ameliorating or managing a disease or condition which comprises administering to a patient in need of such prevention claim 1 , treatment claim 1 , ...

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Номер записи: 89

01-06-2017 дата публикации

Crystalline solvate forms of a pharmaceutical

Номер: US20170152281A1

Автор: Brenton Skylar Wolfe, Igor Ivanisevic, Kyle Stephens, Mark Andres, Steven K. White

Принадлежит: NEURMEDIX Inc

The invention provides and describes solid state 17α-ethynyl-androst-5-ene-3β,7β,17β-triol including amorphous and crystalline forms and specific polymorphic forms thereof. Anhydrates and solvates of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol include Form I anhydrate and Form IV and Form V solvates. The invention further relates to solid and suspension formulations containing 17α-ethynyl-androst-5-ene-3β,7β,17β-triol in a described solid state form and use of the formulations to treat hyperglycemic conditions, such as type 2 diabetes and metabolic syndrome, and autoimmune conditions, such as rheumatoid arthritis, ulcerative colitis and type 1 diabetes, among other inflammation related conditions in subjects or human patients. The invention also relates to methods to make liquid formulations from solid state forms of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol and uses of such formulations in treating the described conditions.

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Номер записи: 90

01-06-2017 дата публикации

NEUROACTIVE 19-ALKOXY-17-SUBSTITUTED STEROIDS, PRODRUGS THEREOF, AND METHODS OF TREATMENT USING SAME

Номер: US20170152282A9

Автор: Covey Douglas, Robichaud Albert Jean

Принадлежит: WASHINGTON UNIVERSITY

The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds. 2. (canceled)3. The compound of claim 1 , wherein the Rgroup is selected from the group consisting of H claim 1 , methyl claim 1 , and trifluoromethyl.4. (canceled)5. The compound of claim 1 , wherein Ris H.6. The compound of claim 1 , wherein Ris substituted methyl.7. The compound of claim 1 , wherein the C—H is in the alpha position.8. The compound of claim 1 , wherein the C—H is in the beta configuration and Rgroup is in the beta configuration.9. The compound of claim 1 , wherein Ris H.10. The compound of claim 1 , wherein Ris ═O claim 1 , methoxy or H.11. The compound of claim 1 , wherein Ris methyl.13. The compound of wherein Ris methyl.14. The compound of claim 12 , wherein Ris beta-methoxy.15. (canceled)16. The compound of claim 12 , wherein Ris beta-cyano.17. The compound of claim 12 , wherein Ris ═O.18. (canceled)19. The compound of claim 12 , wherein Ris beta-CHC(O)—.20. The compound of claim 12 , wherein Ris beta-HOCHC(O)—.22. The compound of claim 21 , wherein Ris methyl.2350-. (canceled)53. (canceled) This application claims priority benefit of U.S. Provisional Patent Application Ser. No. 61/738,822, filed on Dec. 18, 2012, the entire content of which is incorporated herein by reference.The claimed subject matter was developed with Government support under NIH Grant #GM47969, awarded by the National Institute of Health. Accordingly, the Government has certain rights in the claimed subject matter.The present disclosure is generally directed to novel compounds having utility as an anesthetic and/or in the treatment of disorders relating to GABA function and activity. More ...

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Номер записи: 91

01-06-2017 дата публикации

Neuroactive 19-alkoxy-17(20)-z-vinylcyano-substituted steroids, prodrugs thereof, and methods of treatment using same

Номер: US20170152284A9

Автор: Douglas F. Covey

Принадлежит: Washington University in St Louis WUSTL

The present disclosure is generally directed to neuroactive 19-alkoxy-17(20)-Z-vinylcyano-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds.

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Номер записи: 92

21-08-2014 дата публикации

NEUROACTIVE 19-ALKOXY-17-SUBSTITUTED STEROIDS, PRODRUGS THEREOF, AND METHODS OF TREATMENT USING SAME

Номер: US20140235600A1

Автор: Covey Douglas, Robichaud Albert Jean

Принадлежит: WASHINGTON UNIVERSITY

The present disclosure is generally directed to neuroactive 19-alkoxy-17-substituted steroids as referenced herein, and pharmaceutically acceptable salts thereof, for use as, for example, an anesthetic, and/or in the treatment of disorders relating to GABA function and activity. The present disclosure is further directed to pharmaceutical compositions comprising such compounds. 2. The compound of claim 1 , wherein one or both of Ror R claim 1 , when present and other than H claim 1 , are in the beta configuration.3. The compound of claim 1 , wherein the Rgroup is selected from the group consisting of H claim 1 , methyl claim 1 , and trifluoromethyl.4. The compound of claim 1 , wherein Ris selected from the group consisting of H claim 1 , methoxy claim 1 , ethoxy claim 1 , and an optionally substituted morpholinyl ring.5. The compound of claim 1 , wherein Ris H.6. The compound of claim 1 , wherein Ris substituted methyl.7. The compound of claim 1 , wherein the C—H is in the alpha position.8. The compound of claim 1 , wherein the C—H is in the beta configuration and Rgroup is in the beta configuration.9. The compound of claim 1 , wherein Ris H.10. The compound of claim 1 , wherein Ris ═O claim 1 , methoxy or H.11. The compound of claim 1 , wherein Ris methyl.13. The compound of wherein Ris methyl.14. The compound of claim 12 , wherein Ris beta-methoxy.15. The compound of claim 12 , wherein Ris beta-spirooxirane.16. The compound of claim 12 , wherein Ris beta-cyano.17. The compound of claim 12 , wherein Ris ═O.18. The compound of claim 12 , wherein Ris beta-nitro.19. The compound of claim 12 , wherein Ris beta-CHC(O)—.20. The compound of claim 12 , wherein Ris beta-HOCHC(O)—.22. The compound of claim 21 , wherein Ris methyl.2324-. (canceled)26. The compound of claim 25 , wherein Ris OH in the beta configuration.27. The compound of claim 25 , wherein Ris ═O.28. The compound of claim 25 , wherein Ris selected from the group consisting of H claim 25 , methoxy claim 25 , ...

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Номер записи: 93

21-08-2014 дата публикации

PROCESS FOR THE PREPARATION OF ESTETROL

Номер: US20140235882A1

Автор: Coelingh Bennink Herman Jan Tijmen, DAMEN Franciscus Wilhelmus Petrus, PLATTEEUW Johannes Jan, Van Vliet Michiel Christine Alexander

Принадлежит:

The present invention relates to a process for the preparation of estra-1,3,5(10)-trien-3,15α,16α,17β-tetraol (estetrol), via a silyl enol ether derivative 17-B-oxy-3-A-oxy-estra-1,3,5(10),16-tetraene, wherein A is a protecting group and B is —Si(R). The invention further relates to a process for the synthesis of 3-A-oxy-estra-1,3,5(10),15-tetraen-17-one, wherein A is a protecting group, via said silyl enol ether derivative. 2. The process according to claim 1 , wherein step (2) of the process is performed in the presence of an iodine(V) species claim 1 , and wherein the iodine(V) species is present in an amount of 0.1 mol % or more with respect to compound III.3. The process according to claim 2 , wherein the iodine(V) species comprises 2-iodoxybenzoic acid (IBX) claim 2 , stabilised 2-iodoxybenzoic acid (SIBX) claim 2 , 2-iodoxybenzenesulphonic acid (IBS) claim 2 , and/or a derivative thereof.4. The process according to claim 2 , wherein the iodine(V) species comprises a species formed by complexation of IBX claim 2 , IBS and/or a derivative thereof with a ligand.5. The process according to claim 2 , wherein the iodine(V) species comprises 2-iodoxybenzenesulphonic acid (IBS) and/or a derivative thereof claim 2 , and wherein the IBS and/or derivative thereof is present in an amount of 0.1 mol % to 50 mol % with respect to compound III.6. The process according to claim 2 , wherein the solvent in step (2) is selected from the group consisting of DMSO claim 2 , DMF claim 2 , DMA claim 2 , NMP claim 2 , a combination thereof claim 2 , and a combination of DMSO claim 2 , DMF claim 2 , DMA and/or NMP with one or more organic solvents.7. The process according to claim 1 , wherein step (2) of the process is performed in the presence of a transition metal compound claim 1 , and wherein the transition metal compound is present in an amount of 0.1 mol % or more with respect to compound III.8. The process according to claim 7 , wherein the transition metal compound is a ...

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Номер записи: 94

09-06-2016 дата публикации

METHOD FOR SEPARATING ESTROGEN FROM PLACENTA

Номер: US20160159847A1

Автор: CHUANG Lin-Hsiang, CHUANG Ming-Hsi, LIN Hua-Ching, Lin Shu-Mei, LIU Chu-Ting, PENG Chiu-Ying, Wang Be-Jen, YU Zer-Ran

Принадлежит:

The present invention provides a method of separating estrogen from placenta, which uses supercritical fluid technique to load the placenta powder of human body or sheep, pig, deer and other animals into an extraction tank. Under the operating conditions of preset pressure and temperature, supercritical solvent is added into the extraction tank to extract estrogen from placenta, so as to acquire de-estrogen placenta powder and placenta extract liquor. Under the same condition, the de-estrogen placenta extract liquor and supercritical solvent are added by a preset volume flow ratio into an adsorption tank. The estrogen in the placenta extract liquor is adsorbed by the adsorption tank to obtain de-estrogen placenta extract. It is then eluted with ethanol solution by gradient proportion to obtain purified natural estrogen. 1. A method of separating estrogen from placenta , which using a supercritical fluid , comprising the following steps:extraction: under the operating conditions of preset temperature and pressure, load placenta powder in an extraction tank, add supercritical solvent to extract estrogen from placenta powder, and produce placenta extract liquor, wherein said placenta powder is a dry placenta powder of human body or sheep, pig, deer or other animals, and wherein said supercritical solvent is supercritical carbon dioxide/ethanol, and in the extraction step, it is required to load 1 Kg placenta powder in an extraction tank under the operating condition of 20-30 MPa and 40° C., add supercritical solvent into an adsorption tank by a flow ratio of 10˜20:1 (supercritical carbon dioxide/ethanol), extract estrogen after 2-3 h reaction time;adsorption: under the same operating condition, add the extract liquor of de-estrogen placenta and supercritical solvent into an adsorption tank, allow the estrogen in the placenta extract liquor to be adsorbed by the adsorption tank, obtain the de-estrogen placenta extract; andgradient elution: elute the estrogen in the ...

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Номер записи: 95

22-09-2022 дата публикации

INDUSTRIAL PROCESS FOR THE PREPARATION OF HIGH PURITY ESTETROL

Номер: US20220296609A1

Автор: BACSA Ildikó, LOVAS Róbert, MAHÓ Sándor, MAYER Beatrix

Принадлежит:

The invention relates to the preparation of estetrol of formula (I), derivatives thereof protected at positions 3,15α,16α,17β of general formula (III), and 3-hydroxy derivatives thereof protected at positions 15α,16α,17β of general formula (IV), and to the intermediates of general formulae (III) and (IV) applied in the process. Another aspect of the invention is the use of estetrol of formula (I) obtained by the process of the invention for the preparation of a pharmaceutical composition. 2. The process according to claim 1 , wherein the solvent used in step (a) is selected from the group consisting of aliphatic and aromatic hydrocarbons claim 1 , halogenated hydrocarbons claim 1 , esters claim 1 , and ethers.3. The process according to any one of to claim 1 , wherein the reactant used in step (a) is acetic anhydride claim 1 , acetyl chloride or bromide.4. The process according to any one of to claim 1 , wherein the reactant used in step (a) is acetic acid-formic acid mixed anhydride.5. The process according to any one of to claim 1 , wherein step (a) is carried out in the presence of a tertiary amine base.6. The process according to any one of to claim 1 , wherein the step (a) further comprises crystallizing the resulting compound of general formula (III) from Calcohols.7. The process according to any one of to claim 1 , wherein the step (a) is carried out without the purification and/or isolation of the compounds of formula (II).8. The process according to any one of to claim 1 , wherein the step (b) is carried out by catalytic hydrogenation claim 1 , with hydrogen gas claim 1 , wherein the catalyst is selected from the group consisting of palladium or palladium on a support.9. The process according to claim 8 , wherein the solvent used for the catalytic hydrogenation is selected from the group consisting of alcohols claim 8 , esters and ketones.10. The process according to any one of to claim 8 , wherein the step (b) is carried out by transfer hydrogenation using ...

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Номер записи: 96

07-06-2018 дата публикации

PROGESTERONE ANTAGONISTS

Номер: US20180155386A1

Автор: Debnath Baishakhi, Narkunan Kesavaram, Nickisch Klaus, Santhamma Bindu

Принадлежит:

Described herein are compounds which either act as pure antiprogestins or as antiprogestins with partial agonistic activity and methods of treating cancer using such compounds. 19-. (canceled)11. (canceled)12. The method of claim 10 , wherein:{'sup': '7', 'sub': 3', '2', '2', '2', '2, 'Ris —CH═CH—CF, —CH—CF═CF, or —CF—CH═CH.'}1314-. (canceled)16. (canceled)18. (canceled) The present application is a divisional of U.S. patent application Ser. No. 13/193,426, filed Jul. 28, 2011, which is incorporated herein by reference.The present invention relates to the identification of a class of compounds that behave either as pure antiprogestins or as antiprogestins with partial agonistic activity, also called mesoprogestins. Pure antiprogestins has been known to suppress the growth of cancer and other proliferative diseases, whereas mesoprogestins has been shown to be useful in the treatment of fibroids and endometriosis etc. The present invention also relates to processes of preparation and the use in therapy of such novel compounds.In the past, progesterone antagonists have been postulated to be of potential benefit in the treatment of breast cancer where the primary lesion contains both estrogen and progesterone receptors. In a recent study of an in vivo rat model of progesterone receptor positive breast cancer, it was shown that the administration of a new antiprogestin (Proellex, CDB-4124) resulted in a regression of tumor size as well as a decrease in the development of new tumors. shows a series of selected progesterone receptor modulators that have been shown to be effective in vitro and in vivo. The prototype antagonist, Mifepristone (see ), is characterized by the 19-nor-4,9-diene steroid nucleus, the 17α-propynyl-17β-hydroxy functionality, and the 11β-(4-dimethylamino)phenyl functional group which is believed to be responsible for its antagonistic activity. While Mifepristone is a potent progesterone antagonist, its long-term clinical use is limited due to its ...

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Номер записи: 97

23-05-2019 дата публикации

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

Номер: US20190153018A1

Автор: Nair Hareesh, Nickisch Klaus, Santhamma Bindu

Принадлежит:

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

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Номер записи: 98

08-06-2017 дата публикации

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

Номер: US20170158730A1

Автор: DUGAR Sundeep, Mahajan Dinesh, SCHREINER George Frederick

Принадлежит: SPHAERA PHARMA PVT. LTD.

The present invention relates to novel steroidal compounds of formula (I), process for preparation of the same and composition comprising these compounds. 5. The compounds as claimed in 1 , selected from the group comprising:i. (10R,11S,13S,17S)-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-11-hydroxy-10,13-dimethyl-3-oxo-1H-cyclopenta[a]phenanthrene-17-carboxylic acid;ii. (3S,8S,9S,10S,11S,13S,14S,17S)-hexadecahydro-3,11-dihydroxy-N,10,13-trimethyl-1H-cyclopenta[a]phenanthrene-17-carboxamide;iii. (3S,8S,9S,10S,11S,13S,14S,17S)—N-(2-aminoethyl)-hexadecahydro-3,11-dihydroxy-10,13-dimethyl-1H-cyclopenta[a]phenanthrene-17-carboxamide;iv. (3S,5R,6R,10R,11S,13S,17S)-hexadecahydro-6-methoxy-10,13-dimethyl-17-(2-methyl-1,3-dioxolan-2-yl)-1H-cyclopenta[a]phenanthrene-3,5,11-triol;v. (4aR,5S,6aS)-5-hydroxy-4a,6a-dimethyl-4,4a,4b,5,6,6a,9,9a,9b,10-decahydro-1H-indeno[5,4-f]quinoline-2,7βH,8H)-dione;vi. (4a′R,5′S,6a'S)-5′-hydroxy-4a′,5′,6a′-trimethyl-3′,4′,4a′,4b′,5′,6′,6a′,8′,9′,9a′,9b′,10′-dodecahydrospiro[[1,3]dioxolane-2,7′-indeno[5,4-f]quinolin]-2′(1′H)-one;vii. (4aR,5S,6aS)-4,4a,4b,5,6,6a,9,9a,9b,10-decahydro-5-hydroxy-4a,6a-dimethyl-1H-indeno[5,4-f]quinoline-2,7βH,8H)-dione;viii. (4aR,5S,6aS)-7-acetyl-4,4a,4b,5,6,6a,7,8,9,9a,9b,10-dodecahydro-5-hydroxy-4a,5,6a-trimethyl-1H-indeno[5,4-f]quinolin-2(3H)-one;ix. (11S)-7,8,9,11,12,13,14,15,16,17-decahydro-3,11-dihydroxy-6H-cyclopenta[a]phenanthrene-17-carboxylic acid;x. (4aR,6aS)-2,3,4,4a,4b,5,6,6a,7,8,9,9a,9b,10-tetradecahydro-4a,6a-dimethyl-2,5-dioxo-1H-indeno[5,4-f]quinoline-7-carboxylic acid;xi. (17S)-17-acetyl-7,8,13,15,16,17-hexahydro-3-hydroxy-1-methyl-6H-cyclopenta [a]phenanthren-11(9H,12H,14H)-one;xii. (13S,17S)-17-acetyl-7,8,13,15,16,17-hexahydro-3-hydroxy-13-methyl-6H-cyclopenta[a]phenanthren-11(9H,12H,14H)-one;xiii. (10R,11S,13S,17S)-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid;xiv. (10R,11S,13S,17S)-11-hydroxy-N,N,10,13- ...

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Номер записи: 99

28-08-2014 дата публикации

Process for the Production of Estetrol

Номер: US20140243539A1

Автор: Pascal Jean-Claude

Принадлежит: Estetra S.P.R.L.

The present invention relates to a process for the preparation of a compound of formula (I), hydrates or solvates thereof. 2. The process according to claim 1 , wherein Pis RSi(R)(R)— claim 1 , and Pis (R)Si(R)(R)—.3. The process according to or claim 1 , wherein the silylating agent is selected from Calkylsilylchloride claim 1 , Calkylsilyltriflate claim 1 , Carylsilyl chloride claim 1 , Carylsilyltriflate claim 1 , CalkylC6arylsilylchloride claim 1 , or CalkylC6arylsilyltriflate claim 1 , each group being optionally substituted by one or more substituents independently selected from fluoro or Calkyl.5. The process according to any one of to claim 1 , wherein in step (b) said oxidizing agent is potassium permanganate.6. The process according to claim 5 , wherein step (b) is performed in the presence of an acid.8. The process according to claim 7 , wherein Pis RCO—.11. The process according to claim 10 , wherein step (2) is a sulfinylation and the sulfinylation is performed by reacting the compound of formula (Va) with a base and with a sulfinylation reagent.12. The process according to claim 10 , wherein step (2) is a halogenation and the halogenation is performed by reacting the compound of formula (Va) with a halogenating reagent.13. The process according to any one of and claim 10 , wherein step (iii) and step (4) are performed using a reducing agent selected from metal hydride compounds.14. Process according to any one of to claim 10 , wherein the silylating agent is selected from Calkylsilylchloride claim 10 , Calkylsilyltriflate claim 10 , Carylsilylchloride claim 10 , Carylsilyltriflate claim 10 , CalkylCarylsilylchloride claim 10 , CalkylCarylsilyltriflate claim 10 , each group being optionally substituted by one or more substituents independently selected from fluoro or Calkyl.15. Process according to any one of to claim 10 , wherein the acylating agent is selected from CalkenylCalkanoates claim 10 , CalkenylCcycloalkanoate claim 10 , acyl chlorides and ...

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Номер записи: 100

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